Frequency of left ventricular diastolic dysfunction by mitral doppler in healthy elderly individuals

Abstracts

FUNDAMENTO: Idosos sadios frequentemente apresentam alterações nas velocidades do Doppler mitral, características de disfunção diastólica do ventrículo esquerdo (VE) do tipo alteração do relaxamento. OBJETIVO: Determinar a frequência de disfunção diastólica do VE pelo Doppler mitral em idosos sadios e identificar características clínicas e ecocardiográficas associadas a esse achado. MÉTODOS: O total de 73 indivíduos aparentemente sadios e rigorosamente selecionados (64% de mulheres), com idade entre 60 e 80 anos, foram submetidos à avaliação clínica, laboratorial e Doppler-ecocardiográfica, com especial atenção às características do fluxo mitral. RESULTADOS: Encontramos 33 pacientes (45%) com padrão diastólico do VE do tipo alteração do relaxamento (grupo 1), caracterizados pela relação entre as velocidades máximas das ondas do fluxo mitral (relação E/A) <0,75 ou pelo tempo de desaceleração da onda E >240 ms. Outros 40 pacientes (55%) apresentaram padrão normal (grupo 2). O grupo/ 1 apresentou maior diâmetro da raiz da aorta (32,1±4,2 vs 30,3±3,3 mm; p=0,044) e intervalo PR mais longo (156±22 vs 139±23 ms; p=0,002). CONCLUSÃO: Uma grande proporção de indivíduos, com idade entre 60 e 80 anos, apresenta função diastólica normal pela análise Doppler-ecocardiográfica do fluxo mitral. Idosos sadios, portadores de disfunção diastólica do VE do tipo alteração do relaxamento, exibem maior diâmetro da raiz da aorta e intervalo PR mais longo.

Disfunção ventricular esquerda; ecocardiografia Doppler; valva mitral; idoso

FUNDAMENTO: Los adultos mayores sanos presentan frecuentemente alteraciones en las velocidades del Doppler mitral, características de disfunción diastólica del ventrículo izquierdo (VI) del tipo alteración de la relajación. OBJETIVO: Determinar la frecuencia de disfunción diastólica del VI por el Doppler mitral en adultos sanos, e identificar las características clínicas y ecocardiográficas asociadas a este hallazgo. MÉTODOS: El total de 73 individuos aparentemente sanos y rigurosamente seleccionados (el 64% de mujeres), con edad entre 60 y 80 años, se sometieron a la evaluación clínica, laboratorial y Doppler-ecocardiográfica, con especial atención a las características del flujo mitral. RESULTADOS: Los 33 pacientes (45%) revelaron estándar diastólico del VI del tipo alteración de la relajación (grupo 1), caracterizados por la relación entre las velocidades máximas de las ondas del flujo mitral (relación E/A) <0,75 o por el tiempo de desaceleración de la onda E >240 ms. Otros 40 pacientes (55%) presentaron estándar normal (grupo 2). El grupo 1 presentó mayor diámetro da raíz de la aorta (32,1±4,2 vs. 30,3±3,3 mm; p=0,044) e intervalo PR más prolongado (156±22 vs. 139±23 ms; p=0,002). CONCLUSIÓN: Una gran proporción de individuos, con edad entre 60 y 80 años, presenta función diastólica normal por el análisis Doppler-ecocardiográfico del flujo mitral. Adultos sanos, portadores de disfunción diastólica del VI del tipo alteración de la relajación, exhiben mayor diámetro de la raíz de la aorta e intervalo PR más prolongado.

Disfunción ventricular izquierda; ecocardiografía Doppler; válvula mitral; adulto mayor

ORIGINAL ARTICLE

^IHospital Universitário Prof. Edgard Santos - Universidade Federal da Bahia (UFBA)

^IIEscola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador, BA, Brazil

Mailing Address

SUMMARY

BACKGROUND: Healthy elderly individuals present alterations in mitral Doppler velocities, which are characteristic of left ventricular (LV) diastolic dysfunction with impaired relaxation.

