Pathological effects of alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

BACKGROUND: The pathological effects and the mechanisms of action of intracoronary administration of ethanol for alcohol septal ablation (ASA) for the management of hypertrophic obstructive cardiomyopathy (HOCM) are unknown. METHODS: We examined surgical specimens and, in one case, autopsy specimens from four patients who underwent surgical septal myectomy 2 days to 14 months after unsuccessful ASA. RESULTS: Pathological examination early after ASA showed coagulative necrosis of both the myocardium and the septal perforator arteries. Affected arteries were distended and occluded by necrotic intraluminal debris, without platelet-fibrin thrombi. Late after unsuccessful ASA, excised septal tissue was heterogeneous, containing a region of dense scar, and adjacent tissue containing viable myocytes and interspersed scar. CONCLUSIONS: Intracoronary administration of ethanol in patients with HOCM causes acute myocardial infarction with vascular necrosis. The coagulative necrosis of the arteries, their distension by necrotic debris and the absence of platelet-fibrin thrombi distinguish ethanol-induced infarction from that caused by atherosclerotic coronary artery disease. The direct vascular toxicity of ethanol may be an important aspect of the mechanism of successful ASA.

Comparison of the effects of nitric oxide, nitroprusside, and nifedipine on hemodynamics and right ventricular contractility in patients with chronic pulmonary hypertension.

STUDY OBJECTIVES: The effects of inhaled nitric oxide (NO) on hemodynamics and right ventricular (RV) contractility were compared with those of nitroprusside and nifedipine in 14 patients with severe chronic pulmonary hypertension. STUDY DESIGN: Micromanometer and balloon-tipped right heart catheterization were performed. Inhaled NO, IV nitroprusside, and sublingual nifedipine were administered sequentially while patients breathed > 90% oxygen. SETTING: Cardiac catheterization laboratory in a tertiary care teaching hospital. PATIENTS: Fourteen patients with severe pulmonary hypertension unrelated to left ventricular dysfunction. MEASUREMENTS AND RESULTS: During NO inhalation, mean systemic arterial pressure (MAP) was unchanged, but pulmonary artery (PA) pressure ([mean +/- SEM] 49 +/- 2 mm Hg vs 44 +/- 2 mm Hg; p < 0.01), pulmonary vascular resistance (PVR; 829 +/- 68 vs 669 +/- 64 dyne x s x cm(-5); p < 0.01) and RV end-diastolic pressure (RVEDP; 12 +/- 1 vs 10 +/- 1 mm Hg; p < 0.01) decreased. Stroke volume index (SVI; 31 +/- 2 vs 35 +/- 3 mL/m(2); p < 0.05) increased, and the first derivative of RV pressure at 15 mm Hg developed pressure (RV +dP/dt at DP15) was unchanged. During nitroprusside administration, MAP decreased (105 +/- 5 vs 76 +/- 5 mm Hg; p < 0.01), PA was unchanged (48 +/- 2 vs 45 +/- 3 mm Hg; p = not significant), and PVR decreased (791 +/- 53 vs 665 +/- 53 dyne x s x cm(-5); p < 0.01). RV +dP/dt at DP15 increased (425 +/- 22 vs 465 +/- 29 mm Hg/s; p < 0.05), but SVI was unchanged. Nifedipine decreased MAP (103 +/- 5 vs 94 +/- 5 mm Hg; p < 0.01), PA and PVR were unchanged, RVEDP increased (12 +/- 1 vs 14 +/- 2 mm Hg; p < 0.01), and RV +dP/dt at DP15 decreased (432 +/- 90 vs 389 +/- 21 mm Hg/s; p < 0.05). CONCLUSIONS: Inhaled NO is a selective pulmonary vasodilator in patients with chronic pulmonary hypertension that improves cardiac performance without altering RV contractility. Nitroprusside caused a similar degree of pulmonary vasodilation. In contrast to inhaled NO, nitroprusside caused systemic hypotension associated with an increase in RV contractility. Acute administration of nifedipine did not cause pulmonary vasodilation, but RVEDP increased and RV contractility decreased.

Outcome following isolated tricuspid valve replacement.

