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Beta-blockade therapy in chronic heart failure: diastolic function and mitral regurgitation improvement by carvedilol.

BACKGROUND: In patients with chronic heart failure, the use of carvedilol therapy induces clinical and hemodynamic improvement. However, although the benefits of this beta-blocker have been established in patients with chronic heart failure, the mechanisms underlying them and the changes in left ventricular systolic function, diastolic function, and mitral regurgitation during long-term therapy remain unclear. OBJECTIVE: To identify the clinical and functional effects of carvedilol, focusing on diastolic function and mitral regurgitation variations. METHODS: Forty-five consecutive patients with chronic heart failure (ejection fraction 24% +/- 7%), 17 with dilated ischemic and 28 with nonischemic cardiomyopathy, were treated with carvedilol (mean dose 44 +/- 30 mg) and matched for clinical (New York Heart Association functional class and heart failure duration) and hemodynamic (cardiac index and pulmonary wedge pressure) characteristics to a control group. Clinical and echocardiographic variables were measured in the 2 groups at baseline and after 6 months and the results compared. RESULTS: After 6 months of treatment with carvedilol, left ventricular ejection fraction had increased from 24% +/- 7% to 29% +/- 9% (P <.0001); this change was caused by a reduction in end-systolic volume index (106 +/- 41 vs 93 +/- 37 mL/m(2); P <. 0001). Deceleration time of early diastolic filling increased (134 +/- 74 vs 196 +/- 63 ms; P <.0001). Seventeen of the 27 patients with demonstrated improvement of left ventricular diastolic filling moved from having a restrictive filling pattern to having a normal or pseudonormal left ventricular filling pattern. In the control group, no significant changes in deceleration time of early diastolic filling were found (139 +/- 74 vs 132 +/- 45 ms; P = not significant). The effective regurgitant orifice area decreased significantly in the carvedilol group but not in the control group. These changes were associated with a significant reduction of the mitral regurgitant stroke volume in the carvedilol group (50 +/- 25 vs 16 +/- 13 mL; P <.0001) but not in the control group (57 +/- 29 vs 47 +/- 24 mL; P = not significant). These changes of mitral regurgitation were closely associated with significant improvement of forward aortic stroke volume (r = -.57, P <.0001). These findings were not observed in patients in the control group. CONCLUSIONS: The results of this study show that long-term carvedilol therapy in patients with chronic heart failure was able to prevent or partially reverse progressive left ventricular dilatation. The effects on left ventricular remodeling were associated with a concomitant recovery of diastolic reserve and a decrease of mitral regurgitation, which have been demonstrated to be powerful prognostic predictors in such patients. Overall these findings provide important insights into the pathophysiologic mechanisms by which carvedilol improves the clinical course of patients with chronic heart failure.

Adrenergic beta-Antagonists↗

Imaging and diagnostic testing: diastolic dysfunction after coronary artery bypass grafting: a frequent finding of clinical significance not influenced by intravenous calcium.

BACKGROUND: Diastolic dysfunction is common immediately after coronary artery bypass surgery (CABG). The duration of this phenomenon is unknown. Intravenous calcium is frequently administered during separation from cardiopulmonary bypass (CPB). We sought to determine whether intravenous calcium influences perioperative diastolic function and whether diastolic dysfunction persists into the postoperative period. METHODS AND RESULTS: Patients undergoing first-time elective CABG (n = 29) were randomly assigned to receive intravenous calcium chloride (n = 13) or placebo (n = 16) during separation from CPB. Diastolic function was assessed by the pressure-area relation with transesophageal echocardiography and pulmonary capillary wedge pressure (PCWP) measured simultaneously. Left ventricular end-diastolic area (LVEDA) and Doppler indexes were measured at comparable PCWP (within 2 mm Hg) at baseline, after separation from CPB, after sternal closure, and 3 hours after surgery. After CABG, both groups had a significant decrease in LVEDA and mitral E-wave deceleration time that persisted at 3 hours. Because there were no significant differences between the calcium and control groups at any time point, the data for the entire study cohort was analyzed. The LVEDA decreased (stiffness increased) progressively from 16.9 +/- 3.4 cm2 at baseline to 15.8 +/- 2.9 cm2 after CPB, 14.9 +/- 2.5 cm2 after sternal closure, and 14.3 +/- 3.1 cm2 at 3 hours after surgery (P <.0001). The mitral E-wave deceleration time measured at the same time points was 168 +/- 47 ms, 136 +/- 25 ms, 137 +/- 36 ms, and 111 +/- 44 ms (P =.0001). CONCLUSIONS: An increase in left ventricular diastolic chamber stiffness is nearly universal after CABG, and it persists for at least 3 hours after surgery. An intravenous bolus of calcium chloride given during separation from CPB has no measurable negative effect on diastolic function. In the setting of increased chamber stiffness, the PCWP alone does not adequately reflect the volume status and effective preload of the left ventricle.

