Predictors of heart failure readmission and all-cause mortality in patients with acute heart failure.

BACKGROUND: Predischarge risk stratification of patients with acute heart failure (AHF) could facilitate tailored treatment and follow-up, however, simple scores to predict short-term risk for HF readmission or death are lacking. METHODS: We sought to develop a congestion-focused risk score using data from a prospective, two-center observational study in adults hospitalized for AHF. Laboratory data were collected on admission. Patients underwent physical examination, 4-zone, and in a subset 8-zone, lung ultrasound (LUS), and echocardiography at baseline. A second LUS was performed before discharge in a subset of patients. The primary endpoint was the composite of HF hospitalization or all-cause death. RESULTS: Among 350 patients (median age 75 years, 43% women), 88 participants (25%) were hospitalized or died within 90 days after discharge. A stepwise Cox regression model selected four significant independent predictors of the composite outcome, and each was assigned points proportional to its regression coefficient: NT-proBNP ≥2000 pg/mL (admission) (3 points), systolic blood pressure < 120 mmHg (baseline) (2 points), left atrial volume index ≥60 mL/m2 (baseline) (1 point) and ≥ 9 B-lines on predischarge 4-zone LUS (3 points). This risk score provided adequate risk discrimination for the composite outcome (HR 1.48 per 1 point increase, 95% confidence interval: 1.32-1.67, p < 0.001, C-statistic: 0.70). In a subset of patients with 8-zone LUS data (n = 176), results were similar (C-statistic: 0.72). CONCLUSIONS: A four-variable risk score integrating clinical, laboratory and ultrasound data may provide a simple approach for risk discrimination for 90-day adverse outcomes in patients with AHF if validated in future investigations.

Appetite and its Regulation: Are there Palatable Interventions for Heart Failure?

PURPOSE OF REVIEW: Obesity is a major driver of heart failure (HF) incidence, and aggravates its pathophysiology. We summarized key reported and ongoing randomized clinical trials of appetite regulation and/or dietary energy restriction in individuals with HF. RECENT FINDINGS: Weight loss can be achieved by structured supervised diet programs with behavioural change, medications, or surgery. The new glucagon-like peptide-1 receptor agonists alone or in combination with other agents (e.g., glucose-dependent insulinotropic polypeptide and glucagon receptor agonists or amylin analogues) potently and sustainably reduce appetite, and, taken together with dietary advice, can produce substantial, life-changing, weight loss approaching that achieved by surgery. To date, data from the STEP-HFpEF trial show meaningful improvements in health status (Kansas City Cardiomyopathy Questionnaire). Effective weight management could relieve several drivers of HF, to complement the existing treatments for HF with both reduced and preserved ejection fraction. Further trials of weight loss interventions will provide more definitive evidence to understand their effects on clinical events in patients with HF.

A case report of myocardial infarction in a young transgender man with testosterone therapy: raising awareness on healthcare issues in the transgender community and a call for further research.

Background: People who are transgender may utilize masculinizing or feminizing gender-affirming hormonal therapy. Testosterone and oestrogen receptors are expressed throughout the cardiovascular system, yet the effects of these therapies on cardiovascular risk and outcomes are largely unknown. We report the case of a young transgender man with no discernible cardiovascular risk factors presenting with an acute coronary syndrome. Case summary: A 31-year-old transgender man utilizing intramuscular testosterone masculinizing gender-affirming hormonal therapy presented with central chest pain radiating to the left arm. He had no past medical history of hypertension, dyslipidaemia, diabetes, or smoking. Electrocardiography demonstrated infero-septal ST depression, and high-sensitivity troponin-I was elevated and increased to 19 686 ng/L. He was diagnosed with a non-ST-segment elevation myocardial infarction. Inpatient coronary angiography confirmed a critical focal lesion in the mid right coronary artery, which was managed with two drug-eluting stents. Medical management (i.e. aspirin, ticagrelor, atorvastatin, ramipril, and bisoprolol) and surveillance of residual plaque disease evident in the long tubular left main stem, proximal left anterior descending, and proximal circumflex vessels was undertaken. The masculinizing gender-affirming hormonal therapy was continued. Discussion: Despite a greater awareness of the potential risk of increased cardiovascular disease in transgender people, the fundamental lack of data regarding cardiovascular outcomes in transgender people may be contributing to healthcare inequalities in this population. We must implement better training, awareness, and research into transgender cardiovascular health to facilitate equitable and evidence-based outcomes.

