Deborah L. Fuller

Prevalence and clinical outcome of mitral-valve prolapse

BACKGROUND Mitral-valve prolapse has been described as a common disease with frequent complications. To determine the prevalence of mitral-valve prolapse in the general population, as diagnosed with the use of current two-dimensional echocardiographic criteria, we examined the echocardiograms of 1845 women and 1646 men (mean [+/-SD] age, 54.7+/-10.0 years) who participated in the fifth examination of the offspring cohort of the Framingham Heart Study. METHODS Classic mitral-valve prolapse was defined as superior displacement of the mitral leaflets of more than 2 mm during systole and as a maximal leaflet thickness of at least 5 mm during diastasis, and nonclassic prolapse was defined as displacement of more than 2 mm, with a maximal thickness of less than 5 mm. RESULTS A total of 84 subjects (2.4 percent) had mitral-valve prolapse: 47 (1.3 percent) had classic prolapse, and 37 (1.1 percent) had nonclassic prolapse. Their age and sex distributions were similar to those of the subjects without prolapse. None of the subjects with prolapse had a history of heart failure, one (1.2 percent) had atrial fibrillation, one (1.2 percent) had cerebrovascular disease, and three (3.6 percent) had syncope, as compared with unadjusted prevalences of these findings in the subjects without prolapse of 0.7, 1.7, 1.5, and 3.0 percent, respectively. The frequencies of chest pain, dyspnea, and electrocardiographic abnormalities were similar among subjects with prolapse and those without prolapse. The subjects with prolapse were leaner (P<0.001) and had a greater degree of mitral regurgitation than those without prolapse, but on average the regurgitation was classified as trace or mild. CONCLUSIONS In a community based sample of the population, the prevalence of mitral-valve prolapse was lower than previously reported. The prevalence of adverse sequelae commonly associated with mitral-valve prolapse in studies of patients referred for that diagnosis was also low.

Mitral annular calcification and the risk of stroke in an elderly cohort.

BACKGROUND Previous clinical studies have suggested that there is an association between mitral annular calcification and the risk of stroke, but it is unclear whether this association is independent of the traditional risk factors for stroke. We examined the relation between mitral annular calcification and the incidence of stroke in a population-based study. METHODS Subjects in the Framingham Study receiving a routine examination underwent M-mode echocardiography to determine the presence and severity (thickness in millimeters) of mitral annular calcification. The incidence of stroke during eight years of follow-up was analyzed with a proportional-hazards model adjusting for the calcification, age, sex, systolic blood pressure, diabetes mellitus, cigarette smoking, atrial fibrillation, and coronary heart disease or congestive heart failure. RESULTS Among 1159 subjects whose echocardiograms could be assessed for mitral annular calcification and who had no history or current evidence of stroke at the index examination (51 percent of all subjects), the prevalence of mitral annular calcification was 10.3 percent in the men and 15.8 percent in the women. Multivariate analysis demonstrated that the presence of mitral annular calcification was associated with a relative risk of stroke of 2.10 (95 percent confidence interval, 1.24 to 3.57; P = 0.006). There was a continuous relation between the incidence of stroke and the severity of mitral annular calcification; each millimeter of thickening as shown on the echocardiogram represented a relative risk of stroke of 1.24 (95 percent confidence interval, 1.12 to 1.37; P less than 0.001). Furthermore, even when subjects with coronary heart disease or congestive heart failure were excluded from the analysis, subjects with mitral annular calcification still had twice the risk of stroke. CONCLUSIONS In an elderly, longitudinally followed population-based cohort, mitral annular calcification was associated with a doubled risk of stroke, independently of traditional risk factors for stroke. Whether such calcification contributes causally to the risk of stroke or is merely a marker of increased risk because of its association with other precursors of stroke remains unknown.

Determinants of Doppler indexes of left ventricular diastolic function in normal subjects (the Framingham heart study)

