Giovanna Branzi

Intermittent levosimendan infusions in advanced heart failure: favourable effects on left ventricular function, neurohormonal balance, and one-year survival.

Abstract: The role of repeated infusions of Levosimendan (LEVO) in patients with chronic advanced heart failure is still unclear. Thirty-three patients with chronic heart failure presenting clinical deterioration were randomized 2:1 to receive monthly infusions of LEVO (n = 22) or Furosemide (Controls, n = 11). At the first drugs administration, noninvasive hemodynamic evaluation was performed; before and after each infusion, we assessed NYHA class, systolic and diastolic function, functional mitral regurgitation, and brain natriuretic peptide (BNP) levels. Noninvasive hemodynamic in the LEVO group showed vasodilation and decrease in thoracic conductance (index of pulmonary congestion), whereas in Controls, only a reduced thoracic conductance was observed. In the LEVO group, systolic and diastolic function, ventricular volumes, severity of mitral regurgitation, and BNP levels improved over time from baseline and persisted 4 weeks after the last infusion (P < 0.01). In Controls, no change developed over time in cardiac function and BNP levels. In LEVO-treated patients, 1-year mortality tended to be lower than in those treated with Furosemide. In conclusion, serial LEVO infusions in advanced heart failure improved ventricular performance and favorably modulated neurohormonal activation. Multicenter randomized studies are warranted to test the effect of LEVO on long-term outcome.

Long-term Treatment with the β-Blocker Carvedilol Restores Autonomic Tone and Responsiveness in Patients with Moderate Heart Failure

The authors performed two studies on the effects of carvedilol on autonomic tone and responsiveness in patients with heart failure. In study 1, the autonomic responses of 25 patients (age, 60 years+/-2; New York Heart Association [NYHA] class, 2.6+/-0.5; pVO2, 16.6 mL/Kg/min+/-1.1) treated with angiotensin-converting enzyme inhibitors, diuretics, and carvedilol (38.0 mg/d+/-2.5) were compared to those of 25 patients of similar age, therapy, NYHA class, and pVO2 in whom carvedilol was not yet administered. In study 2, autonomic tone and responsiveness were studied in 20 patients (age, 57 years+/-9; NYHA class, 2.5+/-0.2; pVO2, 15.6 mL/Kg/min+/-3.4), before and 6 months after additional carvedilol treatment (40.0 mg/d+/-12.5). Autonomic evaluation was performed with autoregressive power spectral analysis of RR variability during 10 minutes of supine rest (control), breathing 20 times per minute (vagal stimulus), and standing (sympathetic activation). The ratio between low-frequency (LF) and high-frequency (HF) components of the autospectra indicated the sympathovagal interaction. In study 1, spectral analysis in controls showed sympathetic hyperactivity which was blunted in patients receiving carvedilol (LF/HF ratio: 10.4+/-1.4 vs. 7.0+/-1.1; P<0.05) who responded to vagal and adrenergic stimuli (LF/HF, -35% with regular breathing and 72% standing). In study 2, left ventricular function, volumes, and exercise performance improved with carvedilol (EF, 31%; EDLV volume, -22%; pVO2, 11%; P<0.05). Sympathetic hyperactivity in control was reduced (LF/HF ratio, 4.9+/-0.8 from 7.9+/-1.3; P<0.05), whereas a response to vagal and adrenergic activation on breathing and standing reemerged (LF/HF ratio, -31% during regular breathing and 88% on standing). Therefore, combined autonomic and hemodynamic effects may determine the favorable effects of beta-blockers in heart failure.

Markers of electrical instability in hypertensive patients with and without ventricular arrhythmias. Are they useful in identifying patients with different risk profiles

