Valentina Lazzarini

Is Worsening Renal Function an Ominous Prognostic Sign in Patients with Acute Heart Failure? The Role of Congestion and Its Interaction with Renal Function

Background— Worsening renal function (WRF), traditionally defined as an increase in serum creatinine levels ≥0.3 mg/dL, is a frequent finding in patients with acute heart failure (AHF) and has been associated with poorer outcomes in some but not all studies. We hypothesized that these discrepancies may be caused by the interaction between WRF and congestion in AHF patients. Methods and Results— We measured serum creatinine levels on a daily basis during the hospitalization and assessed the persistence of signs of congestion at discharge in 599 consecutive patients admitted at our institute for AHF. They had a postdischarge mortality and mortality or AHF readmission rates of 13% and 43%, respectively, after 1 year. Patients were subdivided into 4 groups according to the development or not of WRF and the persistence of ≥1 sign of congestion at discharge. Patients with WRF and no congestion had similar outcomes compared with those with no WRF and no congestion, whereas the risk of death or of death or AHF readmission was increased in the patients with persistent congestion alone and in those with both WRF and congestion (hazard ratio, 5.35; 95% confidence interval, 3.0–9.55 at univariable analysis; hazard ratio, 2.44; 95% confidence interval, 1.24–4.18 at multivariable analysis for mortality; hazard ratio, 2.14; 95% confidence interval, 1.39–3.3 at univariable analysis; and hazard ratio, 1.39; 95% confidence interval, 0.88–2.2 at multivariable analysis for mortality and rehospitalizations). Conclusions— WRF alone, when detected using serial serum creatinine measurements, is not an independent determinant of outcomes in patients with AHF. It has an additive prognostic value when it occurs in patients with persistent signs of congestion.Background— Worsening renal function (WRF), traditionally defined as an increase in serum creatinine levels ≥0.3 mg/dL, is a frequent finding in patients with acute heart failure (AHF) and has been associated with poorer outcomes in some but not all studies. We hypothesized that these discrepancies may be caused by the interaction between WRF and congestion in AHF patients. Methods and Results— We measured serum creatinine levels on a daily basis during the hospitalization and assessed the persistence of signs of congestion at discharge in 599 consecutive patients admitted at our institute for AHF. They had a postdischarge mortality and mortality or AHF readmission rates of 13% and 43%, respectively, after 1 year. Patients were subdivided into 4 groups according to the development or not of WRF and the persistence of ≥1 sign of congestion at discharge. Patients with WRF and no congestion had similar outcomes compared with those with no WRF and no congestion, whereas the risk of death or of death or AHF readmission was increased in the patients with persistent congestion alone and in those with both WRF and congestion (hazard ratio, 5.35; 95% confidence interval, 3.0–9.55 at univariable analysis; hazard ratio, 2.44; 95% confidence interval, 1.24–4.18 at multivariable analysis for mortality; hazard ratio, 2.14; 95% confidence interval, 1.39–3.3 at univariable analysis; and hazard ratio, 1.39; 95% confidence interval, 0.88–2.2 at multivariable analysis for mortality and rehospitalizations). Conclusions— WRF alone, when detected using serial serum creatinine measurements, is not an independent determinant of outcomes in patients with AHF. It has an additive prognostic value when it occurs in patients with persistent signs of congestion.

Is Worsening Renal Function an Ominous Prognostic Sign in Patients With Acute Heart Failure?Clinical Perspective