A review of current key guidelines for managing high-risk patients with diabetes and heart failure and future prospects.

We reviewed recent guidelines on the management of heart failure (HF) in patients with diabetes. Major recommendations in European and US society guidelines were scrutinized. First, sodium-glucose co-transporter 2 inhibitors are now recommended treatments for all patients with symptomatic HF (stage C and D; New York Heart Association class II-IV), irrespective of the presence of type 2 diabetes and left ventricular ejection fraction (LVEF). Second, patients with HF and reduced EF (LVEF ≤40%) should have foundational therapies from four drug classes (sodium-glucose co-transporter 2 inhibitor, angiotensin-receptor neprilysin inhibitor, beta-blocker and mineralocorticoid receptor antagonist). Third, patients with HF with mildly reduced (41%-49%) and preserved (≥50%) LVEF may also benefit from angiotensin-receptor neprilysin inhibitor, beta-blocker and mineralocorticoid receptor antagonist therapy, although evidence for these is less robust. Fourth, selected patients should be considered for other therapies such as diuretics (if congestion), anticoagulation (if atrial fibrillation) and cardiac device therapy. Fifth, glucose-lowering therapies such as thiazolidinediones and certain dipeptidyl peptidase-4 inhibitors (such as saxagliptin and alogliptin) should be avoided in patients with HF. Sixth, guidelines recommend enrolment of patients with HF into exercise rehabilitation and multidisciplinary HF management programmes. Particular attention should be paid to important comorbidities such as obesity, alongside pharmacological therapies. As diabetes and obesity are major risk factors for HF, earlier consideration of, and diagnosis of HF, followed by guideline-directed medical therapy can meaningfully improve patients' lives. Diabetes doctors would do well to understand the basics of such guidelines to help improve all aspects of HF diagnosis and care.

Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials.

BACKGROUND: GLP-1 receptor agonists reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes. However, uncertainty regarding kidney outcomes persists and whether benefits extend to exendin-4-based GLP-1 receptor remains uncertain. We aimed to meta-analyse the most up-to-date evidence on the cardiovascular benefits and risks of GLP-1 receptor agonists from outcome trials in patients with type 2 diabetes. METHODS: We did a meta-analysis, including new data from AMPLITUDE-O, using a random effects model to estimate overall hazard ratio (HR) for MACE; its components; all-cause mortality; hospital admission for heart failure; a composite kidney outcome consisting of development of macroalbuminuria, doubling of serum creatinine, or at least 40% decline in estimated glomerular filtration rate (eGFR), kidney replacement therapy, or death due to kidney disease; worsening of kidney function, based on eGFR change; and odds ratios for key safety outcomes (severe hypoglycaemia, retinopathy, pancreatitis, and pancreatic cancer). We also examined MACE outcome in patient subgroups on the basis of MACE incidence rates in the placebo group, presence or absence of cardiovascular disease, HbA1c level, trial duration, treatment dosing interval, structural homology to human GLP-1 or exendin-4, BMI, age, and eGFR. We searched PubMed for eligible trials reporting MACE (ie, cardiovascular death, myocardial infarction, or stroke), up to June 9, 2021. We meta-analysed data from published randomised placebo-controlled trials testing either injectable or oral GLP-1 receptor agonists in patients with type 2 diabetes. We restricted the search to trials of more than 500 patients with a primary outcome that included cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. This meta-analysis was registered on PROSPERO, CRD42021259711. FINDINGS: Of 98 articles screened, eight trials comprising 60 080 patients fulfilled the prespecified criteria and were included. Overall, GLP-1 receptor agonists reduced MACE by 14% (HR 0·86 [95% CI 0·80-0·93]; p<0·0001), with no significant heterogeneity across GLP-1 receptor agonist structural homology or eight other examined subgroups (all pinteraction≥0·14). GLP-1 receptor agonists reduced all-cause mortality by 12% (HR 0·88 [95% CI 0·82-0·94]; p=0·0001), hospital admission for heart failure by 11% (HR 0·89 [95% CI 0·82-0·98]; p=0·013), and the composite kidney outcome by 21% (HR 0·79 [95% CI 0·73-0·87]; p<0·0001), with no increase in risk of severe hypoglycaemia, retinopathy, or pancreatic adverse effects. In sensitivity analyses removing the only trial restricted to patients with an acute coronary syndrome (ELIXA), all benefits marginally increased, including the outcome of worsening of kidney function, based on eGFR change (HR 0·82 [95% CI 0·69-0·98]; p=0·030). INTERPRETATION: GLP-1 receptor agonists, regardless of structural homology, reduced the risk of individual MACE components, all-cause mortality, hospital admission for heart failure, and worsening kidney function in patients with type 2 diabetes. FUNDING: None.

