Inotropic effect of nicardipine in patients with heart failure: Assessment by left ventricular end-systolic pressure-volume analysis

AbstractNicardipine, a new dihydropyridine calcium channel blocker, has been investigated for the treatment of coronary artery disease and heart failure. To assess the inotropic effect of nicardipine in humans independent of its vasodilator effect, equihypotensive doses of intravenous nitroprusside (mean infusion rate 65 ± 13 μg/min) and nicardipine (mean dose 5.2 ± 0.4 mg) were administered to 15 patients with heart failure (New York Heart Association functional classes II to IV, radionuclide left ventricular ejection fraction 0.15 ± 0.02). Left ventricular micromanometer pressure and simultaneous radionuclide left ventricular volume were obtained at baseline, during nitroprusside infusion, during a second baseline period and during nicardipine infusion.Heart rate did not change significantly with either nitroprusside or nicardipine. Mean systemic arterial pressure decreased by an average of 21 mm Hg with both drugs. A greater decrease in left ventricular end-diastolic pressure occurred with nitroprusside (27 ± 2 to 14 ± 2 mm Hg, p < 0.01) than with nicardipine (27 ± 2 to 23 ± 3 mm Hg, p < 0.05), and pulmonary capillary wedge pressure decreased significantly only with nitroprusside. Cardiac index increased from 1.8 ± 0.1 to 2.1 ± 0.1 liters/min per m2(p < 0.05) with nitroprusside and to a greater extent from 1.7 ± 0.1 to 2.4 ± 0.1 liters/min per m2(p < 0.01) with nicardipine. Left ventricular ejection fraction increased with nicardipine (0.15 ± 0.01 to 0.19 ± 0.01, p < 0.01), but not with nitroprusside.Peak positive first derivative of left ventricular pressure (dP/dt) decreased by 9% with both agents. Left ventricular pressure-volume loops were constructed for 14 patients. In 12 patients, the left ventricular end-systolic pressure-volume relation was shifted rightward with nicardipine, indicating a negative inotropic effect, with no shift in the remaining 2 patients.Thus, nicardipine has a negative inotropic effect in patients with heart failure. Despite this effect, left ventricular ejection fraction and cardiac index increased with nicardipine. This overall improvement in ventricular systolic performance was due to a reduction in afterload

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

AbstractObjectives. 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 ≥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

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

AbstractAtrial 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 < 0.05) and by a greater amount with nitroprusside (90 ± 4 to 73 ± 3 mm Hg, p < 0.05). Left ventricular end-diastolic pressure also decreased with atrial natriuretic peptide (24 ± 2 to 16 ± 3 mm Hg, p < 0.05) and by a greater amount with nitroprusside (24 ± 2 to 13 ± 3 mm Hg, p < 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 < 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. Both agents shortened the time constant of isovolumetric relaxation calculated by the logarithmic method, but only nitroprusside shortened the time constant calculated by the derivative method. Peak filling rate was unchanged from baseline with either agent. Atrial natriuretic peptide did not shift the end-diastolic pressure-volume point away from the relation constructed from baseline and nitroprusside points.It is concluded that atrial natriuretic peptide has no direct effect on myocardial contractile or diastolic function in patients with heart failure

A clinical and histopathologic comparison of cardiac sarcoidosis and idiopathic giant cell myocarditis

The goal of this study was to determine the prognostic value of clinical data available at presentation and histology in cardiac sarcoidosis (CS) and idiopathic giant cell myocarditis (IGCM). The prognosis of patients with nonischemic cardiomyopathy is partly dependent on the histologic diagnosis. Survival in IGCM is poor. The prognosis of a histologically related entity, cardiac sarcoidosis (CS), is less well established, and the prognostic value of the distinction between CS and IGCM on endomyocardial biopsy (EMB) is unknown. We identified 115 patients from the Multicenter IGCM Registry with CS (n = 42) and IGCM (n = 73). We compared the clinical data for these two groups using Cox proportional-hazards models to assess the association between histologic diagnosis and survival. In order to determine whether histologic features could reliably differentiate these two entities, two cardiac pathologists semiquantitatively graded the inflammatory infiltrate components and compared the results between groups. Black race was more frequent in the CS group (31% vs. 4%, p < 0.0001). Syncope and atrioventricular block were also more frequently observed in CS than IGCM (31% vs. 5%, p = 0.0002 and 50% vs. 15%, p < 0.0001, respectively). Left-sided heart failure was more common in IGCM (40% vs. 64%, p = 0.013). In CS patients diagnosed by EMB, the five-year transplant-free survival after diagnosis was 69.8% versus 21.9% for IGCM (p < 0.0001, log-rank test). In multivariate models, presentation with heart failure predicted IGCM, and presentation with heart block or more than nine weeks of symptoms predicted CS. Eosinophils, myocyte damage, and foci of lymphocytic myocarditis were more frequent in IGCM, while granulomas and fibrosis were more frequent in CS. Transplant-free survival is better for patients with CS than for IGCM diagnosed by EMB. Presentation with heart failure predicted IGCM, and presentation with heart block or more than nine weeks of symptoms predicted CS