Neuroadrenergic activation and response to dobutamine in congestive heart failure secondary to idiopathic dilated cardiomyopathy.

Detection of contractile reserve is important in heart failure patients. To determine if detection of contractile reserve is influenced by neuroadrenergic activation, we examined the relation between dobutamine stress echocardiography (DSE) findings and plasma norepinephrine levels (NE) at rest in 35 patients with nonischemic left ventricular (LV) dysfunction (New York Heart Association class >III in all; LV ejection fraction 0.27 +/- 0.5). Changes in global wall motion score (WMS), and separately in WMS of hypokinetic segments and akinetic segments, were analyzed. A patient was considered to be responsive to dobutamine if the change in global WMS was >/=4. Twenty-three patients were responsive and 12 were not responsive to dobutamine. Plasma NE and baseline heart rate were significantly higher in nonresponsive patients (p <0.001). Changes in global WMS and in hypokinetic segment WMS were inversely related to either plasma NE (r -0.68 and -0.67, respectively) or baseline heart rate (r -0.60 and -0.66, respectively). The change in akinetic segment WMS was related to plasma NE only (r -0.50). Changes in WMS were not related to age, diastolic and systolic LV volume, baseline global WMS, or number of akinetic segments at baseline. Plasma NE >602 pg/ml predicted a blunted or absent contractile reserve at DSE (sensitivity 92%; specificity 87%). Neuroadrenergic activation may influence contractile reserve found at DSE in patients with heart failure due to nonischemic LV dysfunction.

Amlodipine in ischaemic left ventricular dysfunction with mild to moderate heart failure.

OBJECTIVE: In this study, we evaluated the effectiveness of amlodipine in patients with severe ischaemic left ventricular dysfunction (LVD) and mild to moderate heart failure, but not current angina, assessing the effects of the drug on symptoms, left ventricular function and exercise capacity. PATIENTS AND METHODS: We studied 36 patients with ischaemic LVD (radionuclide ejection fraction <40%, left ventricular end-diastolic dimension >60mm) and mild to moderate heart failure (NYHA class II or III) without angina treated with ACE inhibitors (36 of 36), digitalis (34 of 36) and diuretics (30 of 36). Among the 36 recruited patients, 33 fulfilled the study protocol, including 2 weeks of run-in (standard therapy), 8 weeks of treatment (standard therapy + amlodipine 5mg once daily) and 2 weeks of washout (standard therapy). Symptoms graded on a 10-point scale (heart failure score; a higher score representing improvement in symptoms), radionuclide left ventricular ejection fraction (rLVEF), echocardiographic left ventricular end-diastolic dimension (LVEDD), peak aerobic capacity (VO(2max)), exercise time (ET) and total work load (TWL) were measured after run-in, treatment and washout periods. All patients underwent coronary angiography and (201)Thallium (Tl) myocardial scintigraphy. RESULTS: With respect to baseline and washout, after amlodipine treatment the HF score improved (6.6 +/- 1.3 after amlodipine vs 5.9 +/- 1 at baseline and 5.9 +/- 1.1 at washout; p < 0.02), rLVEF increased (33.12 +/- 9.02% vs 29.74 +/- 7.72% and 30.02 +/- 7.39%, respectively; p < 0.001), and VO(2max) (14.35 +/- 4.05 ml/kg/min vs 12.68 +/- 3.21 ml/kg/min and 12.62 +/- 3.59 ml/kg/min, respectively; p < 0.003), ET (440 +/- 169 sec vs 395 +/- 158 sec and 402 +/- 162 sec, respectively; p < 0.02) and TWL (2183.2 +/- 439 kpm vs 1615.5 +/- 427 kpm and 1708.8 +/- 437 kpm, respectively; p < 0.01) were also increased. The increase in VO(2max) was related to systolic blood pressure at rest and at the peak of exercise, and to the presence of viable and/or ischaemic myocardium at (201)Tl myocardial scintigraphy. CONCLUSION: Amlodipine, in addition to standard therapy (including in all cases an ACE inhibitor), reduced symptoms and improved exercise capacity and ventricular function in patients with mild to moderate heart failure due to myocardial ischaemia. Thus, amlodipine is useful in patients with ischaemic LVD and heart failure without angina. The improvement in exercise capacity was greater in patients with scintigraphic evidence of viable and/or ischaemic myocardium and higher blood pressure. However, our study presented some limitations (i.e. an open study with few patients), and only generated a hypothesis that could lead to a wider, multicentre, cooperative trial. Treatment of patients with chronic ischaemic left ventricular dysfunction (LVD) with heart failure symptoms but without angina is a difficult clinical problem. Despite the fact that surgical myocardial revascularisation may improve survival, most patients are not good candidates for surgery. Thus, 'polypharmacy' remains the principal option for these individuals. ACE inhibitors have become a cornerstone in the treatment of all forms of LVD, and have been demonstrated to improve functional class and survival. Nitrates, digitalis and diuretics are also commonly used for their effects on symptoms. Despite there being no evidence that calcium antagonists are useful for the treatment of heart failure or impaired ventricular function after myocardial infarction, these drugs are still prescribed to many patients with ischaemic LVD. However, it is possible that the concomitant administration of ACE inhibitors could reduce the reflex neurohumoral activity caused by some calcium antagonists, while preserving some of the beneficial properties of these agents. Among other calcium antagonists, amlodipine does not adversely affect the clinical status of patients. Some studies have shown that it reduces symptoms, improves exercise tolerance and does not result in neurohormonal stimulation. Moreover, amlodipine appears to have a mortality benefit in patients with dilated cardiomyopathy but not in patients with underlying coronary disease where it appears to have a 'neutral' effect. Thus, it is not clear whether amlodipine is useful in patients with ischaemic LVD, particularly in patients with silent coronary artery disease. In this study, we evaluated the effectiveness of amlodipine, in addition to standard therapy, in patients with ischaemic LVD and mild to moderate heart failure, assessing the effects of the drug on symptoms, LV function and exercise capacity.