Petar Seferovic

Assessing and grading congestion in acute heart failure: a scientific statement from the Acute Heart Failure Committee of the Heart Failure Association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine

Patients with acute heart failure (AHF) require urgent in‐hospital treatment for relief of symptoms. The main reason for hospitalization is congestion, rather than low cardiac output. Although congestion is associated with a poor prognosis, many patients are discharged with persistent signs and symptoms of congestion and/or a high left ventricular filling pressure. Available data suggest that a pre‐discharge clinical assessment of congestion is often not performed, and even when it is performed, it is not done systematically because no method to assess congestion prior to discharge has been validated. Grading congestion would be helpful for initiating and following response to therapy. We have reviewed a variety of strategies to assess congestion which should be considered in the care of patients admitted with HF. We propose a combination of available measurements of congestion. Key elements in the measurement of congestion include bedside assessment, laboratory analysis, and dynamic manoeuvres. These strategies expand by suggesting a routine assessment of congestion and a pre‐discharge scoring system. A point system is used to quantify the degree of congestion. This score offers a new instrument to direct both current and investigational therapies designed to optimize volume status during and after hospitalization. In conclusion, this document reviews the available methods of evaluating congestion, provides suggestions on how to properly perform these measurements, and proposes a method to quantify the amount of congestion present.

Recommendations on pre-hospital and early hospital management of acute heart failure : a consensus paper from the Heart Failure Association of the European Society of Cardiology, the European Society of Emergency Medicine and the Society of Academic Emergency Medicine - short version

Despite several critical steps forward in the management of chronic heart failure (CHF), the area of acute heart failure (AHF) has remained relatively stagnant. As stated in the updated ESC HF guidelines, clinicians responsible for managing patients with AHF must frequently make treatment decisions without adequate evidence, usually on the basis of expert opinion consensus.2 Specifically, the treatment of acute HF remains largely opinion-based with little good evidence to guide therapy. Acute heart failure is a syndrome in which emergency physicians, cardiologists, intensivists, nurses, and other healthcare providers have to cooperate to provide ‘rapid’ benefit to the patients. We hereby would like to underscore the wider experience grown in different settings of the area of intensive care on acute heart failure, actually larger and more composite than that got in specialized Care Units. The distillate of such different experiences is discussed and integrated in the present document. Hence, the authors of this consensus paper believe a common working definition of AHF covering all dimensions and modes of presentations has to be made, with the understanding that most AHF presentations are either acute decompensations of chronic underlying HF or the abrupt onset of dyspnoea associated with significantly elevated blood pressure. Secondly, recent data show that, much like acute coronary syndrome, AHF might have a ‘time to therapy’ concept. Accordingly, ‘pre-hospital’ management is considered a critical component of care. Thirdly, most patients with AHF have normal or high blood pressure at presentation, and are admitted with symptoms and/or signs of congestion. This is in contradiction to the presentation where low cardiac output leads to symptomatic hypotension and signs/symptoms of hypoperfusion, a circumstance that is relatively rare, present in coronary care unit/intensive care unit (CCU/ICU) but associated with a particularly poor outcome. Hence, it is important to note that appropriate therapy requires appropriate identification of the specific AHF phenotype.3 The aim of the current paper is not to replace guidelines, but, to provide contemporary perspective for early hospital management within the context of the most recent data and to provide guidance, based on expert opinions, to practicing physicians and other healthcare professionals (Figure 1). We believe that the experience accrued in the different settings from the emergency department through to the ICU/CCU is collectivel valuable in determining how best to manage the patients with AHF. Herein, a shortened version mainly including group recommendations is provided. Full version of the consensus paper is provided as Supplementary material online.

European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT): 1-year follow-up outcomes and differences across regions

The European Society of Cardiology Heart Failure Long‐Term Registry (ESC‐HF‐LT‐R) was set up with the aim of describing the clinical epidemiology and the 1‐year outcomes of patients with heart failure (HF) with the added intention of comparing differences between participating countries.

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Aims Cardiopoietic cells, produced through cardiogenic conditioning of patients’ mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. Methods and results This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein–Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann–Whitney estimator 0.54, 95% confidence interval [CI] 0.47–0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200–370 mL (60% of patients) (Mann–Whitney estimator 0.61, 95% CI 0.52–0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. Conclusion The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.