Normative Doppler values and determinants of left ventricular (LV) diastolic function in healthy subjects have not been fully elucidated. Subjects from the Framingham Heart Study were examined to describe reference values and determinants of echocardiographic Doppler indexes of diastolic function. One hundred twenty-seven randomly selected, rigorously defined, normal subjects, approximately evenly distributed by sex and age from the third through the eighth decades were studied by Doppler echocardiography. Normative values for 7 frequently used Doppler indexes of LV diastolic function are presented. Doppler indexes of LV diastolic function change dramatically with age; the peak velocity of early filling divided by late filling (peak velocity E/A) ranges from a mean of 2.08 +/- 0.55 for subjects in their third decade to 0.84 +/- 0.29 for those in their eighth decade. A peak velocity E/A ratio less than 1 is abnormal in subjects aged less than 40 years, but occurs in most subjects aged greater than or equal to 70 years. The high correlations between age and Doppler indexes of LV diastolic function are not greatly attenuated after adjustment for other clinical parameters associated with diastolic function; the multivariate partial correlation coefficient between age and peak velocity E/A is -0.80 (p less than 0.0001). Heart rate, PR interval, LV systolic function, sex and systolic blood pressure are minor determinants of Doppler indexes of diastolic function. Body mass index, left atrial diameter, and LV wall thickness, internal dimension and mass have little or no association with Doppler indexes in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitral valve prolapse in the general population: the benign nature of echocardiographic features in the Framingham Heart Study.

OBJECTIVE The aim of this study was to examine the echocardiographic features and associations of mitral valve prolapse (MVP) diagnosed by current two-dimensional echocardiographic criteria in an unselected outpatient sample. BACKGROUND Previous studies of patients with MVP have emphasized the frequent occurrence of echocardiographic abnormalities such as significant mitral regurgitation (MR) and left atrial (LA) enlargement that are associated with clinical complications. These studies, however, have been limited by the use of hospital-based or referral series. METHODS We quantitatively studied all 150 subjects with possible MVP by echocardiography and 150 age- and gender-matched subjects without MVP from the 3,491 subjects in the Framingham Heart Study. Based on leaflet morphology, subjects were classified as having classic (n = 46), nonclassic (n = 37), or no MVP. RESULTS Leaflet length, MR degree, and LA and left ventricular size were significantly but mildly increased in MVP (p < 0.0001 to 0.004), with mean values typically within normal range. Average MR jet area was 15.1 +/- 1.4% (mild) in classic MVP and 8.9 +/- 1.5% (trace) in nonclassic MVP; MR was severe in only 3 of 46 (6.5%) subjects with classic MVP, and LA volume was increased in only 8.7% of those with classic MVP and 2.7% of those with nonclassic MVP. CONCLUSIONS Although the echocardiographic characteristics of subjects with MVP in the Framingham Heart Study differ from those without MVP, they display a far more benign profile of associated valvular, atrial, and ventricular abnormalities than previously reported in hospital- or referral-based series. Therefore, these findings may influence the perception of and approach to the outpatient with MVP.

Impact of heart rate and PR interval on Doppler indexes of left ventricular diastolic filling in an elderly cohort (the Framingham Heart Study).

The relations of heart rate and PR interval to Doppler-derived diastolic indexes were examined in 260 men (mean age 75 years) and 462 women (mean age 76 years) from the Framingham Heart Study. Subjects receiving any antihypertensive or cardiac medications were excluded from eligibility; those with mitral stenosis or prosthesis, pacemaker, atrial fibrillation, arrhythmia, left bundle branch block, congestive heart failure, previous myocardial infarction, and technically inadequate Doppler study were also excluded. Peak velocity of early (E) and late (A) diastolic left ventricular (LV) filling, ratio of peak velocities E/A, ratio of time velocity integrals E/A, and atrial filling fraction were studied by multivariable analyses adjusting for age, sex, blood pressure, heart rate and PR interval. Heart rate was a major determinant of all 5 Doppler indexes of diastolic filling; heart rate was inversely associated with peak velocity E, E/A, and time velocity integral E/A, and was directly associated with peak velocity A and atrial filling fraction. PR interval was inversely associated with time velocity integral E/A (p < 0.01) and directly associated with atrial filling fraction. The results were largely unaltered after further adjustment for LV wall thickness, LV end-diastolic diameter and left atrial diameter (in addition to age, sex and blood pressure). Heart rate and PR interval are independent contributors to Doppler-assessed LV diastolic filling in the elderly. The atrial contribution to LV filling depends on its timing in the cardiac cycle and on heart rate. Failure to account for heart rate and PR interval may lead to inappropriate assessment of Doppler diastolic filling.