OBJECTIVE: To determine the frequency of LV diastolic dysfunction by mitral Doppler in healthy elderly individuals and identify clinical and echocardiographic characteristics associated to this finding.

METHODS: Seventy-three apparently healthy individuals (64% women, aged 60 to 80) were carefully selected and submitted to clinical, laboratory and Doppler-echocardiographic assessment, with particular regard to the characteristics of the mitral flow.

RESULTS: A total of 33 patients (45%) presented an impaired LV relaxation pattern (group I), characterized by the association between the maximum velocities of the mitral wave flow (E/A ratio) <0.75 or E-wave deceleration time >240 ms, and 40 (55%) with a normal pattern (group II). Group I presented a larger aortic root diameter (32.1±4.2 vs. 30.3±3.3 mm; p=0.044) and a longer PR interval (156±22 vs. 139±23 ms; p=0.002).

CONCLUSION: A large proportion of individuals aged 60 to 80 years present normal diastolic function at the Doppler-echocardiographic assessment of the mitral flow. Healthy elderly individuals with impaired LV relaxation filling have a larger aortic root diameter and longer PR interval.

Key Words: Ventricular dysfunction, left; echocardiography, Doppler; mitral valve, elderly.

Introduction

One can observe significant modifications in the transmitral Doppler, tissue Doppler imaging of mitral annulus and pulmonary venous Doppler profiles at the older age ranges, similar to those found in diseases that course with impaired left ventricular (LV) relaxation filling^1-7. However, not all elderly individuals exhibit altered mitral and pulmonary venous Doppler profiles^8,9. More recently, it was demonstrated in a large epidemiological study with individuals older than 65 years that the diagnosis of diastolic dysfunction, based on a stricter criterion, was an independent predictor of congestive heart failure¹⁰.

The objective of the present study was to evaluate the frequency of diastolic dysfunction by mitral Doppler in apparently healthy individuals aged >60 years, as well as to identify the clinical and echocardiographic characteristics associated to this finding.

Methods

Study population

Retired employees of the Federal University of Bahia and patients treated at a private health institution, aged 60 years or older, were invited to participate in the study. Individuals that met one or more of the following criteria were excluded from the study: (1) A diagnosis of systemic arterial hypertension based on the regular use of anti-hypertensive drug or persistently high blood pressure measurement by either the casual measurement with a sphygmomanometer or by ambulatory blood pressure monitoring; (2) a diagnosis of coronary artery disease, either by the history of angina pectoris or myocardial infarction, or the presence of myocardial ischemia or electrically inactive region at the ECG; (3) clinical picture of heart failure, or echocardiographic signs of LV systolic dysfunction (through the qualitative analysis of two-dimensional echocardiogram or ejection fraction <55%); (4) use of artificial pacemaker; (5) use of drug with cardiovascular action (diuretic, digital, beta-blocker, calcium channel antagonist, nitrate or antiarrhythmic); (6) presence of left branch blockage; (7) presence of atrial fibrillation; (8) diagnosis of hypertrophic cardiomyopathy, defined by the finding of interventricular septum diastolic thickness >15/ mm and at least 1.3-fold the thickness of the LV posterior wall; (9) diagnosis of restrictive cardiomyopathy, such as endomyocardial fibrosis and amyloidosis; (10) presence of mitral or aortic valvular failure > mild; (11) presence of any degree of mitral or aortic stenosis; (12) diagnosis of diabetes mellitus, i.e., fasting glycemia >126 mg/dl, use of insulin, or use of oral hypoglycemic agents; (13) history of chronic disease capable of affecting the cardiocirculatory function, such as renal failure, hyperthyroidism, chronic pulmonary disease or collagenosis; (14) heart rate >100 beats per minute, at the moment of the echocardiographic assessment; (15) technically inadequate echocardiographic image ; (16) and refusal to participate in the study.

Clinical and Laboratory Data

All individuals enrolled in the study were submitted to a clinical examination, electrocardiogram and laboratory assessment, which included hematocrit, glycemia, creatinine, total cholesterol, HDL-cholesterol and triglycerides. Whenever possible, the LDL-cholesterol was calculated by Friedewald's formula¹¹.