Aged↗

Doppler diastolic filling indexes in relation to disease states.

This study compares mean Doppler-derived diastolic filling indexes in a variety of disease states in a large, population-based sample. Pulse-wave Doppler was used to examine 880 eligible participants of the Framingham Heart Study. Peak velocity of early flow and late flow, ratio of early to late peak velocities, atrial filling fraction, and early filling wave acceleration and deceleration times were obtained. Multiple linear regression analyses were performed comparing mean values for individuals with hypertension, diabetes, coronary disease, cardiovascular disease, and pulmonary disease. Hypertension was associated with a greater peak velocity late flow (0.027 m/sec; 95% confidence interval, 0.006, 0.047; p = 0.011), and diabetes was associated with a larger mean deceleration time (0.12 sec, confidence interval, 0.002, 0.021; p = 0.016). In multivariate analyses, hypertension continued to show a strong association with altered Doppler diastolic filling patterns, p value 0.009, whereas in diabetes, the multivariate p value was 0.28.

Adult↗

Effects of long-term adrenergic beta-blockade on left ventricular diastolic filling in patients with acute myocardial infarction.

BACKGROUND: Left ventricular (LV) systolic and diastolic function are known to be affected in the wake of a myocardial infarction (MI). beta-Adrenergic blocking agents have demonstrated improvement of LV systolic and diastolic function in patients with dilated cardiomyopathy and theoretically would have same beneficial effects in MI. beta-Adrenergic blocking agents are widely used in MI; however only few reports on changes of LV systolic and diastolic function during long-term treatment after acute MI are available. METHODS: Two-dimensional and Doppler echocardiography were used to evaluate LV diastolic filling in 77 patients randomly assigned to placebo (n = 38) or metoprolol (n = 39). The patients were randomly assigned at day 5 to 7 (baseline) after acute MI and were treated for 12 months. LV diastolic filling was assessed by pulsed Doppler measurements of transmitral and pulmonary venous flow. RESULTS: Mitral E-wave deceleration time was prolonged in the metoprolol group (baseline vs 12 months: 167 +/- 51 ms to 218 +/- 36 ms; P =. 01) versus the placebo group (baseline vs 12 months: placebo 174 +/- 46 ms to 189 +/- 41 ms), which implies a less restrictive filling of the LV in the metoprolol group. This was supported by a decrease of E/A ratio (baseline vs 12 months: placebo, 1.06 +/- 0.40 to 0.96 +/- 0.29; metoprolol, 1.09 +/- 0.33 to 0.80 +/- 0.21; P =.05) and prolongation of the isovolumetric relaxation time in the metoprolol treated group (baseline vs 12 months: placebo, 83 +/- 19 ms to 95 +/- 20 ms; metoprolol, 82 +/- 23 ms to 117 +/- 22 ms; P =.01). The difference between mitral A wave and pulmonary venous flow reversal duration was significantly changed during follow-up (baseline vs 12 months: placebo, 22 +/- 11 ms to 24 +/- 11; metoprolol, 11 +/- 21 to 32 +/- 17 ms; P =.02). Patients with normal LV filling pattern at baseline in the metoprolol group preserved a normal LV filling pattern during the study, and patients with restrictive LV filling pattern in the metoprolol group had a nonrestrictive LV filling pattern develop. Maximal or near maximal changes of the diastolic Doppler measurements occurred by 3 months of follow-up, whereas a significant increase in LV ejection fraction was noted after 12 months treatment with metoprolol. CONCLUSIONS: Long-term treatment with the beta-blocking agent metoprolol seems to improve LV diastolic filling after acute MI. Less restrictive LV filling was noted during beta-blockade indicated by a significant prolongation of the mitral E deceleration time, which was predominantly noted in patients with restrictive LV filling. This observation might have prognostic implications because this LV filling pattern is known to be associated with poor outcome. The changes of LV diastolic filling occurred during the first 3 months, whereas systolic recovery was seen at up to 12 months of treatment.