ExtraHF survey: the first European survey on implementation of exercise training in heart failure patients

In heart failure (HF), exercise training programmes (ETPs) are a well‐recognized intervention to improve symptoms, but are still poorly implemented. The Heart Failure Association promoted a survey to investigate whether and how cardiac centres in Europe are using ETPs in their HF patients.

Cardio-Renal Effects of the A1 Adenosine Receptor Antagonist SLV320 in Patients With Heart Failure

Background—Blocking the tubuloglomerular feedback mechanism with adenosine A1 receptor antagonists seems to improve diuresis and sodium excretion without compromising the glomerular filtration rate in patients with heart failure. However, the direct cardiac effects of this compound class have not been investigated to date. Methods and Results—In total, 111 patients (109 men and 2 women) received a 1-hour infusion of 5, 10, and 15 mg SLV320, an adenosine A1 receptor antagonist, placebo, or 40 mg furosemide. Mean age was 57.9 years, mean ejection fraction was 28.1%, 82 patients were of New York Heart Association class II, and 29 patients were of New York Heart Association class III. Hemodynamic parameters (heart rate, blood pressure, pulmonary capillary wedge pressure, mean pulmonary arterial pressure, systemic vascular resistance, right atrial pressure, and cardiac output) were determined. Kidney function was assessed by cystatin C measurements and by analysis of urine output and urine electrolytes. In addition, pharmacokinetics of SLV320 and ex vivo inhibition of adenosine A1 receptor activity were performed. SLV320 was well tolerated, and no serious adverse events were observed. Heart rate, blood pressure, pulmonary capillary wedge pressure, mean pulmonary arterial pressure, right atrial pressure, and cardiac output were not altered by any dose of SLV320. Pulmonary capillary wedge pressure was significantly (P=0.04) decreased by furosemide (−6.2±5.9 mm Hg). Systemic vascular resistance was significantly (P=0.04) increased in the furosemide group (+166.70±261.87 dynes · s−1 · cm−5), whereas all SLV320 groups showed no significant alterations of systemic vascular resistance. Changes from baseline cystatin C plasma concentrations decreased after 10 mg SLV320 (−0.093±0.137 mg/L, P=0.046), whereas furosemide resulted in a significant (P=0.03) increase of cystatin C (+0.052±0.065 mg/L) versus baseline. All values represent mean changes±SD from baseline at 3 hours postdosing: SLV320 (10 and 15 mg) increased significantly sodium excretion and diuresis compared with placebo during the 0- to 6-hour collection period postdosing. Conclusions—SLV320 infusion shows no immediate effects on cardiac hemodynamics. SLV320 might improve glomerular filtration rate while simultaneously promoting natriuresis and diuresis. Clinical Trial Registration—clinicaltrials.gov Indentifier: NCT00160134.

Rationale and benefits of trimetazidine by acting on cardiac metabolism in heart failure

Heart failure is a systemic and multiorgan syndrome with metabolic failure as a fundamental mechanism. As a consequence of its impaired metabolism, other processes are activated in the failing heart, further exacerbating the progression of heart failure. Recent evidence suggests that modulating cardiac energy metabolism by reducing fatty acid oxidation and/or increasing glucose oxidation represents a promising approach to the treatment of patients with heart failure. Clinical trials have demonstrated that the adjunct of trimetazidine to the conventional medical therapy improves symptoms, cardiac function and prognosis in patients with heart failure without exerting negative hemodynamic effects. This review focuses on the rationale and clinical benefits of trimetazidine by acting on cardiac metabolism in heart failure, and aims to draw attention to the readiness of this agent to be included in all the major guidelines dealing with heart failure.

