Effects of verapamil on left ventricular diastolic function at rest and during isometric exercise in patients with hypertrophic cardiomyopathy

Ten patients with hypertrophic cardiomyopathy were examined with echocardiography before and during verapamil treatment to evaluate short-term and long-term effects of verapamil on left ventricular diastolic function. All patients were in sinus rhythm and in NYHA functional class I. Effects on filling and myocardial relaxation were documented by digitized echocardiography obtained at rest and during isometric exercise before treatment, after two weeks (short-term) and four months (long-term) treatment, respectively. At rest a significant decrease of the myocardial relaxation time was found during verapamil treatment. A few patients, however, returned to almost baseline conditions after an initial improvement. A small increase in the peak rate of dimension change, a parameter of filling, reached statistical significance at the end of the long-term treatment period. Isometric exercise did not induce any changes in the diastolic parameters during verapamil treatment. A positive effect of verapamil was thus seen on both myocardial relaxation and left ventricular filling, but only in resting conditions.     

Relation between left ventricular diastolic function and exercise tolerance in patients with left ventricular dysfunction

Previous studies show no correlation between resting systolic left ventricular performance assessed as the ejection fraction and exercise tolerance. This study examined the relation between left ventricular diastolic performance and exercise tolerance in 63 patients with left ventricular dysfunction (ejection fraction less than 50%) due to known or suspected coronary artery disease. The 51 men and 12 women, aged 54 +/- 8 years (mean +/- standard deviation), underwent symptom-limited upright exercise testing on a bicycle ergometer. The exercise end-points were angina (n:5), dyspnea (n:16), and fatigue (n:42). The patients were divided into three groups: group 1 (n:28) with normal exercise tolerance (9.5 +/- 2.4 minutes), group 2 (n:18) with mild exercise intolerance (5.8 +/- 0.5 minutes), and group 3 (n:17) had severe exercise intolerance (3.7 +/- 0.9 minutes). The three groups did not differ in age, ejection fraction, end-diastolic volume, exercise end-point, exercise heart rate, and left ventricular peak filling rate at rest. The exercise peak filling rate was, however, significantly higher in group 1 (p = 0.03). Stepwise multivariate discriminant analysis of important variables identified the exercise peak filling rate as the only predictor of exercise tolerance (F = 6.0). Thus, variation in exercise peak filling rate may in part explain the variability of exercise tolerance in patients with left ventricular dysfunction; patients with preserved exercise capacity have higher exercise peak filling rate than those with exercise intolerance.     

Prognostic implications of left ventricular function during exercise in asymptomatic patients with aortic regurgitation

Few data are available that address the prognostic implications of the response of the left ventricle (LV) to exercise in asymptomatic patients with aortic regurgitation (AR) who have normal resting LV function. Thirty-one such patients were contacted two to seven years after rest and exercise radionuclide ventriculography. Eleven had had significant cardiovascular events. Event-free survival at forty-eight months was 64%. Ten of eleven events occurred in 21 patients with decline in ejection fraction (EF), but the magnitude of decline did not further separate the group with regard to prognosis. Eight events (73% of total events) occurred in the 11 patients (35% of total patients) with an EF during exercise of 0.55 or less. The short and intermediate outlook for asymptomatic patients with AR and normal resting LV function is good regardless of the response of the EF to exercise, but an exercise EF less than or equal to 0.55 does identify a relatively high-risk subset for deterioration beyond twenty-four months.     

Left ventricular diastolic and systolic function during isometric exercise: an echocardiographic study

Normal subjects of both sexes between 20 and 63 years were examined with M-mode echocardiography. Blood pressure (BP), heart rate (HR), and left ventricular (LV) diastolic and systolic function were measured at rest and at the end of a standardized maximal isometric handgrip test. BP and HR increased about 25%. This increase in cardiac work had no significant influence on LV systolic function. Diastolic function (myocardial relaxation and maximum rate of LV filling), however, improved significantly. Isometric handgrip test is a suitable exercise test in combination with M-mode echocardiography. Studies on LV function during exercise may improve the sensitivity for detection of mild LV dysfunction.     