Adrenergic beta-Antagonists↗

Longitudinal changes and prognostic implications of left ventricular diastolic function in first acute myocardial infarction.

BACKGROUND: Left ventricular (LV) diastolic dysfunction contributes to signs and symptoms of clinical heart failure and may be related to prognosis in heart diseases. LV diastolic dysfunction is reported to be present in acute myocardial infarction (MI); however, little is known about the time course of changes in LV diastolic function and its relation to prognosis after acute MI. METHODS AND RESULTS: Two-dimensional and Doppler echocardiographic examinations were performed in 58 consecutive patients with first acute MI. The patients were studied serially within 1 hour and at days 5, 90, and 360 after arrival to the coronary care unit. LV diastolic function was assessed by Doppler measurements of transmitral and pulmonary venous flow. On the basis of mitral inflow, patients with MI were stratified at baseline to 3 LV diastolic filling patterns: normal, impaired relaxation, or pseudonormal/restrictive. Patients with MI were observed for development of congestive heart failure (Killip class >I) during hospitalization and for death during 1-year follow-up, and these complications were related to LV diastolic function. LV diastolic dysfunction was present in the very early phase of acute MI, with signs of impaired relaxation or restrictive LV filling dynamics in 38% and 24% of the patients, respectively, whereas 38% had normal LV filling characteristics. Impaired relaxation of the LV was most pronounced and found in 60% after 1-year follow-up. In-hospital congestive heart failure (Killip class >I) was found in 50% of the patients with initial impaired LV relaxation and in 71% of the patients with initially pseudonormal or restrictive LV filling dynamics, whereas patients with normal LV filling were free of heart failure. Patients with initial impaired relaxation and restrictive LV filling dynamics demonstrated a significant LV dilation during 1-year follow-up. Patients with initial pseudonormal/restrictive LV filling pattern were more frequently readmitted to the hospital for heart failure and had significant higher New York Heart Association class score compared with patients with normal or impaired relaxation during follow-up. Cardiac death was (n = 6) only observed in patients with pseudonormal or restrictive LV filling pattern. In a multivariate stepwise regression analysis, mitral E deceleration time </=140 ms and age were identified as independent variables related to development of in-hospital congestive heart failure and cardiac death during 12 months of follow-up. CONCLUSIONS: LV diastolic dysfunction is present in the very early phase of MI. LV remodeling and development of in-hospital congestive heart failure appear in patients with very early signs of LV diastolic dysfunction. Furthermore, mitral E deceleration time </=140 ms best identified patients at risk of development of in-hospital congestive heart failure and cardiac death after MI.

Adult↗

Pulsed Doppler tissue imaging in endurance athletes: relation between left ventricular preload and myocardial regional diastolic function.

The aim of this study was to assess the effects of endurance training on myocardial regional systolic and diastolic function by pulsed Doppler tissue imaging (DTI). Twenty male water polo players and 20 male control subjects underwent standard Doppler echocardiography and pulsed DTI, performed in apical views by placing a sample volume on left ventricular (LV) basal septal and inferior walls. Age, body surface area, and blood pressure were comparable between the 2 groups, with lower heart rate in athletes (p <0.001). They had significantly increased LV mass index (due to both higher wall thickness and end-diastolic diameter), greater endocardial fractional shortening, higher transmitral early/atrial (E/A) peak velocities ratio. In athletes, DTI analysis showed significantly prolonged myocardial deceleration time and greater myocardial E/A peak velocity ratio of septal and inferior walls, whereas myocardial early peak velocity was increased (p <0.01) only at the inferior wall. In the overall group, we found univariate relations of septal and inferior E/A peak velocity ratio and myocardial deceleration time with LV mass levels, and, in particular, with the sum of wall thickness. By separate multivariate analyses, however, these relations disappeared, being dependent on heart rate degree. Another association found between LV end-diastolic diameter and myocardial early diastolic wave peak velocity of the inferior wall (r = 0.68, p <0.0001) remained significant (standardized beta coefficient 0.60, p <0.00001), even after adjusting for heart rate, body surface area, age, and stroke volume (R(2) = 0.71, p <0.00001). In conclusion, DTI is a useful tool for detecting regional changes in myocardial function induced by training, because athletes present with an improvement in diastolic passive properties of myocardium. The higher early diastolic velocity of the inferior wall and its relation to increased preload may represent an indicator of aerobic training, allowing quantification of the degree of LV adaptation to endurance exercise.

