Florence Beauvais

Heart Failure and Diabetes Mellitus: Epidemiology and Management of an Alarming Association

Diabetes mellitus is a growing epidemic with a prevalence among patients with heart failure (HF) approaching 30%. Diabetes worsens the prognosis of HF, and the pathophysiology is complex and multifactorial. Early detection of subtle alterations in cardiac function by modern tools, such as Doppler echocardiography or brain natriuretic peptide dosage, is thus important in these patients. All drugs known to be effective in HF with systolic dysfunction are also effective in patients with diabetes. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists also seem particularly useful. Overall, however, little is known about the treatment of diabetic patients with HF, especially in case of preserved systolic function. Ongoing and future trials should help to determine the best treatment for these patients with or without associated diabetes. This review assesses the relationships between diabetes mellitus and HF and discusses the various medical strategies.

Benefits of exercise training in chronic heart failure

Exercise training performed in cardiac rehabilitation centres is an adjuvant therapy in chronic heart failure patients with left ventricular dysfunction; it decreases the deleterious consequences of chronic heart failure. Exercise training attenuates neurohormonal stimulation, the production of proinflammatory cytokines and natriuretic peptide overexpression. Trained patients showed a significant decrease in the peripheral organ injuries encountered in chronic heart failure, with a reduction in vascular resistance and improvements in endothelial dysfunction and the oxidative capacity of peripheral muscles, without a deleterious effect on left ventricular remodelling. Ultimately, exercise training leads to a notable improvement in ventilatory capacity. These beneficial effects are accompanied by improvements in symptoms at rest, exercise capacity and quality of life. Several training programmes are in current use: exercise training sessions always include endurance exercise performed either at a constant load intensity or with interval training, combining periods of exercise performed at high intensity with periods performed at low intensity. Most of the time, training programmes also include resistance training sessions, which improves large muscle strength. Exercise training programmes seem to have a favourable effect on prognosis, even if the results of Heart Failure: a Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) remain controversial, emphasizing the difficulty in monitoring observance and the importance of compliance with a long-term exercise training programme. Patients who do not improve their exercise capacity significantly after an exercise training programme have a poorer prognosis.

Absence of Exercise Capacity Improvement After Exercise Training Program A Strong Prognostic Factor in Patients With Chronic Heart Failure