OBJECTIVES: The clinical outcome of isolated tricuspid valve replacement is not well defined because this procedure is usually performed concomitantly with other valve surgery. METHODS: We retrospectively studied the short and long-term outcome of 15 consecutive patients (six men and nine women, aged 61+/-3 years) undergoing isolated tricuspid valve replacement from 1984 to 1996. The cause of valve dysfunction was rheumatic heart disease in 12 patients, healed endocarditis in two patients, and sarcoidosis in one patient. The tricuspid valve was stenotic in one patient, regurgitant in eight patients, and both stenotic and regurgitant in six patients. A St. Jude Medical prosthesis was placed in eight patients, Carpentier-Edwards in five patients, and Björk-Shiley and Starr-Edwards in one patient each. RESULTS: The median survival was only 1.2 years. Three patients (20%) died < or =30 days after the surgery or before discharge, and six other patients (40%) died within 3 years of surgery. Anasarca was the only predictor of short-term mortality (P=0.03), while the predictors of long-term mortality were anemia (P=0.01), rheumatic heart disease (P=0.04), previous stroke (P=0.04), and previous mitral valve surgery (P=0.04). CONCLUSIONS: Isolated tricuspid valve replacement is characterized by a poor short and long-term outcome.

Coronary endothelial dysfunction in patients with acute-onset idiopathic dilated cardiomyopathy.

OBJECTIVES: This study sought to determine whether coronary endothelial dysfunction exists in patients with acute-onset idiopathic dilated cardiomyopathy (DCM) and to explore its relation to recovery of left ventricular systolic function in this patient population. BACKGROUND: Coronary endothelial dysfunction exists in chronic DCM, but its importance in the development and progression of ventricular dysfunction is not known. To address this issue we studied coronary endothelial function in patients with idiopathic DCM <6 months in duration and explored the relation between coronary endothelial function and subsequent changes in left ventricular ejection fraction (LVEF). METHODS: Ten patients with acute-onset idiopathic DCM (duration of heart failure symptoms 2.0 +/- 0.4 months [mean +/- SEM]) and 11 control patients with normal left ventricular function underwent assessment of coronary endothelial function during intracoronary administration of the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator adenosine. Coronary cross-sectional area (CSA) was determined by quantitative coronary angiography and coronary blood flow (CBF) by the product of coronary CSA and CBF velocity measured by an intracoronary Doppler catheter. Patients with DCM underwent assessment of left ventricular function before and several months after the study. RESULTS: Acetylcholine infusion produced no change in coronary CSA in control patients but significant epicardial constriction in patients with DCM (-36 +/- 11%, p < 0.01). These changes were associated with increases in CBF in control patients (+118 +/- 49%, p < 0.01) but no change in patients with DCM. Infusion of adenosine produced increases in coronary caliber and blood flow in both groups. Follow-up assessment of left ventricular function was obtained in nine patients with DCM 7.0 +/- 1.7 months after initial study, at which time LVEF had improved by > or =0.10 in four patients. Multiple linear regression revealed a positive correlation between both the coronary CSA (r2 = 0.57, p < 0.05) and CBF (r2 = 0.68, p < 0.01) response to acetylcholine and the subsequent improvement in LVEF. CONCLUSIONS: Coronary endothelial dysfunction exists at both the microvascular and the epicardial level in patients with acute-onset idiopathic DCM. The preservation of coronary endothelial function in this population is associated with subsequent improvement in left ventricular function.

Hemodynamic effects of inhaled nitric oxide in heart failure.

OBJECTIVES: This study was performed to assess the utility of inhaled nitric oxide as a selective pulmonary vasodilator in patients with severe chronic heart failure and to compare its hemodynamic effects with those of nitroprusside, a nonselective vasodilator. BACKGROUND: Preoperative pulmonary vascular resistance is a predictor of right heart failure after heart transplantation. Non-selective vasodilators administered preoperatively to assess the reversibility of pulmonary vasoconstriction cause systemic hypotension, limiting their utility. METHODS: Systemic and pulmonary hemodynamic measurement were made at baseline, during oxygen inhalation and with the addition of graded doses of inhaled nitric oxide or intravenous nitroprusside in 16 patients with New York Heart Association class III or IV heart failure referred for heart transplantation. RESULTS: Pulmonary vascular resistance decreased to a greater extent with 80 ppm nitric oxide (mean +/- SEM 256 +/- 41 to 139 +/- 14 dynes.s.cm-5) than with the maximally tolerated dose of nitroprusside (264 +/- 49 to 169 +/- 30 dynes.s.cm-5, p < 0.05, nitric oxide vs. nitroprusside). Pulmonary capillary wedge pressure increased with 80 ppm nitric oxide (26 +/- 2 to 32 +/- 2 mm Hg, p < 0.05). Mean arterial pressure did not change with nitric oxide but decreased with nitroprusside. Seven of the 16 patients, including 1 patient who did not have an adequate decrease in pulmonary vascular resistance with nitroprusside but did with nitric oxide, have undergone successful heart transplantation. CONCLUSIONS: Inhaled nitric oxide is a selective pulmonary vasodilator in patients with pulmonary hypertension due to left heart failure and may identify patients with reversible pulmonary vasoconstriction in whom agents such as nitroprusside cause systemic hypotension. Inhaled nitric oxide causes an increase in left ventricular filling pressure by an unknown mechanism.

