Right ventricular diastolic function in patients with hypertrophic cardiomyopathy--an invasive study.

To assess diastolic function of the right ventricle (RV) in patients with hypertrophic cardiomyopathy (HCM), biplane RV angiograms and RV pressures were analyzed in 19 HCM patients and in 13 normal subjects. RV and left ventricle (LV) pressures were measured using catheter-tip manometers. RV volumes were obtained from frame-by-frame tracings of angiograms. Ventricular relaxation was assessed by the time constant of isovolumic pressure decay (T). The peak filling rate (PFR) and the time to PFR (TPFR) were used as parameters of early diastolic filling, and the right atrial contribution to RV filling (%AF) was used as a parameter of late diastolic filling. The T for the RV was significantly prolonged in HCM patients. However, there was no significant correlation between the T for the RV and LV, nor did the T for the RV correlate with the RV ejection fraction or interventricular septal wall thickness. The TPFR, but not PFR, was significantly greater in HCM patients, and the %AF tended to be increased in HCM, but not significantly. The RV diastolic pressure-volume relations in the HCM patients shifted upward. In conclusion, impaired isovolumic relaxation and delayed diastolic filling and decreased diastolic distensibility are present in the RV of HCM patients.

Hypertrophic cardiomyopathy: MR measurement of coronary blood flow and vasodilator flow reserve in patients and healthy subjects.

PURPOSE: To evaluate coronary blood flow per gram of myocardial mass and vasodilator flow reserve in patients with hypertrophic cardiomyopathy (HCM) and in healthy subjects by using breath-hold velocity-encoded cine (VEC) magnetic resonance (MR) imaging. MATERIALS AND METHODS: Twenty-nine patients with HCM and nine healthy volunteers were examined. Fast VEC MR images were obtained in an oblique imaging plane perpendicular to the coronary sinus before and after intravenous injection of dipyridamole (0.56 mg/kg). The products of mean velocity and cross-sectional area of the vessel were integrated to measure blood flow. Breath-hold cine MR images encompassing the entire left ventricle were acquired to quantify the left ventricular mass. RESULTS: In the basal state, the coronary blood flow per gram of myocardial mass was 0.74 mL/min/g +/- 0.23 in healthy subjects and 0.62 mL/min/g +/- 0.27 in patients with HCM. After administration of dipyridamole, coronary blood flow in patients with HCM increased to a level significantly less than that in healthy subjects (1.03 mL/min/g +/- 0.40 vs 2.14 mL/min/g +/- 0.51; P < .01), resulting in a severely depressed flow reserve ratio in patients with HCM compared with that in healthy subjects (1.72 +/- 0.49 vs 3.01 +/- 0.75; P < .01). CONCLUSION: Breath-hold VEC MR imaging is a noninvasive technique for evaluating coronary flow per gram of myocardial mass and coronary flow reserve.

Prognosis of completely asymptomatic adult patients with hypertrophic cardiomyopathy.

OBJECTIVES: We investigated the long-term prognosis of completely asymptomatic adult patients with hypertrophic cardiomyopathy (HC). Diagnosis of HC was suspected because of an abnormal electrocardiogram and/or cardiac murmur and confirmed by echocardiography and/or left ventricular angiography, and hemodynamic investigation. BACKGROUND: Hypertrophic cardiomyopathy shows marked heterogeneity in clinical expression and prognosis. The prognosis of asymptomatic patients with HC has not been fully defined. METHODS: Of 128 consecutive adult patients with HC, 58 asymptomatic patients (Group 1, mean age 42.8 years) and 70 symptomatic patients (Group 2, mean age 50.4 years) were studied to assess cardiac mortality. Mean follow-up periods were 11.0 years for Group 1 and 9.1 years for Group 2. RESULTS: At presentation, Group 1 patients were younger and had smaller left atrial dimensions than did Group 2 patients. The annual cardiac mortality rate and the rate for sudden death alone in Group 1 were significantly lower than in Group 2 (0.9% vs. 1.9%, p < 0.05, 0.1% vs. 1.4%, p < 0.05, respectively). Although about one-third of the survivors in Group 1 had cardiac symptoms at their most recent evaluation, only one patient died suddenly compared with eight in Group 2. The annual mortality rate due to heart failure was similar in each group. Only a syncopal episode was associated with both cardiac death and sudden death for both groups combined. CONCLUSIONS: The cardiac mortality rate for completely asymptomatic adult patients with HC was very low, significantly lower than that of symptomatic patients, and there was a disproportionately low incidence of sudden death.