Impaired left ventricular rapid filling during exercise in patients with hypertrophic cardiomyopathy

The influence of exercise on left ventricular diastolic filling was evaluated in 14 patients with hypertrophic cardiomyopathy (HCM) and 14 normal controls (NC) by dynamic exercise echocardiography. Using X-Y digitizer and computer, normalized peak rate of change of the left ventricular dimension during systole (pVs) and the rapid filling phase (pVd) were determined from the left ventricular echocardiograms at rest and during exercise when heart rate reached 100 beats/min. At rest and during exercise, pVs was significantly higher in HCM (3.2 +/- 0.4/s at rest, 4.3 +/- 1.4/s during exercise) than in NC (2.4 +/- 0.5/s at rest, 3.0 +/- 0.4s during exercise) (p less than 0.001, p less than 0.001, respectively), but pVd in HCM (4.2 +/- 1.0/s at rest, 5.8 +/- 1.0/s during exercise) was not significantly different from that in NC (4.1 +/- 1.0/s at rest, 6.0 +/- 0.7/s during exercise). The ratio of pVd to pVs (pVd/pVs) in HCM did not show significant increment during exercise (1.35 +/- 0.38 to 1.43 +/- 0.35), though that ratio in NC was significantly increased by exercise (1.67 +/- 0.22/s to 1.97 +/- 0.19/s, p less than 0.001). There was no correlation between pVd and the degree of left ventricular hypertrophy. These results suggest that diastolic reserve to exercise is depressed in HCM and that other factors besides left ventricular hypertrophy may account for diastolic abnormality.     

Color M-mode flow propagation velocity and conventional doppler indices in the assessment of diastolic left ventricular function during isometric exercise

BACKGROUND AND OBJECTIVE: Color M-mode flow propagation velocity (Vp) was shown to be a preload-independent measure of diastolic function. To study the effects of an increase in afterload induced by isometric handgrip exercise on diastolic function assessment in patients with cardiomyopathy, we measured Vp and conventional Doppler indices at baseline and at 30% of predetermined maximum handgrip strength. METHODS: Twenty-four patients with systolic dysfunction were divided into two groups: Group I comprising 12 patients with E/A < 1 (early filling velocity/atrial contraction velocity) and Group II comprising 12 patients with E/A > 1. All the patients underwent measurement of Vp, E velocity, its deceleration time (DT), A velocity, isovolumic relaxation time (IVRT), and pulmonary atrial flow reversal velocity (PFR) at baseline and at 30% of predetermined maximum handgrip strength. Twelve healthy controls underwent these same measurements. RESULTS: When comparing baseline to peak echocardiographic data, no significant changes were noted in Vp in any of the groups while a shift of pulsed Doppler indices of Group I toward a pattern closer to that of Group II was noted and a decrease in E velocity and E/A ratio with an increase in IVRT occurred in healthy controls. CONCLUSIONS: Color M-mode flow propagation velocity seems to be an afterload-independent measure of diastolic function in patients with moderate to severe cardiomyopathy while pulsed Doppler indices are more sensitive to loading conditions induced by isometric exercise.     

Left ventricular diastolic function in trained male weight lifters at rest and during isometric exercise

