Biomarker profiles associated with reverse ventricular remodelling in patients with heart failure and a reduced ejection fraction:Insights from the echocardiographic substudy of the VICTORIA trial

Aims: Reverse ventricular remodelling, defined as a decrease in left ventricular end-systolic volume indexed to body surface area (LVESVI) or an increase in left ventricular ejection fraction (LVEF), is associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, the underlying pathophysiological mechanisms remain unclear. Methods and results: We evaluated paired core-lab assessed echocardiograms and measurements of 92 biomarkers at baseline and 8 months thereafter in 419 participants with HFrEF. Reverse ventricular remodelling was defined as a &gt;5% LVEF increase or &gt;15% LVESVI relative decrease between baseline and 8 months. We evaluated the association between baseline biomarkers and their changes with reverse ventricular remodelling in the prospectively randomized controlled VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) trial. Of 419 patients (median age 66 [interquartile range 57–74] years, 27.4% women), 206 (49.2%) had reverse ventricular remodelling (either a 5% LVEF increase or a 15% LVESVI decrease). There were no differences in baseline biomarker concentrations between patients with versus those without reverse ventricular remodelling on follow-up. However, in patients with reverse ventricular remodelling there were significant decreases in biomarkers relating to inflammation and cardiac metabolism; particularly the tumour necrosis factor superfamily member 13B (ratio 0.82, 95% confidence interval [CI] 0.77–0.88), growth differentiation factor-15 (ratio 0.74, 95% CI 0.66–0.84), and insulin-like growth factor binding protein 7 (ratio 0.80, 95% CI 0.73–0.88). Conclusions: Reverse ventricular remodelling in patients with HFrEF is associated with a decrease of biomarkers related to inflammation and cardiac metabolism.</p

Biomarker profiles associated with reverse ventricular remodelling in patients with heart failure and a reduced ejection fraction:Insights from the echocardiographic substudy of the VICTORIA trial

Aims: Reverse ventricular remodelling, defined as a decrease in left ventricular end-systolic volume indexed to body surface area (LVESVI) or an increase in left ventricular ejection fraction (LVEF), is associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, the underlying pathophysiological mechanisms remain unclear. Methods and results: We evaluated paired core-lab assessed echocardiograms and measurements of 92 biomarkers at baseline and 8 months thereafter in 419 participants with HFrEF. Reverse ventricular remodelling was defined as a &gt;5% LVEF increase or &gt;15% LVESVI relative decrease between baseline and 8 months. We evaluated the association between baseline biomarkers and their changes with reverse ventricular remodelling in the prospectively randomized controlled VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) trial. Of 419 patients (median age 66 [interquartile range 57–74] years, 27.4% women), 206 (49.2%) had reverse ventricular remodelling (either a 5% LVEF increase or a 15% LVESVI decrease). There were no differences in baseline biomarker concentrations between patients with versus those without reverse ventricular remodelling on follow-up. However, in patients with reverse ventricular remodelling there were significant decreases in biomarkers relating to inflammation and cardiac metabolism; particularly the tumour necrosis factor superfamily member 13B (ratio 0.82, 95% confidence interval [CI] 0.77–0.88), growth differentiation factor-15 (ratio 0.74, 95% CI 0.66–0.84), and insulin-like growth factor binding protein 7 (ratio 0.80, 95% CI 0.73–0.88). Conclusions: Reverse ventricular remodelling in patients with HFrEF is associated with a decrease of biomarkers related to inflammation and cardiac metabolism.</p

Vericiguat in patients with atrial fibrillation and heart failure with reduced ejection fraction:insights from the VICTORIA trial

Aims We evaluated the relation between baseline and new-onset atrial fibrillation (AF) and outcomes, and assessed whether vericiguat modified the likelihood of new-onset AF in patients with worsening heart failure (HF) with reduced ejection fraction in VICTORIA. Methods and results Of 5050 patients randomized, 5010 with recorded AF status at baseline were analysed. Patients were classified into three groups: no known AF (n = 2661, 53%), history of AF alone (n = 992, 20%), and AF on randomization electrocardiogram (n = 1357, 27%). Compared with those with no AF, those with history of AF alone had a higher risk of cardiovascular death [adjusted hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.01-1.47] without excess myocardial infarction or stroke; neither type of AF was associated with a higher risk of the primary composite outcome (time to cardiovascular death or first HF hospitalization), HF hospitalizations, or all cause-death. The beneficial effect of vericiguat on the primary composite outcome and its components was evident irrespective of AF status at baseline. Over a median follow-up of 10.8 months, new-onset AF occurred in 6.1% of those with no AF and 18.3% with history of AF alone (P < 0.0001). These events were not influenced by vericiguat treatment (adjusted HR 0.93, 95% CI 0.75-1.16; P = 0.51), but were associated with an increase in the hazard of both primary and secondary outcomes. Conclusions Atrial fibrillation was present in nearly half of this high-risk population with worsening HF. A history of AF alone at baseline portends an increased risk of cardiovascular death. Neither type of AF affected the beneficial effect of vericiguat. Development of AF post-randomization was associated with an increase in both cardiovascular death and HF hospitalization which was not influenced by vericiguat