Calcium sensitizers in chronic heart failure: inotropic interventions-reservation to preservation.

Newly developed Ca2+ sensitizers possess different mechanisms of action on contractile machinery. Increasing maximal Ca(2+)-activated force in addition to enhancing Ca2+ sensitivity (MCI-154, EMD 53998, and EMD 57033) could exert pronounced positive inotropy and may provide a mechanoenergetic advantage over the classic Ca2+ mobilization in the chronically failing heart. EMD 53998 and EMD 57033 prolong crossbridge attachment time, resulting in negative lusitropy. In contrast, pimobendan, levosimendan, and MCI-154 accelerate left ventricular relaxation in heart failure, because Ca2+ sensitizing action of these agents may be prominent during the early phases of contraction. Therefore, Ca2+ sensitizers can avoid the legacy of problems associated with conventional inotropic interventions and may break through "reservation" to "preservation" in the treatment of chronic heart failure.

Left ventricular inotropic and lusitropic responses to pacing-induced tachycardia in patients with varying degrees of ventricular dysfunction.

BACKGROUND: In the failing human heart contractile reserve during tachycardia is attenuated or absent. However, it is not known whether during tachycardia diminished inotropic reserve depends on the degree of ventricular dysfunction or lusitropic reserve is also diminished in patients with left ventricular (LV) dysfunction. METHODS: We studied 18 patients with dilated cardiomyopathy or mildly depressed LV function and 13 subjects in a control group (ejection fraction 0.67+/-0.09). The patients were classified into two groups based on whether their ejection fraction was less than or more than 0.40 (group 1, ejection fraction 0.27+/-0.05; group 2, ejection fraction 0.49+/-0.07). LV pressures were measured with a catheter-tip manometer during incremental right atrial pacing up to a heart rate of 150 beats/min. RESULTS: With incremental pacing LV peak positive dP/dt rose progressively in both the normal group and in group 2, but the increase was less for group 2 than for the normal group; in group 1 the increase was slight or absent. In contrast, a significant and progressive decrease occurred in the time constant of LV relaxation in all three groups. Although their values remained significantly different at each heart rate, no intergroup differences in absolute or percent changes were present. CONCLUSIONS: These findings suggest that during tachycardia LV inotropic reserve may be diminished depending on the degree of ventricular dysfunction, and lusitropic reserve may be preserved in patients with depressed function despite an attenuated inotropic response.

Abdominal aortic thrombosis in a patient with nephrotic syndrome.

We report a patient who presented with severe nephrotic syndrome complicated with infrarenal aortic and right renal arterial thrombosis. The nephrotic syndrome frequently causes thromboembolic complications in veins, but arterial thrombosis is relatively rare, especially in the aorta. Various predisposing factors leading to thromboembolic complications are discussed. In this case, the thromboembolic complication may have some clinical association with the hypercoagulable state in nephrotic syndrome.

Increased lung uptake of iodine-123-MIBG in diabetics with sympathetic nervous dysfunction.