Individuals involved in intense resistance training present with increased absolute left ventricular (LV) wall thickness and mass and show good systolic responses to isometric exercise. There is no consensus regarding diastolic features and no available information regarding diastolic function in athletes during isometric exertion itself. Therefore, the main aim of this study was to assess diastolic LV function at baseline and during exercise in athletes. The population consisted of 96 men (mean age 29 +/- 7 years): 48 weight lifters who trained for 15 to 20 hours/week and 48 sedentary men. All weight lifters had been active for >6 years, including the 6 months before the study. Ultrasound was performed using a commercially available Doppler echocardiographic system. Isometric exercise was performed in the supine position using a standard 2-hand bar dynamometer. The man end-diastolic volumes at rest were 97 +/- 6 ml in sedentary subjects and 101 +/- 5 ml in weight lifters, increasing to 100 +/- 6 and 118 +/- 11 ml during exercise (p = 0.06 and p <0.01, respectively). End-systolic volumes at rest were similar in the 2 groups, showing significantly greater reductions during exercise in the weight lifters. The mean absolute LV mass was 167 +/- 30 g in sedentary subjects and 202 +/- 32 g in weight lifters (p <0.0001). The mean stroke volume increased from 65 +/- 7 to 86 +/- 7 ml in sedentary subjects and from 70 +/- 6 to 107 +/- 11 ml in weight lifters (intergroup significance p = 0.05 and p <0.01, respectively). A similar pattern of response was documented for the ejection fraction (i.e., significantly greater increases during exercise in weight lifters). Regarding diastolic indexes, in the weight lifters, the mean peak early velocity at rest was 68 +/- 7 cm/s, the mean acceleration rate was 1,242 +/- 176 cm/s/s, and the mean deceleration rate was 414 +/- 44 cm/s/s. All these values were significantly higher than in sedentary subjects, with further increases during exercise (p <0.0001). In weight lifters, the mean peak atrial velocity at rest was 37 +/- 6 cm/s, the mean acceleration time was 55 +/- 4 ms, the mean isovolumic relaxation time was 63 +/- 3 ms, and the mean deceleration time was 164 +/- 4 ms; these values were lower than in sedentary subjects (p <0.0001 for all). In conclusion, intense resistance training leads to enhanced LV diastolic function at rest and during isometric exercise despite the markedly increased LV mass.     

Relation between exercise capacity and left ventricular systolic versus diastolic function during exercise in patients after myocardial infarction

BACKGROUND: It is known that left ventricular systolic function at rest does not correlate well with exercise capacity of patients with heart failure. However, the contribution of left ventricular diastolic dysfunction, especially during exercise, to exercise capacity of cardiac patients remains to be determined. OBJECTIVE: To determine the impact of left ventricular systolic and diastolic function during exercise on exercise capacity of patients with left ventricular dysfunction after myocardial infarction. METHODS: A symptom-limited exercise test was performed with measurements for hemodynamics and uptake of oxygen (Vo2) of 26 men who had previously suffered myocardial infarction. These patients were divided into two groups according to their peak Vo2 (group 1 with peak Vo2 > or = 16 ml/kg per min, n= 13; and group 2 with peak Vo2 < 16 ml/kg per min, n= 13). Pulmonary arterial pressure, left ventricular and systemic arterial pressure, and cardiac output were measured at rest and during exercise. RESULTS: At rest, there was no difference between the two groups in terms of hemodynamic parameters except for minimal dP/dt, minimal left ventricular pressure (LVP) and time constant for decay of left ventricular pressure (tau). During peak exercise, cardiac output, left ventricular end-diastolic pressure (EDP), minimal dP/dt, minimal LVP, and tau for the two groups were significantly different. Furthermore, peak Vo2 was significantly correlated with T, minimal LVP, minimal dP/dt, EDP, and maximal dP/dt during peak exercise for the whole group of patients. CONCLUSION: Left ventricular diastolic function during exercise, i.e. diastolic reserve, may be an important determinant of exercise capacity of patients with left ventricular dysfunction after myocardial infarction.     

Gender-related difference in left ventricular diastolic elastance during exercise in patients with diabetes mellitus

Background Because the ratio of mitral inflow and annular velocity to stroke volume has been reported as an index of diastolic elastance (Ed), the hypothesis tested in the present study was that Ed during exercise would be more abnormal in female than in male patients with type 2 diabetes. Methods and Results Ed was measured at rest and during graded supine bicycle exercise (25W, 3-min increments) in 53 patients (27 males, mean age 53+/-14 years) with type 2 diabetes and 53 age- and gender-matched controls. The patients with diabetes were divided into 2 groups by gender. Ed was not significantly different at rest between men and women, but was significantly higher during exercise in women than in men (25 W, 0.15+/-0.04 vs 0.20+/-0.07, p=0.009; 50 W, 0.16+/-0.05 vs 0.21+/-0.08, p=0.0175). Conclusion Left ventricular (LV) diastolic elastance is abnormal during exercise, but not at rest, in patients with diabetes without overt heart disease. Female gender was associated with increased LV stiffness during exercise among patients with type 2 diabetes. (Circ J 2008; 72: 1443 - 1448).     