Intra- and interobserver reproducibility of Doppler-assessed indexes of left ventricular diastolic function in a population-based study (the Framingham Heart Study)

The reproducibility of a variety of Doppler indexes of diastolic function in an epidemiologic setting and in atrial fibrillation have not been reported. This study examined the reproducibility of left ventricular inflow in subjects in sinus rhythm (n = 80) and atrial fibrillation (n = 12), randomly selected from the original cohort of the Framingham Heart Study. The following Doppler indexes were assessed for all subjects: peak and integral of early (E) diastolic inflow velocity, acceleration slope and time, deceleration slope and time, and pressure half-time. For subjects in sinus rhythm, the following parameters also were measured: the peak and integral of late (A) diastolic inflow velocity, ratios of peak velocities and integrals E/A, and atrial filling fraction. Intraobserver and interobserver variability were evaluated by statistical methods including Students t test of the systematic differences (bias), percent bias, correlation coefficients, measurement precision, and percent precision. In subjects in sinus rhythm, although the interobserver bias was statistically significant for most of the parameters, it was < 10% for all but 1 parameter (acceleration time). For the peak and integral measures, the intra- and interobserver correlations were > or = 0.89, with intra- and interobserver percent precision measures within 2.2 to 13.0% of the corresponding mean values. The acceleration, deceleration and pressure half-time measures had somewhat lower correlations (interobserver correlations ranging from 0.59 to 0.96), with percent precision measures further from the corresponding means (interobserver percent precision ranging from 10.1 to 19.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Reference Values for Doppler Indexes of Left Ventricular Diastolic Filling in the Elderly

Congestive heart failure increases in prevalence with age. A large number of elderly subjects with heart failure have either normal or slightly reduced left ventricular (LV) systolic function; their symptoms are due to diastolic LV dysfunction. Reference values for Doppler indexes of LV diastolic filling in a large sample of the very elderly (> 70) have not been reported previously. The objective of this study was to generate reference values for Doppler indexes of LV filling in a population of apparently healthy elderly men and women. A total of 1201 surviving original subjects of the Framingham Heart Study were evaluated by Doppler echocardiography. A subset of 114 rigorously selected healthy subjects (26 men and 88 women) aged 70 to 87 years (mean 76) constituted the study group. Measurements of seven commonly used Doppler indexes were obtained. Mean and 2.5, 5, 10, 25, 50, 75, 90, 95, and 97.5 percentile values for Doppler diastolic indexes were generated. Stepwise regression analyses were performed to determine the relation of diastolic LV filling to age group (70 to 74 years, 75 to 79 years, and 80 years and over), sex, and other clinical variables. Reference values for the various Doppler parameters were generated on the basis of this healthy elderly cohort. There was evidence for a slight progressive decline in indexes of LV inflow with age. In 87% of this elderly population the ratio of peak early to late velocities of LV diastolic inflow was less than 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiographic Assessment of Left Ventricular Structure and Diastolic Filling in Elderly Subjects with Borderline Isolated Systolic Hypertension (the Framingham Heart Study)

Abnormalities in left ventricular (LV) structure and function have been shown in patients with diastolic hypertension and recently in subjects with isolated systolic hypertension. The purpose of this study was to determine whether abnormalities of cardiac structure or function are present in elderly subjects with borderline isolated systolic hypertension (defined as systolic blood pressure [BP] between 140 and 159 mm Hg, and diastolic BP < 90 mm Hg). Ninety-one subjects (mean age 77 years) from the original Framingham Heart Study with untreated borderline isolated systolic hypertension, who were free of cardiovascular disease, were compared with 139 normotensive (BP < 140/90 mm Hg) subjects (mean age 76 years). Measurements included M-mode values for LV structure, and 6 Doppler indexes of LV diastolic filling. Subjects with borderline isolated systolic hypertension and the control group differed in mean systolic (147 vs 125 mm Hg) and diastolic (76 vs 70 mm Hg) BP. Borderline systolic hypertension was the most frequent form of untreated hypertension in this elderly group. The sum of LV wall thicknesses (septum+posterior wall) was significantly higher in borderline hypertensive subjects than in normotensive ones (20.5 vs 19.7 mm; p = 0.002). No difference was detected in LV internal dimension or systolic function. After adjustment for age and other clinical variables, comparisons between the groups revealed significant differences in indexes of Doppler diastolic filling. Peak velocity of early filling, and the ratio of early to late peak velocities were lower in the hypertensive group (40 vs 44 cm/s [p = 0.03] and 0.69 vs 0.76 [p = 0.01], respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence, Clinical Correlates, and Prognosis of Discrete Upper Septal Thickening on Echocardiography: The Framingham Heart Study