Echocardiogram

The echocardiographic assessment was carried out in an Apogee equipment (model CX 200) or Philips Envisor CHD, by the same professional.

The dimensions of the left atrium, left ventricle and aorta were obtained by the analysis of the M-mode, according to the criteria defined by the Penn Convention and corrected by height¹². The relative thickness of the LV walls was determined by dividing the sum of the diastolic thickness of the interventricular septum (IVS) and the posterior wall (PW) by the LV diastolic diameter (LVDD). The ventricular mass was obtained through the formula: LV mass (g) = 1.04 [(LVDD + IVS + PW)³ - (LVDD)³ - 13.6)]; and corrected for the body surface area¹³.

Doppler examination of the mitral inflow was performed from the apical 4-chamber view with the sample volume placed between the mitral leaflet tips. Doppler mitral inflow recordings were considered inadequate if the angle between the echo beam and the mitral inflow was >30°., the sample volume was inadequately positioned, and the Doppler envelope was too indistinct to measure accurately. The following transmitral flow variables were measured for each patient in three cardiac cycles: E-wave maximum velocity (EV_max), A-wave maximum velocity (AV_max), ratio between the maximum velocities of E and A waves (E/A ratio) and the E-wave deceleration time (EDT). The arithmetic means of these measurements were considered.

The reproducibility of the Doppler measurements was verified in 10 study patients, randomly selected by drawing lots. The videotape of selected cases was reviewed by a second echocardiographer blinded to the study data and then, Pearson's coefficients of correlation were calculated: E/A ratio = 0.91 and EDT = 0.82.

Individuals with an E/A ratio <0.75 or EDT >240 ms were considered as having impaired left ventricular relaxation.

Statistical Analysis

Categorical variables were compared between the groups with and without diastolic dysfunction by Chi-square test or Fisher's exact test, when appropriate. Student's t test or non-parametric Mann-Whitney test was used to compare the quantitative data when the variable did not follow the normal distribution. All tests were two-tailed. The level of significance was pre-established as 5%. The numerical data are expressed as means ± standard deviations. We also calculated the 5th and 95th percentiles of the mitral Doppler index.

Ethical Aspects

The research project was approved by the Committe of Ethics in Research of Hospital Universitario Prof. Edgard Santos. Each individual invited to participate in the study was informed on the nature, objective and possible consequences of the study and signed the free and informed consent form. All collected data were kept under complete confidentiality.

Results

Among the 73 individuals considered eligible for and included in the study, we identified 33 (45%; confidence interval: 34-57%) that presented an impaired LV relaxation pattern (Group I) and 40 (55%; confidence interval: 43-67%) with a mitral Doppler pattern considered normal (Group II).

The clinical and laboratory characteristics of each group are summarized in Table 1. The groups did not show any difference regarding most of the tested clinical and laboratory variables. However, Group I presented a longer PR interval (156±22 vs. 139±23 ms; p=0.002) and the diastolic arterial pressure was slightly higher in Group I, with a borderline statistical significance (80±5 vs. 77±6 mmHg; p=0.062).

The aortic root diameter was slightly larger in Group I (32.1±4.2 vs. 30.3±3.3 mm; p=0.044), with consequent decrease in the left atrium/aorta ratio (1.02±0.18 vs. 1.12±0.14 mm; p=0.007). None of the findings were modified after the echocardiographic dimensions were corrected for height (Table 2).

Table 3 shows the means, standard deviations, minimum and maximum values as well as the 5^th and 95^th percentiles of the mitral Doppler indexes. The EV_max and AV_max in the studied sample were, respectively: 0.75±0.16 m/s and 0.80±0.16 m/s, with E/A ratio = 0.96±0.24 and EDT = 234±42 ms.