Background—Exercise training is established as adjuvant therapy for chronic heart failure, but the prognostic value of improvement in exercise capacity after exercise training has never been evaluated. Methods and Results—In this prospective bicentric study, all chronic heart failure patients with left ventricular ejection fraction <45% who underwent an exercise training program in a cardiac rehabilitation center between January 2004 and September 2006 were consecutively included. Improvement in exercise capacity was assessed by change in peak oxygen consumption (&dgr;PVo2) and in PVo2 expressed as a percentage of predicted PVo2 (&dgr;%PPVo2) measured before and after the training program. We included 155 patients (54±12 years old, male 81%, left ventricular ejection fraction=29.5±7.1%). Patients underwent 20 (10–30) training sessions. PVo2 and %PPVo2 were significantly increased after the training program (14% and 13%, respectively, P<0.001 for both). After 16±6 months follow-up, 27 patients had a cardiac event (death [n=12], cardiac transplantation [n=5], hospitalization for acute heart failure [n=10]). Univariate analysis revealed that among 17 significant predictors of cardiac events, the 2 more powerful ones were level of B-type natriuretic peptide at baseline (P<0.0001) and improvement in exercise capacity as assessed by &dgr;PVo2 and &dgr;%PPVo2 (P<0.0001). Multivariate analysis revealed B-type natriuretic peptide level and &dgr;%PPVo2 as only independent predictive factors of outcome (P=0.01). The risk ratio of cardiac events for nonresponse versus response to the training program (defined as median &dgr;%PPVo2<6%) was 8.2 (P=0.0006). Conclusions—Among patients with chronic heart failure, the lack of improvement in exercise capacity after an exercise training program has strong prognostic value for adverse cardiac events independent of classical predictive factors such as left ventricular ejection fraction, New York Heart Association class, and B-type natriuretic peptide level.Background— Exercise training is established as adjuvant therapy for chronic heart failure, but the prognostic value of improvement in exercise capacity after exercise training has never been evaluated. Methods and Results— In this prospective bicentric study, all chronic heart failure patients with left ventricular ejection fraction <45% who underwent an exercise training program in a cardiac rehabilitation center between January 2004 and September 2006 were consecutively included. Improvement in exercise capacity was assessed by change in peak oxygen consumption (δPVo2) and in PVo2 expressed as a percentage of predicted PVo2 (δ%PPVo2) measured before and after the training program. We included 155 patients (54±12 years old, male 81%, left ventricular ejection fraction=29.5±7.1%). Patients underwent 20 (10–30) training sessions. PVo2 and %PPVo2 were significantly increased after the training program (14% and 13%, respectively, P <0.001 for both). After 16±6 months follow-up, 27 patients had a cardiac event (death [n=12], cardiac transplantation [n=5], hospitalization for acute heart failure [n=10]). Univariate analysis revealed that among 17 significant predictors of cardiac events, the 2 more powerful ones were level of B-type natriuretic peptide at baseline ( P <0.0001) and improvement in exercise capacity as assessed by δPVo2 and δ%PPVo2 ( P <0.0001). Multivariate analysis revealed B-type natriuretic peptide level and δ%PPVo2 as only independent predictive factors of outcome ( P =0.01). The risk ratio of cardiac events for nonresponse versus response to the training program (defined as median δ%PPVo2<6%) was 8.2 ( P =0.0006). Conclusions— Among patients with chronic heart failure, the lack of improvement in exercise capacity after an exercise training program has strong prognostic value for adverse cardiac events independent of classical predictive factors such as left ventricular ejection fraction, New York Heart Association class, and B-type natriuretic peptide level. Received February 26, 2008; accepted September 23, 2008.

Acute hypoxic hepatitis (‘liver shock’): still a frequently overlooked cardiological diagnosis

The diagnosis of acute hypoxic hepatitis remains problematic. We describe a series of 14 patients who were initially hospitalized in an hepatic care unit with a diagnosis of fulminant hepatitis, and were subsequently found to have acute hypoxic hepatitis (‘liver shock’) secondary to heart failure. A diagnostic algorithm is proposed.

Optimization of heart FailUre medical Treatment after hospital discharge according to left ventricUlaR Ejection fraction: the FUTURE survey.

BACKGROUND No clinical practice guidelines are available for the treatment of heart failure (HF) in patients with preserved left ventricular ejection fraction (LVEF). AIMS To determine how cardiologists manage medical treatment in HF patients after hospital discharge, according to LVEF. METHODS The FUTURE study was a cross-sectional survey conducted in HF outpatients by French private cardiologists between September 2007 and August 2008. Patients had to have been hospitalized within the previous 18 months with a diagnosis of HF. Clinical data and HF treatments (angiotensin-converting enzyme inhibitors [ACEIs], angiotensin receptor blockers [ARBs], beta-blockers, diuretics and aldosterone antagonists) were recorded retrospectively, with precise information on drug doses, at two successive time points (at hospital discharge and at the index consultation). HF treatment was compared in patients with reduced (less than or equal to 40%) versus preserved (more than 40%) LVEF. RESULTS Completed data were available for 1137 HF patients enrolled by 424 cardiologists. Mean patient age was 72±11 years; LVEF was reduced in 56% and preserved in 44%. The therapeutic approach was similar in the two groups, both at hospital discharge and at the index consultation. At the index consultation, HF treatment was: beta-blocker (74%); ACEI/ARB (83%); loop diuretic (86%); aldosterone antagonist (31%). The majority of patients (62%) received a beta-blocker plus an ACEI or an ARB; 56% reached more than or equal to 50% of the target dose for each treatment. There were no major differences in treatments and dosages between the groups with low and preserved LVEF. In 15% of cases where the drug dose was not increased, fear of adverse events was reported as the reason. CONCLUSION The FUTURE survey showed a similar approach to HF treatment irrespective of LVEF. Compared with previous studies, we saw an improvement in the use of recommended HF drugs, especially beta-blockers. However, achievement of target doses could be improved.