Adult↗

Congestive heart failure despite normal left ventricular systolic function in a population-based sample: the Strong Heart Study.

In selected clinical series, > or = 50% of adults with congestive heart failure (CHF) do not have left ventricular (LV) systolic dysfunction. Little is known of the prevalence of this phenomenon in population samples. Therefore, clinical examination and echocardiography were used in the second examination of the Strong Heart Study (3,184 men and women, 47 to 81 years old) to identify 95 participants with CHF, 50 of whom had normal LV ejection fraction (EF) (> 54%), 19 of whom had mildly reduced EF (40% to 54%), and 26 of whom had EF < or = 40%. Compared with those with no CHF, participants with CHF and no, mild, or severe decrease in EF had higher creatinine levels (2.34 to 2.85 vs 1.01 mg/dl, p < 0.001) and higher prevalences of diabetes (60% to 70% vs 50%) and hypertension (75% to 96% vs 46%, p < 0.05). Compared with those with no CHF, participants with CHF and normal EF had prolonged deceleration time (233 vs 204 ms, p < 0.05) and a reduced E/A, whereas those with CHF and EF < or = 40% had short deceleration time (158 ms, p < 0.05) and high E/A (1.70, p < 0.001); patients with CHF and normal EF had higher LV mass (98 vs 84 g/m2, p < 0.001) and relative wall thickness (0.37 vs 0.35, p < 0.05) than those without CHF. Patients with CHF with normal EF were, compared with those without CHF or with CHF and EF < or = 40%, disproportionately women (mean 84% vs 63% and 42%, p < 0.001), older (mean 64 vs 60 years and 63 years, respectively, p < 0.01), had higher body mass index (mean 33.1 vs 31.0 and 27.7 kg/m2, p < 0.05), and higher systolic blood pressure (mean 137 vs 130 and 128 mm Hg, both p < 0.05). Thus, in a population-based sample, patients with CHF and normal LV EF were older and overweight, more often women, had renal dysfunction, impaired early diastolic LV relaxation, and concentric LV geometry, whereas patients with CHF and severe LV dysfunction were more often men, had lower body mass index, a restrictive pattern of LV filling, and eccentric LV hypertrophy.

Adult↗

Gender difference in diastolic function in hypertension (the HyperGEN study).

Although several studies indicate that there are gender differences in left ventricular (LV) systolic function, it remains unclear whether similar differences exist with regard to diastolic function. Accordingly, Doppler echocardiograms were analyzed in 515 male and 839 female, mostly treated (95%) hypertensive participants enrolled in the Hypertension Genetic Epidemiology Network (HyperGEN) study with no evidence of abnormal wall motion or significant valvular heart disease. There was no difference in age between genders, but after adjusting for age and race, men had lower body mass indexes (29.8 +/- 5.2 vs 32.3 +/- 7.6 kg/m(2)) and heart rates (67 +/- 12 vs 69 +/- 11 beats/min) and higher systolic and diastolic blood pressures (BP) than women (134 +/- 20 vs 130 +/- 21 and 80 +/- 11 vs 72 +/- 11 mm Hg, all p <0.001). LV mass/height(2.7) was slightly greater in women than in men (43 +/- 10 vs 42 +/- 9 g/m(2.7), p <0.05). After adjusting for age, race, systolic BP, body mass index, heart rate, and LV hypertrophy, both mitral E-wave (70 +/- 18 vs 77 +/- 19) and A-wave (74 +/- 15 vs 79 +/- 17, both p <0.001) velocities were lower in men than in women, but the mitral E/A ratio and atrial filling fraction were nearly identical in both genders. Deceleration time (221 +/- 55 vs 214 +/- 46 cm/s, p = 0.018) and isovolumic relaxation time (IVRT) were longer in men than in women (85 +/- 18 vs 81 +/- 17 cm/s, p <0.001). Prolonged IVRT was present in more men than women (14% vs 7%, p <0.05). In analyses of covariance, adjusting for age, race, systolic BP, body mass index, heart rate, and medications, male gender remained related to prolonged deceleration time and IVRT. Thus, in this population-based sample of hypertensive adults, men had evidence of slower early diastolic LV filling than women. This gender difference in diastolic function may provide insight into gender differences in congestive heart failure and other specific cardiovascular diseases.