Impaired left ventricular diastolic function in acromegaly: an echocardiographic study

To study diastolic function we digitized M-mode echocardiograms in 18 acromegalic patients (A) and compared them to an age matched control population (C). Wall thickness and left ventricular (LV) mass index are frankly increased in A (p less than 0.001). Filling pattern of the LV shows in A a prolongation of the isovolumic relaxation period (IRP) (p less than 0.001), an increase of the percentage dimension change of LV during IRP (p less than 0.001) and a reduction of the percentage dimension change during the rapid filling period (p less than 0.01). Our results indicate that relaxation is abnormal in A; this abnormality should be interpreted as a mere consequence of LV hypertrophy.     

等长运动对正常人、冠心病患者左室心功能的影响

目的 :通过核素心血池显像测定静息状态和等长运动后正常人、冠心病患者左室心功能指标的变化 ,探讨等长运动对冠心病诊断的临床价值。方法 :45例正常人、10 0例冠心病患者常规核素平衡法门电路心血池显像测定左室心功能。在静息状态下采集后 ,保持探头和患者体位不变 ,双手握力 5～ 10 min并同时进行采集从而获得静息和握力运动状态下两组血流动力学指标和时间—放射性曲线。11例正常人和 10 0例冠心病患者行冠状动脉及左心室造影 ,两项检查间隔不超过两周。运用 SPSS9.0统计软件进行 t检验和直线相关分析。结果 :左室射血分数（L VEF）、高峰充盈率 （PFR）、左室舒张末期容积 （L VEDV ）、左室收缩末期容积 （L VESV ）和心率 （HR）在静息（Rest）状态下 ,对照组和冠心病组分别为 （5 2± 9） % vs（4 5± 9% ） ,P<0 .0 1;2 .7± 0 .8EDV/s vs2 .0± 0 .8EDV/s,P<0 .0 1;1.33± 0 .12 vs 1.2 8± 0 .11,P <0 .0 5 ;0 .6 3± 0 .10 vs 0 .0 7± 0 .0 8,P<0 .0 1;7.0± 10 m in- 1 vs 6 9± 9min- 1 ,P>0 .0 5。在等长握力运动 （Stress）状态下 ,对照组和冠心病组分别为 （5 6± 10 ） % vs（4 2± 10 ） % ,P<0 .0 1;3.1± 0 .8EDV/s vs 1.8± 0 .7EDV/s.P<0 .0 1;1.35± 0 .14vs 1.2 5± 0 .12 ,P<0 .0 1;0 .6 0± 0 .1     

Impaired left ventricular function during exercise in coronary artery disease and exertional hypotension

To characterize the hemodynamic abnormalities responsible for exertional hypotension coronary artery disease, we studied 11 patients with exertional hypotension during supine cycle ergometer exercise, defined as greater than 10 mm Hg decrease in systolic blood pressure during exercise, and 11 patients without exertional hypotension (controls). Patients were similar with respect to age, left ventricular ejection fraction at rest, and the intensity of exercise relative to maximal treadmill exercise capacity. Peak exercise ejection fraction, determined by radionuclide ventriculography, was significantly lower in patients with, than in those without exertional hypotension (50 +/- 3 vs. 56 +/- 3%; p less than 0.025). Ejection fraction and stroke volume decreased with exercise in patients with exertional hypotension but not in the controls even though changes in end-diastolic volume and mean blood pressure were similar in both groups. Peak exercise systolic blood pressure and rate pressure product were significantly lower in the patients with exertional hypotension than those without. The exercise-induced regional left ventricular contraction abnormalities were more prominent, extensive and frequent in patients with exertional hypotension than controls. Impairment of left ventricular contractile function was further evident by an abnormal end-systolic volume-systolic blood pressure relation in patients with exertional hypotension. These patients attained a much smaller increase in systolic blood pressure compared with controls despite no statistically significant differences in end-systolic volume response to exercise. These findings suggest that exertional hypotension in patients with ischemic heart disease is associated with exercise-induced left ventricular systolic dysfunction secondary to extensive myocardial ischemia.     