Discussion

Few studies have described the frequency of impaired LV relaxation filling in the elderly population. In the subset of 114 healthy subjects of the Framingham Heart Study, aged 70 to 87 years, 87% had E/A ratio <1, which is a criterion of abnormal LV relaxation pattern recommended by the American Society of Echocardiography^8,14. Subsequently, in a study with 288 normal individuals aged 20 to 80 years, a gradual decrease in the E wave and increase in the A wave were observed with aging, with most individuals presenting equivalent waves in the sixth decade⁴. Based on this observation, an E/A ratio between 0.75 and 1.5 is presumed as a criterion of normality in the population older than 50 years^15,16. The EDT undergoes less variation with aging and it is considered normal when <240 ms¹⁷. Using these criteria to diagnose diastolic dysfunction in the elderly population allowed the identification of those presenting a higher risk of death and congestive heart failure^10,18,19.

In our study, which involved apparently healthy adults between 60 and 80 years of age, 55% of the sample presented mitral Doppler results within the normal range. We then tried to find an explanation why the remainder of the population presented a pattern of impaired LV relaxation filling.

Age, gender, PR interval, arterial blood pressure and heart rate are physiological variables that interfere with the mitral Doppler parameters^5,20. The present study showed a significant difference between the groups only regarding the PR interval, which was longer in the individuals classified as having diastolic dysfunction. That is in accordance with the data from the Framingham Heart Study, which showed an inverse correlation between the PR interval and EV_max, in a population aged 20 to 80 years²⁰. Two mechanisms can explain the contribution of the PR interval to the mitral Doppler pattern. First, the longer the PR interval, the higher the ventricular filling in the end-diastolic phase. Finally, the short time for the left ventricular passive filling results in a higher atrial volume at the beginning of the atrial systole, a principle of Starling's law.

In elderly individuals, the heart rate is positively associated with the AV_max and inversely associated with the EV_max and the E/A ratio^5,21. In the present study, the heart rate variation was small, as we excluded individuals with more than 100 beats per minute, which can explain the similarity between the groups.

In the normal elderly population, there is evidence of an association between the mitral Doppler index and the diastolic blood pressure²². We restricted our study sample to normotensive individuals. We observed that the diastolic blood pressure was 3 mmHg higher in the group with diastolic dysfunction, with a borderline level of significance (0.062), which explains, in part, the alterations in the mitral Doppler pattern.

We tested epidemiological variables related to lifestyle habits and family history. Although it has been demonstrated that regular physical activity, alcohol consumption and estrogen replacement favorably alter the left ventricular relaxation^22,23 and that acute smoking causes a decrease in the E/A ratio^24,25, we did not observe any difference regarding the frequency of these variables between the groups. However, our study did not have enough power to measure the influence of these factors on the diastolic function.

Patients at older age ranges show a larger aortic root diameter^26,27. In these individuals, the alteration in the composition of the central arterial walls has been considered responsible for the decreased arterial compliance observed²⁸. We found a subtle, but significant difference between the studied groups, explained by the higher degeneration and lower distensibility of the aorta in the group with diastolic dysfunction. Further studies are necessary to evaluate this hypothesis.

The groups did not differ regarding the linear dimensions of the left atrium and left ventricle, as well as the LV thickness, mass and ejection fraction. Although the volume measurement allows a more accurate assessment of the asymmetric remodeling of the left atrium, linear measurements are also useful in clinical and epidemiological researches^29,30.

To the best of our knowledge, this is the first study in Brazil that presents the 5^th and 95^th percentiles of the mitral Doppler in an elderly population selected as being healthy, which makes it useful in clinical practice. It can be considered that individuals in the distribution extremities are really pathological. Although we did not perform a broad epidemiological study to select the study sample, the patients were consecutively invited to participate in the study if they did not meet any of the exclusion criteria.

Study Limitations

We did not assess the Doppler of pulmonary venous flow or the tissue Doppler imaging in the studied sample. This could imply in the classification of some patients with a "pseudonormal" diastolic pattern as having a normal one. It is not possible to guarantee that all of them exhibited normal left atrial pressure, as the E/E' ratio was not calculated (the E/E' ratio >10 indicates elevated left atrial pressure³¹). However, the exclusion of several morbid conditions - such as the LV systolic dysfunction, hypertrophic cardiomyopathy and systemic arterial hypertension - makes these two situations very unlikely. The classification of the individuals as healthy was based on a noninvasive strategy, but an ergometric test for the detection of subclinical coronary artery disease was not performed. Nevertheless, all the individuals included in the study were asymptomatic for myocardial ischemia and exhibited normal overall and segmental LV contractility at the two-dimensional echocardiogram. The data were not analyzed in a multivariate model due to the study design. The authors plan to present more refined data in a new study.