Non-invasive radial pulse wave assessment for the evaluation of left ventricular systolic performance in heart failure.

Left ventricular (LV) developed pressure (dP/dt) is a classical index of myocardial contractility related to prognosis during heart failure. We sought to assess the reproducibility and feasibility of use of the maximal first derivative of the radial pulse, Rad dP/dt, as a peripheral criterion of ventricular contractility in patients with heart failure.

Beneficial effects of carvedilol on angiotensin-converting enzyme activity and renin plasma levels in patients with chronic heart failure

To assess the effects of carvedilol treatment on the renin–angiotensin system in patients with chronic heart failure (CHF).

Absence of Exercise Capacity Improvement After Exercise Training ProgramCLINICAL PERSPECTIVE

Background—Exercise training is established as adjuvant therapy for chronic heart failure, but the prognostic value of improvement in exercise capacity after exercise training has never been evaluated. Methods and Results—In this prospective bicentric study, all chronic heart failure patients with left ventricular ejection fraction <45% who underwent an exercise training program in a cardiac rehabilitation center between January 2004 and September 2006 were consecutively included. Improvement in exercise capacity was assessed by change in peak oxygen consumption (&dgr;PVo2) and in PVo2 expressed as a percentage of predicted PVo2 (&dgr;%PPVo2) measured before and after the training program. We included 155 patients (54±12 years old, male 81%, left ventricular ejection fraction=29.5±7.1%). Patients underwent 20 (10–30) training sessions. PVo2 and %PPVo2 were significantly increased after the training program (14% and 13%, respectively, P<0.001 for both). After 16±6 months follow-up, 27 patients had a cardiac event (death [n=12], cardiac transplantation [n=5], hospitalization for acute heart failure [n=10]). Univariate analysis revealed that among 17 significant predictors of cardiac events, the 2 more powerful ones were level of B-type natriuretic peptide at baseline (P<0.0001) and improvement in exercise capacity as assessed by &dgr;PVo2 and &dgr;%PPVo2 (P<0.0001). Multivariate analysis revealed B-type natriuretic peptide level and &dgr;%PPVo2 as only independent predictive factors of outcome (P=0.01). The risk ratio of cardiac events for nonresponse versus response to the training program (defined as median &dgr;%PPVo2<6%) was 8.2 (P=0.0006). Conclusions—Among patients with chronic heart failure, the lack of improvement in exercise capacity after an exercise training program has strong prognostic value for adverse cardiac events independent of classical predictive factors such as left ventricular ejection fraction, New York Heart Association class, and B-type natriuretic peptide level.Background— Exercise training is established as adjuvant therapy for chronic heart failure, but the prognostic value of improvement in exercise capacity after exercise training has never been evaluated. Methods and Results— In this prospective bicentric study, all chronic heart failure patients with left ventricular ejection fraction <45% who underwent an exercise training program in a cardiac rehabilitation center between January 2004 and September 2006 were consecutively included. Improvement in exercise capacity was assessed by change in peak oxygen consumption (δPVo2) and in PVo2 expressed as a percentage of predicted PVo2 (δ%PPVo2) measured before and after the training program. We included 155 patients (54±12 years old, male 81%, left ventricular ejection fraction=29.5±7.1%). Patients underwent 20 (10–30) training sessions. PVo2 and %PPVo2 were significantly increased after the training program (14% and 13%, respectively, P <0.001 for both). After 16±6 months follow-up, 27 patients had a cardiac event (death [n=12], cardiac transplantation [n=5], hospitalization for acute heart failure [n=10]). Univariate analysis revealed that among 17 significant predictors of cardiac events, the 2 more powerful ones were level of B-type natriuretic peptide at baseline ( P <0.0001) and improvement in exercise capacity as assessed by δPVo2 and δ%PPVo2 ( P <0.0001). Multivariate analysis revealed B-type natriuretic peptide level and δ%PPVo2 as only independent predictive factors of outcome ( P =0.01). The risk ratio of cardiac events for nonresponse versus response to the training program (defined as median δ%PPVo2<6%) was 8.2 ( P =0.0006). Conclusions— Among patients with chronic heart failure, the lack of improvement in exercise capacity after an exercise training program has strong prognostic value for adverse cardiac events independent of classical predictive factors such as left ventricular ejection fraction, New York Heart Association class, and B-type natriuretic peptide level. Received February 26, 2008; accepted September 23, 2008.