Effect of Neprilysin Inhibition on Left Ventricular Remodeling in Patients With Asymptomatic Left Ventricular Systolic Dysfunction Late After Myocardial Infarction.

BACKGROUND: Patients with left ventricular (LV) systolic dysfunction after myocardial infarction are at a high risk of developing heart failure. The addition of neprilysin inhibition to renin angiotensin system inhibition may result in greater attenuation of adverse LV remodeling as a result of increased levels of substrates for neprilysin with vasodilatory, antihypertrophic, antifibrotic, and sympatholytic effects. METHODS: We performed a prospective, multicenter, randomized, double-blind, active-comparator trial comparing sacubitril/valsartan 97/103 mg twice daily with valsartan 160 mg twice daily in patients ≥3 months after myocardial infarction with a LV ejection fraction ≤40% who were taking a renin angiotensin system inhibitor (equivalent dose of ramipril ≥2.5 mg twice daily) and a ß-blocker unless contraindicated or intolerant. Patients in New York Heart Association class ≥II or with signs and symptoms of heart failure were excluded. The primary outcome was change from baseline to 52 weeks in LV end-systolic volume index measured using cardiac magnetic resonance imaging. Secondary outcomes included other magnetic resonance imaging measurements of LV remodeling, change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin I, and a patient global assessment of change questionnaire. RESULTS: From July 2018 to June 2019, we randomized 93 patients with the following characteristics: mean age, 60.7±10.4 years; median time from myocardial infarction, 3.6 years (interquartile range, 1.2-7.2); mean LV ejection fraction, 36.8%±7.1%; and median NT-proBNP, 230 pg/mL (interquartile range, 124-404). Sacubitril/valsartan, compared with valsartan, did not significantly reduce LV end-systolic volume index; adjusted between-group difference, -1.9 mL/m2 (95% CI, -4.9 to 1.0); P=0.19. There were no significant between-group differences in NT-proBNP, high-sensitivity cardiac troponin I, LV end-diastolic volume index, left atrial volume index, LV ejection fraction, LV mass index, or patient global assessment of change. CONCLUSIONS: In patients with asymptomatic LV systolic dysfunction late after myocardial infarction, treatment with sacubitril/valsartan did not have a significant reverse remodeling effect compared with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03552575.

Invasive versus medically managed acute coronary syndromes with prior bypass (CABG-ACS): insights into the registry versus randomised trial populations.