Age Distribution↗

Effects of left ventricular systolic function on left ventricular diastolic filling patterns in severe mitral regurgitation.

Significant mitral regurgitation (MR) may alter the normal pattern of Doppler detected left ventricular (LV) filling by causing a prominent early filling (E) wave velocity. The manner and extent to which the typical filling pattern of uncomplicated MR is affected by concomitant impaired LV systolic function has not been characterized. Twenty patients with severe LV systolic dysfunction (2-dimensional echocardiographic estimation of ejection fraction < or = 30%) and 21 age- and sex-matched case controls with normal systolic function (ejection fraction > or = 55%) were selected. In addition, 20 subjects with normal LV systolic function and no MR were analyzed as a reference group. Maximal E-wave velocity was increased and highest among MR patients with preserved LV systolic function (124 +/- 37 cm/s) than among those with LV systolic dysfunction (101 +/- 25 cm/s; p <0.05) and normal controls (74 +/- 18 cm/s; p <0.001). Concurrently, A-wave velocity was lowest in patients with systolic dysfunction and MR (47 +/- 23 cm/s; p <0.001) than in patients with normal systolic function and MR (79 +/- 33 cm/s) and normal controls (74 +/- 20 cm/s). Deceleration time of the E wave was longest among those with normal systolic function and MR (203 +/- 41 ms) than among those with systolic dysfunction and MR (152 +/- 35 ms; p <0.001) and normal controls (167 +/- 53 ms; p <0.05). Thus, systolic LV dysfunction in patients with severe MR, compared to patients with MR and normal LV systolic function, is associated with important changes in diastolic inflow velocities, including reduction of the maximal A-wave velocity to a greater extent than the E wave, resulting in an increased E/A ratio and shortening of deceleration time of the E wave.

Aged↗

Doppler indexes of left ventricular filling after exercise in 50-year-old healthy persons.

Exercise-induced myocardial ischemia has been shown to alter left ventricular (LV) diastolic filling. An abnormal response of Doppler indexes of LV filling during and after exercise testing has been demonstrated to be a sensitive marker of coronary artery disease. A paucity of data is available regarding reference values and the physiological variation in LV filling indexes after exercise in healthy subjects of similar age. We therefore evaluated 77 healthy subjects (33 men and 44 women) aged 50 years by Doppler echocardiography at rest and 15 and 60 minutes after exercise testing. The peak velocity of early diastolic filling (E-wave), the peak velocity of atrial filling (A-wave), the early to atrial peak velocity (E/A) ratio and the deceleration time of early velocity were measured. There was a decrease in the E/A ratio 15 minutes after exercise compared with the E/A ratio at rest in women (1.13 +/- 0.23 vs 1.23 +/- 0.27; p <0.001) and men (1.03 +/- 0.22 vs 1.15 +/- 0.20; p <0.001). The E/A ratio 60 minutes after exercise did not differ significantly from rest in women (1.23 +/- 0.27 vs 1.18 +/- 0.24; p = NS), but men had a lower E/A ratio 60 minutes after than before exercise (1.04 +/- 0.23 vs 1.15 +/- 0.20; p <0.001). There was no difference in deceleration time of the E-wave before and after exercise. Multivariate analysis revealed that the E/A ratio 15 and 60 minutes after exercise was strongly independently associated with the E/A ratio at rest (p <0.001) and heart rate 15 and 60 minutes after exercise (p <0.005) in both women and men. It is concluded that there is a physiological decrease in the E/A ratio 15 minutes after exercise in healthy subjects, and Doppler LV filling indexes after exercise are strongly associated with LV filling indexes at rest and with heart rate.

Analysis of Variance↗

Cardiac morphology and left ventricular function in normotensive morbidly obese patients with and without congestive heart failure, and effect of weight loss.

