Savina Nodari

The Global Health and Economic Burden of Hospitalizations for Heart Failure: Lessons Learned From Hospitalized Heart Failure Registries

Heart failure is a global pandemic affecting an estimated 26 million people worldwide and resulting in more than 1 million hospitalizations annually in both the United States and Europe. Although the outcomes for ambulatory HF patients with a reduced ejection fraction (EF) have improved with the discovery of multiple evidence-based drug and device therapies, hospitalized heart failure (HHF) patients continue to experience unacceptably high post-discharge mortality and readmission rates that have not changed in the last 2 decades. In addition, the proportion of HHF patients classified as having a preserved EF continues to grow and may overtake HF with a reduced EF in the near future. However, the prognosis for HF with a preserved EF is similar and there are currently no available disease-modifying therapies. HHF registries have significantly improved our understanding of this clinical entity and remain an important source of data shaping both public policy and research efforts. The authors review global HHF registries to describe the patient characteristics, management, outcomes and their predictors, quality improvement initiatives, regional differences, and limitations of the available data. Moreover, based on the lessons learned, they also propose a roadmap for the design and conduct of future HHF registries.

Differential Effects of β-Blockers in Patients With Heart Failure: A Prospective, Randomized, Double-Blind Comparison of the Long-Term Effects of Metoprolol Versus Carvedilol

BACKGROUND Both metoprolol and carvedilol produce hemodynamic and clinical benefits in patients with chronic heart failure; carvedilol exerts greater antiadrenergic effects than metoprolol, but it is unknown whether this pharmacological difference results in hemodynamic and clinical differences between the 2 drugs. METHODS AND RESULTS We randomized 150 patients with heart failure (left ventricular ejection fraction </=0.35) to double-blind treatment with either metoprolol or carvedilol. When compared with metoprolol (124+/-55 mg/d), patients treated with carvedilol (49+/-18 mg/d) showed larger increases in left ventricular ejection fraction at rest (+10.9+/-11.0 versus +7.2+/-7.7 U, P=0.038) and in left ventricular stroke volume and stroke work during exercise (both P<0. 05) after 13 to 15 months of treatment. In addition, carvedilol produced greater decreases in mean pulmonary artery pressure and pulmonary wedge pressure, both at rest and during exercise, than metoprolol (all P<0.05). In contrast, the metoprolol group showed greater increases in maximal exercise capacity than the carvedilol group (P=0.035), but the 2 drugs improved symptoms, submaximal exercise tolerance, and quality of life to a similar degree. After a mean of 23+/-11 months of follow-up, 21 patients in the metoprolol group and 17 patients in the carvedilol group died or underwent urgent transplantation. CONCLUSIONS The present study demonstrates that during long-term therapy, carvedilol improves cardiac performance to a greater extent than metoprolol when administered to patients with heart failure in the doses shown to be effective in clinical trials. These differences were likely related to a greater antiadrenergic activity of carvedilol.

Worsening renal function in patients hospitalised for acute heart failure: Clinical implications and prognostic significance

Renal function is a powerful prognostic variable in patients with heart failure (HF). Hospitalisations for acute HF (AHF) may be associated with further worsening of renal function (WRF).

Differential Effects of β-Blockers in Patients With Heart Failure

Background—Both metoprolol and carvedilol produce hemodynamic and clinical benefits in patients with chronic heart failure; carvedilol exerts greater antiadrenergic effects than metoprolol, but it is unknown whether this pharmacological difference results in hemodynamic and clinical differences between the 2 drugs. Methods and Results—We randomized 150 patients with heart failure (left ventricular ejection fraction ≤0.35) to double-blind treatment with either metoprolol or carvedilol. When compared with metoprolol (124±55 mg/d), patients treated with carvedilol (49±18 mg/d) showed larger increases in left ventricular ejection fraction at rest (+10.9±11.0 versus +7.2±7.7 U, P=0.038) and in left ventricular stroke volume and stroke work during exercise (both P<0.05) after 13 to 15 months of treatment. In addition, carvedilol produced greater decreases in mean pulmonary artery pressure and pulmonary wedge pressure, both at rest and during exercise, than metoprolol (all P<0.05). In contrast, the metoprolol gr...