BACKGROUND: Coronary artery bypass graft (CABG) patients are under-represented in acute coronary syndrome (ACS) trials. We compared characteristics and outcomes for patients who did and did not participate in a randomised trial of invasive versus non-invasive management (CABG-ACS). METHODS: ACS patients with prior CABG in four hospitals were randomised to invasive or non-invasive management. Non-randomised patients entered a registry. Primary efficacy (composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction (MI), heart failure) and safety outcomes (composite of bleeding, stroke, procedure-related MI, worsening renal function) were independently adjudicated. RESULTS: Of 217 patients screened, 84 (39%) screenfailed, of whom 24 (29%) did not consent and 60 (71%) were ineligible. Of 133 (61%) eligible, 60 (mean±SD age, 71±9 years, 72% male) entered the trial and 73 (age, 72±10 years, 73% male) entered a registry (preferences: physician (79%), patient (38%), both (21%)).Compared with trial participants, registry patients had more valve disease, lower haemoglobin, worse New York Heart Association class and higher frailty.At baseline, invasive management was performed in 52% and 49% trial and registry patients, respectively, of whom 32% and 36% had percutaneous coronary intervention at baseline, respectively (p=0.800). After 2 years follow-up (694 (median, IQR 558-841) days), primary efficacy (43% trial vs 49% registry (HR 1.14, 95% CI 0.69 to 1.89)) and safety outcomes (28% trial vs 22% registry (HR 0.74, 95% CI 0.37 to 1.46)) were similar. EuroQol was lower in registry patients at 1 year. CONCLUSIONS: Compared with trial participants, registry participants had excess morbidity, but longer-term outcomes were similar. TRIAL REGISTRATION NUMBER: NCT01895751.

Invasive Versus Medical Management in Patients With Prior Coronary Artery Bypass Surgery With a Non-ST Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The benefits of routine invasive management in patients with prior coronary artery bypass grafts presenting with non-ST elevation acute coronary syndromes are uncertain because these patients were excluded from pivotal trials. METHODS: In a multicenter trial, non-ST elevation acute coronary syndromes patients with prior coronary artery bypass graft were prospectively screened in 4 acute hospitals. Medically stabilized patients were randomized to invasive management (invasive group) or noninvasive management (medical group). The primary outcome was adherence with the randomized strategy by 30 days. A blinded, independent Clinical Event Committee adjudicated predefined composite outcomes for efficacy (all-cause mortality, rehospitalization for refractory ischemia/angina, myocardial infarction, hospitalization because of heart failure) and safety (major bleeding, stroke, procedure-related myocardial infarction, and worsening renal function). RESULTS: Two hundred seventeen patients were screened and 60 (mean±SD age, 71±9 years, 72% male) were randomized (invasive group, n=31; medical group, n=29). One-third (n=10) of the participants in the invasive group initially received percutaneous coronary intervention. In the medical group, 1 participant crossed over to invasive management on day 30 but percutaneous coronary intervention was not performed. During 2-years' follow-up (median [interquartile range], 744 [570-853] days), the composite outcome for efficacy occurred in 13 (42%) subjects in the invasive group and 13 (45%) subjects in the medical group. The composite safety outcome occurred in 8 (26%) subjects in the invasive group and 9 (31%) subjects in the medical group. An efficacy or safety outcome occurred in 17 (55%) subjects in the invasive group and 16 (55%) subjects in the medical group. Health status (EuroQol 5 Dimensions) and angina class in each group were similar at 12 months. CONCLUSIONS: More than half of the population experienced a serious adverse event. An initial noninvasive management strategy is feasible. A substantive health outcomes trial of invasive versus noninvasive management in non-ST elevation acute coronary syndromes patients with prior coronary artery bypass grafts appears warranted. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01895751.

Statins in the Prevention and Treatment of Heart Failure: a Review of the Evidence.