Effects of atrial natriuretic peptide on left ventricular function in hypertension.

Atrial natriuretic peptide (ANP) has natriuretic and vasodilator actions that lower arterial pressure and may be beneficial to hypertensive patients. To assess the effects of ANP on left ventricular function in patients with hypertension, we compared it with the pure vasodilator nitroprusside. Simultaneous left ventricular micromanometer pressure and radionuclide volume were obtained at baseline, during nitroprusside infusion, during a second baseline period, and during ANP infusion in 10 patients with hypertension. Mean arterial pressure fell during ANP and nitroprusside. Heart rate and plasma norepinephrine levels increased by similar amounts during the two agents, whereas cardiac index and stroke volume index were unchanged during both. Peak positive left ventricular dP/dt fell similarly during ANP and nitroprusside, but left ventricular dP/dt at a developed pressure of 40 mm Hg, a less load-dependent index of contractility, was unchanged during both. The relation between end-systolic pressure and volume during ANP infusion was not shifted leftward or rightward from that during nitroprusside infusion, indicating no inotropic effect. Both ANP and nitroprusside shortened at time constant of isovolumic relaxation calculated by the logarithmic method but did not change the time constant calculated by the derivative method. Peak filling rate was unchanged from baseline during both agents. ANP did not shift the end-diastolic pressure-volume point away from the relation constructed from baseline and nitroprusside points. We conclude that ANP has no direct effect on myocardial contractile or diastolic function in patients with hypertension.

Exercise capacity and systolic and diastolic ventricular function after recovery from acute dilated cardiomyopathy.

OBJECTIVES: This study was undertaken to determine whether abnormalities in exercise capacity or ventricular function persist after recovery from acute dilated cardiomyopathy. BACKGROUND: Persistent ventricular structural abnormalities could cause abnormalities in exercise capacity or ventricular function. METHODS: The results of rest and exercise first-pass radionuclide ventriculography in 18 patients who were seen within 6 months of the onset of dilated cardiomyopathy and subsequently had a normal rest left ventricular ejection fraction were compared with those of age- and gender-matched control subjects. RESULTS: Patients were studied 144 +/- 34 (mean +/- SEM) days after the onset of left ventricular dysfunction at a time when heart failure symptoms had resolved. Patients with myocyte necrosis, as assessed by endomyocardial biopsy (n = 13) or antimyosin scintigraphy (n = 12), recovered more rapidly than did those without necrosis. Oxygen consumption both at peak exercise (17.7 +/- 1.2 vs. 26.1 +/- 1.5 ml/kg per min, p < 0.05) and at the anaerobic threshold (11.1 +/- 0.5 vs. 17.1 +/- 1.3 ml/kg per min, p < 0.05) was lower in the patients who had recovered from cardiomyopathy than in control subjects. Rest and exercise end-systolic and end-diastolic left ventricular volumes were greater in the patients than in the control subjects, although stroke volumes were similar. Left ventricular filling at rest was lower at diastolic filling intervals of 40% and 90%, and rest and exercise left ventricular early peak filling rate normalized for end-diastolic volume was slower in the patients than in the control subjects. At long-term follow-up of 1,082 +/- 206 days, two patients had a return of heart failure symptoms and a decrease in left ventricular ejection fraction. CONCLUSIONS: Despite the apparent normalization of rest left ventricular ejection fraction, patients who have recovered from dilated cardiomyopathy have abnormalities in aerobic exercise capacity and in left ventricular systolic and diastolic performance.

Continuous wave Doppler echocardiography for noninvasive assessment of left ventricular dP/dt and relaxation time constant from mitral regurgitant spectra in patients.

