Sex Disparities in Longitudinal Use and Intensification of Guideline-Directed Medical Therapy Among Patients With Newly Diagnosed Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Guideline-directed medical therapies (GDMTs) are the mainstay of treatment for heart failure with reduced ejection fraction (HFrEF), but they are underused. Whether sex differences exist in the initiation and intensification of GDMT for newly diagnosed HFrEF is not well established. METHODS: Patients with incident HFrEF were identified from the 2016 to 2020 Optum deidentified Clinformatics Data Mart Database, which is derived from a database of administrative health claims for members of large commercial and Medicare Advantage health plans. The primary outcome was the use of optimal GDMT within 12 months of HFrEF diagnosis. Consistent with the guideline recommendations during the time period of the study, optimal GDMT was defined as ≥50% of the target dose of evidence-based beta-blocker plus ≥50% of the target dose of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, or any dose of angiotensin receptor neprilysin inhibitor plus any dose of mineralocorticoid receptor antagonist. The probability of achieving optimal GDMT on follow-up and predictors of optimal GDMT were evaluated with time-to-event analysis with adjusted Cox proportional hazard models. RESULTS: The study cohort included 63 759 patients (mean age, 71.3 years; 15.2% non-Hispanic Black race; 56.6% male). Optimal GDMT use was achieved by 6.2% of patients at 12 months after diagnosis. Female (compared with male) patients with HFrEF had lower use across every GDMT class and lower use of optimal GDMT at each time point at follow-up. In an adjusted Cox model, female sex was associated with a 23% lower probability of achieving optimal GDMT after diagnosis (hazard ratio [HR], 0.77 [95% CI, 0.71-0.83]; P<0.001). The sex disparities in GDMT use after HFrEF diagnosis were most pronounced among patients with commercial insurance (females compared with males; HR, 0.66 [95% CI, 0.58-0.76]) compared with Medicare (HR, 0.85 [95% CI, 0.77-0.92]); Pinteraction sex×insurance status=0.005) and for younger patients (age <65 years: HR, 0.65 [95% CI, 0.58-0.74]) compared with older patients (age ≥65 years: HR, 87 [95% CI, 80-96]) Pinteraction sex×age=0.009). CONCLUSIONS: Overall use of optimal GDMT after HFrEF diagnosis was low, with significantly lower use among female (compared with male) patients. These findings highlight the need for implementation efforts directed at improving GDMT initiation and titration.

Epidemiology of heart failure in diabetes: a disease in disguise.

Left ventricular diastolic dysfunction (LVDD) without symptoms, and heart failure (HF) with preserved ejection fraction (HFpEF) represent the most common phenotypes of HF in individuals with type 2 diabetes mellitus, and are more common than HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and left ventricular systolic dysfunction (LVSD) in these individuals. However, diagnostic criteria for HF have changed over the years, resulting in heterogeneity in the prevalence/incidence rates reported in different studies. We aimed to give an overview of the diagnosis and epidemiology of HF in type 2 diabetes, using both a narrative and systematic review approach; we focus narratively on diagnosing (using the 2021 European Society of Cardiology [ESC] guidelines) and screening for HF in type 2 diabetes. We performed an updated (2016-October 2022) systematic review and meta-analysis of studies reporting the prevalence and incidence of HF subtypes in adults ≥18 years with type 2 diabetes, using echocardiographic data. Embase and MEDLINE databases were searched and data were assessed using random-effects meta-analyses, with findings presented as forest plots. From the 5015 studies found, 209 were screened using the full-text article. In total, 57 studies were included, together with 29 studies that were identified in a prior meta-analysis; these studies reported on the prevalence of LVSD (n=25 studies, 24,460 individuals), LVDD (n=65 studies, 25,729 individuals), HFrEF (n=4 studies, 4090 individuals), HFmrEF (n=2 studies, 2442 individuals) and/or HFpEF (n=8 studies, 5292 individuals), and on HF incidence (n=7 studies, 17,935 individuals). Using Hoy et al's risk-of-bias tool, we found that the studies included generally had a high risk of bias. They showed a prevalence of 43% (95% CI 37%, 50%) for LVDD, 17% (95% CI 7%, 35%) for HFpEF, 6% (95% CI 3%, 10%) for LVSD, 7% (95% CI 3%, 15%) for HFrEF, and 12% (95% CI 7%, 22%) for HFmrEF. For LVDD, grade I was found to be most prevalent. Additionally, we reported a higher incidence rate of HFpEF (7% [95% CI 4%, 11%]) than HFrEF 4% [95% CI 3%, 7%]). The evidence is limited by the heterogeneity of the diagnostic criteria over the years. The systematic section of this review provides new insights on the prevalence/incidence of HF in type 2 diabetes, unveiling a large pre-clinical target group with LVDD/HFpEF in which disease progression could be halted by early recognition and treatment.Registration PROSPERO ID CRD42022368035.

