Update of the Brazilian Guidelines for Valvular Heart Disease – 2020

Flavio Tarasoutchi Marcelo Westerlund Montera Auristela Isabel de Oliveira Ramos Roney Orismar Sampaio Vitor Emer Egypto Rosa Tarso Augusto Duenhas Accorsi Antonio de Santis João Ricardo Cordeiro Fernandes Lucas José Tachotti Pires Guilherme S. Spina Marcelo Luiz Campos Vieira Paulo de Lara Lavitola Walkiria Samuel Ávila Milena Ribeiro Paixão Tiago Bignoto Dorival Júlio Della Togna Evandro Tinoco Mesquita William Antônio de Magalhães Esteves Fernando Atik Alexandre Siciliano Colafranceschi Valdir Ambrósio Moises Alberto Takeshi Kiyose Pablo M. A. Pomerantzeff Pedro A. Lemos Fabio Sandoli de Brito Junior Clara Weksler Carlos Manuel de Almeida Brandão Robinson Poffo Ricardo Simões Salvador Rassi Paulo Ernesto Leães Ricardo Mourilhe-Rocha José Luiz Barros Pena Fabio Biscegli Jatene Márcia de Melo Barbosa Alexandre Abizaid Henrique Barbosa Ribeiro Fernando Bacal Carlos Eduardo Rochitte José Honório de Almeida Palma da Fonseca Samira Kaissar Nasr Ghorayeb Marcelo Antonio Cartaxo Queiroga Lopes Salvador Vicente Spina Ricardo H. Pignatelli José Francisco Kerr Saraiva About the authors

1. Introduction

There are currently a wide modalities of interventional strategies - both transcatheter and surgical - which can be indicated for patients with valvular heart diseases (VHD), with the objective of reducing the morbidity and mortality. The correct timing for indication and the type of interventional treatment are linked to the precise anatomical and functional diagnosis of the VHD, and comprehensive global evaluation of the patient. The 2020 Update of the Brazilian Guidelines for VHD, in addition to compiling scientific evidence and expert opinion, continues with the ideal of being useful in supporting decision making for patients with VHD, and has three unique characteristics, namely:

  • Maintenance of the innovative flowcharts proposed in the 2017 edition, with sequential steps guiding anatomical, etiological, and functional diagnosis, defining conduct aligned with best practices and rational use of resources (Figure 1);

  • The increase of the recommendations number in the attempt to contemplate the diverse possibilities in view of increasing complexity of patients;

  • Comparison of the recommendations of these guidelines with the leading international ones, the American College of Cardiology/American Heart Association (ACC/AHA) 2017 and the European Society of Cardiology/European Association for Cardiothoracic Surgery (ESC/EACTS) 2017 Guidelines, allowing for individualization of the Brazilian population.11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.

Figure 1
Flowchart showing steps of anatomical, etiological, and functional diagnosis, in addition to the intervention decision making.

This 2020 edition considers the evaluation process for patients with non-severe VHD, and it emphasizes the need to weigh the possibility of transcatheter intervention in elderly patients, regardless of surgical risk, in addition patients with native or prosthetic valves with high surgical risk. Notwithstanding great advances and increased availability of imaging exams, these guidelines maintain the recommendation of detailed clinical evaluation, which continues to be indispensable to diagnosis, decisions making, and the doctor-patient relationship.

Bellow, the 5 recommended steps:

  • First step: verify whether the VHD is anatomically severe; if so, proceed to the second step. In the event of non-severe valvular disease, investigate differential diagnoses in symptomatic patients and monitor evolution in asymptomatic patients;

  • Second step: evaluate etiology, including clinical and past history, beside complementary exams;

  • Third step: evaluate symptoms; this is fundamental to intervention decision making. Pharmacological treatment is indicated to alleviate symptoms until interventional takes place;

  • Fourth step: evaluation of anatomical and/or functional prognostic factors (especially pulmonary hypertension [PH], ventricular remodeling, systolic dysfunction, aneurysmatic dilation of the aorta, and atrial fibrillation [AF]). This can be decisive regarding intervention in asymptomatic patients;

  • Fifth step: type of intervention. The procedure can be surgical or transcatheter, with individualized indication depending on operative risks, comorbidities, and the Heart Team’s decision.

2. The Heart Team

The Heart Team is a group of different professionals with experience in valve diseases who share the decision regarding the most appropriate treatment for a given patient. Given the wide variety of interventional strategies available, the Heart Team is fundamental to risk-benefit and cost-effectiveness analyses and decision making. The Heart Team comprises diverse cardiological subspecialties; the members will play different fundamental roles during each step of care, from the clinical cardiologist, who is responsible for patient selection and indication, besides pre- and post-intervention follow-up, to the cardiac surgeon and the hemodynamicist, who will be responsible to perform the procedures indicated by the Heart Team. The radiologist will also be important to data analysis in order to evaluate the technical possibility of each intervention, and the echocardiographer, in addition to evaluating preoperative data, will also monitor the procedure, collaborating for better results.11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.

3. Operative Risk Evaluation

Indication of intervention for patients with VHD should always be based on the benefits and risks of the proposed procedure. For this purpose, we utilize online scores, including the EuroSCORE II (http://www.euroscore.org/calc.html) and the Society of Thoracic Surgeons (STS) score (http://riskcalc.sts.org/stswebriskcalc/#/calculate), which have been validated in different populations regarding their predictive ability of 30-day mortality. Patients with STS < 4% are conventionally considered at low surgical risk, while those with scores between 4% and 8% have intermediate risk, and those with scores > 8% have high risk. Rearding the EuroSCORE II, patients are considered low risk when it is lower than 4%, and, if the score is > 4%, they are considered at high surgical risk. In the event of a discrepancy between the two scores, we must use the one whose estimated higher risk.33. O'Brien SM, Shahian DM, Filardo G, Ferraris VA, Haan CK, Rich JB, et al. The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 2—isolated valve surgery. Ann Thorac Surg. 2009;88(1):S23-S42.88. Barili F, Pacini D, Capo A, Rasovic O, Grossi C, Alamanni F, et al. Does EuroSCORE II perform better than its original versions? A multicentre validation study. Eur Heart J. 2013;34(1):22-9.

It is important to point that both scores omit some factors related to prognostic outcomes, such as frailty and specific contraindications to procedures, such as porcelain aorta. Furthermore, risk evaluation does not substitute the individual clinical evaluation, and the decision regarding intervention should always be shared with patients and their families.

4. Frailty

Frailty is an entity that denotes a state of vulnerability in elderly patients, associated with physical weakness and low physiological reserve. It is extremely relevant to individualized evaluation, mainly due to the following two factors:

  1. It is a predictor of events, such as mortality, length of hospital stay, and functional decline, after surgical or transcatheter intervention;

  2. It is not taken into consideration in conventional risk scores.

Several scores and tools are available for evaluating and quantifying frailty, through measurement of data related to functional status, instrumental daily activities, nutrition, cognition, independence for activities, and other factors. It is important that evaluation of frailty is not only subjective (“eyeball test”), but rather a set of clinical impression associated with different objective measurements and scores.99. Lee DH, Buth KJ, Martin B-J, Yip AM, Hirsch GM. Frail patients are at increased risk for mortality and prolonged institutional care after cardiac surgery. Circulation. 2010;121(8):973-8.1414. Katz S, Downs TD, Cash HR, Grotz RC. Progress in development of the index of ADL. Gerontologist. 1970;10(1_Part_1):20-30.

5. Mitral Stenosis

Physical examination is the first resource applied for anatomical evaluation of mitral stenosis (MS). Patients with mild to moderate MS may already present an opening snap as well as a decrescendo rumbling diastolic murmur in the mitral area, starting immediately after the click. In patients in sinus rhythm, the murmur shows presystolic reinforcement in the end of diastole. In patients with severe MS, however, these clinical changes become more evident, as electrocardiographic and radiologic changes get evident. The characteristics present in patients with severe MS are shown in Table 1.

Table 1
Step 1: Diagnosis of severe mitral stenosis1515. Nishimura RA, Vahanian A, Eleid MF, Mack MJ. Mitral valve disease—current management and future challenges. Lancet. 2016;387(10025):1324-34.

Echocardiography is the main complementary exam for mitral valve anatomical evaluation, and it is fundamental for defining the severity of VHD, hemodynamic repercussions, and parameters regarding intervention success, with evaluation of the components of the valve (valve annulus, valve cusps, and subvalvular apparatus).

The echocardiographic parameters of severe MS are mitral valve area (MVA), which may be measured by planimetry, pressure half time (PHT), or the continuity equation, and transmitral diastolic gradient.1515. Nishimura RA, Vahanian A, Eleid MF, Mack MJ. Mitral valve disease—current management and future challenges. Lancet. 2016;387(10025):1324-34.

From the epidemiological point of view (Table 2), the main etiology of MS continues to be rheumatic fever (RF), which remains prevalent in developing countries, including Brazil. In these countries, rheumatic valve disease maintains an estimated prevalence of 1 to 7 per 1,000 children in clinical studies; this number is up to 10 times higher when echocardiography is used for population screening. Regarding developed countries, statistics indicate that MS is responsible for 9% of all VHD in Europe, and 0.1% in the United States. In these countries, cases occur predominantly in elderly patients and young immigrants from developing countries.1616. Iung B, Vahanian A. Epidemiology of valvular heart disease in the adult. Nat Rev Cardiol. 2011;8(3):162- 72.1818. Iung B, Baron G, Butchart EG, Delahaye F, Gohlke-Bärwolf C, Levang OW, et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. Eur Heart J. 2003;24(13):1231-43.

Table 2
Step 2: Evaluation of etiology of severe mitral stenosis 1616. Iung B, Vahanian A. Epidemiology of valvular heart disease in the adult. Nat Rev Cardiol. 2011;8(3):162- 72.,1717. Banovic M, Da Costa M. Degenerative mitral stenosis: from pathophysiology to challenging interventional treatment. Curr Probl Cardiol. 2019;44(1):10-35.

In addition to the rheumatic etiology, there is a proportional increase in the number of patients with mitral annulus calcification (MAC), which may extend to the base of the valve leaflets, leading to restricted cusp movement and restriction of atrial emptying. The estimated prevalence of MAC is around 10% of the elderly population and approximately 1% to 2% of these patients develop MS.1919. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet. 2006;368(9540):1005-11.

Other rare causes of MS include: rheumatologic diseases (systemic lupus erythematosus or rheumatoid arthritis), deposit diseases (such as Fabry disease), Whipple disease, therapy with methysergide or anorexigenic drugs, carcinoid syndrome, or congenital anatomical abnormalities of the mitral valve, such as parachute mitral valve or mitral valve hypoplasia.

In patients with severe MS, it is necessary to pay attention to the symptoms (Table 3), the most common being dyspnea (New York Heart Association [NYHA] functional class [FC] II to IV). In particular, dyspnea may appear in situations that lead to increased pulmonary capillary pressure (physical exertion, pregnancy, or AF). Over time, it may also appear at rest, even with orthopnea. Other symptoms that may appear are palpitations, hemoptysis, dysphonia, dysphagia, cough, and embolic events.

Table 3
Evaluation of severe mitral stenosis symptoms

In parallel to the evaluation of symptoms, possible prognostic factors should be investigated (Table 4). With respect to severe MS, relevant signals are the presence of significant PH (systolic pulmonary artery pressure – SPAP above 50 mmHg when resting or above 60 mmHg during exertion) or recent onset AF (triggered in the recent months).

Table 4
Step 4: Evaluation of severe mitral stenosis prognostic factors

Types of intervention and their indications are described in Tables 5 and 6 and Figure 2. Percutaneous balloon mitral valvuloplasty (PBMV) remains the treatment of choice for patients with MS of rheumatic etiology, wherein calcification and commissural fusion are predominant. There is need for favorable valve anatomy (as evaluated by the Wilkins-Block score [Table 7]) and no procedure contraindications (moderate to severe mitral regurgitation [MR] and left atrium [LA] thrombus). The Wilkins-Block score consists of echocardiographic evaluation of the mitral valve, with emphasis on description of structural aspects. The following four parameters are taken into consideration: leaflet mobility, valve thickening, degree of cuspid calcification, and involvement of the subvalvular apparatus. Values from 1 to 4 points for each item result in scores ranging from 4 to 16 points. Patients with Wilkins-Block score less than or equal to 8 are candidates for PBMV, since there are no contraindications. Surgical treatment of the mitral valve is the treatment of choice for patients with unfavorable anatomy or contraindications for PBMV in the presence of symptoms (NYHA FC III or IV) or prognostic factors. Surgery may consist of mitral commissurotomy or, in cases of very significant valve impairment, valve replacement with a biological or mechanical prosthesis.2020. Meneguz-Moreno RA, Costa JR, Gomes NL, Braga SL, Ramos AI, Meneghelo Z, et al. Very long term follow-up after percutaneous balloon mitral valvuloplasty. JACC: Cardiovasc Interv. 2018;11(19):1945-52.,2121. Mitrev L, Desai N, Awad A, Sabir S, editors. Interventional Echocardiography of the MV: what the interventionalist wants to know. Semin Cardiothorac Vasc Anesth.2019;23(1):37-47.

Table 5
Step 5: Type of mitral stenosis intervention1515. Nishimura RA, Vahanian A, Eleid MF, Mack MJ. Mitral valve disease—current management and future challenges. Lancet. 2016;387(10025):1324-34.,1717. Banovic M, Da Costa M. Degenerative mitral stenosis: from pathophysiology to challenging interventional treatment. Curr Probl Cardiol. 2019;44(1):10-35.,2020. Meneguz-Moreno RA, Costa JR, Gomes NL, Braga SL, Ramos AI, Meneghelo Z, et al. Very long term follow-up after percutaneous balloon mitral valvuloplasty. JACC: Cardiovasc Interv. 2018;11(19):1945-52.2525. Sud K, Agarwal S, Parashar A, Raza MQ, Patel K, Min D, et al. Degenerative mitral stenosis: unmet need for percutaneous interventions. Circulation. 2016;133(16):1594-604.
Table 6
Mitral stenosis: Recommendations11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.,1515. Nishimura RA, Vahanian A, Eleid MF, Mack MJ. Mitral valve disease—current management and future challenges. Lancet. 2016;387(10025):1324-34.,1717. Banovic M, Da Costa M. Degenerative mitral stenosis: from pathophysiology to challenging interventional treatment. Curr Probl Cardiol. 2019;44(1):10-35.,2020. Meneguz-Moreno RA, Costa JR, Gomes NL, Braga SL, Ramos AI, Meneghelo Z, et al. Very long term follow-up after percutaneous balloon mitral valvuloplasty. JACC: Cardiovasc Interv. 2018;11(19):1945-52.2525. Sud K, Agarwal S, Parashar A, Raza MQ, Patel K, Min D, et al. Degenerative mitral stenosis: unmet need for percutaneous interventions. Circulation. 2016;133(16):1594-604.
Table 7
Wilkins-Block echocardiographic score
Figure 2
Flowchart for decision making in mitral stenosis. AF: atrial fibrillation; PBMV: percutaneous balloon mitral valvuloplasty.

