Browsing by Author "Flammer, Andreas J. (13007159300)"

Background: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. Methods and Results: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease. Conclusions: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711. © 2018 American Heart Association, Inc.

Aims: We assessed the outcome of hospitalized coronavirus disease 2019 (COVID-19) patients with heart failure (HF) compared with patients with other cardiovascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia). We further wanted to determine the incidence of HF events and its consequences in these patient populations. Methods and results: International retrospective Postgraduate Course in Heart Failure registry for patients hospitalized with COVID-19 and CArdioVascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia) was performed in 28 centres from 15 countries (PCHF-COVICAV). The primary endpoint was in-hospital mortality. Of 1974 patients hospitalized with COVID-19, 1282 had cardiovascular disease and/or risk factors (median age: 72 [interquartile range: 62–81] years, 58% male), with HF being present in 256 [20%] patients. Overall in-hospital mortality was 25% (n = 323/1282 deaths). In-hospital mortality was higher in patients with a history of HF (36%, n = 92) compared with non-HF patients (23%, n = 231, odds ratio [OR] 1.93 [95% confidence interval: 1.44–2.59], P < 0.001). After adjusting, HF remained associated with in-hospital mortality (OR 1.45 [95% confidence interval: 1.01–2.06], P = 0.041). Importantly, 186 of 1282 [15%] patients had an acute HF event during hospitalization (76 [40%] with de novo HF), which was associated with higher in-hospital mortality (89 [48%] vs. 220 [23%]) than in patients without HF event (OR 3.10 [2.24–4.29], P < 0.001). Conclusions: Hospitalized COVID-19 patients with HF are at increased risk for in-hospital death. In-hospital worsening of HF or acute HF de novo are common and associated with a further increase in in-hospital mortality. © 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Background: Cardiac resynchronization therapy (CRT) is a cornerstone in the treatment of selected heart failure patients. However, a relevant proportion of patients do not show beneficial response. Identification of simple, additive, and outcome-relevant selection criteria may improve selection of patients. Objective: We sought to determine whether baseline QRS amplitude is associated with outcome in CRT. Methods: Quantification of intrinsic, pre–CRT implantation QRS amplitude was performed in an observational multinational 2-center retrospective cohort analysis (derivation cohort Zurich, n = 178, 2000–2015; validation cohort Leuven, n = 183, 1999–2016) with a composite end point of all-cause mortality, ventricular assist device implantation, or heart transplantation at 5 years. Results: Higher baseline to peak amplitude in lateral leads (lead I and V6) was associated with a lower risk of reaching the composite end point (lead I: hazard ratio, 0.86 [95% confidence interval, 0.78–0.95] per millivolt, P = .002; lead V6: hazard ratio, 0.94 [95% confidence interval, 0.88–1.00] per millivolt, P = .043). Concordance index–based comparison of quartile, spline, and receiver operating characteristic curve analysis suggested cutoff values of 6 mV for lead I and 3 mV for V6 for optimal discrimination of outcome. External validation confirmed the cutoff of 3 mV in lead V6 as a highly significant discriminator of outcome (P < .001) associated with a risk reduction of 65%. Conclusion: Low QRS amplitude in lateral electrocardiogram leads is associated with higher risk of poor outcome in CRT patients. A cutoff of 3 mV in lead V6 proved highly discriminative. Further studies need to confirm the additive value of QRS amplitude in selection of patients for CRT and to assess whether CRT may be made available to more patients. © 2024

Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology

Acute heart failure (AHF) affects millions of people each year and vasodilators have been a central part of treatment for over 25 years. The haemodynamic effects of vasodilators vary considerably among individual agents. Some vasodilators, such as nitrates, primarily act on the venous system by redistributing the circulating blood volume away from the heart towards the venous capacitance system. Other vasodilators, such as nesiritide, lead to balanced vasodilatation in the arteries and veins, decreasing left ventricular afterload and preload. Considering mechanisms of action, intravenous vasodilators are thought to be effective in patients with AHF, particularly in those with acute pulmonary oedema, where increased cardiac filling pressures and elevated systemic blood pressures occur in the absence of, or with minimal systemic fluid accumulation. However, the 2021 European heart failure guidelines have downgraded the use of vasodilators due to two recent studies and several contemporary meta-analyses failing to show benefit in terms of survival. Thus, there remains no firm recommendation suggesting the use of vasodilator treatment over usual care. In addition, despite repeated efforts to develop new vasodilatory agents, no novel therapy has outperformed traditional AHF management. In parallel with the development of novel vasodilators, changing the design of clinical trials for AHF to consider phenotype diversity of AHF patients remains an unmet need. New randomized clinical trials should particularly focus on subgroups that may mechanistically derive benefit from vasodilators, which may entail moving enrolment of patients to clinical settings close to moment of decompensation, such as the emergency department. © 2025 European Society of Cardiology.

Introduction: The high-risk population of patients with cardiovascular (CV) disease or risk factors (RF) suffering from COVID-19 is heterogeneous. Several predictors for impaired prognosis have been identified. However, with machine learning (ML) approaches, certain phenotypes may be confined to classify the affected population and to predict outcome. This study aimed to phenotype patients using unsupervised ML technique within the International Postgraduate Course Heart Failure Registry for patients hospitalized with COVID-19 and Cardiovascular disease and/or RF (PCHF-COVICAV). Methods: Patients from the eight centres with follow-up data available from the PCHF-COVICAV registry were included in this ML analysis (K-medoids algorithm). Results: Out of 617 patients included into the prospective part of the registry, 458 [median age: 76 (IQR: 65–84) years, 55% male] were analyzed and 46 baseline variables, including demographics, clinical status, comorbidities and biochemical characteristics were incorporated into the ML. Three clusters were extracted by this ML method. Cluster 1 (n = 181) represents mainly women with the least number of overall comorbidities and cardiovascular RF. Cluster 2 (n = 227) is characterized mainly by men with non-CV conditions and less severe symptoms of infection. Cluster 3 (n = 50) mainly represents men with the highest prevalence of cardiac comorbidities and RF, more extensive inflammation and organ dysfunction with the highest 6-month all-cause mortality risk. Conclusions: The ML process has identified three important clinical clusters from hospitalized COVID-19 CV and/or RF patients. The cluster of males with severe CV disease, particularly HF, and multiple RF presenting with increased inflammation had a particularly poor outcome. © 2024 Via Medica.