Background— Worsening renal function (WRF), traditionally defined as an increase in serum creatinine levels ≥0.3 mg/dL, is a frequent finding in patients with acute heart failure (AHF) and has been associated with poorer outcomes in some but not all studies. We hypothesized that these discrepancies may be caused by the interaction between WRF and congestion in AHF patients. Methods and Results— We measured serum creatinine levels on a daily basis during the hospitalization and assessed the persistence of signs of congestion at discharge in 599 consecutive patients admitted at our institute for AHF. They had a postdischarge mortality and mortality or AHF readmission rates of 13% and 43%, respectively, after 1 year. Patients were subdivided into 4 groups according to the development or not of WRF and the persistence of ≥1 sign of congestion at discharge. Patients with WRF and no congestion had similar outcomes compared with those with no WRF and no congestion, whereas the risk of death or of death or AHF readmission was increased in the patients with persistent congestion alone and in those with both WRF and congestion (hazard ratio, 5.35; 95% confidence interval, 3.0–9.55 at univariable analysis; hazard ratio, 2.44; 95% confidence interval, 1.24–4.18 at multivariable analysis for mortality; hazard ratio, 2.14; 95% confidence interval, 1.39–3.3 at univariable analysis; and hazard ratio, 1.39; 95% confidence interval, 0.88–2.2 at multivariable analysis for mortality and rehospitalizations). Conclusions— WRF alone, when detected using serial serum creatinine measurements, is not an independent determinant of outcomes in patients with AHF. It has an additive prognostic value when it occurs in patients with persistent signs of congestion.Background— Worsening renal function (WRF), traditionally defined as an increase in serum creatinine levels ≥0.3 mg/dL, is a frequent finding in patients with acute heart failure (AHF) and has been associated with poorer outcomes in some but not all studies. We hypothesized that these discrepancies may be caused by the interaction between WRF and congestion in AHF patients. Methods and Results— We measured serum creatinine levels on a daily basis during the hospitalization and assessed the persistence of signs of congestion at discharge in 599 consecutive patients admitted at our institute for AHF. They had a postdischarge mortality and mortality or AHF readmission rates of 13% and 43%, respectively, after 1 year. Patients were subdivided into 4 groups according to the development or not of WRF and the persistence of ≥1 sign of congestion at discharge. Patients with WRF and no congestion had similar outcomes compared with those with no WRF and no congestion, whereas the risk of death or of death or AHF readmission was increased in the patients with persistent congestion alone and in those with both WRF and congestion (hazard ratio, 5.35; 95% confidence interval, 3.0–9.55 at univariable analysis; hazard ratio, 2.44; 95% confidence interval, 1.24–4.18 at multivariable analysis for mortality; hazard ratio, 2.14; 95% confidence interval, 1.39–3.3 at univariable analysis; and hazard ratio, 1.39; 95% confidence interval, 0.88–2.2 at multivariable analysis for mortality and rehospitalizations). Conclusions— WRF alone, when detected using serial serum creatinine measurements, is not an independent determinant of outcomes in patients with AHF. It has an additive prognostic value when it occurs in patients with persistent signs of congestion.

Heart failure in elderly patients: distinctive features and unresolved issues.

The prevalence of heart failure (HF) increases with age. While clinical trials suggest that contemporary evidence‐based HF therapies have reduced morbidity and mortality, these trials largely excluded the elderly. Questions remain regarding the clinical characteristics of elderly HF patients and the impact of contemporary therapies on their outcomes. This review presents the epidemiology of HF in the elderly and summarizes the data on the pathophysiology of the ageing heart. The clinical characteristics, treatment patterns, and outcomes of elderly HF patients are explored. Finally, the main gaps regarding HF therapies in the elderly and the opportunities for future trials are highlighted.

A novel discharge risk model for patients hospitalised for acute decompensated heart failure incorporating N-terminal pro-B-type natriuretic peptide levels: a European coLlaboration on Acute decompeNsated Heart Failure: ÉLAN-HF Score

Background Models to stratify risk for patients hospitalised for acute decompensated heart failure (ADHF) do not include the change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels during hospitalisation. Objective The aim of our study was to develop a simple yet robust discharge prognostication score including NT-proBNP for this notorious high-risk population. Design Individual patient data meta-analyses of prospective cohort studies. Setting Seven prospective cohorts with in total 1301 patients. Patients Our study population was assembled from the seven studies by selecting those patients admitted because of clinically validated ADHF, discharged alive, and NT-proBNP measurements available at admission and at discharge. Main outcome measures The endpoints studied were all-cause mortality and a composite of all-cause mortality and/or first readmission for cardiovascular reason within 180 days after discharge. Results The model that incorporated NT-proBNP levels at discharge as well as the changes in NT-proBNP during hospitalisation in addition to age ≥75 years, peripheral oedema, systolic blood pressure ≤115 mm Hg, hyponatremia at admission, serum urea of ≥15 mmol/L and New York Heart Association (NYHA) class at discharge, yielded the best C-statistic (area under the curve, 0.78, 95% CI 0.74 to 0.82). The addition of NT-proBNP to a reference model significantly improved prediction of mortality as shown by the net reclassification improvement (62%, p<0.001). A simplified model was obtained from the final Cox regression model by assigning weights to individual risk markers proportional to their relative risks. The risk score we designed identified four clinically significant subgroups. The pattern of increasing event rates with increasing score was confirmed in the validation group (BOT-AcuteHF, n=325, p<0.001). Conclusions In patients hospitalised for ADHF, the addition of the discharge NT-proBNP values as well as the change in NT-proBNP to known risk markers, generates a relatively simple yet robust discharge risk score that importantly improves the prediction of adverse events.