UNLABELLED: Scintigraphy with 123I-MIBG and 201TI was compared in patients with various diseases including diabetes mellitus, with and without sympathetic nervous dysfunction. This study was done to assess lung uptake of these tracers semiquantitatively. METHODS: Thirty-eight patients with diabetes mellitus, seven patients with dilated cardiomyopathy (DCM), 12 patients with hypertrophic cardiomyopathy (HCM) and eight healthy subjects were studied. Sympathetic nervous dysfunction was observed in 13 of the 38 diabetic patients. Simultaneous imaging with 123I-MIBG and 201TI was performed. The ratio of lung to total injected dose count and washout rate in the lung were calculated from dynamic images acquired in the initial 2 min and static images acquired at 15 min and at 4 hr after injection of the tracers. RESULTS: Lung uptake of 123I-MIBG at 4 hr was significantly increased in the diabetic group as compared with those in the other groups. In diabetic patients with sympathetic nervous dysfunction, the lung uptake ratio of 123I-MIBG at 4 hr was significantly higher than that in the diabetic patients without sympathetic nervous dysfunction, due to decreased clearance of 123I-MIBG from the lung. On the other hand, increased lung uptake of 201TI was observed in DCM patients at both 15 min and 4 hr. There was no significant difference between lung uptake of 201TI in diabetic patients and that in healthy subjects. CONCLUSION: Lung uptake of 123I-MIBG was increased and lung washout of 123I-MIBG was decreased in diabetic patients with sympathetic nervous dysfunction, while lung uptake of 201TI was not altered. lodine-123-MIBG scintigraphy of the lung may provide information on sympathetic nervous activity in diabetic patients. It is a promising method for studying the kinetics of norepinephrine in the lung because MIBG is taken up in the lung by the same mechanism as norepinephrine.

Effects of nicorandil, an antianginal potassium channel opener, on left ventricular systolic and diastolic function in patients with chronic coronary artery disease.

We compared the effects of nicorandil with nitroglycerin and nifedipine on left ventricular function. Intravenous nicorandil may be a balanced-typed vasodilator and useful in patients with left ventricular systolic and diastolic dysfunction.

Relationship between left ventricular diastolic function at rest and exercise capacity in patients who have suffered a previous myocardial infarction.

To assess whether left ventricular (LV) diastolic function is a determinant of exercise capacity in patients who have suffered a previous myocardial infarction (MI), we investigated the relationship between maximum exercise duration and resting LV diastolic function in 65 MI patients. Each patient underwent both a symptom-limited exercise test and LV biplane angiography with simultaneous high-fidelity pressure measurements. LV relaxation was assessed by the time constants (T1/e and T1/2) of isovolumic pressure decay, and LV diastolic distensibility was assessed by the LV end-diastolic volume (V) index-pressure (P) ratio. The time constants of relaxation did not correlate with maximum exercise capacity (r = -0.19 for T1/e, NS; r = - 0.17 for T1/2, NS). LV diastolic distensibility also did not correlate with exercise capacity (r = - 0.08, NS). These results suggest that the resting LV diastolic dysfunction is unlikely to be the principal cause of exercise intolerance in MI patients without congestive heart failure.

Effects of MCI-154, a calcium sensitizer, on left ventricular systolic and diastolic function in pacing-induced heart failure in the dog.

BACKGROUND: MCI-154 is a positive inotropic agent that increases the myofilament response to Ca2+. Whether MCI-154 has beneficial effects on left ventricular dysfunction in chronic heart failure is not known. We examined the effects of MCI-154 on left ventricular systolic and diastolic function in pacing-induced heart failure in dogs. METHODS AND RESULTS: We studied eight anesthetized dogs before and 2 to 4 weeks after rapid right ventricular pacing. Left cineventriculograms with simultaneous left ventricular pressures (tip manometer) were obtained before and during intravenous administration of MCI-154 (I.O. microgram.kg-1.min-1 for 15 minutes) in the control and heart-failure states. Left ventricular volume dynamics was derived from frame-by-frame (20-ms) analyses of left ventricular angiograms. In heart failure, left ventricular contractility as assessed by shifts of the end-systolic pressure-volume ratio, evaluated by inferior vena cava occlusion, was improved by MCI-154 (+ 1.94 mm Hg/mL, P < .05) to an extent similar to that in the control state (+2.47 mm Hg/mL, P < .05). MCI-154 also accelerated left ventricular relaxation, assessed by the time constant of isovolumic pressure decay (T1/2), in both states. The absolute decrease in T1/2 with MCI-154 in heart failure was significantly greater than in the control state (-8.2 versus -3.1 ms, P < .05). In heart failure, MCI-154 shifted the left ventricular diastolic pressure-volume relation clearly downward, suggesting increased diastolic distensibility. CONCLUSIONS: MCI-154 improved not only left ventricular systolic function but also diastolic relaxation and distensibility in a chronic heart failure model.

