Vasiliki Bistola

Effects of levosimendan on coronary artery flow and cardiac performance in patients with advanced heart failure

Levosimendan has inotropic and vasodilatory effects. We investigated the effects of levosimendan on coronary flow and associated changes in neurohormonal activation and cardiac performance in patients with advanced heart failure.

Prognostic Value of Tissue Doppler Right Ventricular Systolic and Diastolic Function Indexes Combined With Plasma B-Type Natriuretic Peptide in Patients With Advanced Heart Failure Secondary to Ischemic or Idiopathic Dilated Cardiomyopathy

Right ventricular (RV) dysfunction adversely affects prognosis in patients with chronic heart failure (CHF) due to left ventricular (LV) dysfunction. However, little evidence exists regarding the prognostic role of RV systolic and diastolic function indexes in combination with plasma B-type natriuretic peptide (BNP) in advanced CHF. Thus, 102 consecutive hospitalized patients with advanced CHF (New York Heart Association classes III to IV) due to LV systolic dysfunction (LV ejection fraction <35%) were studied by 2-dimensional conventional and tissue Doppler imaging (TDI) echocardiography of the left and right ventricles. Plasma BNP was also measured. Patients were followed for 6 months for major cardiovascular events (cardiovascular death and/or CHF-related hospitalization). During follow-up, 13 patients died and 63 patients reached the combined end point of cardiovascular death or CHF-related hospitalization. By univariate analysis, RV TDI systolic velocity, dilated cardiomyopathy, digoxin treatment (all p values <0.01), and female gender (p <0.05) were associated with increased cardiovascular death. Transmitral Doppler to mitral annular TDI early diastolic velocity ratio, RV TDI early diastolic velocity (p <0.05), and ratio of early to late RV diastolic TDI velocities (p <0.01) predicted the combined end point. In multivariate analysis, decreased RV systolic velocity, dilated cardiomyopathy, and female gender (all p values <0.05) were independent predictors of cardiovascular death, whereas increased ratio of early to late RV diastolic TDI velocities (p <0.01) and increased BNP (p <0.05) predicted the combined end point. In conclusion, RV TDI indexes combined with increased plasma BNP additively predict adverse cardiac outcomes in advanced CHF.

Long-term primary cultures of human adult atrial cardiac myocytes: cell viability, structural properties and BNP secretion in vitro.

BACKGROUND Human adult cardiomyocytes (CM) have been used in short-term cultures for in vitro studies of the adult myocardium. However, little information is available regarding human adult CMs cultured for long term (>2 weeks). METHODS Human adult CMs were isolated from atrial specimens of 43 patients undergoing cardiopulmonary bypass surgery. Cell viability, cytoskeletal properties, intercellular junctional mediators and responsiveness to extracellular stimuli were monitored in CM cultures for 8 weeks. RESULTS Absolute numbers of CMs decreased through the first 2 weeks, with substantially lower rates of cell loss thereafter. Apoptosis predominated over necrosis as the principal mode of cell death, affecting 4.1+/-1.6% of freshly dissociated cells, that declined in culture (3.6+/-1.0% week 1, 1.3+/-0.5% week 2). CMs maintained rod-shaped morphology and cross-striated expression pattern of sarcomeric proteins desmin and beta-myosin heavy chain for the first 4 weeks. Levels of desmin remained stable on first 3 weeks, but declined thereafter. CMs expressed cardiac-specific adherence molecule N-cadherin throughout the culture duration, indicating conserved contractile potential. CMs remained functional early in culture, as indicated by BNP secretion, with maximal levels on 1st week that declined gradually by week 4. Cell responsiveness to metabolic stresses (serum deprivation) was detected, inducing an early (6 h) 1.8-fold increase in levels of BNP. CONCLUSION Long-term cultured human adult CMs maintain morphological integrity, adult-type cytoskeletal protein expression, cell-cell communication potential and functionality for 3-4 weeks in vitro.

Acute Heart Failure Syndromes in the Elderly: The European Perspective

Acute heart failure (AHF) in the elderly is an increasingly common clinical problem associated with high in-hospital, short- and long-term mortality rates worldwide. Elderly patients with AHF have different clinical and pathophysiological profiles compared with younger ones. Prevalent cardiovascular comorbidities in the elderly are arterial hypertension and atrial fibrillation, whereas ischemic heart disease and associated risk factors are more common in younger patients. There is a need for greater dissemination of heart failure guidelines and for involvement of multidisciplinary teams for optimizing treatment and eliminating disparities in care in this vulnerable patient group across both sides of the Atlantic.