Conclusion

A high number of individuals aged 60 to 80 years present normal diastolic function at the Doppler-echocardiographic analysis of the mitral flow. Healthy elderly individuals with impaired LV relaxation filling exhibit a longer PR interval and a larger aortic root diameter.

Potential Conflict of Interest

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

Sources of Funding

There were no external funding sources for this study.

Study Association

This article is part of the thesis of Doctoral submitted by Luiz Sérgio Alves-Silva, from Escola/ Bahiana de Medicina e Saúde Pública.

Referências

• 1. Arora RR, Machac J, Goldman ME, Butler RN, Gorlin R, Horowitz SF. Atrial kinetics and left ventricular diastolic filling in the healthy elderly. J Am Coll Cardiol. 1987; 9: 1255-60.
• 2. Pearson AC, Gudipati CV, Labovitz AJ. Effects of aging on left ventricular structure and function. Am Heart J. 1991; 121: 871-5.
• 3. Kitzman DW, Sheikh KH, Beere PA, Philips JL, Higginbotham MB. Age-related alterations of Doppler left ventricular filling indexes in normal subjects are independent of left ventricular mass, heart rate, contractility and loading conditions. J Am Coll Cardiol. 1991; 18: 1243-50.
• 4. Mantero A, Gentile F, Gualtierotti C, Azzollini M, Barbier P, Beretta L, et al. Left ventricular diastolic parameters in 288 normal subjects from 20 to 80 years old. Eur Heart J. 1995; 16: 94-105.
• 5. Gardin JM, Arnold AM, Bild DE, Smith VE, Lima JA, Klopfenstein HS, et al. Left ventricular diastolic filling in the elderly: the cardiovascular health study. Am J Cardiol. 1998; 82: 345-51.
• 6. Tighe DA, Vinch CS, Hill JC, Meyer TE, Goldberg RJ, Aurigemma GP. Influence of age on assessment of diastolic function by Doppler tissue imaging. Am J Cardiol. 2003; 91: 254-7.
• 7. Park HS, Naik SD, Aronow WS, Ahn CW, McClung JA, Belkin RN. Age- and sex-related differences in the tissue Doppler imaging parameters of left ventricular diastolic dysfunction. Echocardiography. 2007; 24: 567-71.
• 8. Sagie A, Benjamin EJ, Galderisi M, Larson MG, Evans JC, Fuller DL, et al. Reference values for Doppler indexes of left ventricular diastolic filling in the elderly. J Am Soc Echocardiogr. 1993; 6: 570-6.
• 9. Marantz PR, Tobin JN, Derby CA, Cohen MV. Age-associated changes in diastolic filling: Doppler E/A ratio is not associated with congestive heart failure in the elderly. South Med J. 1994; 87: 728-35.
• 10. Aurigemma GP, Gottdiener JS, Shemanski L, Gardin J, Kitzman D. Predictive value of systolic and diastolic function for incident congestive heart failure in the elderly: the cardiovascular health study. J Am Coll Cardiol. 2001; 37: 1042-8.
• 11. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18: 499-502.
• 12. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986; 57: 450-8.
• 13. Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man: anatomic validation of the method. Circulation. 1977; 55: 613-8.
• 14. Oh JK, Appleton CP, Hatle LK, Nishimura RA, Seward JB, Tajik AJ. The noninvasive assessment of left ventricular diastolic function with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr. 1997; 10: 246-70.
• 15. Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003; 289: 194-202.
• 16. Abhayaratna WP, Marwick TH, Smith WT, Becker NG. Characteristics of left ventricular diastolic dysfunction in the community: an echocardiographic survey. Heart. 2006; 92: 1259-64.