For patients with degenerative MS, on the other hand, PBMV is not a therapeutic option, as there is no commissural fusion or calcification, but rather valve annulus calcification. Furthermore, in these patients, who are usually elderly and often have multiple comorbidities, surgical risk is significantly higher. The surgical procedure is technical difficulty and is more likely to have complications, including atrioventricular disjunction, circumflex artery injury, and ventricular wall bleeding. The initial treatment of choice is, thus, clinical: heart rate control with betablockers, calcium channel blocker or ivabradine (for patients in sinus rhythm who have not tolerated previous medications), associated with diuretics.2222. Ghadimi N, Kaveh S, Shabaninejad H, Lijassi A, Mehr AZ, Hosseinifard H. Comparative efficacy of ivabradine versus beta-blockers in patients with mitral stenosis in sinus rhythm: systematic review and meta-analysis. Int J Clin Pharm. 2019;41(1):22-9. If this strategy works, patients may continue with medical treatment, without indication for further interventions. For patients who are refractory to clinical treatment, however, it is necessary to consider the possibility of surgical intervention, in cases with low to moderate risk, or eventual transcatheter implantation of a mitral prosthesis. In these cases, transcatheter implantation uses the MAC to support the valve prosthesis, in a procedure routinely referred to as valve-in-MAC. There is still limited experience with this procedure, which is most frequently performed in clinical studies via the transeptal or transapical route. It still has a high rate of complications, including paravalvular leak, left ventricle (LV) outflow tract obstruction, and prosthesis embolization, and the mortality rate may reach 25% in 30 days and 54% in 12 months. Further studies are needed in order to broaden its indications.2323. Guerrero M, Dvir D, Himbert D, Urena M, Eleid M, Wang DD, et al. Transcatheter mitral valve replacement in native mitral valve disease with severe mitral annular calcification: results from the first multicenter global registry. JACC: Cardiovasc Interv. 2016;9(13):1361-71.2525. Sud K, Agarwal S, Parashar A, Raza MQ, Patel K, Min D, et al. Degenerative mitral stenosis: unmet need for percutaneous interventions. Circulation. 2016;133(16):1594-604.

Clinical follow-up of patients, as long as they present non-severe VHD, consists of periodic consultations and echocardiographic reevaluation (Table 8). In patients with non-severe MS, reevaluation may be performed on a yearly basis. Patients with valve area ≥ 1.5 cm22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89. are not normally expected to develop symptoms or prognostic factors. In the event that these changes occur, before the patient develops anatomically severe VHD, it is imperative to consider the possibility that other differential diagnoses are present. Patients with severe MS, on the other hand, should be reevaluated at shorter intervals, usually every 6 to 12 months.

Table 8
Mitral stenosis: Individualized follow-up11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.

6. Primary Chronic Mitral Regurgitation

For the clinical decision making in primary chronic MR, it is recommended that the 5 steps of the flowchart for treating VHD are followed, as detailed below and subsequently summarized in Figure 3.

Figure 3
Flowchart for decision making in primary chronic mitral regurgitation. AF: atrial fibrillation; LVEF: left ventricular ejection fraction; LVSD: left ventricular systolic diameter; SPAP: systolic pulmonary artery pressure.

In addition to confirming the presence of VHD, transthoracic echocardiogram is the main exam used to define the anatomical severity of MR. Diverse parameters may be used for this quantification; detailed, thorough examination is of fundamental importance (Table 9).

Table 9
Step 1: Diagnosis of severe primary mitral regurgitation26-32

Patients with anatomically mild or moderate MR should continue with periodic clinical and echocardiographic follow-up, and there is no indication for intervention (medical or surgical) in order to interrupt the natural history of the valve disease. On the other hand, patients with severe MR should proceed as per the flowchart for specific evaluation, investigating symptoms that are secondary to the VHD and/or the presence of prognostic factors.

In patients with MR, it is necessary to define the etiology of the VHD, given that clinical follow-up and therapeutic planning (timing and type of intervention), when indicated, can be different according to the cause of MR (Table 10). In spite of advances in diagnostic tests, transthoracic echocardiogram remains the first and main exam indicated for anatomical quantification and etiological evaluation of patients with MR. 3333. Krivokapich J, Child JS, Dadourian BJ, Perloff JK. Reassessment of echocardiographic criteria for diagnosis of mitral valve prolapse. Am J Cardiol. 1988;61(1):131-5.3535. Boudoulas H, Kolibash AJ Jr, Baker P, King BD, Wooley CF. Mitral valve prolapse and the mitral valve prolapse syndrome: a diagnostic classification and pathogenesis of symptoms. Am Heart J. 1989;118(4):796-818.

Table 10
Step 2: Evaluation of severe primary mitral regurgitation etiology3333. Krivokapich J, Child JS, Dadourian BJ, Perloff JK. Reassessment of echocardiographic criteria for diagnosis of mitral valve prolapse. Am J Cardiol. 1988;61(1):131-5.3535. Boudoulas H, Kolibash AJ Jr, Baker P, King BD, Wooley CF. Mitral valve prolapse and the mitral valve prolapse syndrome: a diagnostic classification and pathogenesis of symptoms. Am Heart J. 1989;118(4):796-818.

The main symptom in patients with anatomically severe MR is dyspnea, which should be taken in account, even if it does not limit routine activities (NYHA FC II). If there are doubts regarding the presence of symptoms, an exercise test or cardiopulmonary test may be requested (Table 11). Once the presence of symptoms has been confirmed, and if they are secondary to MR, patients should be referred for valvular intervention, as described in Step 5 (Table 12).

Table 11
Step 3: Evaluation of severe primary mitral regurgitation symptoms
Table 12
Step 5: Type of severe primary mitral regurgitation intervention3939. Rosa VEE, Fernandes JRC, Lopes ASdSA, Accorsi TAD, Tarasoutchi F. Recommendation of early surgery in primary mitral regurgitation: pros and cons. Arq Bras Cardiol. 2016;107(2):173-5.5252. Feldman T, Kar S, Rinaldi M, Fail P, Hermiller J, Smalling R, et al. Percutaneous mitral repair with the MitraClip system: safety and midterm durability in the initial EVEREST (Endovascular Valve Edge-to-Edge REpair Study) cohort. J Am Coll Cardiol. 2009;54(8):686-94.

Patients with severe asymptomatic MR should be periodically reevaluated to determine the development of anatomical and/or functional changes secondary to valve disease (Table 13). The following prognostic factors are associated with MR: LV systolic dysfunction (left ventricular ejection fraction [LVEF] < 60%), LV dilation (left ventricular systolic diameter [LVSD] ≥ 40 mm), PH (SPAP ≥ 50 mmHg at rest or ≥ 60 mmHg during exertion), and new onset AF (recent months).3636. Avierinos J-F, Gersh BJ, Melton Iii LJ, Bailey KR, Shub C, Nishimura RA, et al. Natural history of asymptomatic mitral valve prolapse in the community. Circulation. 2002;106(11):1355-61.3838. Grigioni F, Avierinos J-F, Ling LH, Scott CG, Bailey KR, Tajik AJ, et al. Atrial fibrillation complicating the course of degenerative mitral regurgitation: determinants and long-term outcome. J Am Coll Cardiol. 2002;40(1):84-92. Increased LA volume (especially ≥ 60 ml/m22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.) may be considered an anatomical prognostic factor in MR, and it should be taken into consideration for intervention decision, given that it is associated with worse prognosis. In addition, if there is a progressive decline in LVEF or progressive dilation of the LV on serial imaging tests, mitral valve intervention should be considered, even before the previously mentioned limits have been reached.

Table 13
Step 4: Evaluation of severe primary mitral regurgitation prognostic factors3636. Avierinos J-F, Gersh BJ, Melton Iii LJ, Bailey KR, Shub C, Nishimura RA, et al. Natural history of asymptomatic mitral valve prolapse in the community. Circulation. 2002;106(11):1355-61.3838. Grigioni F, Avierinos J-F, Ling LH, Scott CG, Bailey KR, Tajik AJ, et al. Atrial fibrillation complicating the course of degenerative mitral regurgitation: determinants and long-term outcome. J Am Coll Cardiol. 2002;40(1):84-92.

After confirming the existence of anatomically severe MR, with a defined etiology, and, finally, verifying the presence of symptoms that are secondary to the VHD and/or the presence of prognostic factors, the patient should be referred for valvular intervention, if there is no contraindication (Table 13 and 14). In these cases, surgical mitral repair is the treatment of choice, provided that the etiology (especially prolapse) and the anatomy are favorable and that the procedure is performed in a qualified hospital with an experienced surgeon. Otherwise, surgical mitral valve replacement is indicated.3939. Rosa VEE, Fernandes JRC, Lopes ASdSA, Accorsi TAD, Tarasoutchi F. Recommendation of early surgery in primary mitral regurgitation: pros and cons. Arq Bras Cardiol. 2016;107(2):173-5.5252. Feldman T, Kar S, Rinaldi M, Fail P, Hermiller J, Smalling R, et al. Percutaneous mitral repair with the MitraClip system: safety and midterm durability in the initial EVEREST (Endovascular Valve Edge-to-Edge REpair Study) cohort. J Am Coll Cardiol. 2009;54(8):686-94.

Table 14
Primary mitral regurgitation: Recommendations11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.,3939. Rosa VEE, Fernandes JRC, Lopes ASdSA, Accorsi TAD, Tarasoutchi F. Recommendation of early surgery in primary mitral regurgitation: pros and cons. Arq Bras Cardiol. 2016;107(2):173-5.5252. Feldman T, Kar S, Rinaldi M, Fail P, Hermiller J, Smalling R, et al. Percutaneous mitral repair with the MitraClip system: safety and midterm durability in the initial EVEREST (Endovascular Valve Edge-to-Edge REpair Study) cohort. J Am Coll Cardiol. 2009;54(8):686-94.

Indication of transcatheter interventions is restricted to patients with primary MR, and the decision should be made following discussion with the Heart Team. In the same manner, for patients with contraindication or high risk associated with conventional surgery, prior discussion with the Heart Team needs to take place for the best decision making.

When patients, notwithstanding the presence of anatomically severe MR, do not show symptoms or have prognostic factors, they should receive individualized follow-up, with biannual clinical follow-up and echocardiographic evaluation at maximum 1-year intervals (Table 15).

Table 15
Primary mitral regurgitation: Individualized follow-up11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.

On the other hand, patients with anatomically moderate MR should receive annual clinical evaluation and undergo echocardiogram every 2 years.

7. Secondary Mitral Regurgitation

Secondary MR results from ventricular changes (dysfunction and/or dilation), while the mitral valve leaflets and chordae are normal. In this context, additional LV overload occurs due to mitral regurgitation, culminating in worse prognosis. The main etiologies are coronary artery disease (ischemic MR) and dilated cardiomyopathy (annular dilation and/or poor positioning). For these reasons, the ideal treatment is controversial, given that valve correction is not curative. In general, intervention is indicated in patients who remain symptomatic, in spite of optimized medical treatment. Even so, the therapeutic decision must be individualized and, whenever possible, shared with the Heart Team.5353. Grigioni F, Enriquez-Sarano M, Zehr KJ, Bailey KR, Tajik AJ. Ischemic mitral regurgitation: long-term outcome and prognostic implications with quantitative Doppler assessment. Circulation. 2001;103(13):1759-64.

As physical examination for diagnosis of secondary MR is often poor, transthoracic echocardiogram is a fundamental test. There is evidence that lower limits of the regurgitant orifice area and the regurgitant volume are associated with worse prognosis, in comparison with primary MR. Nevertheless, for quantification of anatomical severity of secondary MR, the echocardiographic limits applied are the same as those for primary MR. In the event of disagreement between clinical and echocardiographic findings, hemodynamic study with left ventriculography or magnetic resonance may assist in definition (Table 16).2727. Uretsky S, Gillam L, Lang R, Chaudhry FA, Argulian E, Supariwala A, et al. Discordance between echocardiography and MRI in the assessment of mitral regurgitation severity: a prospective multicenter trial. J Am Coll Cardiol. 2015;65(11):1078-88.3232. Uretsky S, Argulian E, Supariwala A, Marcoff L, Koulogiannis K, Aldaia L, et al. A comparative assessment of echocardiographic parameters for determining primary mitral regurgitation severity using magnetic resonance imaging as a reference standard. J Am Soc Echocardiogr. 2018;31(9):992-9.,5454. Agricola E, Oppizzi M, Pisani M, Meris A, Maisano F, Margonato A. Ischemic mitral regurgitation: mechanisms and echocardiographic classification. European Journal of Echocardiography. 2008;9(2):207-21.

Table 16
Step 1: Diagnosis of severe secondary mitral regurgitation2727. Uretsky S, Gillam L, Lang R, Chaudhry FA, Argulian E, Supariwala A, et al. Discordance between echocardiography and MRI in the assessment of mitral regurgitation severity: a prospective multicenter trial. J Am Coll Cardiol. 2015;65(11):1078-88.3232. Uretsky S, Argulian E, Supariwala A, Marcoff L, Koulogiannis K, Aldaia L, et al. A comparative assessment of echocardiographic parameters for determining primary mitral regurgitation severity using magnetic resonance imaging as a reference standard. J Am Soc Echocardiogr. 2018;31(9):992-9.,5454. Agricola E, Oppizzi M, Pisani M, Meris A, Maisano F, Margonato A. Ischemic mitral regurgitation: mechanisms and echocardiographic classification. European Journal of Echocardiography. 2008;9(2):207-21.

Echocardiogram provides the main information required for establishing the etiology of secondary MR, especially regarding analysis of LV changes (Table 17). Coronary cineangiography, in turn, plays an important role in diagnosis of obstructive coronary artery disease, which may be the cause of MR.5353. Grigioni F, Enriquez-Sarano M, Zehr KJ, Bailey KR, Tajik AJ. Ischemic mitral regurgitation: long-term outcome and prognostic implications with quantitative Doppler assessment. Circulation. 2001;103(13):1759-64.

Table 17
Step 2: Evaluation of severe secondary mitral regurgitation etiology5353. Grigioni F, Enriquez-Sarano M, Zehr KJ, Bailey KR, Tajik AJ. Ischemic mitral regurgitation: long-term outcome and prognostic implications with quantitative Doppler assessment. Circulation. 2001;103(13):1759-64.

Tests for myocardial viability evaluation (such as nuclear magnetic resonance) may be useful in patients with ischemic MR who are scheduled for myocardial revascularization.

The main symptom present in patients with secondary MR is dyspnea, which may result from LV dysfunction and/or associated mitral regurgitation (Table 18).

Table 18
Step 3: Evaluation of severe secondary mitral regurgitation symptoms

Patients with important symptoms (NYHA FC III and IV) that persist in spite of optimized treatment for heart failure (including resynchronization therapy, when indicated) should be considered for intervention in an individualized manner.

There are no specific prognostic factors for patients with secondary MR, given that the origin of the problem lies in ventricular disease (Table 19). Nonetheless, in the event that LV dilation and/or dysfunction worsen, without any clear causal factor, the concomitant mitral valve disease may be considered responsible.5555. Le Tourneau T, Richardson M, Juthier F, Modine T, Fayad G, Polge AS, et al. Echocardiography predictors and prognostic value of pulmonary artery systolic pressure in chronic organic mitral regurgitation. Heart. 2010;96(16):1311-7.,5656. Asgar AW, Mack MJ, Stone GW. Secondary mitral regurgitation in heart failure: pathophysiology, prognosis, and therapeutic considerations. J Am Coll Cardiol. 2015;65(12):1231-48.

Table 19
Step 4: Evaluation of severe secondary mitral regurgitatio nprognostic factors5555. Le Tourneau T, Richardson M, Juthier F, Modine T, Fayad G, Polge AS, et al. Echocardiography predictors and prognostic value of pulmonary artery systolic pressure in chronic organic mitral regurgitation. Heart. 2010;96(16):1311-7.,5656. Asgar AW, Mack MJ, Stone GW. Secondary mitral regurgitation in heart failure: pathophysiology, prognosis, and therapeutic considerations. J Am Coll Cardiol. 2015;65(12):1231-48.

