Valvular Heart Disease Emergencies: A Comprehensive Review Focusing on the Initial Approach in the Emergency Department

Accorsi, Tarso Augusto Duenhas; Paixão, Milena Ribeiro; Souza Júnior, José Leão de; Gaz, Marcus Vinicius Burato; Cardoso, Ricardo Galesso; Köhler, Karen Francine; Lima, Karine De Amicis; Tarasoutchi, Flavio; ,

Tarso Augusto Duenhas Accorsi

Conception and design of the research

Analysis and interpretation of the data

Writing of the manuscript

Unidade de Pronto Atendimento, Hospital Israelita Albert Einstein, São Paulo, SP – Brazil

Instituto do Coração (InCor), Faculdade de Medicina, USP, São Paulo, SP – Brazil

http://orcid.org/0000-0002-8023-3466

Milena Ribeiro Paixão

Conception and design of the research

Writing of the manuscript

Critical revision of the manuscript for important intellectual content

Unidade de Pronto Atendimento, Hospital Israelita Albert Einstein, São Paulo, SP – Brazil

Instituto do Coração (InCor), Faculdade de Medicina, USP, São Paulo, SP – Brazil

http://orcid.org/0000-0002-1565-3915

José Leão de Souza Júnior

Conception and design of the research

Critical revision of the manuscript for important intellectual content

Unidade de Pronto Atendimento, Hospital Israelita Albert Einstein, São Paulo, SP – Brazil

http://orcid.org/0000-0001-6017-7682

Marcus Vinicius Burato Gaz

Conception and design of the research

Analysis and interpretation of the data

Unidade de Pronto Atendimento, Hospital Israelita Albert Einstein, São Paulo, SP – Brazil

http://orcid.org/0000-0001-5139-4079

Ricardo Galesso Cardoso

Conception and design of the research

Analysis and interpretation of the data

Unidade de Pronto Atendimento, Hospital Israelita Albert Einstein, São Paulo, SP – Brazil

http://orcid.org/0000-0002-1935-607X

Karen Francine Köhler

Conception and design of the research

Critical revision of the manuscript for important intellectual content

Unidade de Pronto Atendimento, Hospital Israelita Albert Einstein, São Paulo, SP – Brazil

http://orcid.org/0000-0002-8348-4623

Karine De Amicis Lima

Conception and design of the research

Critical revision of the manuscript for important intellectual content

Unidade de Pronto Atendimento, Hospital Israelita Albert Einstein, São Paulo, SP – Brazil

http://orcid.org/0000-0002-9936-2436

Flavio Tarasoutchi

Conception and design of the research

Critical revision of the manuscript for important intellectual content

Instituto do Coração (InCor), Faculdade de Medicina, USP, São Paulo, SP – Brazil

http://orcid.org/0000-0002-9964-3289

INTEGRATE Investigadores

Mailing Address: Tarso Augusto Duenhas Accorsi • Hospital Israelita Albert Einstein – Secretaria da Unidade de Pronto Atendimento – Av. Albert Einstein, 627, Bloco B, 2º andar. Postal Code 05652-900, São Paulo, SP – Brazil E-mail: tarsoa@einstein.br

Potential conflict of interest

No potential conflict of interest relevant to this article was reported.

Symptoms
Dyspnea, orthopnea, paroxysmal nocturnal dyspnea, edema Chest pain Syncope Palpitation Embolic events, such as stroke
Signs	Valvulopathy
Murmur: – Holosystolic at the apex – Systolic crescendo-decrescendo at the right upper sternal border – Diastolic rumble at the apex, often with an opening snap – Diastolic decrescendo usually heard at the third left intercostal space – Holosystolic, increasing during inspiration at the left lower sternal border – Short mid-diastolic rumble heard loudest at the apex in the absence of an opening snap associated to holosystolic murmur	Mitral regurgitation Aortic stenosis Mitral stenosis Aortic regurgitation Tricuspid regurgitation Mitral valvulitis in acute RF (Carey Coombs)
Pulse: – Bounding pulse (Watson’s water hammer or Corrigan’s) – Late weak pulse ( parvus et tardus )	Aortic regurgitation Aortic stenosis
Head: – Rosy-purple cheeks (mitral facies) – Bobbing head with each heartbeat (de Musset) – Visible pulsation of the uvula (Muller) – Visible pulsation of pupils (Landolfi)	Mitral stenosis Aortic regurgitation
Eyes: – White centered retinal hemorrhage (Roth spots)	Infective endocarditis
Neck: – Giant systolic pulsations with prominent V-waves (Lancisi) – Dancing carotids (Corrigan)	Tricuspid regurgitation Aortic regurgitation
Fingers: – Capillary pulsation with light compression of the nail (Quincke) – Digital clubbing – Splinter lesions	Aortic regurgitation Congenital heart diseases, infective endocarditis Infective endocarditis
Abdomen: – Pulsation of the spleen (Gerhardt) and liver (Rosenbach)	Aortic regurgitation
Skin: – Subcutaneous nodules – Erythema marginatum – Osler nodules – Janeway lesions – Petechiae	Acute rheumatic fever Infective endocarditis