The upper interventricular septum may be prominent in elderly individuals, a finding referred to as discrete upper septal thickening (DUST). We examined the prevalence, clinical and echocardiographic correlates, and prognostic significance of DUST in a community‐based sample. We evaluated Framingham Study participants who underwent routine echocardiography. In 3562 Framingham Study participants (mean age 58 years, 57% women), DUST was observed in 52 participants. The clinical correlates of DUST were increasing age (odds ratio [OR] per 10 year increment 2.59, 95% confidence intervals [CI] 1.64–4.08) and systolic blood pressure (OR per SD increment 1.55, 95% CI 1.15–2.09). DUST was positively associated with left ventricular (LV) fractional shortening and mitral annular calcification but inversely with LV diastolic dimensions (P < 0.02 for all). On follow‐up (mean 15 years), 732 individuals died (33 with DUST) and 560 experienced a cardiovascular disease (CVD) event (18 with DUST). Adjusting for cardiovascular risk factors, DUST was not associated with CVD or mortality risk (P > 0.30 for both). The follow‐up component of our study suggests that DUST is not independently associated with adverse prognosis.

Evolution of Mitral Valve Prolapse Insights From the Framingham Heart Study

Background— Longitudinal studies of mitral valve prolapse (MVP) progression among unselected individuals in the community, including those with nondiagnostic MVP morphologies (NDMs), are lacking. Methods and Results— We measured longitudinal changes in annular diameter, leaflet displacement, thickness, anterior/posterior leaflet projections onto the annulus, coaptation height, and mitral regurgitation jet height in 261 Framingham Offspring participants at examination 5 who had available follow-up imaging 3 to 16 years later. Study participants included MVP (n=63); NDMs, minimal systolic displacement (n=50) and the abnormal anterior coaptation phenotype (n=10, with coaptation height >40% of the annulus similar to posterior MVP); plus 138 healthy referents without MVP or NDMs. At follow-up, individuals with MVP (52% women, 57±11 years) had greater increases of leaflet displacement, thickness, and jet height than referents (all P <0.05). Eleven participants with MVP (17%) had moderate or more severe mitral regurgitation (jet height ≥5 mm) and 5 others (8%) underwent mitral valve repair. Of the individuals with NDM, 8 (80%) participants with abnormal anterior coaptation progressed to posterior MVP; 17 (34%) subjects with minimal systolic displacement were reclassified as either posterior MVP (12) or abnormal anterior coaptation (5). In comparison with the 33 participants with minimal systolic displacement who did not progress, the 17 who progressed had greater leaflet displacement, thickness, coaptation height, and mitral regurgitation jet height (all P <0.05). Conclusions— NDM may evolve into MVP, highlighting the clinical significance of mild MVP expression. MVP progresses to significant mitral regurgitation over a period of 3 to 16 years in one-fourth of individuals in the community. Changes in mitral leaflet morphology are associated with both NDM and MVP progression. # CLINICAL PERSPECTIVES {#article-title-33}Background— Longitudinal studies of mitral valve prolapse (MVP) progression among unselected individuals in the community, including those with nondiagnostic MVP morphologies (NDMs), are lacking. Methods and Results— We measured longitudinal changes in annular diameter, leaflet displacement, thickness, anterior/posterior leaflet projections onto the annulus, coaptation height, and mitral regurgitation jet height in 261 Framingham Offspring participants at examination 5 who had available follow-up imaging 3 to 16 years later. Study participants included MVP (n=63); NDMs, minimal systolic displacement (n=50) and the abnormal anterior coaptation phenotype (n=10, with coaptation height >40% of the annulus similar to posterior MVP); plus 138 healthy referents without MVP or NDMs. At follow-up, individuals with MVP (52% women, 57±11 years) had greater increases of leaflet displacement, thickness, and jet height than referents (all P<0.05). Eleven participants with MVP (17%) had moderate or more severe mitral regurgitation (jet height ≥5 mm) and 5 others (8%) underwent mitral valve repair. Of the individuals with NDM, 8 (80%) participants with abnormal anterior coaptation progressed to posterior MVP; 17 (34%) subjects with minimal systolic displacement were reclassified as either posterior MVP (12) or abnormal anterior coaptation (5). In comparison with the 33 participants with minimal systolic displacement who did not progress, the 17 who progressed had greater leaflet displacement, thickness, coaptation height, and mitral regurgitation jet height (all P<0.05). Conclusions— NDM may evolve into MVP, highlighting the clinical significance of mild MVP expression. MVP progresses to significant mitral regurgitation over a period of 3 to 16 years in one-fourth of individuals in the community. Changes in mitral leaflet morphology are associated with both NDM and MVP progression.