Indication of intervention for patients with secondary MR is controversial (Tables 20 e 21). In patients with ischemic MR who are candidates for myocardial revascularization surgery, simultaneous approach to the mitral valve disease should be considered. On the other hand, in patients who are not indicated for revascularization, isolated surgical approach to MR is associated with high mortality and high rates of MR recurrence, and there is no evidence of its benefit in terms of survival.5353. Grigioni F, Enriquez-Sarano M, Zehr KJ, Bailey KR, Tajik AJ. Ischemic mitral regurgitation: long-term outcome and prognostic implications with quantitative Doppler assessment. Circulation. 2001;103(13):1759-64.,5757. Grossi EA, Goldberg JD, LaPietra A, Ye X, Zakow P, Sussman M, et al. Ischemic mitral valve reconstruction and replacement: comparison of long-term survival and complications. J Thorac Cardiovasc Surg. 2001;122(6):1107-24.6666. Tatum JM, Bowdish ME, Mack WJ, Quinn AM, Cohen RG, Hackmann AE, et al. Outcomes after mitral valve repair. A single-center 16-year experience. J Thorac Cardiovasc Surg. 2017;154(3):822-30.

Table 20
Step 5: Type of severe secondary mitral regurgitatio n intervention5353. Grigioni F, Enriquez-Sarano M, Zehr KJ, Bailey KR, Tajik AJ. Ischemic mitral regurgitation: long-term outcome and prognostic implications with quantitative Doppler assessment. Circulation. 2001;103(13):1759-64.,5757. Grossi EA, Goldberg JD, LaPietra A, Ye X, Zakow P, Sussman M, et al. Ischemic mitral valve reconstruction and replacement: comparison of long-term survival and complications. J Thorac Cardiovasc Surg. 2001;122(6):1107-24.7272. Alkhouli M, Wolfe S, Alqahtani F, Aljohani S, Mills J, Gnegy S, et al. The feasibility of transcatheter edge-to-edge repair in the management of acute severe ischemic mitral regurgitation. JACC: Cardiovasc Interv. 2017;10(5):529-31.
Table 21
Secondary mitral regurgitation: Recommendations11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.,5353. Grigioni F, Enriquez-Sarano M, Zehr KJ, Bailey KR, Tajik AJ. Ischemic mitral regurgitation: long-term outcome and prognostic implications with quantitative Doppler assessment. Circulation. 2001;103(13):1759-64.,5757. Grossi EA, Goldberg JD, LaPietra A, Ye X, Zakow P, Sussman M, et al. Ischemic mitral valve reconstruction and replacement: comparison of long-term survival and complications. J Thorac Cardiovasc Surg. 2001;122(6):1107-24.7272. Alkhouli M, Wolfe S, Alqahtani F, Aljohani S, Mills J, Gnegy S, et al. The feasibility of transcatheter edge-to-edge repair in the management of acute severe ischemic mitral regurgitation. JACC: Cardiovasc Interv. 2017;10(5):529-31.

In patients with MR secondary to dilated cardiomyopathy, indication of intervention in mitral valve disease is even more restricted. While isolated mitral valve surgery has not demonstrated a benefit in this scenario, new evidences have shown a benefit to transcatheter intervention in patients with secondary MR and LVEF ≥ 20%, who remained symptomatic in spite of optimized clinical treatment, provided that the procedure is not indicated in more advanced phases of the natural history of VHD. 6767. Iung B, Armoiry X, Vahanian A, Boutitie F, Mewton N, Trochu JN, et al. Percutaneous repair or medical treatment for secondary mitral regurgitation: outcomes at 2 years. Eur J Heart Fail.2019;21(12):1619-27.7272. Alkhouli M, Wolfe S, Alqahtani F, Aljohani S, Mills J, Gnegy S, et al. The feasibility of transcatheter edge-to-edge repair in the management of acute severe ischemic mitral regurgitation. JACC: Cardiovasc Interv. 2017;10(5):529-31.

For more appropriate indication and more thorough approach, cases of secondary MI should be discussed with the Heart Team before the decision is made (Figure 4).

Figure 4
Flowchart for decision making in secondary mitral regurgitation.FC: functional class.

8. Aortic Stenosis

Aortic stenosis (AS) shows a growing prevalence due to increased life expectancy and consequent aging of the Brazilian population. The most common cause of AS is aortic calcification/degeneration, which mainly affects elderly patients. Transcatheter treatment has become an alternative to surgical valve replacement, not only in frail and high-risk patients, but also in patients with intermediate or low risk. Therefore, Heart Team is becoming increasingly important and necessary in decision making regarding intervention in these patients.73

According to current evidence and following the recommendations of the 2017 Brazilian guidelines, the first step for evaluating patients with AS is to define the VHD severity (Table 22). To date, only patients with anatomically severe AS benefit from intervention. Severe AS is defined in echocardiography as an aortic valve area (AVA) ≤ 1.0 cm² and/or indexed AVA ≤ 0.6 cm²/m² in the presence of mean transaortic gradient ≥ 40 mmHg or maximum aortic jet velocity ≥ 4.0 m/s. Patients with low-flow, low-gradient AS (AVA ≤ 1.0 cm² and mean transaortic gradient < 40 mmHg), once anatomical severity has been confirmed, may also undergo intervention. In cases with low-flow, low-gradient AS and preserved LVEF, it is necessary to measure aortic calcium score (severe AS if over 1,300 AU for women and over 2,000 AU for men).7474. Clavel M-A, Pibarot P, Messika-Zeitoun D, Capoulade R, Malouf J, Aggarval S, et al. Impact of aortic valve calcification, as measured by MDCT, on survival in patients with aortic stenosis: results of an international registry study. J Am Coll Cardiol. 2014;64(12):1202-13.8282. Minners J, Allgeier M, Gohlke-Baerwolf C, Kienzle RP, Neumann FJ, Jander N. Inconsistent grading of aortic valve stenosis by current guidelines: haemodynamic studies in patients with apparently normal left ventricular function. Heart. 2010;96(18):1463-8. In patients with low-flow, low-gradient AS and low LVEF, dobutamine stress echocardiogram is indicated. Severe AS is defined when, in the presence of contractile reserve, AVA remains reduced,.8383. Clavel MA, Magne J, Pibarot P. Low-gradient aortic stenosis. Eur Heart J. 2016;37(34):2645-57.8686. deFilippi CR, Willett DL, Brickner ME, Appleton CP, Yancy CW, Eichhorn EJ, et al. Usefulness of dobutamine echocardiography in distinguishing severe from nonsevere valvular aortic stenosis in patients with depressed left ventricular function and low transvalvular gradients. Am J Cardiol. 1995;75(2):191-4. In the absence of contractile reserve, it is also necessary to measure valve calcium score in order to define anatomical severity.7474. Clavel M-A, Pibarot P, Messika-Zeitoun D, Capoulade R, Malouf J, Aggarval S, et al. Impact of aortic valve calcification, as measured by MDCT, on survival in patients with aortic stenosis: results of an international registry study. J Am Coll Cardiol. 2014;64(12):1202-13.7878. Pawade T, Sheth T, Guzzetti E, Dweck MR, Clavel M-A. Why and how to measure aortic valve calcification in patients with aortic stenosis. JACC: Cardiovasc Imaging. 2019;12(9):1835-48.,8787. Cueff C, Serfaty J-M, Cimadevilla C, Laissy J-P, Himbert D, Tubach F, et al. Measurement of aortic valve calcification using multislice computed tomography: correlation with haemodynamic severity of aortic stenosis and clinical implication for patients with low ejection fraction. Heart. 2011;97(9):721-6. Patients with no contractile reserve also benefit from surgical or transcatheter intervention.

Table 22
Step 1: Diagnosis of severe aortic stenosis7474. Clavel M-A, Pibarot P, Messika-Zeitoun D, Capoulade R, Malouf J, Aggarval S, et al. Impact of aortic valve calcification, as measured by MDCT, on survival in patients with aortic stenosis: results of an international registry study. J Am Coll Cardiol. 2014;64(12):1202-13.8787. Cueff C, Serfaty J-M, Cimadevilla C, Laissy J-P, Himbert D, Tubach F, et al. Measurement of aortic valve calcification using multislice computed tomography: correlation with haemodynamic severity of aortic stenosis and clinical implication for patients with low ejection fraction. Heart. 2011;97(9):721-6.

The second step is the evaluation of etiology (Table 23).8888. Zusman O, Pressman GS, Banai S, Finkelstein A, Topilsky Y. Intervention versus observation in symptomatic patients with normal flow low gradient severe aortic stenosis. JACC: Cardiovasc Imaging. 2018;11(9):1225-32.,8989. Carter Storch R, Møller JE, Christensen NL, Irmukhadenov A, Rasmussen LM, Pecini R, et al. Postoperative reverse remodeling and symptomatic improvement in normal-flow low-gradient aortic stenosis after aortic valve replacement. Circ Cardiovasc Imaging. 2017;10(12):e006580. In developed countries, there is greater prevalence of degenerative/calcification etiology in elderly patients, whereas, in developing countries, rheumatic and bicuspid etiologies are predominant in young patients. In Brazil, we may observe a bimodal peak in the prevalence AS. In other words, there are patients with all etiologies in different age ranges due to the transitional age pyramid typical of developing countries. The etiology of AS also reflects in the choice of treatment (Step 5). Patients with rheumatic AS are usually young, and have not been considered in transcatheter aortic valve implantation (TAVI) studies. The majority of patients studied had degenerative etiology. There is, however, already evidence regarding the procedure’s feasibility in patients with bicuspid aortic valve.9090. Takagi H, Hari Y, Kawai N, Kuno T, Ando T, Group A. Meta-analysis of transcatheter aortic valve implantation for bicuspid versus tricuspid aortic valves. J Cardiol. 2019;74(1):40-8.

Table 23
Step 2: Evaluation of severe aortic stenosis etiology8888. Zusman O, Pressman GS, Banai S, Finkelstein A, Topilsky Y. Intervention versus observation in symptomatic patients with normal flow low gradient severe aortic stenosis. JACC: Cardiovasc Imaging. 2018;11(9):1225-32.,8989. Carter Storch R, Møller JE, Christensen NL, Irmukhadenov A, Rasmussen LM, Pecini R, et al. Postoperative reverse remodeling and symptomatic improvement in normal-flow low-gradient aortic stenosis after aortic valve replacement. Circ Cardiovasc Imaging. 2017;10(12):e006580.

The third step is the evaluation of symptoms related to the VHD (Table 24). Intervention is unequivocally indicated for patients with severe AS and dyspnea, angina, or syncope.

Table 24
Step 3: Evaluation of severe aortic stenosis symptoms

In cases where there are no symptoms, we must evaluate the presence of prognostic factors that justify indication of intervention (Table 25).9191. Rosenhek R, Binder T, Porenta G, Lang I, Christ G, Schemper M, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med. 2000;343(9):611-7.9595. Dal Bianco JP, Khandheria BK, Mookadam F, Gentile F, Sengupta PP. Management of asymptomatic severe aortic stenosis. J Am Coll Cardiol. 2008;52(16):1279-92. The following prognostic factors are currently taken into consideration in the current guidelines:

Table 25
Step 4: Evaluation of severe aortic stenosis prognostic factors9191. Rosenhek R, Binder T, Porenta G, Lang I, Christ G, Schemper M, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med. 2000;343(9):611-7.9898. Das P, Rimington H, Chambers J. Exercise testing to stratify risk in aortic stenosis. Eur Heart J. 2005;26(13):1309-13.
  1. Echocardiogram: LV dysfunction (LVEF < 50%) and/or markers of very severe AS (AVA < 0.7 cm22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89., maximum aortic jet velocity > 5.0 m/s, mean transaortic gradient > 60 mmHg).9696. Connolly HM, Oh JK, Orszulak TA, Osborn SL, Roger VL, Hodge DO, et al. Aortic valve replacement for aortic stenosis with severe left ventricular dysfunction: prognostic indicators. Circulation. 1997;95(10):2395-400.

  2. Exercise test (ergometry): absence of inotropic reserve and/or low functional capacity, arterial hypotension during exertion (20 mmHg decrease in systolic arterial pressure) and/or presence of symptoms with low loads.9797. Amato M, Moffa P. Prognosis of asymptomatic aortic valve stenosis evaluated with exercise test. Arq Bras Cardiol. 1998;70(4):251-5.,9898. Das P, Rimington H, Chambers J. Exercise testing to stratify risk in aortic stenosis. Eur Heart J. 2005;26(13):1309-13.

The fifth and final step is choice of intervention (Tables 26 and 27 and Figures 5, 6, and 7). Transfemoral TAVI is preferable in relation to other thoracic access approaches (transaortic and transapical). Transfemoral approach is less invasive, and has a lower rate of complications. For this reason, other approachs are recommended only when there is a technical contraindication to femoral access.

Table 26
Step 5: Type of severe aortic stenosis intervention9090. Takagi H, Hari Y, Kawai N, Kuno T, Ando T, Group A. Meta-analysis of transcatheter aortic valve implantation for bicuspid versus tricuspid aortic valves. J Cardiol. 2019;74(1):40-8.,9999. Reardon MJ, Van Mieghem NM, Popma JJ, Kleiman NS, Søndergaard L, Mumtaz M, et al. Surgical or transcatheter aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2017;376(14):1321-31.132132. Kapadia SR, Goel SS, Yuksel U, Agarwal S, Pettersson G, Svensson LG, et al. Lessons learned from balloon aortic valvuloplasty experience from the pre-transcatheter aortic valve implantation era. J Interv Cardiol. 2010;23(5):499-508.
Table 27
Aortic stenosis: Recommendations11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.,9090. Takagi H, Hari Y, Kawai N, Kuno T, Ando T, Group A. Meta-analysis of transcatheter aortic valve implantation for bicuspid versus tricuspid aortic valves. J Cardiol. 2019;74(1):40-8.,9999. Reardon MJ, Van Mieghem NM, Popma JJ, Kleiman NS, Søndergaard L, Mumtaz M, et al. Surgical or transcatheter aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2017;376(14):1321-31.132132. Kapadia SR, Goel SS, Yuksel U, Agarwal S, Pettersson G, Svensson LG, et al. Lessons learned from balloon aortic valvuloplasty experience from the pre-transcatheter aortic valve implantation era. J Interv Cardiol. 2010;23(5):499-508.
Figure 5
Flowchart for decision making in aortic stenosis. BAV: balloon aortic valvuloplasty; ET: exercise test; LVEF: left ventricular ejection fraction; TAVI: transcatheter aortic valve implantation.
Figure 6
Flowchart for confirming anatomical severity of low-flow, low-gradient aortic stenosis with low ejection fraction. CT: computerized tomography; LVEF: left ventricular ejection fraction.
Figura 7
Flowchart for decision making in paradoxical aortic stenosis. BAV: balloon aortic valvuloplasty; BP: blood pressure; ET: exercise test; iAVA: indexed aortic valve area; LVEF: left ventricular ejection fraction; TAVI: transcatheter aortic valve implantation.

All current guidelines consider TAVI the preferred intervention, rather than surgery, for patients who are inoperable or frail and/or patients with high surgical risk (evaluated by the STS and EuroSCORE II scores).9999. Reardon MJ, Van Mieghem NM, Popma JJ, Kleiman NS, Søndergaard L, Mumtaz M, et al. Surgical or transcatheter aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2017;376(14):1321-31.113113. Webb JG, Pasupati S, Humphries K, Thompson C, Altwegg L, Moss R, et al. Percutaneous transarterial aortic valve replacement in selected high-risk patients with aortic stenosis. Circulation. 2007;116(7):755-63. However, following the publication of American and European guidelines, 4 studies comparing TAVI and surgery in patients with low surgical risk were published. Meta-analysis of these studies demonstrated reduced 1-year mortality in transfemoral TAVI. These results suggest that transfemoral TAVI should be the preferred treatment in these patients. However, it is relevant to note that the mean age of the studied population was 75.4 years. Thus, in low-risk patients, extending to intermediate risk, we should avoid TAVI in patients under 70 years of age, until more robust data have been published regarding the durability of the prostheses. 100100. Leon MB, Smith CR, Mack MJ, Makkar RR, Svensson LG, Kodali SK, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2016;374(17):1609-20.,114114. Blackman DJ, Saraf S, MacCarthy PA, Myat A, Anderson SG, Malkin CJ, et al. Long-term durability of transcatheter aortic valve prostheses. J Am Coll Cardiol. 2019;73(5):537-45.120120. Siontis GC, Overtchouk P, Cahill TJ, Modine T, Prendergast B, Praz F, et al. Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treatment of symptomatic severe aortic stenosis: an updated meta-analysis. Eur Heart J. 2019;40(38):3143-53.