Management of organic perfusion in hypotensive patients
	Aortic stenosis	Aortic regurgitation	Mitral stenosis	Mitral regurgitation
Fluid therapy: Crystalloid a) Isotonic b) Avoid hypertonic and hypotonic solutions No strong evidence for colloid volume expanders.	Attention: most patients are congested. Usually, fluid therapy is not appropriate and may induce respiratory distress. Fluids should be administered with unequivocal clinical and ultrasonographic signs of hypovolemia.
	Normal LVEF + “ kissing walls ” + IVC < 10mm + absence of B-lines Highly preload dependent	Normal LVEF + IVC < 10mm + absence of B-lines	HR < 100 bpm (usually on medication) + RV diameter < LV diameter + absence of D-shape + IVC < 10 mm + absence of B-lines	LVEF + RV diameter < LV diameter + absence of D-shape + IVC < 10 mm + absence of B-lines
Vasopressors	Low dose dobutamine – avoid tachycardia.	Dobutamine	Avoid dobutamine (avoid tachycardia)	Dobutamine
Vasopressors	Low dose norepinephrine – avoid tachycardia	Norepinephrine	Low dose norepinephrine – avoid tachycardia.	Norepinephrine
Other drugs	Short-acting vasoactive amines are options (phenylephrine)	No strong supportive evidence	If tachycardia (even sinus rhythm), beta blocker may be used; short-acting vasoactive amines may be options (phenylephrine). Milrinone if PAH.	Milrinone if PAH
Intra-aortic balloon	Possible benefit	Contraindicated	No evidence	Possible benefit
Interventionist / other strategies	Consider the percutaneous balloon valvuloplasty as a bridge for definitive intervention; extracorporeal membrane oxygenation as a bridge for definitive intervention	No strong supportive evidencea	Consider percutaneous balloon mitral valvuloplasty if favorable (anatomical criteria and absence of contraindications)	Percutaneous ventricular assist device as a bridge for definitive intervention. Without current evidence for MitraClip
Management of hypoxemia
	Aortic stenosis	Aortic regurgitation	Mitral stenosis	Mitral regurgitation
Non-invasive ventilation: avoid deep sedation and opioids	Possible, even in mild hypotension	Possible, even in mild hypotension	Possible, even in mild hypotension; avoid in severe PAH and/or RV dysfunction	Possible, even in mild hypotension; avoid in severe PAH and/or RV dysfunction
Advanced airway management No strong evidence for premedication with lidocaine Sedation strategies (choose one): a) Propofol b) Etomidate c) Ketamine d) Midazolam plus (choose one): a) Succinylcholine b) Rocuronium Initial mechanical ventilation: tidal volume 6 mL/Kg, plateau pressure < 30 mmHg, titrated PEEP and driving pressure < 20 mmHg	Hypotension often occurs after intubation; attention to the choice of medications during sedation and maintain vasopressors readily available	Intubation is usually well tolerated	Avoid ketamine; marked hypotension after intubation when there is PAH	Intubation is usually well tolerated
Diuretics (furosemide; no evidence for other classes in emergency setting)	Administer only if lung congestion; avoid if compensated oxygenation	Usually necessary	Usually necessary	Usually necessary
ptimize the pressure-volume curve until definitive treatment
	Aortic stenosis	Aortic regurgitation	Mitral stenosis	Mitral regurgitation
Rhythm Amiodarone can be used in all scenarios according to clinical judgment in stable patients with acute supraventricular arrhythmia.	Maintain sinus rhythm if possible	Consider chronic stable AF as sinus tachycardia. Diltiazem and esmolol may be carefully used.	Maintain sinus rhythm if possible	Consider chronic stable AF as sinus tachycardia. Diltiazem and esmolol may be carefully used.
Heart rate	Avoid excessive tachycardia in non-sinus rhythm with amiodarone, diltiazem, verapamil, esmolol, metoprolol tartrate, lanatoside C	Avoid routine use of beta blockers. Diltiazem and esmolol may be carefully used.	Avoid tachycardia in all rhythms with amiodarone, diltiazem, verapamil, esmolol, metoprolol tartrate, lanatoside C	80–100 bpm Avoid intense decrease. Diltiazem and esmolol may be carefully used
Preload: POCUS should monitor IVC and other dynamic parameters	Avoid diuretics and nitrates (nitroglycerin, isosorbide)	In stable patients with lung congestion, it is reasonable to use of vasodilator regardless of class -nicardipin, hydralazine, captopril, and enalapril	Avoid routine use of vasodilators	In stable patients with lung congestion, it is reasonable to use of vasodilator regardless of class -nicardipin, hydralazine, captopril, and enalapril
Afterload	Nitroprusside if MAP > 60 mmHg, especially if low LVEF; avoid fast SV reduction (worsening of coronary perfusion)	Nitroprusside. Nitroglycerin should be an alternative. In stable patients with lung congestion, it is reasonable to use of vasodilator regardless of class -nicardipin, hydralazine, captopril, and enalapril	Avoid low afterload (decreases coronary perfusion)	Prevent increase; nitroprusside; nitroglycerin should be an alternative. In stable patients with lung congestion is reasonable to use of vasodilator regardless of class -nicardipin, hydralazine, captopril, and enalapril
Contractility	Levosimendan	No strong supportive evidence	No strong supportive evidence	Avoid myocardial depression

