Silvia Bugatti

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).

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.

Effect of Spironolactone on Left Ventricular Ejection Fraction and Volumes in Patients With Class I or II Heart Failure

The beneficial effects of spironolactone in chronic heart failure (HF) have been demonstrated in patients with New York Heart Association (NYHA) class III to IV HF. This study examined the effect of spironolactone on left ventricular (LV) function and functional capacity of patients with mild to moderate HF (NYHA class I to II). One hundred sixty-eight patients with NYHA class I to II HF and LV ejection fraction ≤40% were randomized to spironolactone or placebo and assessed by echocardiography, gated single-photon emission computed tomography, technetium-99m sestamibi single-photon emission computed tomographic radionuclide ventriculography, and cardiopulmonary exercise testing at baseline and after 6 months of treatment. In the spironolactone group LV ejection fraction increased from 35.2 ± 0.7% to 39.1 ± 3.5% (p <0.001), with a decrease in LV end-diastolic and end-systolic volumes and myocardial mass and an improvement in LV diastolic filling pattern. Cardiopulmonary exercise testing parameters did not change. In conclusion, administration of spironolactone to patients with NYHA class I to II HF has beneficial effects on LV remodeling and diastolic function.

Acute heart failure: Multiple clinical profiles and mechanisms require tailored therapy

Acute heart failure (HF) is the most common diagnosis at discharge in patients aged >65years. It carries a dismal prognosis with a high in-hospital mortality and very high post-discharge mortality and re-hospitalization rates. It is a complex clinical syndrome that cannot be described as a single entity as it varies widely with respect to underlying pathophysiologic mechanisms, clinical presentations and, likely, treatments. It is the aim of this paper to describe some of the main clinical presentations of acute HF. Amongst them, we will consider de novo HF versus acutely decompensated chronic HF, HF caused, and/or worsened, by myocardial ischemia, acute HF with low, normal, or high systolic blood pressure, acute HF caused by lung congestion or fluid retention or fluid redistribution to the lungs, and acute HF with comorbidities (diabetes, anemia, renal insufficiency, etc.). Different pathophysiologic mechanisms and clinical presentations may coexist in the same patient. Identification and, whenever possible, treatment of underlying pathophysiologic mechanisms may become important for acute HF management.

Nebivolol: Haemodynamic Effects and Clinical Significance of Combined β-Blockade and Nitric Oxide Release

Nebivolol is a third-generation beta-adrenergic receptor antagonist (beta-blocker) with high selectivity for beta(1)-adrenergic receptors. In addition, it causes vasodilatation via interaction with the endothelial L-arginine/nitric oxide (NO) pathway. This dual mechanism of action underlies many of the haemodynamic properties of nebivolol, which include reductions in heart rate and blood pressure (BP), and improvements in systolic and diastolic function. With respect to BP lowering, the NO-mediated effects cause a reduction in peripheral vascular resistance and an increase in stroke volume with preservation of cardiac output. Flow-mediated dilatation and coronary flow reserve are also increased during nebivolol administration. Other haemodynamic effects include beneficial effects on pulmonary artery pressure, pulmonary wedge pressure, exercise capacity and left ventricular ejection fraction. In addition, nebivolol does not appear to have adverse effects on lipid metabolism and insulin sensitivity like traditional beta-blockers. The documented beneficial haemodynamic effects of nebivolol are translated into improved clinical outcomes in patients with hypertension or heart failure. In patients with hypertension, the incidence of bradycardia with nebivolol is often lower than that with other currently available beta-blockers. This, along with peripheral vasodilatation and NO-induced benefits such as antioxidant activity and reversal of endothelial dysfunction, should facilitate better protection from cardiovascular events. In addition, nebivolol has shown an improved tolerability profile, particularly with respect to events commonly associated with beta-blockers, such as fatigue and sexual dysfunction. Data from SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure) showed that significantly fewer nebivolol versus placebo recipients experienced the primary endpoint of all-cause mortality or cardiovascular hospitalization. The benefits of nebivolol therapy were shown to be cost effective. Thus, nebivolol is an effective and well tolerated agent with benefits over and above those of traditional beta-blockade because of its effects on NO release, which give it unique haemodynamic effects, cardioprotective activity and a good tolerability profile.

Neurohormonal Activation in Acute Heart Failure: Results from VERITAS

Objectives: Recent heart failure studies have suggested that inflammatory and immune system activation are associated with increased levels of cytokines, chemokines and inflammatory proteins during acutely decompensated heart failure. The objectives of this substudy were to evaluate the role of neurohormonal and inflammatory activation in the pathogenesis and outcome of acute heart failure (AHF) and the correlation between biomarker levels and clinical outcomes. Methods: Serum levels of B-type natriuretic peptide-32 (BNP-32), endothelin-1 (ET-1), norepinephrine, troponins I and T, C-reactive protein (CRP), von Willebrand factor, plasminogen activator inhibitor-1, interleukin-6 (IL-6) and tissue plasminogen activator (TPA) were measured at baseline, 24 and 48 h and 7 and 30 days in 112 patients with AHF recruited to the Value of Endothelin Receptor Inhibition with Tezosentan in Acute Heart Failure Study neurohormonal substudy. Results: On univariable analysis, CRP, BNP and ET-1 were predictive of worsening heart failure by day 30; when considered together, only CRP and BNP were significantly associated with this outcome. On adjustment for age, baseline blood pressure, serum sodium and serum creatinine, only age and BNP remained significant. CRP, IL-6 and TPA levels were significantly correlated with 180-day mortality on univariable analysis. Conclusion: Circulating markers of inflammation may be useful in gauging prognosis in patients with AHF.

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.

A Scombroid Poisoning Causing a Life-Threatening Acute Pulmonary Edema and Coronary Syndrome in a Young Healthy Patient

Scombroid poisoning, also called histamine fish poisoning, is an allergy-like form of food poisoning that represents one of the major problems in seafood safety. It consists in a clinical syndrome associated with consumption of fish and, less frequently, cheese containing high levels of histamine [1, 2]. Usually certain families of dark meat fish are involved, mainly Scombroidae and Scomberesocidae (e.g., tuna, mackerel, skipjack, Bonito, and Cero). Other nonscombroid fish (e.g., mahi—mahi, herring, anchovies, sardines, Australian salmon, swordfish) was also reported to be associated with scombroid fish poisoning [1–5]. High fish histamine concentrations have been found responsible for this kind of poisoning. Histamine and histamine-like substances are generated from histidine by a decarboxylase activity of bacteria such as Proteus, Klebsiella, Aerobacter, Serratia, Enterobacter, and Escherichia coli [6, 7]. The presence of this bacteria and the massive histamine production detected in the fish is usually secondary to contamination of handlers and improper refrigeration [7]. The clinical presentation is generally characterized by flushing, rash, swelling of face or tongue, sweating, headache, dizziness, abdominal cramps, diarrhea, nausea, vomiting, palpitations, respiratory distress, and hypotension. The onset of symptoms generally occurs few minutes after ingestion of contaminated food. Usually the course is selflimiting and antihistamines can be used to relieve symptoms. We report a rare case of a life-threatening scombroid poisoning with myocardial ischemia and acute pulmonary edema after tuna ingestion.

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.