Another relevant aspect which is unanimous in Brazilian and international guidelines is the need for a Heart Team to evaluate each case. Other aspects, such as technical feasibility, risks and benefits of each procedure, patient choice, local experience, and availability of procedures, should also be taken into consideration when choosing the type of intervention.

The following groups of patients should be monitored frequently, due to the risk of progression of the VHD (Table 28):

Table 28
Aortic stenosis: Individualized follow-up11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.
  1. Severe asymptomatic AS, without prognostic factors: To date, these patients are indicated for valve surgery only if other invasive cardiovascular procedures are indicated (coronary revascularization, ascending aorta, or other valve procedures). Studies are underway to evaluate the benefit of early intervention in this group of patients.

  2. Moderate AS, defined as AVA between 1.0 and 1.5 cm² and mean transaortic gradient 25 to 39 mmHg: These patients are indicated for valve surgery only if other invasive cardiovascular procedures are indicated (coronary revascularization, ascending aorta, or other valve procedures).

  3. Mild AS, defined as AVA > 1.5 cm² and mean transaortic gradient < 25 mmHg: Clinical and echocardiographic follow-up.

9. Chronic Aortic Regurgitation

The five-step clinical approach (Figure 8) is also recommended for management of chronic aortic regurgitation (AR). The first step consists of charactering AR anatomical severity, especially identifying patients with anatomically severe AR. Table 29 shows the main findings of clinical examination and complementary methods for defining severe AR.133133. Detaint D, Messika-Zeitoun D, Maalouf J, Tribouilloy C, Mahoney DW, Tajik AJ, et al. Quantitative echocardiographic determinants of clinical outcome in asymptomatic patients with aortic regurgitation: a prospective study. JACC: Cardiovasc Imaging. 2008;1(1):1-11.,134134. Myerson SG, d'Arcy J, Mohiaddin R, Greenwood JP, Karamitsos TD, Francis JM, et al. Aortic regurgitation quantification using cardiovascular magnetic resonance: association with clinical outcome. Circulation. 2012;126(12):1452-60. In general, transthoracic echocardiogram continues to be the main tool for diagnosing and scoring the severity of AR. Three-dimensional echocardiography has been increasingly incorporated into complementary evaluation, especially in cases where two-dimensional analysis is limited (eccentric jets or anatomical determination, for example, in bicuspid valve disease). Furthermore, there has recently been an increase of studies on cardiac magnetic resonance for evaluation of AR, making it possible to acquire new diagnostic and prognostic parameters, such as regurgitant fraction and estimated LV end diastolic volume.134134. Myerson SG, d'Arcy J, Mohiaddin R, Greenwood JP, Karamitsos TD, Francis JM, et al. Aortic regurgitation quantification using cardiovascular magnetic resonance: association with clinical outcome. Circulation. 2012;126(12):1452-60.

Table 29
Step 1: Diagnosis of severe aortic regurgitation 133133. Detaint D, Messika-Zeitoun D, Maalouf J, Tribouilloy C, Mahoney DW, Tajik AJ, et al. Quantitative echocardiographic determinants of clinical outcome in asymptomatic patients with aortic regurgitation: a prospective study. JACC: Cardiovasc Imaging. 2008;1(1):1-11.,134134. Myerson SG, d'Arcy J, Mohiaddin R, Greenwood JP, Karamitsos TD, Francis JM, et al. Aortic regurgitation quantification using cardiovascular magnetic resonance: association with clinical outcome. Circulation. 2012;126(12):1452-60.
Figure 8
Flowchart for decision making in chronic aortic regurgitation. LVDD: left ventricular diastolic diameter; LVEF: left ventricular ejection fraction; LVSD: left ventricular systolic diameter.

For the second step (Table 30), it is necessary to verify the etiology of AR. From the etiopathogenic point of view, chronic AR is related to anatomical abnormalities related to the valve leaflets and/or pathologies of the aortic valve annulus. The following causes are related to dysfunction of the valve leaflets: rheumatic fever (still one of the main etiologies in Brazil), infective endocarditis (IE), degenerative causes, congenital malformations such as bicuspid valve disease, and myxomatous degeneration. With respect to abnormalities related to the aortic valve annulus, it is worth underscoring dissection of the ascending aorta, aneurysmatic dilatation (mainly provoked by systemic arterial hypertension and collagen diseases such as Marfan and Ehlers-Danlos syndromes), seronegative spondyloarthropathies (ankylosing spondylitis and Reiter’s disease), syphilitic aortitis, and Takayasu arteritis.135135. Fox ER, Wilson RS, Penman AD, King JJ, Towery JG, Butler KR, et al. Epidemiology of pure valvular regurgitation in the large middle-aged African American cohort of the Atherosclerosis Risk in Communities study. Am Heart J. 2007;154(6):1229-34.,136136. d'Arcy JL, Coffey S, Loudon MA, Kennedy A, Pearson-Stuttard J, Birks J, et al. Large-scale community echocardiographic screening reveals a major burden of undiagnosed valvular heart disease in older people: the OxVALVE Population Cohort Study. Eur Heart J. 2016;37(47):3515-22.

Table 30
Step 2: Evaluation of severe aortic regurgitation etiology135135. Fox ER, Wilson RS, Penman AD, King JJ, Towery JG, Butler KR, et al. Epidemiology of pure valvular regurgitation in the large middle-aged African American cohort of the Atherosclerosis Risk in Communities study. Am Heart J. 2007;154(6):1229-34.,136136. d'Arcy JL, Coffey S, Loudon MA, Kennedy A, Pearson-Stuttard J, Birks J, et al. Large-scale community echocardiographic screening reveals a major burden of undiagnosed valvular heart disease in older people: the OxVALVE Population Cohort Study. Eur Heart J. 2016;37(47):3515-22.

The third step (Table 31) is characterized by evaluation of symptoms related to AR. Identification of symptoms may be a difficult task during routine healthcare, especially in elderly patients who frequently have physical self-limitation. In these cases, provocative functional tests, such as ergospirometry, can assist in identification of these “pseudo-asymptomatic” patients. Given the high morbidity and mortality related to symptoms, once they are identified, patients should be referred for surgical intervention.

Table 31
Step 3: Evaluation of severe aortic regurgitation symptoms

The fourth step (Table 32) focuses on evaluation of prognostic factors. This step is especially relevant for asymptomatic patients. The main prognostic factor of AR is low LV systolic function, related to systolic stress and ventricular dilation. In a retrospective study, Chaliki et al. found reduced survival in patients who had AR with LVEF below 50%. Postoperative mortality rates were also influenced by ventricular function (14% for patients with LVEF below 35%, 6.7% for LVEF between 35% and 50%, and 3.7% for patients with LVEF above 50%, p = 0.02). 137137. Chaliki HP, Mohty D, Avierinos J-F, Scott CG, Schaff HV, Tajik AJ, et al. Outcomes after aortic valve replacement in patients with severe aortic regurgitation and markedly reduced left ventricular function. Circulation. 2002;106(21):2687-93.

Table 32
Step 4: Evaluation of severe aortic regurgitation prognostic factors134134. Myerson SG, d'Arcy J, Mohiaddin R, Greenwood JP, Karamitsos TD, Francis JM, et al. Aortic regurgitation quantification using cardiovascular magnetic resonance: association with clinical outcome. Circulation. 2012;126(12):1452-60.,137137. Chaliki HP, Mohty D, Avierinos J-F, Scott CG, Schaff HV, Tajik AJ, et al. Outcomes after aortic valve replacement in patients with severe aortic regurgitation and markedly reduced left ventricular function. Circulation. 2002;106(21):2687-93., 137137. Chaliki HP, Mohty D, Avierinos J-F, Scott CG, Schaff HV, Tajik AJ, et al. Outcomes after aortic valve replacement in patients with severe aortic regurgitation and markedly reduced left ventricular function. Circulation. 2002;106(21):2687-93.139139. Dujardin KS, Enriquez-Sarano M, Schaff HV, Bailey KR, Seward JB, Tajik AJ. Mortality and morbidity of aortic regurgitation in clinical practice: a long-term follow-up study. Circulation. 1999;99(14):1851-7.,141141. Azevedo CF, Nigri M, Higuchi ML, Pomerantzeff PM, Spina GS, Sampaio RO, et al. Prognostic significance of myocardial fibrosis quantification by histopathology and magnetic resonance imaging in patients with severe aortic valve disease.J Am Coll Cardiol. 2010;56(4):278-87.

Ventricular remodeling continues to show clinical ambivalence: on one hand, increased ventricular diameters is an adaptive mechanism to volume overload; on the other hand, ventricular remodeling may determine worse prognosis, especially in non-rheumatic populations. In a Brazilian study carried out with 75 asymptomatic patients with rheumatic severe AR, the strategy of indicating surgical treatment based on the appearance of symptoms, even in patients with LV diastolic diameter (LVDD) greater than 75 mm and LVSD greater than 55 mm, with normal LVEF, was capable of promoting improvement in quality of life and reversal of dilation, with a 10-year survival rate of 90.6%.138138. Tarasoutchi F, Grinberg M, Spina GS, Sampaio RO, Rossi EG, Pomerantzeff P, et al. Ten-year clinical laboratory follow-up after application of a symptom-based therapeutic strategy to patients with severe chronic aortic regurgitation of predominant rheumatic etiology. J Am Coll Cardiol. 2003;41(8):1316-24. On the other hand, prospective studies with predominant non-rheumatic AR patients found that LVSD above 50 mm was associated with composite clinical outcomes (death, symptoms, and/or ventricular dysfunction) of up to 19% yearly. There is also evidence that it would be more appropriate to used diameters indexed by body surface area, especially in women. A study of 246 patients with asymptomatic AR found that indexed LVSD values equal to or greater than 25 mm/m22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89. were associated with outcomes (mortality, symptoms, and ventricular dysfunction).139139. Dujardin KS, Enriquez-Sarano M, Schaff HV, Bailey KR, Seward JB, Tajik AJ. Mortality and morbidity of aortic regurgitation in clinical practice: a long-term follow-up study. Circulation. 1999;99(14):1851-7. More recently, studies have evaluated the role of brain natriuretic peptide (BNP) in AR. Cutoff values of 130 pg/mL for BNP and 602 pg/mL for NT-pro-BNP have been associated with adverse clinical outcomes. The combination of these values of BNP with echocardiographic parameters may improve the ability to stratify asymptomatic patients. Persistent elevations in BNP during clinical follow-up have also been related to adverse clinical events.140140. Weber M, Hausen M, Arnold R, Moellmann H, Nef H, Elsaesser A, et al. Diagnostic and prognostic value of N-terminal pro B-type natriuretic peptide (NT-proBNP) in patients with chronic aortic regurgitation. Int J Cardiol. 2008;127(3):321-7.

Echocardiographic parameters such as longitudinal stress are also predictors of evolution in asymptomatic AR, and they also influence postoperative results. The limitation to the clinical use of longitudinal stress in AR lies in the divergence regarding cutoff points.

Another prognostic factor related to AR is late enhancement myocardial fibrosis. Cardiac magnetic resonance with late enhancement is the main imaging method capable of quantification. Studies have demonstrated that the presence of myocardial fibrosis influences the postoperative period, and it is associated with persistence of symptoms, failure to recover ventricular function, and higher mortality.141141. Azevedo CF, Nigri M, Higuchi ML, Pomerantzeff PM, Spina GS, Sampaio RO, et al. Prognostic significance of myocardial fibrosis quantification by histopathology and magnetic resonance imaging in patients with severe aortic valve disease.J Am Coll Cardiol. 2010;56(4):278-87. Also with respect to magnetic resonance, new studies have demonstrated that regurgitant fraction above 33% and LV end diastolic volume above 246 ml were associated with lower surgery-free survival. These new parameters may improve stratification of asymptomatic patients, thus ensuring more precise surgical indications.134134. Myerson SG, d'Arcy J, Mohiaddin R, Greenwood JP, Karamitsos TD, Francis JM, et al. Aortic regurgitation quantification using cardiovascular magnetic resonance: association with clinical outcome. Circulation. 2012;126(12):1452-60.

Finally, the fifth step is to define the intervention in AR (Tables 33 and 34). Surgical aortic valve replacement remains the first choice.142142. Tornos P, Sambola A, Permanyer-Miralda G, Evangelista A, Gomez Z, Soler-Soler J. Long-term outcome of surgically treated aortic regurgitation: influence of guideline adherence toward early surgery. J Am Coll Cardiol. 2006;47(5):1012-7.,143143. Klodas E, Enriquez-Sarano M, Tajik AJ, Mullany CJ, Bailey KR, Seward JB. Optimizing timing of surgical correction in patients with severe aortic regurgitation: role of symptoms. J Am Coll Cardiol. 1997;30(3):746-52. Surgical mortality rates range from 1% (valve replacement procedure alone) to 7% (combined procedures). The presence of symptoms, reduced LVEF, and excessive LV remodeling entail worse prognosis, and they are, therefore, the main indications for surgical treatment. As previously stated, new prognostic factors related to myocardial fibrosis, left ventricular remodeling, and biomarkers may represent potential future parameters for intervention. The clinical follow-up of patients without indication of intervention is described in Table 35.

Table 33
Step 5: Type of severe aortic regurgitation intervention142142. Tornos P, Sambola A, Permanyer-Miralda G, Evangelista A, Gomez Z, Soler-Soler J. Long-term outcome of surgically treated aortic regurgitation: influence of guideline adherence toward early surgery. J Am Coll Cardiol. 2006;47(5):1012-7.,143143. Klodas E, Enriquez-Sarano M, Tajik AJ, Mullany CJ, Bailey KR, Seward JB. Optimizing timing of surgical correction in patients with severe aortic regurgitation: role of symptoms. J Am Coll Cardiol. 1997;30(3):746-52.
Table 34
Aortic regurgitation: Recommendations11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.,142142. Tornos P, Sambola A, Permanyer-Miralda G, Evangelista A, Gomez Z, Soler-Soler J. Long-term outcome of surgically treated aortic regurgitation: influence of guideline adherence toward early surgery. J Am Coll Cardiol. 2006;47(5):1012-7.,143143. Klodas E, Enriquez-Sarano M, Tajik AJ, Mullany CJ, Bailey KR, Seward JB. Optimizing timing of surgical correction in patients with severe aortic regurgitation: role of symptoms. J Am Coll Cardiol. 1997;30(3):746-52.
Table 35
Aortic regurgitation: Individualized follow-up11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.

10. Tricuspid Stenosis

Tricuspid stenosis (TS) is a rare VHD, usually associated with tricuspid regurgitation (TR). Echocardiography remains the main tool to define anatomical severity (Table 36). 144144. Goswami KC, Rao MB, Dev V, Shrivastava S. Juvenile tricuspid stenosis and rheumatic tricuspid valve disease: an echocardiographic study. Int J Cardiol. 1999;72(1):83-6.

Table 36
Step 1: Diagnosis of severe tricuspid stenosis144144. Goswami KC, Rao MB, Dev V, Shrivastava S. Juvenile tricuspid stenosis and rheumatic tricuspid valve disease: an echocardiographic study. Int J Cardiol. 1999;72(1):83-6.