• 17. Khouri SJ, Maly GT, Suh DD, Walsh TE. A practical approach to the echocardiographic evaluation of diastolic function. J Am Soc Echocardiogr. 2004; 17: 290-7.
• 18. Bella JN, Palmieri V, Roman MJ, Liu JE, Welty TK, Lee ET, et al. Mitral ratio of peak early to late diastolic filling velocity as a predictor of mortality in middle-aged and elderly adults: the Strong Heart Study. Circulation. 2002; 105: 1928-33.
• 19. Fox ER, Han H, Taylor HA, Walls UC, Samdarshi T, Skelton TN, et al. The prognostic value of the mitral diastolic filling velocity ratio for all-cause mortality and cardiovascular morbidity in African Americans: the Atherosclerotic Risks in Communities (ARIC) study. Am Heart J. 2006; 152: 749-55.
• 20. Benjamin EJ, Levy D, Anderson KM, Wolf PA, Plehn JF, Evans JC, et al. Determinants of Doppler indexes of left ventricular diastolic function in normal subjects (the Framingham Heart Study). Am J Cardiol. 1992; 70: 508-15.
• 21. Galderisi M, Benjamin EJ, Evans JC, D'Agostino RB, Fuller DL, Lehman B, et al. Impact of heart rate and PR interval on Doppler indexes of left ventricular diastolic filling in an elderly cohort (the Framingham Heart Study). Am J Cardiol. 1993; 72: 1183-7.
• 22. Voutilainen S, Kupari M, Hippelainen M, Karppinen K, Ventila M, Heikkila J. Factors influencing Doppler indexes of left ventricular filling in healthy persons. Am J Cardiol. 1991; 68: 653-9.
• 23. Alecrin IN, Aldrighi JM, Caldas MA, Gebara OC, Lopes NH, Ramires JA. Acute and chronic effects of oestradiol on left ventricular diastolic function in hypertensive postmenopausal women with left ventricular diastolic dysfunction. Heart. 2004; 90: 777-81.
• 24. Alam M, Samad BA, Wardell J, Andersson E, Hoglund C, Nordlander R. Acute effects of smoking on diastolic function in healthy participants: studies by conventional Doppler echocardiography and Doppler tissue imaging. J Am Soc Echocardiogr. 2002; 15: 1232-7.
• 25. Stork T, Mockel M, Danne O, Ewert C, Muller R, Bodemann T, et al. Age-related hemodynamic changes during diastole: a combined M-mode and Doppler echo study. Int J Card Imaging. 1990; 6: 23-30.
• 26. Henry WL, Gardin JM, Ware JH. Echocardiographic measurements in normal subjects from infancy to old age. Circulation. 1980; 62: 1054-61.
• 27. Woo J, Milne M, Crozier I. An echocardiographic assessment of asymptomatic elderly women with radiological cardiac enlargement. Int J Cardiol. 1990; 27: 245-52.
• 28. Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a "set up" for vascular disease. Circulation. 2003; 107: 139-46.
• 29. Gottdiener JS, Bednarz J, Devereux R, Gardin J, Klein A, Manning WJ, et al. American Society of Echocardiography recommendations for use of echocardiography in clinical trials. J Am Soc Echocardiogr. 2004; 17: 1086-119.
• 30. Kizer JR, Bella JN, Palmieri V, Liu JE, Best LG, Lee ET, et al. Left atrial diameter as an independent predictor of first clinical cardiovascular events in middle-aged and elderly adults: the Strong Heart Study (SHS). Am Heart J. 2006; 151: 412-8.
• 31. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997; 30: 1527-33.

Frequency of left ventricular diastolic dysfunction by mitral doppler in healthy elderly individuals

Luiz Sérgio Alves-Silva^{I, II}; Edmundo José Nassri Câmara^I; Carlos Alfredo Marcílio de Souza^{I, II}

Publication Dates

• Publication in this collection
  24 Nov 2009
• Date of issue
  Oct 2009

History

• Received
  10 Aug 2008
• Reviewed
  16 Oct 2008
• Accepted
  21 Oct 2008