OBJECTIVES: We previously demonstrated experimentally that the mitral regurgitant velocity spectrum can be used to estimate left ventricular pressure throughout systole and may provide a new noninvasive method for estimating maximal dP/dt and the relaxation time constant. This study was designed to test this method in patients. BACKGROUND: The maximal first derivative of left ventricular pressure (dP/dt) and the time constant of left ventricular isovolumetric relaxation (tau) are important variables of left ventricular function, but the need for invasive measurement with high fidelity catheters has limited their use in clinical cardiology. METHODS: Twelve patients with mitral regurgitation were studied. The Doppler mitral regurgitant velocity spectrum was recorded simultaneously with micromanometer left ventricular pressure tracings in all patients. The regurgitant velocity profiles were digitized and converted to ventriculoatrial (VA) pressure gradient curves using the simplified Bernoulli equation and differentiated into instantaneous dP/dt. The relaxation time constant (tau) was calculated assuming a zero pressure asymptote from catheter left ventricular pressure decay (tau c) and from the Doppler-derived VA gradient curve with corrections. Two methods were used to correct the Doppler gradient curve to better approximate the left ventricular pressure decay before calculating the relaxation time constant: 1) adding an arbitrary 10 mm Hg (tau 10), and 2) adding the actual mean pulmonary capillary pressure (tau LA). RESULTS: The Doppler-derived maximal positive dP/dt (1,394 +/- 302 mm Hg/s [mean +/- SD]) correlated well (r = 0.91) with the catheter-derived maximal dP/dt (1,449 +/- 307 mm Hg/s). Although the Doppler-derived negative maximal dP/dt differed slightly from catheter measurement (1,014 +/- 289 vs. 1,195 +/- 354 mm Hg/s, p < 0.01), the correlation between Doppler and catheter measurements was similarly good (r = 0.89, p < 0.0001). The correlation between tau 10 and tau c was excellent (r = 0.93, p < 0.01), but the Doppler-derived tau 10 (50.0 +/- 11.0 ms) slightly underestimated the catheter-derived tau c (55.5 +/- 12.8 ms, p < 0.01). This slight underestimation could be corrected by adding the actual pulmonary capillary wedge pressure to the Doppler gradient curve. CONCLUSIONS: Doppler echocardiography provides an accurate and reliable method for estimating left ventricular maximal positive dP/dt, maximal negative dP/dt and the relaxation time constant (tau) in patients with mitral regurgitation.

Long-term outcome of enoximone therapy in patients with refractory heart failure.

Few options are available for patients with severe heart failure that is unresponsive to therapy with digoxin, diuretics, and vasodilators. The clinical responses and predictors of survival were studied in 41 consecutive patients with New York Heart Association (NYHA) class IV heart failure during long-term oral enoximone therapy (mean dose 232 +/- 15 mg/day). The mean age was 60 +/- 1 years, and the initial left ventricular ejection fraction was 0.19 +/- 0.01. The cause of heart failure was either coronary artery disease (n = 23) or dilated cardiomyopathy (n = 18). Symptomatic improvement occurred in the majority (83%) of patients; 24% improved two or more NYHA classes. Although the 12-month mortality rate for the entire group was high (54 +/- 8%), a subgroup of patients with dilated cardiomyopathy achieved a sustained benefit with a decrease in symptoms > 1 NYHA class, fewer hospitalizations, and a survival rate at 24 months of 60%. Multivariate analysis identified the cause of heart failure, left ventricular ejection fraction, and clinical improvement within 60 days of enoximone therapy as predictors of a favorable long-term outcome. The presence of coronary artery disease was most predictive of early mortality (p < 0.0002), with only 5% of patients surviving > 18 months compared to 66% of those with dilated cardiomyopathy. Median survival rates were 132 +/- 31 and 921 +/- 214 days (p < 0.001) for the coronary artery disease and dilated cardiomyopathy populations, respectively. Oral enoximone can provide symptomatic improvement and a palliative option for the majority of patients with refractory heart failure resulting from cardiomyopathy.

Effects of dobutamine on Gorlin and continuity equation valve areas and valve resistance in valvular aortic stenosis.