The most common etiology of TS is rheumatic disease. It generally occurs concomitantly to mitral valve and/or aortic valve disease. Thickening and cusp retraction occur with commissural involvement. Other possible causes of TS, which are even rare, are described in Table 37.145145. Hauck AJ, Freeman DP. Ackermann DM, DanielsonGK, Edwards WD. Surgical pathology of the tricuspid valve: a study of 363 cases spanning 25 years. Mayo Clinic Proc.1988 sep;63(9):551-63.147147. Kulkarni SK, Moorthy N, Ramalingam R. Valvular heart disease in Antiphospholipid antibody syndrome: Isolated Tricuspid stenosis. Echocardiography. 2019;36(3):598-601.

Table 37
Step 2: Evaluation of severe tricuspid stenosis etiology145145. Hauck AJ, Freeman DP. Ackermann DM, DanielsonGK, Edwards WD. Surgical pathology of the tricuspid valve: a study of 363 cases spanning 25 years. Mayo Clinic Proc.1988 sep;63(9):551-63.147147. Kulkarni SK, Moorthy N, Ramalingam R. Valvular heart disease in Antiphospholipid antibody syndrome: Isolated Tricuspid stenosis. Echocardiography. 2019;36(3):598-601.

Both symptoms and physical examination are usually limited to patients with anatomically severe TS. The most commonly found symptom is fatigue, which may be associated with symptoms of right-sided heart failure (Table 38).

Table 38
Step 3: Evaluation of severe tricuspid stenosis symptoms

When asymptomatic patients have severe TS, it is necessary to evaluate whether or not there present prognostic factors (Table 39).

Table 39
Step 4: Evaluation of severe tricuspid stenosis prognostic factors

In the presence of these symptoms or prognostic factors, intervention is indicated. In spite of the rarity of cases and the scarcity of data in the literature, percutaneous balloon tricuspid valvuloplasty (PBTV) remains the treatment of choice (Tables 40 and 41 and Figure 9).148148. Bhardwaj R, Sharma R. Balloon dilatation of isolated severe tricuspid valve stenosis. Indian Heart J. 2015;67:S78-S80.

Table 40
Step 5: Type of severe tricuspid stenosis intervention148148. Bhardwaj R, Sharma R. Balloon dilatation of isolated severe tricuspid valve stenosis. Indian Heart J. 2015;67:S78-S80.
Table 41
Tricuspid stenosis: Recommendations11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.,148148. Bhardwaj R, Sharma R. Balloon dilatation of isolated severe tricuspid valve stenosis. Indian Heart J. 2015;67:S78-S80.
Figure 9
Flowchart for decision making in tricuspid stenosis. AF: atrial fibrillation; PBTV: percutaneous balloon tricuspid valvuloplasty.

11. Tricuspid Regurgitation

Patients with mild TR usually do not require any type of treatment. Patients with moderate to severe TR will need specific follow-up, especially in order to identify the etiology of the VHD and the repercussions associated (Table 42).149149. Rodés-Cabau J, Taramasso M, T O'Gara P. Diagnosis and treatment of tricuspid valve disease: current and future perspectives. Lancet. 2016;388(10058):2431-42.

Table 42
Step 1: Diagnosis of severe tricuspid regurgitation149

TR is usually functional, secondary to dilation of the tricuspid valve annulus, mainly secondary the left heart chambers valve diseases or cardiomyopathies and/or PH. Cases of primary TR are generally related to rheumatic disease, interventions (repeated endomyocardial biopsies, presence of pacemaker electrodes, or implanTable cardioverter defibrillator), consequence of IE or other rare causes (Table 43).150150. Prihadi EA, Delgado V, Leon MB, Enriquez-Sarano M, Topilsky Y, Bax JJ. Morphologic types of tricuspid regurgitation: characteristics and prognostic implications. JACC: Cardiovasc Imaging. 2019;12(3):491-9.

Table 43
Step 2: Evaluation of severe tricuspid regurgitation etiology150150. Prihadi EA, Delgado V, Leon MB, Enriquez-Sarano M, Topilsky Y, Bax JJ. Morphologic types of tricuspid regurgitation: characteristics and prognostic implications. JACC: Cardiovasc Imaging. 2019;12(3):491-9.

During severe TR natural history, symptoms may arise which will have a significant impact on decision making (Table 44).

Table 44
Step 3: Evaluation of severe tricuspid regurgitation symptoms

On the other hand, even in asymptomatic patients, right ventricular remodeling can develop, which may justify valve intervention. Thus, right ventricular dilation or dysfunction (except for severe right ventricular dysfunction) should be considered as a prognostic factor (Table 45).

Table 45
Step 4: Evaluation of severe tricuspid regurgitation prognostic factors

New data have shown the prognostic importance of TR. A recently published study found a prevalence of moderate to severe TR of 0.55%, where 72% of cases were secondary to left VHD (49.5%) or PH (23%). Only 8% of cases were isolated TR. Patients with moderate to severe TR alone show a higher mortality rate (relative risk 1.68, with 95% CI 1.04 to 2.6, p = 0.03), confirming data from the same group published in 2014.151151. Topilsky Y, Maltais S, Inojosa JM, Oguz D, Michelena H, Maalouf J, et al. Burden of tricuspid regurgitation in patients diagnosed in the community setting. JACC Cardiovasc Imaging. 2019 Mar;12(3):433-42. The increase in mortality has also been shown in a recent meta-analysis, including 70 studies, which found almost two-fold mortality in patients with moderate to severe TR (relative risk 1.95, 95% CI 1.75 to 2.17). TR was an independent mortality predictor even after adjusting for the presence of right ventricular dysfunction, PH, AF, MR, or LV dysfunction.152152. Wang N, Fulcher J, Abeysuriya N, McGrady M, Wilcox I, Celermajer D, et al. Tricuspid regurgitation is associated with increased mortality independent of pulmonary pressures and right heart failure: a systematic review and meta-analysis. Eur Heart J. 2019;40(5):476-84.

The interventional treatment of choice, when indicated, is tricuspid valve repair, with a prosthetic ring capable of reducing the tricuspid annulus diameter, improving valve leaflet coaptation, and correcting regurgitation. Valve replacement is reserved for patients who do not have anatomical conditions for repair. It should be noted that the isolated surgical approach to the tricuspid valve currently continues to be rarely indicated, and has surgical mortality rates varying from 8.8% to 9.7%. However, there are still no data showing improved survival with TR surgical treatment alone, despite the increased mortality rate in patients with moderate to severe TR in clinical treatment. For this reason, the main reason for surgical indication, in this population, is still to improve symptoms and prevent severe right ventricular dysfunction.153153. Topilsky Y, Nkomo VT, Vatury O, Michelena HI, Letourneau T, Suri RM, et al. Clinical outcome of isolated tricuspid regurgitation. JACC Cardiovasc Imaging. 2014;7(12):1185-94.155155. Axtell AL, Bhambhani V, Moonsamy P, Healy EW, Picard MH, Sundt III TM, et al. Surgery does not improve survival in patients with isolated severe tricuspid regurgitation. J Am Coll Cardiol. 2019;74(6):715-25.

The number of studies on percutaneous interventional treatment of TR has increased. Several devices have been developed, with strategies based on reducing the tricuspid valve annulus, improving coaptation between the leaflets, or even on transcatheter valve implantation. Further data will be available soon (Tables 46 and 47 and Figure 10) 149149. Rodés-Cabau J, Taramasso M, T O'Gara P. Diagnosis and treatment of tricuspid valve disease: current and future perspectives. Lancet. 2016;388(10058):2431-42.,156156. Nickenig G, Kowalski M, Hausleiter J, Braun D, Schofer J, Yzeiraj E, et al. Transcatheter treatment of severe tricuspid regurgitation with the edge-to-edge MitraClip technique. Circulation. 2017;135(19):1802-14.158158. Asmarats L, Puri R, Latib A, Navia JL, Rodés-Cabau J. Transcatheter tricuspid valve interventions: landscape, challenges, and future directions. J Am Coll Cardiol. 2018;71(25):2935-56.

Table 46
Step 5: Type of severe tricuspid regurgitation intervention149149. Rodés-Cabau J, Taramasso M, T O'Gara P. Diagnosis and treatment of tricuspid valve disease: current and future perspectives. Lancet. 2016;388(10058):2431-42.,151151. Topilsky Y, Maltais S, Inojosa JM, Oguz D, Michelena H, Maalouf J, et al. Burden of tricuspid regurgitation in patients diagnosed in the community setting. JACC Cardiovasc Imaging. 2019 Mar;12(3):433-42.158158. Asmarats L, Puri R, Latib A, Navia JL, Rodés-Cabau J. Transcatheter tricuspid valve interventions: landscape, challenges, and future directions. J Am Coll Cardiol. 2018;71(25):2935-56.
Table 47
Tricuspid regurgitation: Recommendations11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.,149149. Rodés-Cabau J, Taramasso M, T O'Gara P. Diagnosis and treatment of tricuspid valve disease: current and future perspectives. Lancet. 2016;388(10058):2431-42.,151151. Topilsky Y, Maltais S, Inojosa JM, Oguz D, Michelena H, Maalouf J, et al. Burden of tricuspid regurgitation in patients diagnosed in the community setting. JACC Cardiovasc Imaging. 2019 Mar;12(3):433-42.158158. Asmarats L, Puri R, Latib A, Navia JL, Rodés-Cabau J. Transcatheter tricuspid valve interventions: landscape, challenges, and future directions. J Am Coll Cardiol. 2018;71(25):2935-56.
Figure 10
Flowchart for decision making in tricuspid regurgitation. RV: right ventricular.

12. Prosthetic Valve Dysfunction

After valve replacement surgery, periodical clinical and echocardiographic follow-up is needed for early detection of prosthesis dysfunction, as well as identification of anatomical and functional symptoms or prognostic factors.

The main test for diagnosis of prosthesis dysfunction is transthoracic echocardiogram. Nonetheless, transesophageal echocardiogram and aorta angiotomography triggered with electrocardiogram (EKG) are useful especially in the evaluation of bioprosthesis thrombosis (Tables 48 and 49).159159. Al. 2010; Taweel A, Almahmoud MF, Khairandish Y, Ahmad M. Degenerative mitral valve stenosis: Diagnosis and management. Echocardiography. 2019;36(10):1901-9.

Table 48
Step 1: Diagnosis of severe prosthetic valve dysfunction
Table 49
Step 2: Evaluation of severe prosthetic valve dysfunction etiology159159. Al. 2010; Taweel A, Almahmoud MF, Khairandish Y, Ahmad M. Degenerative mitral valve stenosis: Diagnosis and management. Echocardiography. 2019;36(10):1901-9.

The most frequently symptom is dyspnea, resulting from pulmonary capillary congestion (Table 50).

Table 50
Step 3: Evaluation of severe prosthetic valve dysfunction symptoms

The definition of prognostic factors in prosthesis dysfunction is complex. Patient usually already has PH, ventricular dilation, or ventricular dysfunction as a result of prior VHD. Accordingly, the progression of these abnormalities should be taken into consideration for indication of intervention (Table 51).

Table 51
Step 4: Evaluation of severe prosthetic valve dysfunction prognostic factors

New procedures, such as percutaneous treatment of paravalvular regurgitation and valve-in-valve, are already included in recent guidelines (Tables 52 and 53).159159. Al. 2010; Taweel A, Almahmoud MF, Khairandish Y, Ahmad M. Degenerative mitral valve stenosis: Diagnosis and management. Echocardiography. 2019;36(10):1901-9.162162. Tabata N, Sinning J-M, Kaikita K, Tsujita K, Nickenig G, Werner N. Current status and future perspective of structural heart disease intervention. J Cardiol.20;:74(1):1-12.

Table 52
Step 5: Type of severe prosthetic valve dysfunction intervention159159. Al. 2010; Taweel A, Almahmoud MF, Khairandish Y, Ahmad M. Degenerative mitral valve stenosis: Diagnosis and management. Echocardiography. 2019;36(10):1901-9.162162. Tabata N, Sinning J-M, Kaikita K, Tsujita K, Nickenig G, Werner N. Current status and future perspective of structural heart disease intervention. J Cardiol.20;:74(1):1-12.
Table 53
Prosthetic valve dysfunction: Recommendations11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.,159159. Al. 2010; Taweel A, Almahmoud MF, Khairandish Y, Ahmad M. Degenerative mitral valve stenosis: Diagnosis and management. Echocardiography. 2019;36(10):1901-9.162162. Tabata N, Sinning J-M, Kaikita K, Tsujita K, Nickenig G, Werner N. Current status and future perspective of structural heart disease intervention. J Cardiol.20;:74(1):1-12.

13. Multivalvular Disease

Multivalvular disease is a primary involvement of two or more valves. This classification excludes valve involvement secondary to a primary VHD, which is the case with functional TR as a consequence of mitral valve disease and MR secondary to LV remodeling as a consequence of aortic VHD (Table 54).163163. Venneri L, Khattar RS, Senior R. Assessment of complex multi-valve disease and prosthetic valves. Heart Lung Circ. 2019;28(9):1436-46.165165. Watkins DA, Beaton AZ, Carapetis JR, Karthikeyan G, Mayosi BM, Wyber R, et al. Rheumatic heart disease worldwide: JACC scientific expert panel. J Am Coll Cardiol. Cardiol. 2018;72(12):1397-416.

Table 54
Step 1: Diagnosis of severe multivalvular disease163163. Venneri L, Khattar RS, Senior R. Assessment of complex multi-valve disease and prosthetic valves. Heart Lung Circ. 2019;28(9):1436-46.165165. Watkins DA, Beaton AZ, Carapetis JR, Karthikeyan G, Mayosi BM, Wyber R, et al. Rheumatic heart disease worldwide: JACC scientific expert panel. J Am Coll Cardiol. Cardiol. 2018;72(12):1397-416.

In Brazil, multivalvular disease is the result of rheumatic involvement in most cases; there has been, however, a progressive increase in degenerative calcific mitral-aortic disease (Table 55).159159. Al. 2010; Taweel A, Almahmoud MF, Khairandish Y, Ahmad M. Degenerative mitral valve stenosis: Diagnosis and management. Echocardiography. 2019;36(10):1901-9.

Table 55
Step 2: Evaluation of severe multivalvular disease etiology159159. Al. 2010; Taweel A, Almahmoud MF, Khairandish Y, Ahmad M. Degenerative mitral valve stenosis: Diagnosis and management. Echocardiography. 2019;36(10):1901-9.,163163. Venneri L, Khattar RS, Senior R. Assessment of complex multi-valve disease and prosthetic valves. Heart Lung Circ. 2019;28(9):1436-46.165165. Watkins DA, Beaton AZ, Carapetis JR, Karthikeyan G, Mayosi BM, Wyber R, et al. Rheumatic heart disease worldwide: JACC scientific expert panel. J Am Coll Cardiol. Cardiol. 2018;72(12):1397-416.

Symptoms are generally associated with the most severe valvular disease, and, in cases where both are equally severe, the most proximal valvular disease tends to prevail (Table 56).

Table 56
Step 3: Evaluation of symptoms

Prognostic factors, when present, result from the most severe valvular disease (Table 57).

Table 57
Step 4: Evaluation of severe multivalvular disease prognostic factors

The standard treatment of mitral-aortic diseases with symptoms and/or prognostic factors is surgical; nonetheless, transcatheter strategies may be indicated in select cases, especially in patients assumed to be at high risk for conventional surgery (Tables 58 and 59).163163. Venneri L, Khattar RS, Senior R. Assessment of complex multi-valve disease and prosthetic valves. Heart Lung Circ. 2019;28(9):1436-46.165165. Watkins DA, Beaton AZ, Carapetis JR, Karthikeyan G, Mayosi BM, Wyber R, et al. Rheumatic heart disease worldwide: JACC scientific expert panel. J Am Coll Cardiol. Cardiol. 2018;72(12):1397-416.