Noninvasively determined radial dP/dt is a predictor of mortality in patients with heart failure

BACKGROUND The left ventricular (LV) developed pressure is a marker of contractility, associated with a poor prognosis during systolic heart failure. The maximal first derivative or slope of the radial pulse wave (Rad dP/dt) has been proposed as a marker of LV systolic function. This study sought to assess the prognostic value of the baseline dP/dt of the radial pulse in patients with heart failure. METHODS The Rad dP/dt was noninvasively measured by applanation tonometry, and its effect on mortality was analyzed by using multivariate Cox regression models. We studied 310 consecutive patients. Mean follow-up was 327 +/- 187 days, and 64 patients died or were transplanted during this period. RESULTS Death or transplantation was associated with New York Heart Association class III or IV, low systolic or mean blood pressure, low LV ejection fraction, and low Rad dP/dt (634.6 +/- 373.3 vs 730.2 +/- 367.4 mm Hg/s for patients who survived without transplantation, P < .02). A Rad dP/dt <440 mm Hg/s was associated with death or transplantation before and after adjustment for confounding variables (OR [95% CI] 2.19 [1.33-3.58] and 2.88 [1.29-6.38], respectively, P < .01 for both). This relationship was independent of pulse pressure and no significant interaction was found between the Rad dP/dt and the pulse pressure. CONCLUSION This study demonstrates, for the first time, that the Rad dP/dt, proposed as a noninvasive peripheral marker of LV systolic function, is an independent predictor of death or transplantation in patients with HF regardless of LV ejection fraction.

Effects of a cardiac rehabilitation programme on plasma cardiac biomarkers in patients with chronic heart failure

Background Cardiac rehabilitation (CR) improves the symptoms, exercise capacity and quality of life of chronic heart failure (CHF) patients. Its effects on new plasma biomarkers of prognostic importance are unknown. The present study aimed at analysing the effects of a structured CR programme on plasma cardiac biomarkers in a large population of patients with CHF and reduced left ventricular ejection fraction (LVEF). Methods We enrolled 107 consecutive CHF patients with LVEF ≤ 45% in an ambulatory CR programme. Peak VO2 and plasma levels of Galectin-3, mid-regional proANP (MR-proADM), soluble suppressor of tumorigenicity 2 (sST2) and mid-regional pro-adrenomedullin (MR-proANP) were assessed at inclusion and at the end of CR. Twenty-four unenrolled patients were managed with standard medical care and evaluated over the same period (no-CR group). Results Galectin-3, sST2, MR-proADM and MR-proANP plasma levels decreased after CR, with respective median reductions of 6.3% for Galectin 3 (p < 0.001), 7.4% for sST2 (p = 0.036), 6.4% for MR-proADM (p = 0.001) and 16% for MR-proANP (p < 0.001). MR-proADM was negatively correlated with peak VO2 (ρ = −0.529, 95% confidence interval [CI] −0.654 to −0.375, p < 0.001), and so were their relative variations along the course of CR (ρ = −0.357, 95% CI –0.518 to −0.172, p < 0.001). No change occurred in terms of biomarkers in the no-CR group. Conclusions Plasma cardiac biomarkers such as Galectin-3, MR-proADM, sST2 and MR-proANP all decreased after CR in CHF patients, suggesting an overall improvement in the neuro-hormonal profile.