To assess cardiac morphology and left ventricular (LV) function in normotensive morbidly obese patients with and without congestive heart failure (CHF) we performed a physical examination and obtained a transthoracic echocardiogram and cardiac Doppler studies before and after substantial weight loss in patients whose actual body weight was initially equal to or more than twice their ideal body weight and who were free from systemic hypertension and underlying organic heart disease. There were 24 patients with CHF, 14 of whom were studied after weight loss. There were 50 patients without CHF, 39 of whom were studied after weight loss. Compared to patients without CHF, those with CHF had significantly greater mean LV internal dimension in diastole, LV end-systolic wall stress, LV mass/height index values, left atrial dimension and right ventricular internal dimension values, significantly lower mean LV fractional shortening, and transmitral Doppler E/A ratio values, and significantly longer mean transmitral E-wave deceleration time and duration of morbid obesity than patients without CHF. Substantial weight loss in those with and without CHF produced comparable reductions in mean LV internal dimension in diastole, LV end-systolic wall stress, LV mass/height index, transmitral Doppler E-wave deceleration time, and left atrial dimension, and comparable increases in LV fractional shortening and transmitral Doppler E/A ratio. Linear regression analysis identified duration of morbid obesity as the strongest predictor of CHF (p <0.00000002). Thus, LV mass is greater and LV systolic function and diastolic filling are more impaired in normotensive morbidly obese subjects with CHF than in those without CHF. Duration of morbid obesity is the strongest predictor of CHF among the variables studied. Substantial weight loss produces comparable changes in cardiac morphology and function in those with and without CHF.

Adult↗

Comparison of mortality rates and progression of left ventricular dysfunction in patients with idiopathic dilated cardiomyopathy and dilated versus nondilated right ventricular cavities.

This study assesses the influence of right ventricular (RV) dilation on the progression of left ventricular (LV) dysfunction and survival in patients with idiopathic dilated cardiomyopathy (IDC). Using transthoracic echocardiography, we studied 100 patients with IDC aged 20 to 80 years (mean 55 +/- 14); 67% were men. In the apical 4-chamber view, diastolic LV and RV chamber area measurements classified patients into 2 groups: group RV enlargement+ (RV area/LV area > 0.5) included 54 patients; group RV enlargement- (no RV enlargement) had RV area/LV area < or = 0.5. Echocardiographic studies were repeated in all patients after a mean of 33 +/- 16 months. At the time of the initial study, the 2 groups did not differ in age, gender, incidence of atrial fibrillation and diabetes, left ventricular mass, and LV ejection fraction, but the RV enlargement+ group had more severe tricuspid regurgitation and less LV enlargement. After 47 +/- 22 months (range 12 to 96), patients in group RV enlargement+ had lower LV ejection fraction (29% vs 34%, p = 0.006) than patients with initial RV enlargement-. At clinical follow-up, mortality was higher (43%) in patients with initial RV enlargement+ than the RV enlargement- patients (15%), p = 0.002. For survivors, the mitral deceleration time averaged 157 +/- 36 ms; for nonsurvivors or patients who required transplant, the mitral deceleration time averaged 97 +/- 12 ms (p < 0.0001). With use of a multivariate Cox model adjusting for LV ejection fraction, LV size, and age, the relative risk ratio of mortality from initial RV enlargement+ was 4.4 (95% confidence limits 1.7 to 11.1) (p = 0.002). Thus, patients with significant RV dilation had nearly triple the mortality over 4 years and more rapidly deteriorating LV function than patients with less initial RV dilation. In IDC, RV enlargement is a strong marker for adverse prognosis that may represent a different morphologic subset.

Adult↗

Left ventricular Doppler diastolic filling patterns in patients with isolated left bundle branch block.

To evaluate the effect of isolated left bundle branch block (LBBB) on diastolic filling patterns, we evaluated 14 subjects with isolated LBBB and 16 age- and sex-matched healthy subjects with normal ventricular conduction by echocardiography. Maximum E-wave velocity, E/A ratio, deceleration time of E wave, and the slope of deceleration of the E wave were lower in subjects with LBBB compared with subjects with normal ventricular conduction. Doppler filling patterns were significantly altered in subjects with isolated LBBB.

Aged↗

Left ventricular filling pattern in uncomplicated obesity.

To determine if uncomplicated obesity is associated with systolic dysfunction or impairment of left ventricular (LV) filling, 40 normotensive, white, asymptomatic, obese subjects (16 men and 24 women, mean +/- SD age 35 +/- 13 years; body mass index 36 +/- 6 kg/m2) and 40 normotensive, normal-weight, white volunteers matched for age and sex distribution, were studied by Doppler echocardiography. Endocardial and midwall shortening did not show differences between groups (obese = 33 +/- 4% and 17 +/- 2%; normal weight = 33 +/- 3% and 18 +/- 2%, respectively). LV mass index was higher in obese than in normal-weight subjects (p <0.0001). Obese persons had prolonged isovolumic relaxation time (p <0.0001), lower transmitral peak early diastolic filling wave (E) velocity (p <0.02), higher E velocity deceleration time (p <0.002) and lower E/atrial diastolic filling wave (A) flow velocity ratio (p <0.01) than did normal-weight subjects, even after controlling for age and blood pressure. Between-group differences in E and E velocity deceleration time disappeared when controlling for LV mass index, whereas prolonged isovolumic relaxation time in obesity was independent of LV mass, chamber dimension, and end-systolic stress. LV filling variables were not statistically related to endocardial or midwall shortening, both as absolute value or as a percentage of that predicted from wall stress. We conclude that uncomplicated obesity is associated with primary impairment of LV isovolumic relaxation; abnormalities of early passive filling flow in obesity are associated with increased LV mass.