Table 58
Step 5: Type of severe multivalvular disease intervention163163. Venneri L, Khattar RS, Senior R. Assessment of complex multi-valve disease and prosthetic valves. Heart Lung Circ. 2019;28(9):1436-46.165165. Watkins DA, Beaton AZ, Carapetis JR, Karthikeyan G, Mayosi BM, Wyber R, et al. Rheumatic heart disease worldwide: JACC scientific expert panel. J Am Coll Cardiol. Cardiol. 2018;72(12):1397-416.
Table 59
Multivalvular disease: Recommendations11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.,163163. Venneri L, Khattar RS, Senior R. Assessment of complex multi-valve disease and prosthetic valves. Heart Lung Circ. 2019;28(9):1436-46.165165. Watkins DA, Beaton AZ, Carapetis JR, Karthikeyan G, Mayosi BM, Wyber R, et al. Rheumatic heart disease worldwide: JACC scientific expert panel. J Am Coll Cardiol. Cardiol. 2018;72(12):1397-416.

14. Evaluation of Coronary Artery Disease

Before cardiac valve surgery or transcatheter intervention for VHD, patients must undergo evaluation of coronary artery disease with coronary angiography if they meet any of the following criteria: 40 years of age or older, suspected coronary artery disease (risk factors for atherosclerosis [diabetes, dyslipidemia, arterial hypertension, and others], prior events, or angina), LV dysfunction, or in order to evaluate the etiology in secondary MR.166166. Task Force members ATF, Windecker S, Kolh P, Alfonso F, Collet J-P, Cremer J, et al. 2014 ESC/EACTS guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35(37):2541-619.168168. Members WC, Mark DB, Berman DS, Budoff MJ, Carr JJ, Gerber TC, et al. ACCF/ACR/AHA/NASCI/SAIP/SCAI/SCCT 2010 expert consensus document on coronary computed tomographic angiography: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. Circulation. 2010;121(22):2509-43. Coronary tomography angiography may be used in patients with low or intermediate probability of coronary artery disease. If coronary tomography shows significant or unclear lesions, the patient should undergo coronary angiography (Table 60).169169. Gilard M, Cornily J-C, Pennec P-Y, Joret C, Le Gal G, Mansourati J, et al. Accuracy of multislice computed tomography in the preoperative assessment of coronary disease in patients with aortic valve stenosis. J Am Coll Cardiol. 2006;47(10):2020-4.171171. Meijboom WB, Mollet NR, Van Mieghem CA, Kluin J, Weustink AC, Pugliese F, et al. Pre-operative computed tomography coronary angiography to detect significant coronary artery disease in patients referred for cardiac valve surgery. J Am Coll Cardiol. 2006;48(8):1658-65.

Table 60
Intervention in coronary artery disease concomitant to valve Intervention: Recommendations11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.,166166. Task Force members ATF, Windecker S, Kolh P, Alfonso F, Collet J-P, Cremer J, et al. 2014 ESC/EACTS guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35(37):2541-619.171171. Meijboom WB, Mollet NR, Van Mieghem CA, Kluin J, Weustink AC, Pugliese F, et al. Pre-operative computed tomography coronary angiography to detect significant coronary artery disease in patients referred for cardiac valve surgery. J Am Coll Cardiol. 2006;48(8):1658-65.

15. Anticoagulation

The two prognostic factors with the greatest impact on the natural history of valve disease are hemodynamic repercussions and thromboembolism. Stroke is the most clinically significant thromboembolic event, affecting up to 20% of individuals with AF associated with valve disease. The CHA2DS2-VASc score is recommended for decision making regarding anticoagulation, except for patients with rheumatic MS or those with mechanical prostheses. The criteria for anticoagulation are the same for patients with paroxysmal, persistent, or permanent AF. The main indications for anticoagulation are described in Table 61.

Table 61
Indications for oral anticoagulation11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89., 172172. Dangas GD, Tijssen JG, Wöhrle J, Søndergaard L, Gilard M, Möllmann H, et al. A controlled trial of rivaroxaban after transcatheter aortic-valve replacement. N Engl J Med. 2020;382(2):120-9.183183. de Lara Lavitola P, Sampaio RO, de Oliveira WA, Bôer BN, Tarasoutchi F, Spina GS, et al. Warfarin or aspirin in embolism prevention in patients with mitral valvulopathy and atrial fibrillation. Arq Bras Cardiol. 2010;95(6):749-55.

Oral anticoagulation, as a means of preventing thromboembolic events in patients with valve disease, is still predominantly carried out with vitamin K antagonists (VKA); warfarin currently represents this class of drugs in Brazil. It is a safe strategy to start warfarin at a dose of 5 mg/day in individuals under 65 years of age and 2.5 mg/day in individuals over 65 years. Prothrombin time should be measured on the third day to evaluate hyper-responsiveness to the medication and again on the fifth day, after which the dose proceeds to be adjusted. During this phase, exams should be carried out at 5-day intervals until the therapeutic level has been reached. The international normalized ratio (INR) should remain between 2.0 and 3.0, except in patients who have mechanical prostheses in the mitral position, aortic mechanical prosthesis associated with AF, hypercoagulable states, and cardioembolic events while INR is between 2.0 and 3.0. In these cases, the target becomes 2.5 to 3.5. INR control is usually performed on a monthly basis; in patients whose doses have been sTable for a long time and who have not been exposed to any new factors that interact with warfarin (Table 62), the control may be done every two months. In the event that INR is above the target, a new exam should be performed on an earlier basis, in 1 to 2 weeks. Dose adjustments should be, on average, 10% to 15% of the weekly dose, and it is necessary to investigate which factors caused the oscillation in INR. Monitoring of prothrombin time with point of care devices provides quick and reliable information; its availability, however, is still limited due to the high cost of the device and the strips.

Table 62
Warfarin dose adjustments

It is known that greater time in therapeutic range (TTR) is associated with lower risk of thromboembolic events and bleeding. In a study including 119 patients with mitral valve disease and AF, 78.2% of individuals had INR < 2.0 at the time of the thromboembolic event. For INR values < 1.7 the likelihood doubled, and it tripled for values < 1.5. The difficulties of managing VKA are result of the wide variability in individual dose and interactions with foods and medications, in addition to the need for frequent monitoring. Patients should be advised to avoid alcohol consumption and to maintain a balanced diet, especially in relation to foods that are rich in vitamin K, such as greens and vegetables. These foods should not be excluded from the dietary routine.

Over the past years, the role of direct oral anticoagulants (DOACs) has progressively increased. Dosages of medications available in Brazil can be found in Table 63. Multiple clinical trials involving patients with VHD are underway. Most of the current information is from analyses of subgroups of the main studies on DOACs, as well as retrospective cohort studies.

Table 63
Dose of direct oral anticoagulants for prophylaxis of thromboembolic events in atrial fibrillation177177. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-91.180180. De Caterina R, Renda G, Carnicelli AP, Nordio F, Trevisan M, Mercuri MF, et al. Valvular heart disease patients on edoxaban or warfarin in the ENGAGE AF-TIMI 48 trial. J Am Coll Cardiol. 2017;69(11):1372-82.

In patients with mechanical prostheses, pre-clinical trials involving animals have suggested that the use of DOACs could be as safe as warfarin. However, the clinical Dabigatran versus Warfarin in Patients with Mechanical Heart Valves (RE-ALIGN) study, which compared dabigatran and warfarin, was prematurely terminated due to greater occurrence of the combined outcome of stroke, transient ischemic attack, systemic embolism, myocardial infarction, and death (9% versus 5%; hazard ratio 1.94, 95% CI 0.64 to 5.86) and bleeding (27% versus 12%, p < 0.05) in the first group. The study included 252 patients, and it used dabigatran at doses of 150, 220, and 300 mg, administered every 12 hours, according to creatinine clearance, with dose adjustments for serum level above 50 ng/mL. For this reason, we do not indicate the use of DOACs in patients with mechanical prostheses.176176. Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369(13):1206-14.

Although the large clinical trials that have validated the use of DOACs in AF excluded individuals with severe MS and mechanical valve prostheses, these studies did include individuals with other VHD. In the Apixaban versus Warfarin in Patients with Atrial Fibrillation (ARISTOTLE) study, 26.4% of participants had moderate or severe VHD; in the Dabigatran versus Warfarin in Patients with Atrial Fibrillation (RE-LY) study, 21.8%; in the Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation (ROCKET AF) study, 14.1%; and, finally, in the Edoxaban versus Warfarin in Patients with Atrial Fibrillation (ENGAGE AF) study, 13%. Subanalyses of these studies suggest the efficacy of DOACs in comparison with warfarin in individuals with AF and valve disease, excluding patients with mechanical prostheses and severe MS. The ARISTOTLE and ENGAGE-AF studies included individuals with bioprostheses. 177177. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-91.180180. De Caterina R, Renda G, Carnicelli AP, Nordio F, Trevisan M, Mercuri MF, et al. Valvular heart disease patients on edoxaban or warfarin in the ENGAGE AF-TIMI 48 trial. J Am Coll Cardiol. 2017;69(11):1372-82.

Notwithstanding the negative results in individuals with mechanical valve prostheses, dabigatran has been shown to be effective in preventing intracardiac thrombus formation in individuals with aortic and/or mitral biological prosthesis in a Brazilian single-center study, Dabigatran Versus Warfarin After Bioprosthesis Valve Replacement for the Management of Atrial Fibrillation Postoperatively (DAWA).175175. Duraes AR, de Souza Roriz P, de Almeida Nunes B, e Albuquerque FP, de Bulhoes FV, de Souza Fernandes AM, et al. Dabigatran versus warfarin after bioprosthesis valve replacement for the management of atrial fibrillation postoperatively: DAWA pilot study. Drugs R D. 2016;16(2):149-54.

A South Korean cohort with 2,230 patients evaluated individuals with AF and MS of different etiologies and degrees of anatomical severity, comparing off-label use of DOACs in relation to warfarin. Ischemic events occurred in 2.22% yearly in the DOAC group versus 4.19% yearly in the warfarin group (hazard ratio 0.28; 95% CI 0.18 to 0.45), and intracranial bleeding occurred in 0.49% in the DOAC group versus 0.93% in the warfarin group (hazard ratio 0.53; 95% CI 0.22 to 1.26). This study reinforces the hypothesis of the efficacy of DOACs in MS. Attention should be paid to the fact that TTR of INR was not evaluated in this cohort. 181181. Kim JY, Kim S-H, Myong J-P, Kim YR, Kim T-S, Kim J-H, et al. Outcomes of direct oral anticoagulants in patients with mitral stenosis. J Am Coll Cardiol. 2019;73(10):1123-31. In a multi-center observational study, Korean patients had only 31% of INR values within the therapeutic target.

The first antithrombotic regimen adopted for individuals undergoing TAVI in sinus rhythm was dual antiplatelet therapy with ASA and clopidogrel for 6 months, inferring from experience with stents and based on the expected period for endothelialization of the prosthesis to occur. In a meta-analysis of three recent small clinical trials, antiplatelet therapy with ASA or clopidogrel alone did not show an increase in 30-day mortality (odds ratio 5.2 versus 3.2%, p = 0.447) or ischemic events (3.8 versus 3.8%, p = 0.999), when compared with dual antiplatelet therapy; furthermore, there was a higher chance of bleeding in the dual antiplatelet therapy group (odds ratio 2.24; 95% CI 1.12 to 4.46; p = 0.022). 173173. Maes F, Stabile E, Ussia GP, Tamburino C, Pucciarelli A, Masson JB, et al. Meta-analysis comparing single versus dual antiplatelet therapy following transcatheter aortic valve implantation. Am J Cardiol. 2018;122(2):310-5.

There is evidence, from transesophageal echocardiogram and computed tomography angiography, of the occurrence of thickening of the leaflets after TAVI in up to 13% of patients, which may correspond to the formation of thrombi, and it has been associated with increased incidence of transient ischemic attack and stroke.174174. Chakravarty T, Søndergaard L, Friedman J, De Backer O, Berman D, Kofoed KF, et al. Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study. Lancet. 2017;389(10087):2383-92. Observational cohort studies where individuals received VKA or DOACs have indicated that the use of these medications could be safe for prevention of events. However, the recently published multi-center Global Study Comparing a Rivaroxaban-based Antithrombotic Strategy to an Antiplatelet-based Strategy After Transcatheter Aortic Valve Replacement to Optimize Clinical Outcomes (GALILEO) study, which included 1,644 patients without established indication for dual antiplatelet therapy or anticoagulation, comparing the use of rivaroxaban 10 mg/day (associated with ASA 75 – 100 mg/day during the first 3 months) versus ASA 75 – 100 mg (associated with clopidogrel 75 mg/day during the first 3 months). The study was prematurely terminated due to greater occurrence of thrombotic events (9.8 and 7.2 per 100 person-years; hazard ratio 1.35, 95% CI 1.01 to 1.81; p = 0.04), bleeding (4.3 and 2.8 per 100 person-years; hazard ratio 1.5, 95% CI 0.95 to 2.37; p = 0.08), and death (5.8 and 3.4 per 100 person-years; hazard ratio 1.69, 95% CI 1.13 to 2.53) in the rivaroxaban group. 172172. Dangas GD, Tijssen JG, Wöhrle J, Søndergaard L, Gilard M, Möllmann H, et al. A controlled trial of rivaroxaban after transcatheter aortic-valve replacement. N Engl J Med. 2020;382(2):120-9.

15.1. Surgical Procedures

In surgical procedures with low risk of bleeding, where hemostasis is possible, such as cataract surgery, glaucoma surgery, small dermatological surgeries, dental or gum surgeries, periodontal scraping and simultaneous extraction of up to 3 teeth, it is suggested to maintain oral anticoagulation. In the case of warfarin, INR should be within the therapeutic range, as measured 24 to 48 hours before the procedure. In the case of DOACs, ideally, the procedure should not be performed during the hours following use of these medications, in order to avoid their peak plasma concentrations.

With respect to procedures that imply higher risk of bleeding due to the size of the surgery or difficulty in achieving hemostasis, heparin bridging is indicated in individuals using VKA. These procedures include coronary angiography, endoscopy or colonoscopy with polypectomy, postectomy, vasectomy, internal organ biopsies, and larger surgeries. In these cases, warfarin should be suspended during the 5 days preceding the procedure, starting heparin 3 days before the procedure. In the case of low molecular weight heparin, the last dose should be administered 24 hours before the procedure, and unfractionated heparin should be suspended 4 to 6 hours before the surgery. Heparin is generally reintroduced 12 hours later, provided that hemostasis is adequate. Warfarin is, generally, restarted on the following day. INR should be measured in 5 days, and heparin should be suspended as soon as the therapeutic target has been reached. In emergency surgeries, 50 IU/kg prothrombinic complex should, ideally, be administered intravenously.

The rapid onset of action of DOACs (2 to 4 hours) and their short elimination half-life dispense with the need of using a heparin bridge. For elective procedures with low risk of bleeding, suspension is recommended 24 hours before surgery, and, in cases with elevated risk of bleeding or sites with difficult hemostasis, the recommendation is to suspend 48 hours before. In emergency surgery, use of the antidote idarucizumab is recommended in individuals using dabigatran, with a total dose of 5 g endovenously (two 2.5-g aliquots). Andexanet alfa (Andexxa), an antidote to factor Xa inhibitors, is not yet available in Brazil.