Association of mineralocorticoid receptor antagonist use and in-hospital outcomes in patients with acute heart failure

Mineralocorticoid receptor antagonists (MRAs) constitute a beneficial therapy in chronic heart failure, but their use in the acute heart failure (AHF) setting remains rather unexplored. To assess the effect of MRAs administered during hospitalization on in-hospital outcomes of patients with AHF, we performed a post-hoc analysis of the Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF). Patients of the original study cohort (n = 4953) were categorized according to in-hospital MRA treatment status as MRA-treated (n = 1439) and untreated (n = 3514) subjects. Nearest-neighbor propensity score with 1:1 matching yielded a subsample of pairs of MRA-treated and MRA-untreated patients (n = 1003 in each treatment group) that were balanced in an extensive list of baseline characteristics. In-hospital mortality between MRA-treated and untreated patients were assessed by Cox regression analysis before and after adjustment for known prognostic factors and other concomitantly administered intravenous and oral HF specific therapies. In the matched cohort, in-hospital mortality was 4.2 vs 10.8% in MRA-treated vs untreated patients. Treatment with MRAs was associated with a reduction of in-hospital mortality [HR 0.372 (95% CI, 0.261–0.532), p < 0.001]. This association remained significant after adjustment for known prognostic factors and co-administered intravenous and oral HF therapies [HR: 0.618 (95% CI, 0.383–0.995), p = 0.048]. In conclusion, MRA therapy administered during hospitalization for AHF was associated with reduced in-hospital mortality. The role of MRAs in AHF deserves further examination in adequately powered randomized controlled studies.

Combining angiotensin II receptor 1 antagonism and neprilysin inhibition for the treatment of heart failure

ABSTRACT Sacubitril/valsartan is a novel, first-in-class drug, which combines a neprilysin inhibitor with an angiotensin receptor blocker. Sacubitril inhibits neprilysin endopeptidase, blocking the catabolism of natriuretic peptides (NP), thereby increasing their bioavailability. Valsartan counterbalances the increase of angiotensin II that results from neprilysin inhibition, exerting also the beneficial effects of angiotensin receptor blockers seen in previous HF trials. PARADIGM-HF trial has proved the superiority of sacubitril/valsartan (LCZ696) over ACE inhibitor enalapril to reduce mortality and morbidity of symptomatic HF patients with reduced ejection fraction (HFrEF), setting the grounds for the replacement of ACE inhibitors by sacubitril/valsartan in the management of HFrEF. Sacubitril/valsartan is currently being tested in a phase III trial (PARAGON-HF) in patients with HF with preserved EF. PARAGON-HF is also expected to provide further data regarding the long-term safety of sacubitril/valsartan, hopefully to alleviate concerns regarding the effects of neprilysin inhibition on cognitive function.

Possible mechanisms of direct cardiovascular impact of GLP-1 agonists and DPP4 inhibitors

Diabetes mellitus is a leading cause of cardiovascular morbidity and mortality worldwide. Traditional antidiabetic therapies targeting hyperglycemia reduce diabetic microvascular complications but have minor effects on macrovascular complications, including cardiovascular disease. Instead, cardiovascular complications are improved by antidiabetic medications (metformin) and other therapies (statins, antihypertensive medications) ameliorating insulin resistance and other associated metabolic abnormalities. Novel classes of antidiabetic drugs have proven efficacious in improving glycemia, while at the same time exert beneficial effects on pathophysiologic mechanisms of diabetes-related cardiovascular disease. In the present review, we will present current evidence of the cardiovascular effects of two new classes of antidiabetic medications, glucagon-like peptide 1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP4) inhibitors, focusing from mechanistic preclinical and clinical investigation to late-phase clinical testing.