Adult↗

Diastolic heart failure: standard Doppler approach and beyond.

Evidence of normal systolic left ventricular function has been reported in up to 30-40% of patients with clinical signs of congestive heart failure, suggesting that diastolic dysfunction is an important predictor of prognosis and mortality. Doppler echocardiography as a noninvasive diagnostic procedure is able to provide immediate and relevant information on functional and structural changes underlying the clinical syndrome of heart failure. Four distinct early filling/late diastole (E/A) ratio patterns (normal, delayed relaxation, pseudonormal, restrictive) can be discerned if viewed within the context of other available clinical information. These patterns evolve from one to another in a single individual, with changes in disease evolution, treatment, and loading condition. They represent a continuum from normal to severe diastolic dysfunction, showing progressively increasing left ventricular (LV) chamber stiffness and subsequently decreasing deceleration time. The combination of Doppler restrictive filling pattern and decreased deceleration time provides important information that helps to differentiate gradations of diastolic dysfunction and has been found to be a potent predictor of prognosis and mortality in various cardiac conditions. When clinical and transthoracic data alone are not sufficient in guiding therapy of congestive heart failure, transesophageal echocardiography can be used to assess most Doppler flows, especially pulmonary venous and left atrial (LA) appendage flows. The use of the multiplane transducer in multiple intermediate scan planes further improves the possibility of optimizing the Doppler incident angle and obtaining the best Doppler recordings of the left upper or right upper pulmonary venous flow. Whereas LV diastolic dysfunction is common in patients with congestive heart failure and appears to be an important predictor of prognosis, little information is available about right ventricular (RV) diastolic dysfunction. The role of RV function in congestive heart failure has probably been underestimated and it is possible that RV diastolic dysfunction assessment is equally important in the follow-up of heart failure patients. Recently, 2 novel echocardiographic technologies for the assessment of ventricular wall dynamics have been developed--color kinesis and tissue Doppler imaging. Both techniques have recently been shown to provide global as well as regional information on LV contraction and filling. Complementary use of both techniques may allow a more complete noninvasive assessment of global and regional systo-diastolic LV function.

Cardiac Output, Low↗

Early temporal changes in coronary flow velocity patterns in patients with acute myocardial infarction demonstrating the "no-reflow" phenomenon.

Coronary flow velocity pattern in patients with acute myocardial infarction demonstrating no-reflow phenomenon is characterized with early systolic retrograde flow and rapid deceleration of diastolic flow velocity. In this study, we investigated the early temporal changes in microvascular function in patients with the no-reflow phenomenon. Among 144 patients with a first acute myocardial infarction, 33 exhibited sizable no-reflow phenomenon after coronary reperfusion with myocardial contrast echocardiography. We assessed temporal changes in coronary flow velocity patterns with the Doppler guidewire. The early systolic retrograde flow was observed < or = 10 seconds after reperfusion in 16 patients (group A) or later in 17 patients (331 +/- 327 seconds, group B). Diastolic deceleration rate was higher in group A than in group B at 1 minute after reperfusion. It gradually increased in group B and showed comparable value to group A 10 minutes later. Group A had longer elapsed time from symptom onset to reperfusion and a greater number of infarct Q waves before reperfusion than group B (14 +/- 13 vs 5 +/- 2 hours, p <0.01; and 3 +/- 2 vs 2 +/- 1, p <0.02). In contrast, the incidence of transient ST reelevation shortly after reperfusion was higher in group B (76% vs 25%, p <0.01). Thus, the characteristic coronary flow velocity pattern is either established at the moment of coronary reperfusion or progresses thereafter in patients with no-reflow phenomenon. This suggests different mechanisms of developing ischemic microvascular injury.