PURPOSE OF REVIEW: We summarize the best evidence for statins in the prevention and treatment of heart failure. RECENT FINDINGS: In patients with cardiovascular risk factors or established atherosclerotic cardiovascular disease (but without heart failure), statins reduce the risk of incident heart failure-mainly by preventing myocardial infarction although an additional benefit from reducing myocardial ischemia cannot be excluded. However, in patients with established heart failure, statins do not reduce the risk of cardiovascular death, which is mainly caused by pump failure and ventricular arrhythmias. Retrospective analyses, however, suggest that statins may reduce the rate of heart failure hospitalization and atherosclerotic events (which are proportionately much less common in these patients than heart failure hospitalization or death). Statin therapy should probably be continued in patients with coronary artery disease developing heart failure, although the weak evidence and small benefit may not justify the use of this treatment in very elderly patients with a short life expectancy and in which polypharmacy is a problem.

Non-invasive versus invasive management in patients with prior coronary artery bypass surgery with a non-ST segment elevation acute coronary syndrome: study design of the pilot randomised controlled trial and registry (CABG-ACS).

INTRODUCTION: There is an evidence gap about how to best treat patients with prior coronary artery bypass grafts (CABGs) presenting with non-ST segment elevation acute coronary syndromes (NSTE-ACS) because historically, these patients were excluded from pivotal randomised trials. We aim to undertake a pilot trial of routine non-invasive management versus routine invasive management in patients with NSTE-ACS with prior CABG and optimal medical therapy during routine clinical care. Our trial is a proof-of-concept study for feasibility, safety, potential efficacy and health economic modelling. We hypothesise that a routine invasive approach in patients with NSTE-ACS with prior CABG is not superior to a non-invasive approach with optimal medical therapy. METHODS AND ANALYSIS: 60 patients will be enrolled in a randomised clinical trial in 4 hospitals. A screening log will be prospectively completed. Patients not randomised due to lack of eligibility criteria and/or patient or physician preference and who give consent will be included in a registry. We will gather information about screening, enrolment, eligibility, randomisation, patient characteristics and adverse events (including post-discharge). The primary efficacy outcome is the composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction and hospitalisation for heart failure. The primary safety outcome is the composite of bleeding, stroke, procedure-related myocardial infarction and worsening renal function. Health status will be assessed using EuroQol 5 Dimensions (EQ-5D) assessed at baseline and 6 monthly intervals, for at least 18 months. TRIAL REGISTRATION NUMBER: NCT01895751 (ClinicalTrials.gov).

Fractional flow reserve vs. angiography in guiding management to optimize outcomes in non-ST-segment elevation myocardial infarction: the British Heart Foundation FAMOUS-NSTEMI randomized trial.

AIM: We assessed the management and outcomes of non-ST segment elevation myocardial infarction (NSTEMI) patients randomly assigned to fractional flow reserve (FFR)-guided management or angiography-guided standard care. METHODS AND RESULTS: We conducted a prospective, multicentre, parallel group, 1 : 1 randomized, controlled trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% of the lumen diameter assessed visually (threshold for FFR measurement) (NCT01764334). Enrolment took place in six UK hospitals from October 2011 to May 2013. Fractional flow reserve was disclosed to the operator in the FFR-guided group (n = 176). Fractional flow reserve was measured but not disclosed in the angiography-guided group (n = 174). Fractional flow reserve ≤0.80 was an indication for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). The median (IQR) time from the index episode of myocardial ischaemia to angiography was 3 (2, 5) days. For the primary outcome, the proportion of patients treated initially by medical therapy was higher in the FFR-guided group than in the angiography-guided group [40 (22.7%) vs. 23 (13.2%), difference 95% (95% CI: 1.4%, 17.7%), P = 0.022]. Fractional flow reserve disclosure resulted in a change in treatment between medical therapy, PCI or CABG in 38 (21.6%) patients. At 12 months, revascularization remained lower in the FFR-guided group [79.0 vs. 86.8%, difference 7.8% (-0.2%, 15.8%), P = 0.054]. There were no statistically significant differences in health outcomes and quality of life between the groups. CONCLUSION: In NSTEMI patients, angiography-guided management was associated with higher rates of coronary revascularization compared with FFR-guided management. A larger trial is necessary to assess health outcomes and cost-effectiveness.