Valentina Carubelli

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.

Clinical picture and risk prediction of short-term mortality in cardiogenic shock

The aim of this study was to investigate the clinical picture and outcome of cardiogenic shock and to develop a risk prediction score for short‐term mortality.

IVC Diameter in Patients With Chronic Heart Failure : Relationships and Prognostic Significance

OBJECTIVES The aim of this study was to assess the relation between inferior vena cava (IVC) diameter, clinical variables, and outcome in patients with chronic heart failure (HF). BACKGROUND The IVC distends as right atrial pressure rises. Therefore it might represent an index of HF severity independent of left ventricular ejection fraction (LVEF). The relation between IVC diameter and other clinical variables and its prognostic significance in patients with HF has not been explored. METHODS Outpatients attending a community HF service between 2008 and 2010 were enrolled. Heart failure was defined as the presence of relevant symptoms and signs and objective evidence of cardiac dysfunction: either LVEF <45% or the combination of both left atrial dilation (≥4 cm) and raised amino-terminal pro-brain natriuretic peptide (NT-proBNP) ≥400 pg/ml. Patients were followed for a median of 567 (interquartile range: 413 to 736) days. The primary composite endpoint was cardiovascular death and HF hospitalization. RESULTS Among the 693 patients enrolled, median age was 73 years, 33% were women, and 568 had HF. Patients with HF in the highest tertile of IVC diameter were older; had lower body mass index; were more likely to have atrial fibrillation and to be treated with diuretics; and had larger left atrial volumes, higher pulmonary pressures, and less negative values for global longitudinal strain. The LVEF and systolic blood pressure were similar across tertiles of IVC diameter. The IVC diameter and log [NT-proBNP] were correlated (r = 0.55, p < 0.001). During follow-up, 158 patients reached a primary endpoint. In a multivariable Cox regression model, including NT-proBNP, only increasing IVC diameter, urea, and the trans-tricuspid systolic gradient independently predicted a poor outcome. Neither global longitudinal strain nor LVEF were adverse predictors. CONCLUSIONS In patients with chronic HF with or without a reduced LVEF, increasing IVC diameter identifies patients with an adverse outcome.

Renal dysfunction in acute and chronic heart failure: prevalence, incidence and prognosis

Most patients with heart failure have mild or moderate renal dysfunction. This reflects the combined impact of chronic renal parenchymal disease, renal artery disease, renal congestion and hypoperfusion, neuroendocrine and cytokine activation and the effects of treatments for heart failure. Remarkably, with good treatment, the average annual rate of decline in renal function is similar in patients with chronic heart failure and healthy people of a similar age. Urea appears to be a stronger marker of an adverse prognosis than creatinine-based measures of renal function. Recent evidence suggests that minor, transient increases in creatinine in the setting of acute heart failure are not prognostically important but persistent deterioration does indicate a higher mortality. The poor prognosis of patients with worsening renal function ensures that few require renal dialysis but this may change as methods to prevent sudden death improve and new ways are found to control fluid congestion. Reversing renal dysfunction and stopping its progression remain important targets for treatment of heart failure.

Acute heart failure in the elderly: Differences in clinical characteristics, outcomes, and prognostic factors in the Veritas study

BACKGROUND Acute heart failure (HF) is common in the elderly, but the association of age with clinical outcomes and prognostic factors has not been examined thoroughly. METHODS AND RESULTS We analyzed the clinical and laboratory characteristics and the outcomes of 1,347 patients with acute HF enrolled in the VERITAS trial. Subjects were subdivided based on their median age of 72 years. Older patients had a higher prevalence of comorbidities and a higher prevalence of hypertension and atrial fibrillation. During a mean follow-up of 149 ± 61 days, 432 patients (32.1%) reached the composite end point of death, in-hospital worsening HF, or HF rehospitalization by 30 days, and 135 patients (10.4%) died by 90 days, with a worse outcome in elderly patients in both cases. At multivariable analysis, different variables were related with each of these outcomes in elderly compared with younger patients. Regarding deaths at 90 days, plasma urea nitrogen and hemoglobin levels were predictive only in the younger patients, whereas respiratory rate and albumin levels were associated with mortality only in the older patients. CONCLUSIONS Elderly patients with acute HF have different clinical characteristics and poorer outcomes. Prognostic variables differ in elderly compared with younger patients.

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.

Nutrition and Cardiovascular Disease: Finding the Perfect Recipe for Cardiovascular Health

The increasing burden of cardiovascular disease (CVD) despite the progress in management entails the need of more effective preventive and curative strategies. As dietary-associated risk is the most important behavioral factor influencing global health, it appears the best target in the challenge against CVD. Although for many years, since the formulation of the cholesterol hypothesis, a nutrient-based approach was attempted for CVD prevention and treatment, in recent years a dietary-based approach resulted more effective in reducing cardiovascular risk worldwide. After the publication of randomized trials on the remarkable effects of the Mediterranean diet and the Dietary Approach to Stop Hypertension (DASH) diet on CVD, new efforts were put on research about the effects of complex dietary interventions on CVD. The purpose of this paper is to review the evidence on dietary interventions in the prevention and disease modification of CVD, focusing on coronary artery disease and heart failure, the main disease responsible for the enormous toll taken by CVD worldwide.

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.

Old and New Intravenous Inotropic Agents in the Treatment of Advanced Heart Failure

Inotropic agents are administered to improve cardiac output and peripheral perfusion in patients with systolic dysfunction and low cardiac output. However, there is evidence of increased mortality and adverse effects associated with current inotropic agents. These adverse outcomes may be ascribed to patient selection, increased myocardial energy expenditure and oxygen consumption, or to specific mechanisms of action. Both sympathomimetic amines and type III phosphodiesterase inhibitors act through an increase in intracellular cyclic adenosine monophoshate and free calcium concentrations, mechanisms that increase oxygen consumption and favor arrhythmias. Concomitant peripheral vasodilation with some agents (phosphodiesterase inhibitors and levosimendan) may also lower coronary perfusion pressure and favor myocardial damage. New agents with different mechanisms of action might have a better benefit to risk ratio and allow an improvement in tissue and end-organ perfusion with less untoward effects. We have summarized the characteristics of the main inotropic agents for heart failure treatment, the data from randomized controlled trials, and future perspectives for this class of drugs.