Effect of Left Ventricular Assist Device Implantation and Heart Transplantation on Habitual Physical Activity and Quality of Life

The present study defined the short- and long-term effects of left ventricular assist device (LVAD) implantation and heart transplantation (HT) on physical activity and quality of life (QoL). Forty patients (LVAD, n = 14; HT, n = 12; and heart failure [HF], n = 14) and 14 matched healthy subjects were assessed for physical activity, energy expenditure, and QoL. The LVAD and HT groups were assessed postoperatively at 4 to 6 weeks (baseline) and 3, 6, and 12 months. At baseline, LVAD, HT, and HF patients demonstrated low physical activity, reaching only 15%, 28%, and 51% of that of healthy subjects (1,603 ± 302 vs 3,036 ± 439 vs 5,490 ± 1,058 vs 10,756 ± 568 steps/day, respectively, p <0.01). This was associated with reduced energy expenditure and increased sedentary time (p <0.01). Baseline QoL was not different among LVAD, HT, and HF groups (p = 0.44). LVAD implantation and HT significantly increased daily physical activity by 60% and 52%, respectively, from baseline to 3 months (p <0.05), but the level of activity remained unchanged at 3, 6, and 12 months. The QoL improved from baseline to 3 months in LVAD implantation and HT groups (p <0.01) but remained unchanged afterward. At any time point, HT demonstrated higher activity level than LVAD implantation (p <0.05), and this was associated with better QoL. In contrast, physical activity and QoL decreased at 12 months in patients with HF (p <0.05). In conclusion, patients in LVAD and HT patients demonstrate improved physical activity and QoL within the first 3 months after surgery, but physical activity and QoL remain unchanged afterward and well below that of healthy subjects. Strategies targeting low levels of physical activity should now be explored to improve recovery of these patients.

Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology

The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30–40% of patients) and associated with a higher risk of HF hospitalization, all‐cause and cardiovascular (CV) mortality. The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium. T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both disorders in the clinical practice. There are no specific limitations to HF treatment in T2DM. Subanalyses of trials addressing HF treatment in the general population have shown that all HF therapies are similarly effective regardless of T2DM. Concerning T2DM treatment in HF patients, most guidelines currently recommend metformin as the first‐line choice. Sulphonylureas and insulin have been the traditional second‐ and third‐line therapies although their safety in HF is equivocal. Neither glucagon‐like preptide‐1 (GLP‐1) receptor agonists, nor dipeptidyl peptidase‐4 (DPP4) inhibitors reduce the risk for HF hospitalization. Indeed, a DPP4 inhibitor, saxagliptin, has been associated with a higher risk of HF hospitalization. Thiazolidinediones (pioglitazone and rosiglitazone) are contraindicated in patients with (or at risk of) HF. In recent trials, sodium–glucose co‐transporter‐2 (SGLT2) inhibitors, empagliflozin and canagliflozin, have both shown a significant reduction in HF hospitalization in patients with established CV disease or at risk of CV disease. Several ongoing trials should provide an insight into the effectiveness of SGLT2 inhibitors in patients with HFrEF and HFpEF in the absence of T2DM.

Diffusion-weighted MRI versus transient elastography in quantification of liver fibrosis in patients with chronic cholestatic liver diseases

PURPOSE To evaluate the diagnostic value of diffusion-weighted magnetic resonance imaging (DWMRI) and transient elastography (TE) in quantification of liver fibrosis in patients with chronic cholestatic liver diseases. MATERIALS AND METHODS Forty-five patients underwent DWMRI, TE, and liver biopsy for staging of liver fibrosis. Apparent diffusion coefficient (ADC) was calculated for six locations in the liver for combination of five diffusion sensitivity values b=0, 50, 200, 400 and 800 s/mm(2). A receiver operating characteristic (ROC) analysis was performed to determine the diagnostic performance of DWMRI and TE. Segmental ADC variations were evaluated by means of coefficient of variation. RESULTS The mean ADCs (× 10(-3)mm(2)/s; b=0-800 s/mm(2)) were significantly different at stage F1 versus F ≥ 2 (p<0.05) and F2 versus F4. However, no significant difference was found between F2 and F3. For prediction of F ≥ 2 and F ≥ 3 areas under the ROC curves were 0.868 and 0.906 for DWMRI, and 0.966 and 0.960 for TE, respectively. The sensitivity and specificity were 90.9% and 89.3% for F ≥ 2 (ADC ≤ 1.65), and 92.3% and 92.1% for F ≥ 3 (ADC ≤ 1.63). Segmental ADC variation was lowest for F4 (CV=9.54 ± 6.3%). CONCLUSION DWMRI and TE could be used for assessment of liver fibrosis with TE having higher diagnostic accuracy and DWMRI providing insight into liver fibrosis distribution.