Previous studies demonstrated changes in aortic valve area calculated by the Gorlin equation under conditions of varying transvalvular flow in patients with valvular aortic stenosis (AS). To distinguish between flow-dependence of the Gorlin formula and changes in actual orifice area, the Gorlin valve area and 2 other measures of severity of AS, continuity equation valve area and valve resistance, were calculated under 2 flow conditions in 12 patients with AS. Transvalvular flow rate was varied by administration of dobutamine. During dobutamine infusion, right atrial and left ventricular end-diastolic pressures decreased, left ventricular peak systolic pressure and stroke volume increased, and systolic arterial pressure did not change. Heart rate increased by 19%, cardiac output by 38% and mean aortic valve gradient by 25%. The Gorlin valve area increased in all 12 patients by 0.03 to 0.30 cm2. The average Gorlin valve area increased from 0.67 +/- 0.05 to 0.79 +/- 0.06 cm2 (p < 0.001). In contrast, the continuity equation valve area (calculated in a subset of 6 patients) and valve resistance did not change with dobutamine. The data support the conclusion that flow-dependence of the Gorlin aortic valve area, rather than an increase in actual orifice area, is responsible for the finding that greater valve areas are calculated at greater transvalvular flow rates. Valve resistance is a less flow-dependent means of assessing severity of AS.

Positive inotropic and lusitropic effects of intravenous flosequinan in patients with heart failure.

OBJECTIVES: This study was designed to assess the direct effects of flosequinan on myocardial function. BACKGROUND: Flosequinan has been shown to improve symptoms and exercise tolerance in patients with heart failure. Although previous studies have established that flosequinan is a vasodilator, it is not known to what extent direct actions of the drug on myocardial contractility or diastolic properties contribute to its beneficial hemodynamic effects. METHODS: Nitroprusside and intravenous flosequinan were administered sequentially to 18 patients with severe heart failure (New York Heart Association functional class III or IV, left ventricular ejection fraction 0.14 +/- 0.02). Micromanometer left ventricular pressure and radionuclide volume data were combined to construct pressure-volume loops during 1) a baseline period, 2) nitroprusside infusion, 3) a second baseline period, and 4) flosequinan infusion. RESULTS: The peak rate of left ventricular pressure development increased from 899 +/- 84 to 1,070 +/- 94 mm Hg/s (p less than 0.05) with flosequinan. The baseline left ventricular end-systolic pressure-volume relation was constructed in 15 patients from the two baseline pressure-volume loops and from that obtained during afterload manipulation with nitroprusside. During flosequinan administration, the relation between end-systolic pressure and volume was shifted upward and leftward, indicating enhanced contractility, in 14 of 15 patients (p less than 0.001). The maximal rate of decrease in left ventricular pressure during isovolumetric relaxation increased in magnitude with flosequinan from 882 +/- 63 to 1,026 +/- 68 mm Hg/s (p less than 0.05). CONCLUSIONS: These results indicate that intravenous flosequinan has positive inotropic and lusitropic effects in patients with heart failure. Further studies are needed to assess the direct myocardial effects of oral flosequinan.

Effects of atrial natriuretic peptide on myocardial contractile and diastolic function in patients with heart failure.

Atrial natriuretic peptide alters left ventricular performance in patients with heart failure. To assess the direct effects of this hormone on myocardial function, its actions were compared with those of the pure vasodilator nitroprusside in 10 patients with heart failure. Simultaneous left ventricular micromanometer pressure and radionuclide volume were obtained during a baseline period, during nitroprusside infusion, during a second baseline period and during atrial natriuretic peptide infusion. The baseline end-systolic pressure-volume relation was generated in nine patients from pressure-volume loops obtained during the two baseline periods and during afterload reduction with nitroprusside. Mean arterial pressure decreased with atrial natriuretic peptide (89 +/- 3 to 80 +/- 2 mm Hg, p less than 0.05) and by a greater amount with nitroprusside (90 +/- 4 to 73 +/- 3 mm Hg, p less than 0.05). Left ventricular end-diastolic pressure also decreased with atrial natriuretic peptide (24 +/- 2 to 16 +/- 3 mm Hg, p less than 0.05) and by a greater amount with nitroprusside (24 +/- 2 to 13 +/- 3 mm Hg, p less than 0.05). Cardiac index increased during infusion of each agent from 2.0 +/- 0.2 to 2.4 +/- 0.2 liters/min per m2 (p less than 0.01). Heart rate increased slightly with nitroprusside but did not change with atrial natriuretic peptide. Peak positive first derivative of left ventricular pressure (dP/dt), ejection fraction and stroke work index were unchanged by either agent. The relation between end-systolic pressure and volume during atrial natriuretic peptide infusion was shifted slightly leftward from the baseline value in four patients, slightly rightward in four and not at all in one patient, indicating no consistent inotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)