Effects of oral administration of orodispersible levo-carnosine on quality of life and exercise performance in patients with chronic heart failure

OBJECTIVE Chronic heart failure (CHF) is characterized by several micronutrient deficits. Amino acid supplementation may have a positive effect on nutritional and metabolic status in patients with CHF. Levo-carnosine (β-alanyl-L-histidine) is expressed at a high concentration in myocardium and muscle. Preliminary studies with L-carnosine in healthy individuals have suggested a potential role in improving exercise performance. To our knowledge, no study has been conducted in patients with heart failure. The aim of this study was to test the oral supplementation of L-carnosine and its effects on quality of life and exercise performance in patients with stable CHF. METHODS Fifty patients with stable CHF and severe left-ventricular systolic dysfunction on optimal medical therapy were randomized 1:1 to receive oral orodispersible L-carnosine (500 mg OD) or standard treatment. Left-ventricular ejection fraction (LVEF) was measured by echocardiography. Cardiopulmonary stress test, 6-minute walking test (6 MWT) and quality-of-life (visual analog scale score and the EuroQOL five dimensions questionnaire [EQ-5D]) were performed at baseline and after 6 mo. RESULTS Patients receiving orodispersible L-carnosine had an improvement in 6 MWT distance (P = 0.014) and in quality-of-life (VAS score) (P = 0.039) between baseline and follow-up. Compared with controls, diet supplementation with orodispersible L-carnosine was associated with an improvement in peakVO2 (P < 0.0001), VO2 at anaerobic threshold, peak exercise workload, 6 MWT and quality-of-life assessed by the EQ-5D test and the VAS score. CONCLUSION This study suggests that L-carnosine, added to conventional therapy, has beneficial effects on exercise performance and quality of life in stable CHF. More data are necessary to evaluate its effects on left-ventricular ejection fraction and prognosis in CHF.

Acute heart failure in elderly patients: worse outcomes and differential utility of standard prognostic variables. Insights from the PROTECT trial

Previous heart failure (HF) trials suggested that age influences patient characteristics and outcome; however, under‐representation of elderly patients has limited characterization of this cohort. Whether standard prognostic variables have differential utility in various age groups is unclear.

Renal dysfunction in acute heart failure: epidemiology, mechanisms and assessment

Renal dysfunction is often present and/or worsens in patients with heart failure and this is associated with increased costs of care, complications and mortality. The cardiorenal syndrome can be defined as the presence or development of renal dysfunction in patients with heart failure. Its mechanisms are likely related to low cardiac output, increased venous congestion and renal venous pressure, neurohormonal and inflammatory activation and local changes, such as adenosine release. Many drugs, including loop diuretics, may contribute to worsening renal function through the activation of some of these mechanisms. Renal damage is conventionally defined by the increase in creatinine and blood urea nitrogen blood levels. However, these changes may be not related with renal injury or prognosis. New biomarkers of renal injury seem promising but still need to be validated. Thus, despite the epidemiological evidence, we are still lacking of satisfactory tools to assess renal injury and function and its prognostic significance.

Challenging the two concepts in determining the appropriate pre-discharge N-terminal pro-brain natriuretic peptide treatment target in acute decompensated heart failure patients: absolute or relative discharge levels?

NT‐proBNP is a strong predictor for readmissions and mortality in acute decompensated heart failure (ADHF) patients. We assessed whether absolute or relative NT‐proBNP levels should be used as pre discharge treatment target.

Use of Inotropic Agents in Patients with Advanced Heart Failure: Lessons from Recent Trials and Hopes for New Agents

Abnormalities of cardiac function, with high intraventricular filling pressure and low cardiac output, play a central role in patients with heart failure. Agents with inotropic properties are potentially useful to correct these abnormalities. However, with the exception of digoxin, no inotropic agent has been associated with favourable effects on outcomes. This is likely related to the mechanism of action of current agents, which is based on an increase in intracellular cyclic adenosine monophosphate and calcium concentrations. Novel agents acting through different mechanisms, such as sarcoplasmic reticulum calcium uptake, cardiac myosin and myocardial metabolism, have the potential to improve myocardial efficiency and lower myocardial oxygen consumption. These characteristics might allow a haemodynamic improvement in the absence of untoward effects on the clinical course and prognosis of the patients.

Amino acids and derivatives, a new treatment of chronic heart failure?

Amino acids play a key role in multiple cellular processes. Amino acids availability is reduced in patients with heart failure (HF) with deleterious consequences on cardiac and whole-body metabolism. Several metabolic abnormalities have been identified in the failing heart, and many of them lead to an increased need of amino acids. Recently, several clinical trials have been conducted to demonstrate the benefits of amino acids supplementation in patients with HF. Although they have shown an improvement of exercise tolerance and, in some cases, of left ventricular function, they have many limitations, namely small sample size, differences in patients’ characteristics and nutritional supplementations, and lack of data regarding outcomes. Moreover recent data suggest that a multi-nutritional approach, including also antioxidants, vitamins, and metals, may be more effective. Larger trials are needed to ascertain safety, efficacy, and impact on prognosis of such an approach in HF.