Effects of aging on left ventricular relaxation in humans. Analysis of left ventricular isovolumic pressure decay.

BACKGROUND: Some experimental studies in animals have shown that myocardial relaxation is prolonged with aging. However, it is not known whether aging alters ventricular isovolumic relaxation in human subjects. METHODS AND RESULTS: We analyzed high-fidelity left ventricular pressures, measured by use of a catheter-tipped manometer, and biplane left ventriculograms in 55 normal subjects who underwent diagnostic cardiac catheterization but who were found to have normal cardiac anatomy and function. There were 38 men and 17 women, ranging in age from 20 to 77 years. Left ventricular isovolumic relaxation was assessed by the exponential time constants of isovolumic pressure decay with (Tb) and without (Tw) an asymptote pressure. Left ventricular volume, ejection fraction, and wall thickness or mass were calculated from left ventricular angiograms. Neither of the time constants of left ventricular relaxation correlated with age (Tb: r = .001 to .10, P = NS: Tw: r = .02 to .05, P = NS). Left ventricular systolic function (ie, ejection fraction and end-systolic volume index), heart rate, and left ventricular wall thickness or mass, which are major hemodynamic determinants of left ventricular relaxation, were not significantly affected by aging. The multivariate analysis of age and hemodynamic variables against the time constants of left ventricular relaxation also indicated that no significant relation was found between age and left ventricular relaxation. CONCLUSIONS: In the absence of coronary artery disease, systemic hypertension, left ventricular systolic dysfunction, or hypertrophy, left ventricular relaxation assessed by the time constant of isovolumic pressure decay remains essentially unchanged with normal adult aging, at least until the eighth decade.

Exercise-induced coronary spasm: comparison of treadmill and bicycle exercise in patients with vasospastic angina.

BACKGROUND: We investigated whether exercise-induced coronary spasms are influenced by the different exercise modes. METHODS: We compared ischaemic ECG responses in 67 patients with vasospastic angina who underwent both treadmill and bicycle ergometer exercise and also coronary angiography. RESULTS: ECG ST-segment elevation was provoked more frequently during treadmill exercise than it was during bicycle exercise (19 versus 9%, P < 0.05). Of 45 patients without significant coronary stenosis (coronary artery luminal diameter narrowing < 75%), 19 patients manifested ST-segment depression during treadmill exercise, whereas only seven patients did during bicycle exercise (42 versus 16%, P < 0.01). All patients with ST-segment elevation or depression during bicycle ergometer exercise also had ST-segment changes during treadmill exercise. Although higher systemic blood pressure levels and lower heart rates were found during bicycle exercise compared with during treadmill exercise the pressure-rate products at peak exercise did not differ between the two exercise tests. CONCLUSIONS: It seems that treadmill and bicycle exercise are different stressors in patients with vasospastic angina, and that coronary spasms are provoked more frequently during treadmill exercise than they are during bicycle exercise. The cause of this difference is not known, but it may be related in part to the difference in systemic haemodynamic or neurohumoral response.

Alterations of expression and distribution of the Ca(2+)-storing proteins in endo/sarcoplasmic reticulum during differentiation of rat cardiomyocytes.