Age, sex, and setting in the etiology of stroke study (ASSESS): Study design and protocol

RATIONALE: Stroke etiology and risk factors vary by age, sex, setting (hospital or community-based) and by region. Identifying these differences would improve our understanding of stroke etiology, diagnosis, and treatment. AIM: The Age, Sex and Setting in the Etiology of Stroke Study (ASSESS) is a multicenter cohort study to assess differences in stroke etiology. METHODS AND DESIGN: Data from all centers will be categorized according to age, sex, setting, stroke subtypes. Centers with extensive hospital- or community-based data regarding stroke from Argentina, Australia, Canada, India, Iran, Italy, Ghana, Nigeria, Thailand, the United Kingdom and the United States have agreed to participate so far. STUDY OUTCOMES: The primary outcome includes differences in stroke etiology in study centers. The secondary outcomes include stroke incidence, risk factors, preventive strategies, and short- and long-term outcomes. CONCLUSION: ASSESS will enable comparisons of data from different regions to determine the age and sex distribution of the most common causes of stroke in each setting. This will help clinicians to tailor the assessment and treatment of stroke patients on the basis of their specific local characteristics. It will also empower stroke epidemiologists to design preventive measures by targeting the specific characteristics of each population

Empagliflozin in acute myocardial infarction in patients with and without type 2 diabetes : A pre-specified analysis of the EMPACT-MI trial

Aims: In the EMPACT-MI trial, empagliflozin reduced heart failure (HF) hospitalizations but not mortality in acute myocardial infarction (MI). Contemporary reports of clinical event rates with and without type 2 diabetes mellitus (T2DM) in acute MI trials are sparse. The treatment effect of empagliflozin in those with and without T2DM in acute MI is unknown. Methods and results: A total of 6522 patients with acute MI with newly reduced left ventricular ejection fraction (LVEF) to <45%, congestion, or both, were randomized to empagliflozin 10 mg or placebo. The primary endpoint was time to first HF hospitalization or all-cause death. Rates of endpoints with and without T2DM and the efficacy and safety of empagliflozin according to T2DM status were assessed. Overall, 32% had T2DM; 14% had pre-diabetes; 16% were normoglycaemic; 38% had unknown glycaemic status. Patients with T2DM, compared to those without T2DM, were at higher risk of time to first HF hospitalization or all-cause death (hazard ratio [HR] 1.44; 95% confidence interval [CI] 1.06-1.95) and all-cause death (HR 1.70; 95% CI 1.13-2.56). T2DM did not confer a higher risk of first HF hospitalization (HR 1.22, 95% CI 0.82-1.83). Empagliflozin reduced first and total HF hospitalizations, but not all-cause mortality, regardless of presence or absence of T2DM. The safety profile of empagliflozin was the same with and without T2DM. Conclusion: Patients with acute MI, LVEF <45% and/or congestion who had T2DM were at a higher risk of mortality than those without T2DM. Empagliflozin reduced first and total HF hospitalizations regardless of the presence or absence of T2DM

World Stroke Organization Brain & hEart globAl iniTiative Program

Introduction. The World Stroke Organization (WSO) Brain & Heart Task Force developed The Brain & hEart globAl iniTiative (BEAT), a pilot feasibility implementation program aimed at establishing clinical collaborations between cardiologists and stroke physicians who work at large healthcare facilities. Methods. The WSO BEAT pilot project focused on atrial fibrillation (AF) and patent foramen ovale (PFO) detection and management, and post-stroke cardiovascular complications known as the stroke-heart syndrome. The program included 10 sites from 8 countries: Brazil, China, Egypt, Germany, Japan, Mexico, Romania, and the USA. The primary composite feasibility outcome was the achievement of the following 3 implementation metrics (1) developing site-specific clinical pathways for the diagnosis and management of AF, PFO, and the stroke heart syndrome; (2) establishing regular Neurocardiology rounds (e.g., monthly); and (3) incorporating a cardiologist to the stroke team. The secondary objectives were (1) to identify implementation challenges to guide a larger program and (2) to describe qualitative improvements.Results. The WSO BEAT pilot feasibility program achieved the pre-specified primary composite outcome in 9 of 10 (90%) sites. The most common challenges were the limited access to specific medications (e.g., direct oral anticoagulants) and diagnostic (e.g., prolonged cardiac monitoring) or therapeutic (e.g., PFO closure devices) technologies. The most relevant qualitative improvement was the achievement of a more homogeneous diagnostic and therapeutic approach.Discussion/Conclusion. The WSO BEAT pilot program showed that developing Neurocardiology collaborations is feasible. The long-term sustainability of the WSO BEAT program and its impact on quality of stroke care and clinical outcomes needs to be tested in a larger and longer-duration program