Outpatient Worsening Among Patients With Mildly Reduced and Preserved Ejection Fraction Heart Failure in the DELIVER Trial.

BACKGROUND: Hospitalization is recognized as a sentinel event in the disease trajectory of patients with heart failure (HF), but not all patients experiencing clinical decompensation are ultimately hospitalized. Outpatient intensification of diuretics is common in response to symptoms of worsening HF, yet its prognostic and clinical relevance, specifically for patients with HF with mildly reduced or preserved ejection fraction, is uncertain. METHODS: In this prespecified analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure), we assessed the association between various nonfatal worsening HF events (those requiring hospitalization, urgent outpatient visits requiring intravenous HF therapies, and outpatient oral diuretic intensification) and rates of subsequent mortality. We further examined the treatment effect of dapagliflozin on an expanded composite end point of cardiovascular death, HF hospitalization, urgent HF visit, or outpatient oral diuretic intensification. RESULTS: In DELIVER, 4532 (72%) patients experienced no worsening HF event, whereas 789 (13%) had outpatient oral diuretic intensification, 86 (1%) required an urgent HF visit, 585 (9%) had an HF hospitalization, and 271 (4%) died of cardiovascular causes as a first presentation. Patients with a first presentation manifesting as outpatient oral diuretic intensification experienced rates of subsequent mortality that were higher (10 [8-12] per 100 patient-years) than those without a worsening HF event (4 [3-4] per 100 patient-years) but similar to rates of subsequent death after an urgent HF visit (10 [6-18] per 100 patient-years). Patients with an HF hospitalization as a first presentation of worsening HF had the highest rates of subsequent death (35 [31-40] per 100 patient-years). The addition of outpatient diuretic intensification to the adjudicated DELIVER primary end point (cardiovascular death, HF hospitalization, or urgent HF visit) increased the overall number of patients experiencing an event from 1122 to 1731 (a 54% increase). Dapagliflozin reduced the need for outpatient diuretic intensification alone (hazard ratio, 0.72 [95% CI, 0.64-0.82]) and when analyzed as a part of an expanded composite end point of worsening HF or cardiovascular death (hazard ratio, 0.76 [95% CI, 0.69-0.84]). CONCLUSIONS: In patients with HF with mildly reduced or preserved ejection fraction, worsening HF requiring oral diuretic intensification in ambulatory care was frequent, adversely prognostic, and significantly reduced by dapagliflozin. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03619213.

Management of Atrial Fibrillation Across the Spectrum of Heart Failure With Preserved and Reduced Ejection Fraction.

Atrial fibrillation (AF) is the most common arrhythmia among patients with heart failure (HF), and HF is the most common cause of death for patients presenting with clinical AF. AF is frequently associated with pathological atrial myocardial dysfunction and remodeling, a triad that has been called atrial myopathy. AF can be the cause or consequence of clinical HF, and the directionality varies between individual patients and across the spectrum of HF. Although initial trials suggested no advantage for a systematic rhythm control strategy in HF with reduced ejection fraction, recent data suggest that select patients may benefit from attempts to maintain sinus rhythm with catheter ablation. Preliminary data also show a close relationship among AF, left atrial myopathy, mitral regurgitation, and HF with preserved ejection, with potential clinical benefits to catheter ablation therapy. The modern management of AF in HF also requires consideration of the degree of atrial myopathy and chronicity of AF, in addition to the pathogenesis and phenotype of the underlying left ventricular HF. In this review, we summarize the contemporary management of AF and provide practical guidance and areas in need of future investigation.