Beta-blocker therapy influences the hemodynamic response to inotropic agents in patients with heart failure: A randomized comparison of dobutamine and enoximone before and after chronic treatment with metoprolol or carvedilol

OBJECTIVE We compared the hemodynamic effects of dobutamine and enoximone administration before and after long-term beta-blocker therapy with metoprolol or carvedilol in patients with chronic heart failure (HF). BACKGROUND Patients with HF on beta-blocker therapy may need hemodynamic support with inotropic agents, and the hemodynamic response may be influenced by both the inotropic agent and the beta-blocker used. METHODS The hemodynamic effects of dobutamine (5 to 20 microg/kg/min intravenously) and enoximone (0.5 to 2 mg/kg intravenously) were assessed by pulmonary artery catheterization in 29 patients with chronic HF before and after 9 to 12 months of treatment with metoprolol or carvedilol at standard target maintenance oral doses. Hemodynamic studies were performed after >/=12 h of wash-out from all cardiovascular medications, except the beta-blockers that were administered 3 h before the second study. RESULTS Compared with before beta-blocker therapy, metoprolol treatment decreased the magnitude of mean pulmonary artery pressure (PAP) and pulmonary wedge pressure (PWP) decline during dobutamine infusion and increased the cardiac index (CI) and stroke volume index (SVI) response to enoximone administration, without any effect on other hemodynamic parameters. Carvedilol treatment abolished the increase in heart rate, SVI, and CI and caused a rise, rather than a decline, in PAP, PWP, systemic vascular resistance, and pulmonary vascular resistance during dobutamine infusion. The hemodynamic response to enoximone, however, was maintained or enhanced in the presence of carvedilol. CONCLUSIONS In contrast with its effects on enoximone, carvedilol and, to a lesser extent, metoprolol treatment may significantly inhibit the favorable hemodynamic response to dobutamine. No such beta-blocker-related attenuation of hemodynamic effects occurs with enoximone.

Developing Therapies for Heart Failure with Preserved Ejection Fraction: Current State and Future Directions

The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the Food and Drug Administration and included representatives from academia, industry, and regulatory agencies. This document summarizes the proceedings from this meeting.

The role of plasma biomarkers in acute heart failure. Serial changes and independent prognostic value of NT‐proBNP and cardiac troponin‐T

Brain natriuretic peptide (BNP), NT‐proBNP and troponins are useful for the assessment of patients with heart failure. Few data exist about their serial changes and their prognostic value in patients with acute heart failure (AHF).

β‐Blocker treatment of patients with diastolic heart failure and arterial hypertension. A prospective, randomized, comparison of the long‐term effects of atenolol vs. nebivolol

We compared the effects of 6 months administration of atenolol or nebivolol on resting and exercise hemodynamic parameters and maximal exercise capacity, in 26 patients with hypertension and left ventricular (LV) diastolic dysfunction (ejection fraction >50%, end‐diastolic diameter <60 mm and increased pulmonary wedge pressure at rest and/or at peak exercise). Both atenolol and nebivolol administration was associated with a significant decrease in the resting and peak exercise heart rate and blood pressure and in LV mass, with an increase in the E/A ratio. This latter effect was greater with nebivolol. Nebivolol was associated with an increase in the peak VO2, VO2 at the anaerobic threshold and with a decrease in the VE/VCO2 ratio. With regards to the hemodynamic parameters, compared to patients on atenolol, those on nebivolol showed a lower reduction in the cardiac index, a greater increase in the stroke volume index and a decline in the mean pulmonary artery pressure and pulmonary wedge pressure, both at rest and peak exercise. Thus, although the two β‐blockers have a similar antihypertensive action, nebivolol administration was associated with a greater hemodynamic improvement, compared to atenolol.

Serum levels of carbohydrate antigen 125 in patients with chronic heart failure: relation to clinical severity, hemodynamic and Doppler echocardiographic abnormalities, and short-term prognosis.