World Stroke Organization Brain & hEart globAl iniTiative Program

Introduction. The World Stroke Organization (WSO) Brain & Heart Task Force developed The Brain & hEart globAl iniTiative (BEAT), a pilot feasibility implementation program aimed at establishing clinical collaborations between cardiologists and stroke physicians who work at large healthcare facilities. Methods. The WSO BEAT pilot project focused on atrial fibrillation (AF) and patent foramen ovale (PFO) detection and management, and post-stroke cardiovascular complications known as the stroke-heart syndrome. The program included 10 sites from 8 countries: Brazil, China, Egypt, Germany, Japan, Mexico, Romania, and the USA. The primary composite feasibility outcome was the achievement of the following 3 implementation metrics (1) developing site-specific clinical pathways for the diagnosis and management of AF, PFO, and the stroke heart syndrome; (2) establishing regular Neurocardiology rounds (e.g., monthly); and (3) incorporating a cardiologist to the stroke team. The secondary objectives were (1) to identify implementation challenges to guide a larger program and (2) to describe qualitative improvements.Results. The WSO BEAT pilot feasibility program achieved the pre-specified primary composite outcome in 9 of 10 (90%) sites. The most common challenges were the limited access to specific medications (e.g., direct oral anticoagulants) and diagnostic (e.g., prolonged cardiac monitoring) or therapeutic (e.g., PFO closure devices) technologies. The most relevant qualitative improvement was the achievement of a more homogeneous diagnostic and therapeutic approach.Discussion/Conclusion. The WSO BEAT pilot program showed that developing Neurocardiology collaborations is feasible. The long-term sustainability of the WSO BEAT program and its impact on quality of stroke care and clinical outcomes needs to be tested in a larger and longer-duration program

Left Ventricular Function, Congestion, and Effect of Empagliflozin on Heart Failure Risk After Myocardial Infarction

Background: Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). Objectives: This study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI. Methods: In the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both, to empagliflozin (10 mg daily) or placebo and were followed up for a median of 17.9 months. Results: Among 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF <45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95% CI: 1.31-1.69; P < 0.0001), first HF hospitalization (HR: 1.64; 95% CI: 1.37-1.96; P < 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95% CI: 1.51-2.36; P < 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95% CI: 0.60-0.98) and total (RR: 0.67; 95% CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status. Conclusions: In patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion. (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction [EMPACT-MI]; NCT04509674

Ischemic Stroke Prevention in Patients Atrial Fibrillation and a Recent Ischemic Stroke, TIA, or Intracranial Hemorrhage; a World Stroke Organisation (WSO) Scientific Statement.

BACKGROUND: Secondary stroke prevention in patients with atrial fibrillation (AF) is one of the fastest growing areas in the field of cerebrovascular diseases. This Scientific statement from the World Stroke Organization Brain & Heart Task Force provides a critical analysis of the strength of current evidence this topic, highlights areas of current controversy, identifies knowledge gaps, and proposes priorities for future research. METHODS: We select topics with the highest clinical relevance and perform a systematic search to answer specific practical questions. Based on the strength of available evidence and knowledge gaps, we identify topics that need to be prioritized in future research. For this purpose, we adopt a novel classification of evidence strength based on the availability of publications in which the primary population is patients with recent (<6 months) cerebrovascular events, whether the primary study endpoint is a recurrent ischemic stroke, and the quality of the studies (e.g., observational vs. randomized controlled trial). SUMMARY: Priority areas include AF screening, molecular biomarkers, AF subtype classification, anticoagulation in device-detected AF, timing of anticoagulation initiation, effective management of breakthrough strokes on existing anticoagulant therapy, the role of left atrial appendage closure, novel approaches, and antithrombotic therapy post-intracranial hemorrhage. Strength of currently available evidence varies across the selected topics, with early anticoagulation being the one showing more consistent data. CONCLUSION: Several knowledge gaps persist in most areas related to secondary stroke prevention in AF. Prioritizing research in this field is crucial to advance current knowledge and improve clinical care

Left Ventricular Function, Congestion, and Effect of Empagliflozin on Heart Failure Risk After Myocardial Infarction

Background: Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). Objectives: This study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI. Methods: In the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF&lt;45%, congestion, or both, to empagliflozin (10 mg daily) or placebo and were followed up for a median of 17.9 months. Results: Among 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF &lt;45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95% CI: 1.31-1.69; P &lt; 0.0001), first HF hospitalization (HR: 1.64; 95% CI: 1.37-1.96; P &lt; 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95% CI: 1.51-2.36; P &lt; 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95% CI: 0.60-0.98) and total (RR: 0.67; 95% CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status. Conclusions: In patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion.</p