16. Prosthetic Valve Thrombosis

Prosthetic valve thrombosis is an uncommon event; it is more frequent in mechanical prostheses, especially in the mitral position, and it is associated with high morbimortality. It may be asymptomatic or it may manifest with heart failure syndrome, low output, and even death. Diagnosis and suspicion are usually made after transthoracic echocardiogram, and they may be confirmed by the transesophageal method (Tables 64, 65, and 66).

Table 64
Step 1: Diagnosis of prosthetic valve thrombosis
Table 65
Step 2: Evaluation of prosthetic valve thrombosis etiology
Table 66
Step 3: Evaluation of prosthetic valve thrombosis symptoms

The main prognostic factor of thrombosis is thrombus size, due to the risk of embolism and valve obstruction (Table 67).

Table 67
Step 4: Evaluation of prosthetic valve thrombosis prognostic factors

The recommendations of international guidelines are heterogeneous in relation to treatment, and there is a lack of randomized studies in this area (Tables 68 and 69). In prosthesis thrombosis without significant hemodynamic repercussion (NYHA FC I and II), without valve obstruction on complementary tests, oral anticoagulation and outpatient monitoring with imaging are indicated. In the event of a large (especially greater than 8 mm) and/or mobile thrombus, which has an elevated risk of embolization, hospitalization with parenteral anticoagulation is indicated. In the event that the thrombus is not reduced on imaging tests, performed every 5 to 7 days, fibrinolysis and/or surgery may be considered.184184. Biteker M, Altun I, Basaran O, Dogan V, Yildirim B, Ergun G. Treatment of prosthetic valve thrombosis: current evidence and future directions. J Clin Med Res. 2015;7(12):93-6.,185185. Castilho F, De Sousa M, Mendonca A, Ribeiro A, Cáceres-Lóriga F. Thrombolytic therapy or surgery for valve prosthesis thrombosis: systematic review and meta-analysis. J Thromb Haemost. 2014;12(8):1218-28.

Table 68
Step 5: Type of prosthetic valve thrombosis intervention184184. Biteker M, Altun I, Basaran O, Dogan V, Yildirim B, Ergun G. Treatment of prosthetic valve thrombosis: current evidence and future directions. J Clin Med Res. 2015;7(12):93-6.,185185. Castilho F, De Sousa M, Mendonca A, Ribeiro A, Cáceres-Lóriga F. Thrombolytic therapy or surgery for valve prosthesis thrombosis: systematic review and meta-analysis. J Thromb Haemost. 2014;12(8):1218-28.
Table 69
Prosthesis thrombosis: Recommendations11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eu Heart J.2017;38(36):2739-91.,22. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-89.,184184. Biteker M, Altun I, Basaran O, Dogan V, Yildirim B, Ergun G. Treatment of prosthetic valve thrombosis: current evidence and future directions. J Clin Med Res. 2015;7(12):93-6.,185185. Castilho F, De Sousa M, Mendonca A, Ribeiro A, Cáceres-Lóriga F. Thrombolytic therapy or surgery for valve prosthesis thrombosis: systematic review and meta-analysis. J Thromb Haemost. 2014;12(8):1218-28.

In cases where there is a more significant hemodynamic impairment (NYHA FC III and IV), fibrinolytic therapy or valve surgery is usually indicated. Recently, there has been a trend to prioritize fibrinolysis over surgery, based on data from a meta-analysis of 48 studies. When deciding on these two strategies, discussion with the Heart Team is recommended, and the risks of fibrinolysis (preferred procedure) and surgery should be weighed individually. The following factors make fibrinolysis favorable: high surgical risk, low risk of bleeding, involvement of the right valves, first episode of valve thrombosis, and thrombus smaller than 1 cm². If there is hemodynamic instability, the treatment of choice is surgery, and fibrinolysis may be considered in individuals with elevated surgical risk. The following factors make surgical procedure favorable: contraindication to fibrinolysis, high risk of bleeding, low surgical risk, suspicion of pannus associated with thrombosis, and need for other concomitant cardiac surgical procedures (for example, myocardial revascularization).184184. Biteker M, Altun I, Basaran O, Dogan V, Yildirim B, Ergun G. Treatment of prosthetic valve thrombosis: current evidence and future directions. J Clin Med Res. 2015;7(12):93-6.,185185. Castilho F, De Sousa M, Mendonca A, Ribeiro A, Cáceres-Lóriga F. Thrombolytic therapy or surgery for valve prosthesis thrombosis: systematic review and meta-analysis. J Thromb Haemost. 2014;12(8):1218-28.

17. Prophylaxis of Rheumatic Fever

RF and consequent chronic rheumatic heart disease remain the most important cause of acquired VHD in Brazil. Rheumatic disease is one of the most costly diseases for the Brazilian Unified Health System and the community in general, because it affects very young individuals, and it frequently leads to multiple hospitalizations and surgeries. It continues to be the main cause of acquired VHD in Brazil. The goal of decreasing its incidence is of the utmost importance, considering that it is certainly the most easily prevenTable cardiovascular disease.

17.1. Primary Prophylaxis of Rheumatic Fever

In order to decrease the incidence of RF, the measure with the greatest impact is primary prophylaxis, preventing susceptible individuals from contracting the disease (Tables 70 and 71). We have recently encountered serious difficulties in carrying out primary prophylaxis; supplies of benzathine penicillin G are unreliable, with frequent shortages of the medication. Furthermore, restrictions on locations where the medication may be administered, due to concerns regarding allergic reactions and lack of familiarity with intramuscular application on the part of primary healthcare professionals, have made it increasingly difficult to perform primary prophylaxis via the intramuscular route. This fact will certainly contribute to increased incidence of the disease in the coming years.

Table 70
Medications and posology indicated for streptococcal pharyngotonsillitis – primary prophylaxis of rheumatic fever186186. Gerber MA, Baltimore RS, Eaton CB, Gewitz M, Rowley AH, Shulman ST, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation. 2009;119(11):1541-51.193193. Cohen R, Reinert P, De La Rocque F, Levy C, Boucherat M, Robert M, et al. Comparison of two dosages of azithromycin for three days versus penicillin V for ten days in acute group A streptococcal tonsillopharyngitis. Pediatr Infect Dis J.21(4):297-303.
Table 71
Recommendations for primary prophylaxis of rheumatic fever186186. Gerber MA, Baltimore RS, Eaton CB, Gewitz M, Rowley AH, Shulman ST, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation. 2009;119(11):1541-51.193193. Cohen R, Reinert P, De La Rocque F, Levy C, Boucherat M, Robert M, et al. Comparison of two dosages of azithromycin for three days versus penicillin V for ten days in acute group A streptococcal tonsillopharyngitis. Pediatr Infect Dis J.21(4):297-303.

Oral therapies should not be used routinely, because 10 days of therapy are generally necessary in order to completely eradicate streptococci from the oropharynx. For this reason, there is a very high risk of non-adherence to the complete treatment, placing patients at the risk of developing a rheumatic attack. Treatments based on 5 days of azithromycin have been proposed, but there are still no clinical studies validating its use in pharyngotonsillitis.186186. Gerber MA, Baltimore RS, Eaton CB, Gewitz M, Rowley AH, Shulman ST, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation. 2009;119(11):1541-51.193193. Cohen R, Reinert P, De La Rocque F, Levy C, Boucherat M, Robert M, et al. Comparison of two dosages of azithromycin for three days versus penicillin V for ten days in acute group A streptococcal tonsillopharyngitis. Pediatr Infect Dis J.21(4):297-303.

17.2. Secondary Prophylaxis of Rheumatic Fever

For patients who have already been diagnosed with RF, secondary prophylaxis is indicated in order to prevent new attacks of acute RF (Tables 72 and 73). The drug of choice is benzathine benzylpenicillin, at the same doses of 600,000 IU for children weighing up to 27 kg and 1,200,000 IU above this weight, at a maximum interval of three weeks. Monthly applications of benzathine penicillin do not promote adequate protection in patients with rheumatic disease in countries with high endemicity of the disease, like Brazil.194194. Lue H-C, Wu M-H, Wang J-K, Wu F-F, Wu Y-N. Three-versus four-week administration of benzathine penicillin G: effects on incidence of streptococcal infections and recurrences of rheumatic fever. Pediatrics. 1996;97(6):984-8.198198. Meira ZMA, Mota CdCC, Tonelli E, Nunan EA, Mitre AMMC, Moreira NSdPC. Evaluation of secondary prophylactic schemes, based on benzathine penicillin G, for rheumatic fever in children. J Pediatr. 1993;123(1):156-8. For patients who are allergic to penicillin, sulfadiazine is indicated at a dose of 1 g daily, and it is necessary to control possible leukopenic conditions.

Table 72
Secondary prophylaxis of rheumatic fever: Recommended medications and posology194194. Lue H-C, Wu M-H, Wang J-K, Wu F-F, Wu Y-N. Three-versus four-week administration of benzathine penicillin G: effects on incidence of streptococcal infections and recurrences of rheumatic fever. Pediatrics. 1996;97(6):984-8.200200. Seppälä H, Nissinen A, Järvinen H, Huovinen S, Henriksson T, Herva E, et al. Resistance to erythromycin in group A streptococci. N Engl J Med. 1992;326(5):292-7.
Table 73
Recommendations for secondary prophylaxis of rheumatic fever194194. Lue H-C, Wu M-H, Wang J-K, Wu F-F, Wu Y-N. Three-versus four-week administration of benzathine penicillin G: effects on incidence of streptococcal infections and recurrences of rheumatic fever. Pediatrics. 1996;97(6):984-8.200200. Seppälä H, Nissinen A, Järvinen H, Huovinen S, Henriksson T, Herva E, et al. Resistance to erythromycin in group A streptococci. N Engl J Med. 1992;326(5):292-7.

Considering the recent shortage of benzathine penicillin G, the alternative is sulfadiazine, which is frequently available for rheumatologic diseases in the public health system and is listed in high-cost medication regimens. We must also remember that only benzathine penicillin G and sulfadiazine have proven efficacy for secondary prophylaxis of RF, based on controlled studies.199199. Coonan KM, Kaplan EL. In vitro susceptibility of recent North American group A streptococcal isolates to eleven oral antibiotics. Pediatr Infect Dis J. 1994;13(7):630-5.-200200. Seppälä H, Nissinen A, Järvinen H, Huovinen S, Henriksson T, Herva E, et al. Resistance to erythromycin in group A streptococci. N Engl J Med. 1992;326(5):292-7.

17.3. Criteria for Suspending Prophylaxis (Table 74)

Table 74
Duration of secondary prophylaxis of rheumatic fever
  1. Patients without cardiac involvement, with only joint manifestation or “pure” chorea – suspend at 18 years of age or 5 years after the last rheumatic attack;

  2. Patients with carditis during the acute attack who do not have late sequelae or who have very mild sequelae – suspend at 25 years of age or 10 years after the last rheumatic attack;

  3. In patients whose prophylaxis is suspended and symptoms recur, prophylaxis should be maintained for 5 more years.

  4. Patients with even mild cardiac involvement should receive prolonged prophylaxis, preferably lifelong; when this is not possible, until the fourth decade life. When deciding to suspend the prophylaxis, we must always investigate occupational exposure to sources of streptococci.

18. Prophylaxis of Infective Endocarditis in VHD

IE is a severe complication of VHD, and it is frequently fatal. For this reason, when prophylaxis is possible, it should be applied. For this purpose, several antibiotic regimens have been utilized, with little evidence from controlled studies, mainly due to the difficulty of conducting large controlled studies with medications that are already in the public domain.

Streptococci are part of the normal oropharynx and gastrointestinal tract flora, and they cause at least 50% of acquired IE cases in the Brazilian community. Bacteremia due to viridans streptococci has been demonstrated in up to 61% of patients following tooth extraction and periodontal surgery (36% to 88%), and experimental studies in animals have shown that antibiotic prophylaxis was capable of avoiding IE due to viridans streptococci and enterococci.201201. Okell C, Elliott MB. Bacteriaemia and Oral Sepsis with Special Reference to the Aetiology of Subacute Endocarditis. Lancet. 1935;226(5851):869-72.,202202. Roberts G, Gardner P, Longhurst P, Black A, Lucas V. Intensity of bacteraemia associated with conservative dental procedures in children. Br Dental J. 2000;188(2):95-8.

More recently, it has been observed that spontaneous bacteremia, especially originating in the teeth and gums, occurs in everyday situations. Thus, ordinary routine activities, such as tooth brushing (0% to 50%), use of dental floss (20% to 68%), use of toothpicks, and even chewing during meals (7% to 51%), are associated with bacteremia. In this manner, the burden of spontaneous bacteremia, not caused by dental intervention, would be higher than that caused by dental treatments. A theoretical study of cumulative bacteremia, lasting approximately one year, calculated that everyday bacteremia is six times greater than bacteremia caused by isolated tooth extraction. Considering that dental prophylaxis indications recommend two annual visits to the dentist, everyday activities have a greater impact on the generation of bacteremia than dental intervention itself. Recent epidemiological studies have not shown a relation between dental treatment two weeks before and episodes of IE.203203. Glauser M, Bernard J, Moreillon P, Francioli P. Successful single-dose amoxicillin prophylaxis against experimental streptococcal endocarditis: evidence for two mechanisms of protection. J Infect Dis. 1983;147(3):568-75.208208. Roberts GJ. Dentists are innocent! “Everyday” bacteremia is the real culprit: A review and assessment of the evidence that dental surgical procedures are a principal cause of bacterial endocarditis in children. Pediatr Cardiol. 1999;20(5):317-25.

For this reason, maintenance of optimal oral health in patients with VHD is more important than prophylaxis before dental procedures. Patients with good oral health have lower chances of bacteremia from everyday activities. We must, thus, focus more on non-pharmacological prevention than on pharmacological prophylaxis. Part of non-pharmacological prophylaxis of IE is to reinforce, during all consultations, the need to maintain excellent oral health and to increase the frequency of dental consultations, from two (recommendation for the general population) to four times a year. It is necessary to underline that many of the dental conditions that most frequently cause IE are oligosymptomatic, such as gingivitis and periapical endodontic lesions.209209. Drangsholt MT. A new causal model of dental diseases associated with endocarditis. Ann Periondontol. 1998;3(1):184-96.

For patients undergoing dental interventions, there is growing evidence that antibiotic prophylaxis prevents only a very small number of cases of IE. There is, however, recent evidence that completely abolishing antibiotic prophylaxis could lead to increased incidence of IE. The British National Institute for Health and Care Excellence (NICE) proposed that prophylaxis of IE should not be applied on any occasion.210210. Centre for Clinical Practice at NICE (UK). Prophylaxis against infective endocarditis: antimicrobial prophylaxis against infective endocarditis in adults and children undergoing interventional procedures. 2008.[Cited in 2019 May 20] Available from: https://www.ncbi.nlm.nih.gov/pubmed/21656971
https://www.ncbi.nlm.nih.gov/pubmed/2165...
As a consequence, a decrease was observed in the prescription of antibiotic prophylaxis before dental treatments, followed by an increase in the number of cases of IE.211211. Dayer MJ, Jones S, Prendergast B, Baddour LM, Lockhart PB, Thornhill MH. Incidence of infective endocarditis in England, 2000–13: a secular trend, interrupted time-series analysis. Lancet. 2015;385(9974):1219-28. We thus have empirical evidence that completely abolishing antibiotic prophylaxis could lead to an increase in cases of IE. We accordingly recommend maintaining antibiotic prophylaxis before dental, gastrointestinal, and genitourinary procedures.

All patients with moderate to severe VHD, whether of rheumatic or degenerative etiology, and patients with prosthetic valves should receive non-pharmacological and pharmacological prophylaxis for IE, once all patients with IE have high morbimortality.