Adult↗

Serial changes and prognostic implications of a Doppler-derived index of combined left ventricular systolic and diastolic myocardial performance in acute myocardial infarction.

The purpose of this study was to investigate the serial changes and prognostic value of a nongeometric Doppler-derived index of myocardial function that combines systolic and diastolic time intervals of the left ventricle in acute myocardial infarction (AMI). The Doppler index was measured in 60 consecutive patients with AMI and in 30 patients admitted to hospital with suspected but disproved AMI who served as controls. The patients were studied at days 1, 5, 90, and 360 after arrival in the coronary care unit. The index was defined as the sum of isovolumetric contraction time, and isovolumetric relaxation time divided by ejection time was measured from mitral inflow and left ventricular outflow Doppler velocity profiles. The index was significantly higher in patients with AMI than in control subjects at days 1 and 360 (day 1, 0.58 +/- 0.09 vs 0.41 +/- 0.08, p <0.0001; day 360, 0.50 +/- 0.09 vs 0.39 +/- 0.07, p <0.01, respectively). The index decreased significantly in patients with AMI during follow-up (p <0.01). The index was significantly higher in patients who developed congestive heart failure or died compared with survivors who were free of congestive heart failure (day 1, 0.63 +/- 0.10 vs 0.53 +/- 0.10, p <0.01; day 360, 0.56 +/- 0.08 vs 0.48 +/- 0.10, p <0.01, respectively). During 20.2 +/- 8.5 months' follow-up, 10 patients died of cardiac causes and 13 developed congestive heart failure. Univariate analyses demonstrated that the Doppler index > or =0.60 (chi-square 8.3, p <0.0001), deceleration time < or =140 ms (chi-square 8.5, p <0.0001), ejection fraction < or =0.40% (chi-square 3.3, p <0.005), anterior wall AMI (chi-square 3.2, p <0.01), and age (chi-square 1.06/ year increase, p <0.01) were significant predictors of outcome. Multivariate stepwise analysis showed that the index < or =0.60 (chi-square 3.4, p <0.05), deceleration time < or =140 ms (chi-square 4.2, p <0.02), and age (chi-square 1.06/year increase, p <0.02) were independent predictors of outcome. The Doppler index reflects severity of left ventricular function and has incremental prognostic value in patients with AMI.

Age Factors↗

Left ventricular filling patterns in patients with systemic hypertension and left ventricular hypertrophy (the LIFE study). Losartan Intervention For Endpoint.

Abnormal left ventricular (LV) filling may exist in early stages of hypertension. Whether this finding is related to LV hypertrophy is currently controversial. This study was undertaken to assess relations between abnormal diastolic LV filling and LV geometry in a large series of hypertensive patients with electrocardiographic LV hypertrophy. M-mode, 2-dimensional, and pulsed Doppler echocardiographic recordings of mitral inflow velocity and isovolumetric relaxation time (IVRT) were obtained in 750 patients with stage I to III hypertension and LV hypertrophy determined by electrocardiography (sex-adjusted Cornell voltage duration criteria or Sokolow-Lyon voltage criteria) after 14 days of placebo treatment. The patients' mean age was 67+/-7 years and 44% were women. One hundred forty patients (19%) had normal LV geometric pattern, 79 (11%) had concentric remodeling, 342 (45%) had eccentric LV hypertrophy, and 189 (25%) had concentric LV hypertrophy. A normal LV filling pattern was found in 116 patients (16%), abnormal relaxation in 519 (69%), "pseudonormal" filling was found in 83 (11%), and a restrictive filling pattern in 32 (4%). Prolonged IVRT was associated with LV hypertrophy (p<0.01) as well as elevated relative wall thickness (p<0.05). A stronger difference (p<0.01) in IVRT was found between groups with and without LV hypertrophy. Multiple regression analysis revealed that increased LV mass correlated with prolonged IVRT, whereas LV mass and geometry were not associated with peak early LV filling velocity (E), peak atrial filling velocity (A) ratio or mitral valve E-peak deceleration time, although IVRT was found to be an independent correlate of E/A ratio and deceleration time. Thus, abnormal IVRT was highly prevalent in all LV geometric subgroups among hypertensive patients with electrocardiographic LV hypertrophy, even in those with normal LV geometry determined by echocardiography. We found that IVRT differed significantly among patient groups with different LV geometric patterns, primarily because of the association of IVRT to LV mass.

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