Congestion in acute heart failure with reduced vs. preserved left ventricular ejection fraction: differences, similarities and remaining gaps: Editorial comment

Acute heart failure (AHF) is defined as the rapid onset or worsening of symptoms and/or signs of heart failure, requiring urgent evaluation and treatment.1 It imposes a significant burden on both patients and health care systems, due to the high mortality rate (30% one year post-discharge) and need for repeated hospitalizations (20% within 30 days and 50% 6 months post-discharge).2 Under the general definition of AHF is encompassed a wide spectrum of clinical presentations, with varying precipitating factors, underlying aetiology, pathophysiologic mechanisms and clinical outcomes. In several large AHF registries, patients with AHF and reduced (HFrEF) vs. preserved ejection fraction (HFpEF) constitute approximately equal 50% fractions of hospitalized patients. These populations differ in their demographic and clinical characteristics and outcomes.2 Patients with HFrEF are more frequently younger males, with history of chronic heart failure and coronary artery disease. They usually present with normal or low blood pressure, weight gain and signs of systemic venous congestion. On the other hand, HFpEF patients are usually older women with new-onset heart failure and several cardiometabolic co-morbidities, presenting with increased blood pressure, less systemic venous congestion and usually no significant weight gain. Although in-hospital mortality is higher in HFrEF, both groups are equally affected by high rates of post-discharge mortality, unplanned outpatient visits and rehospitalizations.3 Venous congestion is the cardinal manifestation in AHF. Two main pathophysiologic mechanisms have been implicated in the development of congestion: first, rapid redistribution of blood volume from the systemic to the pulmonary venous circulation and, second, intravascular volume accumulation in the setting of chronic cardiorenal dysfunction and impaired sodium and water

Nitroxyl donors for acute heart failure: promising newcomers

Acute heart failure (AHF) constitutes a heterogeneous clinical syndrome, which remains a significant challenge for everyday clinical practice, clinical research, and drug development. From the clinical perspective, AHF is characterized by high mortality rates reaching 30% within 1 year following the acute event and the increased need for repeated hospitalizations (20% within 30 days and 50% within 6 months).1 Currently available treatment modalities for AHF offer symptomatic relief in a substantial number of cases, but have failed to improve short and long term outcomes.2 Meanwhile, advances in therapeutic management of AHF have been extremely limited, with several new molecules failing to result in meaningful clinical benefits. Possible reasons for these treatment failures include diverse syndrome pathophysiology [patients with acute decompensation of chronic heart failure (ADCHF) or de novo heart failure with preserved or reduced left ventricular ejection fraction (LVEF)], heterogeneity in patient demographic and clinical characteristics, and inappropriate therapeutic targets/molecules or trial design.3 Regardless of the specific underlying pathophysiology, common contributors to AHF development include impaired cardiac mechanics, cardiac injury, vasoconstriction, endothelial dysfunction, excess neurohormonal activation, and renal dysfunction.4 Clinical manifestations in this setting are predominantly due to a combination of reduced cardiac output, increased left and right heart pressures, and systemic (venous and arterial) vasoconstriction, causing cardiac overload and venous congestion. Although AHF phenotypes share common pathophysiological pathways, the individual contribution of these pathways and the complex interplays among them result in diverse AHF phenotypes, requiring individualized management. In this regard, ADCHF with preserved or reduced LVEF is observed as part of the natural course of the syndrome, may develop during early or advanced clinical stages in patients receiving or not neurohormonal antagonists, and may be precipitated by specific factors (i.e. infection, uncontrolled

Natriuretic peptides in acute coronary syndromes: A new role to predict recurrent ischemic event-related mortality?

Risk stratification in acute coronary syndromes (ACS) has been previously based on the severity of acute clinical presentation, presence of cardiovascular comorbidities, and abnormalities of ischemia-specific biomarkers, most importantly troponins. Natriuretic peptides (NPs), which become elevated upon increased myocardial wall stress, are established diagnostic and prognostic biomarkers in patients with heart failure. Recently, their prognostic potential in ACS has been reported, specifically as predictors of future new-onset heart failure or left ventricular (LV) systolic dysfunction. In the current issue of the Hellenic Journal of Cardiology, a new role of NPs is suggested in ACS as predictors of long-term mortality associated with recurrent cardiac ischemic events, specifically in patients with preserved or mid-range LV ejection fraction upon index ACS. Potential pathophysiological mechanisms that explain the association between augmented NP levels with recurrent myocardial ischemia are hypothesized including the potential of NPs to reflect augmented local and/or systemic inflammation, prothrombotic state, and vascular dysregulation.