Left ventricular diastolic function and cardiac performance during exercise in patients with acromegaly

Exercise-induced impairment of left ventricular (LV) ejection fraction is common in patients with acromegaly and normal resting systolic function. This study aimed to clarify whether diastolic dysfunction plays a role in the abnormal adaptation to exercise in these patients. Forty-eight patients with active acromegaly underwent LV radionuclide angiography at rest and during exercise. Doppler echocardiography was also performed to assess LV mass index and diastolic function by combined analysis of mitral and pulmonary flow velocity curves. LV ejection fraction at peak exercise was related to rest ejection fraction (r = 0.78; P < 0.001), peak filling rate (r = 0.55; P < 0.01), LV mass index (r = -0.56; P < 0.001), and the difference between duration of diastolic reverse pulmonary vein flow and mitral flow at atrial contraction (Delta duration) (r = -0.54; P < 0.01). At stepwise regression analysis, rest ejection fraction and Delta duration were the only variables that independently influenced (P < 0.001) ejection fraction at peak exercise. Diastolic dysfunction is important in determining cardiac performance during exercise in patients with acromegaly and normal resting systolic function. Combined analysis of pulmonary vein and mitral flow velocity curves allows the identification of impaired LV diastolic function in such patients.     

Influence of isometric exercise on left ventricular diastolic function in the normal subjects and in patients with hypertension and coronary heart disease]

To evaluate the influence of isometric exercise on left ventricular (LV) diastolic function, transmittal flow velocity was measured by pulsed Doppler echocardiography before and after handgrip in 15 normal subjects and the patients with hypertension as well as 18 patients with coronary heart disease (CHD). Statistically significant differences in peak velocity of early rapid filling (Ev), the ratios of peak early to late diastolic velocity (Ev/Av) and early to late velocity-time integral (Ei/Ai) between normal subjects and both the patients with hypertension and CHD were noted at rest. After isometric exercise, significant increase in Av (0.70 +/- 0.13 vs 0.76 +/- 0.14, P less than 0.01) and Ai/total VTi (0.35 +/- 0.07 vs 0.42 +/- 0.08, P less than 0.05) were showed in the hypertension group. In CHD, multiple Doppler parameters changed after isometric exercise with increase in Av (0.70 +/- 0.16 vs 0.85 +/- 0.18, P less than 0.01) and Ai/total VTi (0.36 +/- 0.08 vs 0.42 +/- 0.08, P less than 0.01) as well as decrease in Ev/Av (0.95 +/- 0.22 vs 0.82 +/- 0.15, P less than 0.05) and Ei/Ai (1.64 +/- 0.51 vs 1.35 +/- 0.34, P less than 0.05). However, there was no significant difference in any Doppler indices of LV diastolic function in the present normal subjects after isometric exercise. Thus, isometric exercise further enhanced late LV diastolic filling in the patients with impaired LV diastolic function in resting states greater than normal subjects, and myocardial ischemia induced by handgrip may play partial role in more changes in Doppler indices of LV diastolic function in CHD than the patients with hypertension.     

Effects of nifedipine on left ventricular diastolic function in patients with asymptomatic or minimally symptomatic hypertrophic cardiomyopathy