Manifestation	Prevalence (%)	Signs and symptoms
Carditis	50–70	Valvulitis is the main manifestation, although myocarditis and pericarditis can also occur; if valvulitis is severe, acute heart failure can occur; subclinical carditis refers to echocardiographic diagnosis in the absence of auscultatory findings.
Arthritis	35–66	Migratory polyarthritis, remaining 1 to 7 days in each joint; larger joints are chiefly affected: knees, ankles, elbows, and wrists; pain is more intense than the clinical findings; absence of long-term deformity; early onset of NSAID can induce monoarthritis, due to its rapid improvement.
Sydenham chorea	10–30	Involuntary, abrupt, nonrhythmic movements of trunk, extremities, head, face, and tongue; related to emotional lability and muscle weakness; disappears during sleep; usually starts three months after GAS infection and lasts 2 to 3 months.
Subcutaneous nodules	0–10	Firm, painless, up to 2 centimeters, often 3 to 4 nodules, located over a bone or extensor surface of tendons (commonly on the olecranon), with normal skin surrounding; appears 1 to 2 weeks after other manifestations and lasts less than a month; related to carditis; almost never occurs as the only RF manifestation.
Erythema marginatum	< 6	Pink rash with pale center and rounded or with serpiginous borders on the trunk or proximal extremities (face preserved); lesions blanches with pressure and can appear, disappear, and reappear in hours; related to carditis; almost never occurs as the only RF manifestation.

	High risk groups (living in an endemic setting, personal history and age < 40 years, prior residence or frequent or recent travel in a setting of high risk for rheumatic disease)	Low risk groups (no high-risk conditions)
Major manifestations	carditis (including subclinical evidence of valvulitis on echocardiogram) polyarthritis or aseptic monoarthritis or polyarthralgia Sydenham chorea erythema marginatum subcutaneous nodules	carditis (including subclinical evidence of valvulitis on echocardiogram) polyarthritis Sydenham chorea erythema marginatum subcutaneous nodules
Minor manifestations	fever > 38ºC monoarthralgia erythrocyte sedimentation rate > 30 mm/h or C-reactive protein > 30 mg/L d) prolonged PR interval on ECG	fever > 38.5ºC polyarthralgia or aseptic monoarthritis erythrocyte sedimentation rate > 60 mm/h or C-reactive protein > 30 mg/L dprolonged PR interval on ECG
Definite initial episode of acute RF	2 major manifestations + evidence of preceding GAS infection; OR 1 major + 2 minor manifestations + evidence of preceding GAS infection.
Definite recurrent episode of acute RF in patients with documented history of acute RF or RHD	2 major manifestations + evidence of preceding GAS infection; OR 1 major + 2 minor manifestations + evidence of preceding GAS infection; OR 3 minor manifestations + evidence of preceding GAS infection.
Probable or possible acute RF (initial or recurrence)	1 major or 1 minor manifestations; OR no evidence of preceding GAS infection. Probable acute RF rather than highly suspect Possible acute RF rather than uncertain