18.1. Non-pharmacological Prophylaxis of Infective Endocarditis

Non-pharmacological prophylaxis of IE may be more effective than pharmacological prophylaxis, as it acts toward primary prevention of proven sources of bacteremia (Table 75). As priority measures for patients with VHD, we highlight maintaining excellent oral health and avoiding invasive body art procedures, such as piercings and tattoos.

Table 75
Non-pharmacological prophylaxis of infective endocarditis

Body art (procedures such as tattoos and piercings) should be contraindicated. Piercings lead to the formation of a tract that needs to be epithelialized, and until that process is complete, it is a source of continuous bacteremia, with many reports of IE related to piercings in the literature, some of them with fatal outcomes. It is important for patients to be informed regarding the risks of this procedure, in the same manner that physicians should always cover this issue when treating patients who have or intend to have body art.212212. Armstrong ML, DeBoer S, Cetta F. Infective endocarditis after body art: a review of the literature and concerns. J Adolesc Health. 2008;43(3):217-25.

18.2. Prophylaxis of Infective Endocarditis for Dental Procedures (Tables 76, 77, and 78)

Table 76
Indications of prophylaxis for dental procedures
Table 77
Antibiotic prophylaxis of IE in VHD
Table 78
Regimens for prophylaxis of infective endocarditis before dental procedures

The antibiotic should be administered one hour before the procedure. The regimen used should prevent bacteremia due to streptococci viridans, whenever tissue from the gums or the periapical region of the tooth is to be manipulated. The antibiotic of choice, if the patient is not allergic, is amoxicillin, due to its adequate absorption and to the susceptibility of the infectious agent. However, resistance to the antibiotic has been reported in several strains of the microorganism. For patients who are allergic to penicillin, the following may be used: clindamycin, azithromycin, or clarithromycin.

18.3. Prophylaxis of Infective Endocarditis for Respiratory Tract Procedures

Patients who will undergo incision or biopsy of the mucosa of the respiratory tract, such as otorhinolaryngological surgery, should receive antibiotic regimens similar to those used for conditions affecting the mouth.

18.4. Prophylaxis of Infective Endocarditis for Genitourinary or Gastrointestinal Tract Procedures

Enterococci are part of the the gastrointestinal tract flora, and they can cause IE. Thus, considering the lack of adequate scientific evidence, American and European guidelines no longer indicate antibiotic prophylaxis before interventions in these locations.213213. Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta J-P, Del Zotti F, et al. 2015 ESC guidelines for the management of infective endocarditis: the task force for the management of infective endocarditis of the European Society of Cardiology (ESC) endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;36(44):3075-128.,214214. Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison M, et al. Prevention of infective endocarditis: guidelines from the American heart association: a guideline from the American heart association rheumatic fever, endocarditis, and Kawasaki disease committee, council on cardiovascular disease in the young, and the council on clinical cardiology, council on cardiovascular surgery and anesthesia, and the quality of care and outcomes research interdisciplinary working group. Circulation. 2007;116(15):1736-54. Though, considering the severity of an eventual occurrence of IE by these sources, in the current document, we have chosen to consider prophylaxis for patients with high risk of severe IE who will undergo genitourinary or gastrointestinal procedures associated with mucosal injury. (Table 79).215215. Strom BL, Abrutyn E, Berlin JA, Kinman JL, Feldman RS, Stolley PD, et al. Risk factors for infective endocarditis: oral hygiene and nondental exposures. Circulation. 2000;102(23):2842-8. In the presence of infections that have installed in the genitourinary and gastrointestinal tracts, treatment should include antibiotics that act against enterococcus.

Table 79
Parenteral antibiotic prophylaxis for procedures in the gastrointestinal and genitourinary tracts

19. Pregnancy, Family Planning, and Contraception

19.1. Pre-Pregnancy Counseling

Risk stratification of valve diseases during pregnancy planning must be based on anatomical diagnosis of the valve lesion in order to classify the risks of pregnancy as high, intermediate, or accepTable (Table 80).

Table 80
Classification of risks of valve diseases to pregnancy

Concomitance of prognostic factors should be considered as worsening maternal and fetal prognosis (Table 81).216216. van Hagen IM, Thorne SA, Taha N, Youssef G, Elnagar A, Gabriel H, et al. Pregnancy outcomes in women with rheumatic mitral valve disease: results from the registry of pregnancy and cardiac disease. Circulation. 2018;137(8):806-16.

Table 81
Conditions that worsen prognosis of pregnancy in patients with valve disease216216. van Hagen IM, Thorne SA, Taha N, Youssef G, Elnagar A, Gabriel H, et al. Pregnancy outcomes in women with rheumatic mitral valve disease: results from the registry of pregnancy and cardiac disease. Circulation. 2018;137(8):806-16.

During pregnancy planning, keep in mind that percutaneous or surgical valve intervention should be indicated in patients with severe valve disease, even in asymptomatic patients, because NYHA FC I/II does not mean good maternal evolution in severe obstructive lesions (Table 82).217217. Avila WS, Rossi EG, Ramires JAF, Grinberg M, Bortolotto MRL, Zugaib M, et al. Pregnancy in patients with heart disease: experience with 1,000 cases. Clinical Cardiology: An International Indexed and Peer-Reviewed Journal for Advances in the Treatment of Cardiovasc Disease. 2003;26(3):135-42.

Table 82
Recommendations for treatment in acquired native VHD, during family planning and pregnancy217217. Avila WS, Rossi EG, Ramires JAF, Grinberg M, Bortolotto MRL, Zugaib M, et al. Pregnancy in patients with heart disease: experience with 1,000 cases. Clinical Cardiology: An International Indexed and Peer-Reviewed Journal for Advances in the Treatment of Cardiovasc Disease. 2003;26(3):135-42.

In contrast, regurgitation lesions have better prognosis when LVEF fraction is preserved, and the rare cases with complications are those that already had surgical indication prior to pregnancy.

During pregnancy, the basic principle for prevention and treatment of complications is to prioritize general measures and to choose non-teratogenic drugs with doses adjusted to gestational age. Table 83 lists the drugs and daily doses most frequently used to control complications of valve disease during pregnancy.218218. Sliwa K, Johnson MR, Zilla P, Roos-Hesselink JW. Management of valvular disease in pregnancy: a global perspective. Eur Heart J. 2015;36(18):1078-89.

Table 83
General and pharmacological recommendations during pregnancy218218. Sliwa K, Johnson MR, Zilla P, Roos-Hesselink JW. Management of valvular disease in pregnancy: a global perspective. Eur Heart J. 2015;36(18):1078-89.

Interventional measures in valve diseases during pregnancy are reserved for cases that are refractory to clinical treatment. Percutaneous procedures should be given preference over surgery, and the proposed treatments should be discussed with the Heart Team and shared with the Obstetric Team. Balloon valvuloplasty in AS has been indicated when etiology is congenital or as an attempt to save the mother’s life in extremely severe cases. In contrast, PBMV is safe, with results equivalent to those of surgery; it nevertheless requires the classical indication criteria, such as absence of thrombus in the LA, no more than mild MR, and Wilkins-Block echocardiographic score ≤ 8.

19.2. Valve Prostheses

From the hemodynamic point of view, both mechanical and biological prostheses improve functional capacity, and they promote similar clinical evolution during pregnancy; nevertheless, biological prostheses appear to be more advantageous because they do not require anticoagulation (Table 84). Their limited durability, with the possibility of short-term reoperation, including during pregnancy, are the main restrictions to implantation of biological prostheses in young women.

Table 84
Prosthetic valve with normal function and risks to pregnancy

The management in cases of prosthesis dysfunction during pregnancy should always prioritize the mother’s life, and the proposed treatments should be discussed with the Heart Team and shared with the Obstetric Team (Table 85).

Table 85
Treatment in prosthesis dysfunction during pregnancy

Anticoagulation regimens for patients with mechanical prosthesis remain controversial.218218. Sliwa K, Johnson MR, Zilla P, Roos-Hesselink JW. Management of valvular disease in pregnancy: a global perspective. Eur Heart J. 2015;36(18):1078-89.,219219. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomstrom-Lundqvist C, Cifkova R, De Bonis M, et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Kardiol Pol (Polish Heart Journal). 2019;77(3):245-326. To date, there are no uniform guidelines that have been widely accepted. Factors that must be considered include the following: patient preference, expertise of the attending doctor, local resources, and availability of adequate coagulation control.

The recommendations for preventing thromboembolism in mechanical prostheses are intended to meet the ideal requirements of a position based on the literature and on the authors’ experience, and they should be effective for the reality of diverse healthcare services. It is understood that the dynamics of permanent anticoagulation in patients with mechanical prostheses is multidisciplinary, and it is divided into five phases: pre-conception, each trimester, delivery, and postpartum, shown in Table 86 and Figure 11. Vigilant control of anticoagulation and doses of anticoagulants should be adjusted according to conventional targets.

Table 86
Anticoagulation control in patients with mechanical prosthesis during pregnancy
Figura 11
Flowchart with recommendations for anticoagulation in patients with mechanical prostheses during pregnancy, delivery, and postpartum. βHCG: beta-human chorionic gonadotropin; IV UFH: intravenous unfractionated heparin; SC LMWH: subcutaneous low-molecular-weight heparin; VKA: vitamin K antagonist.

Phase 1 - orientations regarding early diagnosis of pregnancy: Clarify that it is mandatory to maintain anticoagulation and discuss the availability of anticoagulants and their risks during all phases of pregnancy, delivery, and postpartum. Advice includes information regarding the importance of early diagnosis of pregnancy in order to reduce the occurrence of embryopathy, which occurs between the sixth and ninth week of pregnancy. During this consultation, the patient receives a request for beta-human chorionic gonadotropin (βHCG) measurement, which should take place as soon as there are doubts regarding late menstruation.

Phase 2 - first trimester: Once pregnancy has been confirmed (βHCG and obstetric ultrasound), warfarin should be substituted by heparin which makes it possible to balance between the benefit of preventing maternal thrombosis and the harm of embryopathy. In patients whose first medical consultation occurs after the sixth week of gestation, warfarin should not be suspended. The couple should be informed that there is a possibility of embryopathy and that the risks of substituting warfarin for heparin are no longer justified.

Phase 3 - second trimester: Return to oral anticoagulant. The return to warfarin is based on the benefit of shortening the use of heparin and lowering the risk of embryopathy. The proposal is to maintain the warfarin dosage in accordance with pre-pregnancy goals, with weekly or biweekly INR control. Reintroduction of warfarin should take place simultaneously with the use of subcutaneous low-molecular-weight heparin or intravenous unfractionated heparin until the target INR has been reached.

Phase 4 - third trimester: Consider hospitalization, return to parenteral anticoagulation and schedule delivery. Hospitalization should be scheduled at week 36 of pregnancy for use of subcutaneous low-molecular-weight heparin or intravenous unfractionated heparin.

Phase 5 - postpartum: Reintroduction of oral anticoagulation and hospital discharge. Six hours after delivery, if there are not maternal complications, intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin should be reintroduced in therapeutic doses. Warfarin should be prescribed 48 hours after delivery, following the transition dynamic in conjunction with heparin until the INR value of 2.0 has been reached, at which point the patient is discharged from the hospital.

19.3. Delivery and Postpartum

Delivery planning should be multidisciplinary, starting at week 34 of pregnancy. Vaginal delivery is considered to be more advantageous because it is associated with less blood loss and lower risks of thrombosis and infection. Sequential anesthesia techniques, with neuraxial anesthesia, have hemodynamic advantages because they allow a gradual form of sympathetic block. In general, cases of maternal indication for cesarean delivery require general anesthesia (Table 87).

Table 87
Recommendations for route of delivery and anesthesia in patients with valve disease

19.4. Contraception

The choice of contraceptive method for women with valve diseases requires multidisciplinary effort, involving the gynecologist and the cardiologist, in order to seek safety, efficacy, tolerance, and easy access. Accordingly, guidelines for prescription should be based on the Contraceptive Eligibility Criteria, which classify contraceptives in four risk categories, and on the Pearl index, which calculates the effectiveness of a method considering the number of pregnancies per 100 women during the first year of use.220220. World Health Organization. (WHO) Health Worker Role in Providing Safe Abortion Care and Post Abortion Contraception. Geneva;2015.,221221. Poli MEH, Mello CR, Machado RB, Pinho Neto JS, Spinola PG, Tomas G, et al. Manual de anticoncepção da FEBRASGO. Femina. 2009;37(9):459-92. For patients with valve disease, the current tendency is to indicate methods that contain only progesterone or combinations of progesterone and natural estrogen in monthly injecTable forms, because they are safe, effective, and easily accessible (Table 88). Although intrauterine devices are classified as category 2, they have not been indicated in patients with valve diseases, due to the presumed inherent risk of IE.

Table 88
Medical eligibility criteria (modified)* and index of effectiveness for contraceptive use in patients with valve disease220220. World Health Organization. (WHO) Health Worker Role in Providing Safe Abortion Care and Post Abortion Contraception. Geneva;2015.,221221. Poli MEH, Mello CR, Machado RB, Pinho Neto JS, Spinola PG, Tomas G, et al. Manual de anticoncepção da FEBRASGO. Femina. 2009;37(9):459-92.

  • Development: Departamento de Cardiologia Clínica da Sociedade Brasileira de Cardiologia (DCC-SBC)
  • Norms and Guidelines Council (2020-2021): Brivaldo Markman Filho, Antonio Carlos Sobral Sousa, Aurora Felice Castro Issa, Bruno Ramos Nascimento, Harry Correa Filho, Marcelo Luiz Campos Vieira
  • Norms and Guidelines Coordinator (2020-2021): Brivaldo Markman Filho
  • Note: These updates are for information purposes and are not to replace the clinical judgment of a physician, who must ultimately determine the appropriate treatment for each patient.

    List of Abbreviations:
  • βHCG:  beta-human chorionic gonadotropin
  • ACC/AHA:  American College of Cardiology/American Heart Association
  • AF:  atrial fibrillation
  • AR:  aortic regurgitation
  • aPTT:  activated partial thromboplastin time
  • AS:  aortic stenosis
  • ASA:  acetylsalicylic acid
  • AVA:  aortic valve area
  • PBMV:  percutaneous balloon mitral valvuloplasty
  • BNP:  brain natriuretic peptide
  • PBTV:  percutaneous balloon tricuspid valvuloplasty
  • CHC:  combined hormonal contraceptive
  • DOACs:  direct oral anticoagulants
  • ECG:  electrocardiogram
  • EOA:  effective orifice area
  • EROA:  effective regurgitant orifice area
  • ESC/EACTS:  European Society of Cardiology/European Association for Cardiothoracic Surgery
  • FC:  functional class
  • IE:  infective endocarditis
  • INR:  international normalized ratio
  • IUD:  intrauterine device
  • LA:  left atrium
  • LV:  left ventricle
  • LVDD:  left ventricular diastolic diameter
  • LVEF:  left ventricular ejection fraction
  • LVSD:  left ventricular systolic diameter
  • MAC:  mitral annulus calcification
  • MR:  mitral regurgitation
  • MS:  mitral stenosis
  • MVA:  mitral valve area
  • NYHA:  New York Heart Association
  • PH:  pulmonary hypertension
  • PHT:  pressure half time
  • RA:  right atrium
  • RF:  rheumatic fever
  • rTPA:  recombinant tissue plasminogen activator
  • SBC:  Sociedade Brasileira de Cardiologia (Brazilian Society of Cardiology)
  • SPAP:  systolic pulmonary artery pressure
  • STS:  Society of Thoracic Surgeons
  • TAVI:  transcatheter aortic valve implantation
  • TR:  tricuspid regurgitation
  • TS:  tricuspid stenosis
  • TTR:  time in therapeutic range
  • VHD:  valvular heart disease
  • VKA:  vitamin K antagonists

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Publication Dates

  • Publication in this collection
    23 Oct 2020
  • Date of issue
    Oct 2020
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