We investigated the effects of nifedipine on left ventricular diastolic function in 17 asymptomatic or minimally symptomatic patients with hypertrophic cardiomyopathy by simultaneously measuring left ventricular pressure and volume with a catheter-tipped manometer and biplane cineangiography. Studies were performed before and 20 minutes after sublingual administration of nifedipine (20 mg). Heart rates were held constant (79 +/- 12 beats/min, mean +/- SD) by right atrial pacing. Left ventricular volumes and instantaneous rates of left ventricular volume were derived from frame-by-frame (20-msec) analyses of left ventricular biplane angiograms. Left ventricular peak systolic pressure (from 122 +/- 21 to 108 +/- 13 mm Hg, p less than 0.01 vs. control) and mean aortic pressure (from 96 +/- 15 to 87 +/- 11 mm Hg, p less than 0.01) decreased significantly with nifedipine. With afterload reduction, left ventricular ejection fraction (from 0.69 +/- 0.12 to 0.74 +/- 0.08, p less than 0.01) and cardiac output (from 6.4 +/- 2.0 to 7.2 +/- 2.2 l/mm, p less than 0.05) increased significantly. However, there was a slight but significant increase in left ventricular end-diastolic pressure (from 15 +/- 8 to 18 +/- 8 mm Hg, p less than 0.05). Nifedipine did not improve left ventricular relaxation as assessed by the time constants of isovolumic pressure decay (t1/2, from 39.8 +/- 6.6 to 39.4 +/- 7.7 msec, NS; t1/e, from 53.8 +/- 9.0 to 54.4 +/- 10.7 msec, NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired coronary microvascular and left ventricular diastolic functions in patients with ankylosing spondylitis

BackgroundIt has been shown that the patients with inflammatory rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis have an increased risk of developing atherosclerosis. However, the association of ankylosing spondylitis (AS) to atherosclerosis and related diseases is still controversial. Accordingly, we investigated coronary flow reserve (CFR) and left ventricular (LV) diastolic function in patients with AS using transthoracic Doppler echocardiography.MethodsCFR and LV diastolic function were studied in 40 patients with AS (38.9 ± 10.2 years, 26 males) and 35 healthy volunteers (37.5 ± 6.4 years, 23 males). Coronary diastolic peak flow velocities (DPFV) were measured at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline DPFV. LV diastolic function was assessed by both standard and tissue Doppler imaging.ResultsDemographic features and coronary risk factors except diastolic blood pressure were similar between the groups. CFR were significantly lower in the AS group than in the control group (2.20 ± 0.46 versus 3.02 ± 1.50, P < 0.0001). Reflecting LV diastolic function mitral A-wave and E/A ratio were borderline significant, and mitral E-wave deceleration time and isovolumic relaxation time were significantly different between the groups. Serum hsCRP and TNF-α levels were significantly higher in the patients with AS, and hsCRP and TNF-α levels independently correlated with CFR.ConclusionThese findings show that CFR reflecting coronary microvascular function and LV diastolic function are impaired in patients with AS, and severity of these impairments correlate well with hsCRP and TNF-α. These results suggest that impaired CFR may be an early manifestation of cardiac involvement in patients with AS.     

Effect of autonomic blockade, postural changes and isometric exercise on Doppler indexes of diastolic left ventricular function

Previous studies have demonstrated substantial changes in Doppler-derived indexes of left ventricular (LV) diastolic function in response to changes in loading conditions. To assess the influence of autonomic reflexes on these indexes, 2-dimensional and Doppler echophonocardiography were performed in 8 normal male subjects before and during autonomic blockade (0.2 mg/kg of propranolol and 0.04 mg/kg of atropine, intravenously) in the supine, passive upright 80 degree tilt and passive leg-raised positions, and during supine isometric exercise. During autonomic blockade in the supine position, there were significant increases in transmitral peak late filling velocity (A) (mean +/- standard error of the mean +34 +/- 7%) and isovolumic relaxation time (+18 +/- 9%), and significant decreases in transmitral peak early filling velocity (E) (-20 +/- 7%), deceleration time (-35 +/- 7%) and E/A ratio (-40 +/- 5%). E/A ratio decreased from 2.0 +/- 0.1 to 1.2 +/- 0.1 with autonomic blockade. When either upright tilt or isometric handgrip exercise was combined with autonomic blockade, the pattern of diastolic filling became distinctly "abnormal," with E/A ratio decreasing to 0.9 +/- 0.1. The effect of volume loading (increased end-diastolic volume and increased peak E) was seen in the legs-raised position only during autonomic blockade. It is concluded that autonomic blockade substantially alters the Doppler indexes of LV diastolic filling and modifies both hemodynamic response and Doppler indexes produced by positional changes and by isometric exercise.