	Treatment
All cases	Eradication of the GAS infection: – Benzathine benzylpenicillin G 1,200,000 units (child < 20 kg: 600,000 units; ≥ 20 kg: 1,200,000 units) intramuscular single dose – Penicillin hypersensitivity: cephalexin 1 g (child: 25 mg/kg up to 1 g) orally, 12-hourly for 10 days or azithromycin 500 mg (child: 12 mg/kg up to 500 mg) orally daily for 5 days
Carditis	Rest, with mobilization as symptoms allow Prednisone/prednisolone 1–2 mg/kg up to a maximum of 80 mg orally, once daily or in divided doses for 4 to 8 weeks in mild carditis and 12 weeks in moderate/severe carditis. After 2 to 3 weeks, if symptoms improve, reduce the dose by 20 to 25% weekly. In refractory cases, 30 mg/kg/day weekly. Pediatric dosing: furosemide 1–2 mg/kg orally as a single dose, then 0.5–1 mg/kg (to a maximum of 6 mg/kg) orally, 6- to 24-hourly; spironolactone 1–3 mg/kg (initially) up to 100 mg orally, daily in 1 to 3 divided doses (round dose to a multiple of 6.25 mg – a quarter of a 25 mg tablet); enalapril 0.1 mg/kg orally, daily in 1 or 2 divided doses increased gradually over 2 weeks to a maximum of 1 mg/kg orally, daily in 1 or 2 divided doses, other ACE inhibitors (captopril, lisinopril, ramipril, perindopril) can be used. Adult dosing: Furosemide 20–40 mg oral or intravenous as a single dose followed by 20–40 mg oral or intravenous 8–12 hourly; spironolactone may be added for patients having limited or no response to loop diuretic, 12.5–25 mg spironolactone orally daily; nitrate therapy may be added for patients with limited or no response to diuretic therapy, whose systolic blood pressure is greater than 90 mmHg; the ACE inhibitor is recommended in patients with moderate or severe left ventricular systolic dysfunction, unless contraindicated. Valve surgery for life-threatening acute carditis (rare)
Arthritis	Lasts about one month without treatment Rapid improvement with NSAID, often 1 to 2 weeks (may be up to 12 weeks) – Naproxen immediate-release 250–500 mg (child 10–20 mg/kg/day) orally twice daily, up to a maximum of 1250 mg daily – Ibuprofen 200–400 mg (child 5-10 mg/kg) orally thrice daily, up to a maximum of 2400 mg daily – Aspirin adults and children 50–60 mg/kg/day orally, in 4 to 5 divided doses; dose can be escalated up to a maximum of 80–100 mg/kg/day in 4 to 5 divided doses Proton pump inhibitor should be considered. Corticosteroids are used if intolerance or allergy to NSAID or if indicated to treat another manifestation, i.e., carditis.
Chorea	No pharmacological treatment for mild cases; for moderate/severe cases: – Haloperidol 0.5 mg per dose orally, twice daily (can be increased 0.5 mg/day until 5mg/day) – Carbamazepine 3.5–10 mg/kg per dose orally, twice daily – Sodium valproate 7.5–10 mg/kg per dose orally, twice daily Consider adding corticosteroid: prednisone/prednisolone 1–2 mg/kg up to a maximum of 80 mg orally, once daily or in divided doses
Prophylaxis	Penicillin G benzathine intramuscular – Adults > 20 kg: 1.2 million units every 21 to 28 days – Children ≤ 20 kg: 600,000 units every 21 to 28 days If penicillin allergy: – Sulfadiazine: < 30 kg 500 mg orally, once daily; ≤ 30 kg: 1 g orally, once daily – Erythromycin: 250 mg orally, twice daily Rheumatic fever without carditis: 5 years or until 21 years of age (whichever is longer) Rheumatic fever with carditis but no residual heart disease (no clinical or echocardiographic evidence of valvular disease): 10 years or until 21 years of age (whichever is longer) Rheumatic fever with carditis and residual heart disease (persistent valvular disease): 10 years or until 40 years of age (whichever is longer); sometimes lifelong prophylaxis (i.e., healthcare professionals, infant professors)

Type of infective endocarditis	Antibiotic regimen and dose
Native valve endocarditis or prosthetic valve (> 1 year of surgery)	Ampicillin 2 g IV every 4 hours + Oxacillin 2 g IV every 4 hours + Gentamicin* 1 to 3 mg/Kg of current body weight IV every 24 h or divided in 3 doses Alternative in cases of low probability of enterococci: ceftriaxone 1g every 12 hours instead of ampicillin + oxacillin 2g IV every 4 hours	4 to 6 weeks 4 to 6 weeks 2 weeks 4 to 6 weeks
Prosthetic valve (< 1 year of surgery)	Vancomycin 15 mg/Kg IV every 12 hours or Daptomycin 8 to 10 mg/Kg IV every 24 hours Meropenem 2 g IV every 8 hours or Cefepime 2 g IV every 8 hours + Gentamicin* 1 to 3 mg/Kg of actual body weight IV every 24 h or divided in 3 doses	6 weeks 6 weeks 2 weeks

[1] Mailing Address: Tarso Augusto Duenhas Accorsi • Hospital Israelita Albert Einstein – Secretaria da Unidade de Pronto Atendimento – Av. Albert Einstein, 627, Bloco B, 2º andar. Postal Code 05652-900, São Paulo, SP – Brazil E-mail: tarsoa@einstein.br

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Valvular Heart Disease Emergencies: A Comprehensive Review Focusing on the Initial Approach in the Emergency Department

Abstract