Background Markers of electrical instability of the ventricular myocardium, namely abnormal repolarization and late potentials, are frequently observed in patients with hypertension when both ventricular arrhythmias and left ventricular hypertrophy are present. This information cannot be extrapolated to the population of hypertensive patients with ventricular arrhythmias but without left ventricular hypertrophy. Objective To evaluate QT duration, QT dispersion and the incidence of ventricular late potentials in patients with essential hypertension, already on anti-hypertensive therapy, both with and without non-sustained ventricular arrhythmia. Design The study population consisted of 49 patients with essential hypertension who were compared to 89 control normotensive subjects both with and without frequent (> 30 per h) ventricular ectopic beats (VPBs). Patients were divided into four groups: (1) hypertensive patients without VPBs (H, n = 19), (2) hypertensive patients with VPBs (HA, n = 30), (3) normotensive subjects without VPBs (C, n = 28), and (4) normotensive subjects with VPBs (CA, n = 61). Methods Echocardiographic parameters, QT interval, QT dispersion and signal-averaged ECG were evaluated without withdrawing anti-hypertensive drugs. Results In no case was left ventricular hypertrophy documented. The number of VPBs during 24 h Holter recording (median 11 343 versus 7617) and the incidence of repetitive VPBs (37 versus 46% of patients) were similar in the two groups of patients (HA versus CA). Signal-averaged ECG parameters were normal and not different between the four groups. QT interval was longer in hypertensive patients compared to controls irrespective of the presence of VPBs. QT dispersion was slightly greater in subjects with VPBs, both hypertensive and normotensive, compared to subjects without arrhythmias. Conclusions In patients with hypertension well-controlled by drug therapy and without left ventricular hypertrophy, frequent VPBs are not associated with markers indicating an electrophysiological substrate for re-entrant arrhythmias. However, QT prolongation suggests the persistence of a higher risk of cardiovascular mortality that is independent of the presence of VPBs.

Different ventricular remodelling and autonomic modulation after long-term beta-blocker treatment in hypertensive, ischaemic and idiopathic dilated cardiomyopathy.

Objective In this retrospective analysis, we investigated the influence of aetiology on autonomic modulation and reverse ventricular remodelling induced by β-blockade in heart failure. Methods Twenty-three heart failure patients without comorbidities (mean age 61 ± 4 years, New York Heart Association class 3.1 ± 0.1, treated with angiotensin-converting enzyme inhibitors and diuretics) were divided into three groups according to aetiology: hypertensive (group 1, n = 7), ischaemic (group 2, n = 6), and idiopathic (group 3, n = 10). Before and after 6 months of carvedilol (53 ± 10 mg/day), patients underwent cardiopulmonary test, echocardiography and autonomic evaluation with spectral analysis of RR variability (10 min of rest plus 10 min of standing: the low frequency/high frequency ratio between low and high frequency components of each spectrum was the index of sympathovagal balance). Results Carvedilol improved New York Heart Association class and exercise performance. In group 1, ejection fraction and left ventricular end-diastolic volume normalised, and interventricular septum thickness increased. No remodelling occurred in group 2. In group 3, interventricular septum thickness was unchanged, ejection fraction and left ventricular end-diastolic volume improved. Also autonomic modulation differed. At baseline, adrenergic activation was observed either at rest or during standing. After carvedilol treatment, group 1 did not show any change in the low frequency/high frequency ratio in both conditions, whereas groups 2 and 3 showed reduced adrenergic activation at rest and normal response to standing. Conclusions Despite favourable ventricular remodelling, the poor autonomic modulation observed with β-blockade indicates a persistent central adrenergic activation in hypertensive heart failure patients.

Prognostic value of noninvasive hemodynamic evaluation of the acute effect of levosimendan in advanced heart failure

Aims Optimization of inotropic treatment in worsening heart failure sometimes requires invasive hemodynamic assessment in selected patients. Impedance cardiography (ICG) may be useful for a noninvasive hemodynamic evaluation. Methods ICG was performed in 40 patients (69u200a±u200a8 years; left ventricular ejection fraction 27.5u200a±u200a5.6%; New York Heart Association 3.18u200a±u200a0.34; Interagency Registry for Mechanically Assisted Circulatory Support 5.48u200a±u200a0.96, before and after infusion of Levosimendan (0.1–0.2u200a&mgr;g/kg per min for up to 24u200ah). Echocardiogram, ICG [measuring cardiac index (CI), total peripheral resistances (TPRs) and thoracic fluid content (TFC)] and plasma levels of brain natriuretic peptide (BNP) were obtained; in nine patients, right heart catheterization was also carried out. Results When right catheterization and ICG were performed simultaneously, a significant relationship was observed between values of CI and TPR, and between TFC and pulmonary wedge pressure. ICG detected the Levosimendan-induced recovery of the hemodynamic status, associated with improved systolic and diastolic function and reduction in BNP levels. One-year mortality was 4.4%. At multivariate analysis, independent predictors of mortality were: no improvement in the severity of mitral regurgitation, a persistent restrictive filling pattern (E/E’u200a>u200a15), a reduction of BNP levels below 30% and a change below 10% in CI, TPR and TFC. When combined, absence of hemodynamic improvement at ICG could predict 1-year mortality with better sensitivity (86%) and specificity (85%) than the combination of echocardiographic and BNP criteria only (sensitivity 80% and specificity 36%). Conclusion Noninvasive hemodynamic evaluation of heart failure patients during infusion of inodilator drugs is reliable and may help in their prognostic stratification.