OBJECTIVES The aim of this study was to evaluate the serum levels of carbohydrate antigen 125 (CA125) in patients with congestive heart failure (CHF). BACKGROUND CA125 is a glycoprotein produced by serosal epithelium, found to be increased in ovarian cancer. METHODS Serum levels of CA125 were obtained in 286 patients (122 males and 164 females; age 69 +/- 13 years) with CHF (left ventricular ejection fraction 30 +/- 11%). A non-invasive evaluation was obtained by Doppler echocardiography; right heart catheterization was performed in 88 patients. An attempt to adjust medical therapy to maximally tolerated doses was done, and CA125 was repeated after 18 days (range 7 to 40) in 80 patients. The mean follow-up duration was 6 +/- 3 months in 240 patients. RESULTS The mean value of CA125 was 68 +/- 83 U/ml (range 3 to 537): 71 +/- 85 in men and 56 +/- 64 U/ml in women (p = NS). CA125 above the normal value (<35 U/ml) was found in 152 (53%) of 286 patients; it was higher in patients with advanced New York Heart Association (NYHA) functional class (n = 140 in class I/II: 15 +/- 9 U/ml; n = 63 in class III: 57 +/- 18 U/ml; n = 83 in class IV: 167 +/- 94 U/ml; p < 0.005). CA125 was related to the deceleration time of early filling on transmitral Doppler (r = -0.63, p < 0.05) and to pulmonary artery wedge pressure (r = 0.66, p < 0.05) and right atrial pressure (r = 0.69, p < 0.05). During 6 +/- 3 months of follow-up, a combined end point of mortality and CHF hospitalization was observed in 16 of 127 patients with CA125 <35 U/ml, compared with 70 of 113 patients with CA125 >35 U/ml (p < 0.01). After medical treatment optimization, NYHA class decreased by more than one grade in 56 of 80 patients and was unchanged or increased in 24 patients: CA125 decreased from 125 +/- 98 to 53 +/- 61 U/ml (p < 0.001) in the former and changed from 130 +/- 81 to 153 +/- 61 U/ml (p = NS) in the latter. CONCLUSIONS Our data suggest that CA125 is related to CHF severity and short-term prognosis. Furthermore, fluctuations of CA125 serum levels over time may reflect changes induced by therapy. Therefore, measurements of CA 125 serum levels might be proposed for the serial assessment of CHF patients.

Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy.

OBJECTIVES This study was designed to test the effects of n-3 polyunsaturated fatty acids (PUFAs) on left ventricular (LV) systolic function in chronic heart failure (HF) due to nonischemic dilated cardiomyopathy (NICM). BACKGROUND One hundred thirty-three patients with NICM and minimal symptoms on standard therapy were randomized to 2 g of n-3 PUFAs or placebo. LV function and functional capacity were assessed prospectively by echocardiography and cardiopulmonary exercise testing at baseline and at 12 months after randomization. METHODS Patients with chronic HF due to NICM and minimal symptoms while receiving evidence-based therapy were enrolled. LV function and functional capacity were assessed prospectively by echocardiography, cardiopulmonary exercise test, and New York Heart Association functional class at baseline and at 12 months after randomization to either 2 g of n-3 PUFAs or placebo. RESULTS At 12 months after randomization, the n-3 PUFAs group and the placebo group differed significantly (p <0.001) in regard to: 1) LV ejection fraction (increased by 10.4% and decreased by 5.0%, respectively); 2) peak VO(2) (increased by 6.2% and decreased by 4.5%, respectively); 3) exercise duration (increased by 7.5% and decreased by 4.8%, respectively); and 4) mean New York Heart Association functional class (decreased from 1.88 ± 0.33 to 1.61 ± 0.49 and increased from 1.83 ± 0.38 to 2.14 ± 0.65, respectively). The hospitalization rates for HF were 6% in the n-3 PUFAs and 30% in the placebo group (p = 0.0002). CONCLUSIONS In patients with NICM and minimal symptoms in response to evidence-based medical therapy, n-3 PUFAs treatment increases LV systolic function and functional capacity and may reduce hospitalizations for HF. Given these promising results, larger studies are in order to confirm our findings.