Calsequestrin (CS) is a Ca(2+)-storing protein present in the sarcoplasmic reticulum (SR) of muscle cells. Calreticulin (CR) is a functional homologue of CS in the endoplasmic reticulum (ER) of non-muscle cells. During skeletal muscle differentiation, the major Ca(2+)-storing protein switches from CR to CS. To study the regulation of CS and CR expression in cardiomyocytes and the morphological maturation of Ca(2+)-storing sites in the SR, we examined rat hearts at various developmental stages and cultured adult cardiomyocytes by Western blotting and immunocytochemical analyses. CR was expressed in 14-day-old fetal rat cardiomyocytes, but disappeared gradually by 1 week after birth. CR reappeared in dedifferentiated adult cardiomyocytes in long-term culture. On Western blots, the concentration of CS in the heart did not change during development. Immunostaining for CS in fetal or neonatal rat cardiomyocytes revealed as scattered dots. CS-positive structures increased with development, and the regular striated distribution of CS at Z lines was completed around 3 weeks after birth. These results indicated that (1) CR expression is downregulated during cardiac differentiation and upregulated during dedifferentiation, and (2) maturation of SR involves the organization of CS-positive structure after birth.

Regression of left ventricular hypertrophy with long-term treatment of nifedipine in systemic hypertension.

We investigated the regression of left ventricular (LV) hypertrophy with long-term treatment of nifedipine in patients with systemic hypertension. Echocardiograms of the LV were obtained in nine patients before and at a mean of 50 months (13-105 months) after nifedipine monotherapy (30-60 mg/day). Nifedipine significantly reduced both systolic and diastolic blood pressures (BP) by a mean of -46 mmHg and -21 mmHg, respectively. With systemic BP reduction, LV mass was significantly reduced by a mean of -15%, associated with a decrease in LV posterior wall thickness and end-diastolic dimension. There was no significant change in LV fractional shortening. We conclude that nifedipine may cause regression of LV hypertrophy in systemic hypertension, and that reversal of the increase in LV mass could be maintained during long-term nifedipine treatment.

[Which time constant of left ventricular relaxation is the most sensitive measure in acute myocardial ischemia?].

To investigate which time constant of isovolumic left ventricular pressure (LVP) decay is the most sensitive measure in acute myocardial ischemia, the time constant of isovolumic relaxation (IR) was calculated by two different models, the semilogarithmic model assuming a zero of LVP decline (TL) and an exponential model (Texp) with an asymptote (extrapolated baseline pressure to which LVP would fall if decay continued indefinitely), in 10 patients before and during ergonovine-induced vasospastic angina. Two time constants were derived from the exponential method as the times for LVP at peak negative dP/dt to decline by 1/e (Texp (1/e)) and by one half (Texp (1/2)). Three changes in LVP during isovolumic relaxation were analyzed and fitted to the two models described above: the LVP from the peak negative dP/dt 1) to when LVP fell to 5 mmHg above LV end-diastolic pressure (EDP), 2) until 40 msec had passed, and 3) to the LVP level 5 mmHg above LVEDP during coronary spasm. There were significant increases in TL, Texp (1/e) and Texp (1/2) in each period of the LVP during vasospastic angina. However, no significant change in Texp or asymptote was observed during angina. We concluded that TL measured by the semilogarithmic model assuming a zero of LVP decline and Texp (1/e) or Texp (1/2) derived from the exponential model are adequately sensitive for detecting acute myocardial ischemia due to coronary spasm.

Left ventricular diastolic pulsus alternans in hypertrophic cardiomyopathy.

We examined left ventricular (LV) diastolic pulsus alternans associated with systolic pulsus alternans in a patient with hypertrophic cardiomyopathy. Alternation in abnormal LV diastolic pressure waveforms persistently declining into mid-diastole (incomplete relaxation) and normal diastolic pressure were noted. Diastolic pulsus alternans was not corrected by isoproterenol and may possibly be independent of systolic pulsus alternans.