High cortisol levels are associated with oxidative stress and mortality in maintenance hemodialysis patients.

BACKGROUND: Chronic stimulation of the mineralocorticoid receptor has been suggested as one of the potential causes of cardiovascular events and death in patients with end-stage renal disease. This observational cohort study was performed to demonstrate that serum cortisol might be a predictive marker for patient mortality and to evaluate its association with oxidized low-density lipoprotein (oxLDL) in hemodialysis (HD) patients. METHODS: Patients receiving HD three times a week were screened for enrollment at two institutions. Baseline cortisol levels were measured before each HD session, and the patients were divided into two groups according to the median value of serum cortisol before analysis. The baseline characteristics and laboratory values of the high and low cortisol groups were compared. Serum cortisol, adrenocorticotropic hormone, renin, aldosterone, and oxLDL were measured in 52 patients to evaluate the effect of oxidative stress on serum cortisol levels. RESULTS: A total of 133 HD patients were enrolled in this cohort study. Compared to the patients with low serum cortisol levels, the patients with high serum cortisol levels (baseline cortisol ≥ 10 µg/dL) showed higher rates of cardiovascular disease (59.7% vs. 39.4%, P=0.019) and left ventricular systolic dysfunction (LVSD) (25.9% vs. 8.0%, P=0.016). The patients in the high cortisol group demonstrated higher all-cause mortality than those in the low cortisol group. The serum cortisol level was an independent risk factor for patient mortality (hazard ratio 1.234, 95% confidence interval 1.022-1.49, P=0.029). Among the 52 patients with oxLDL measurements, oxLDL was an independent risk factor for elevated serum cortisol levels (Exp(B) 1.114, P=0.013) and LVSD (Exp(B) 12.308, P=0.045). However, plasma aldosterone levels did not affect serum cortisol levels. CONCLUSIONS: Serum cortisol is a useful predictive marker for all-cause death among patients receiving HD. OxLDL is an independent marker for elevated serum cortisol among HD patients.

Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist.

RATIONALE: Gq signaling in cardiac myocytes is classically considered toxic. Targeting Gq directly to test this is problematic, because cardiac myocytes have many Gq-coupled receptors. OBJECTIVE: Test whether Gq coupling is required for the cardioprotective effects of an alpha-1A-AR (adrenergic receptor) agonist. METHODS AND RESULTS: In recombinant cells, a mouse alpha-1A-AR with a 6-residue substitution in the third intracellular loop does not couple to Gq signaling. Here we studied a knockin mouse with this alpha-1A-AR mutation. Heart alpha-1A receptor levels and antagonist affinity in the knockin were identical to wild-type. In wild-type cardiac myocytes, the selective alpha-1A agonist A61603-stimulated phosphoinositide-phospholipase C and myocyte contraction. In myocytes with the alpha-1A knockin, both A61603 effects were absent, indicating that Gq coupling was absent. Surprisingly, A61603 activation of cardioprotective ERK (extracellular signal-regulated kinase) was markedly impaired in the KI mutant myocytes, and A61603 did not protect mutant myocytes from doxorubicin toxicity in vitro. Similarly, mice with the α1A KI mutation had increased mortality after transverse aortic constriction, and A61603 did not rescue cardiac function in mice with the Gq coupling-defective alpha-1A receptor. CONCLUSIONS: Gq coupling is required for cardioprotection by an alpha-1A-AR agonist. Gq signaling can be adaptive.

Excess Mortality Associated With Functional Tricuspid Regurgitation Complicating Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Functional tricuspid regurgitation (FTR) is common in heart failure with reduced ejection fraction and mostly consequent to pulmonary hypertension. However, the intrinsic clinical implications of FTR are not fully understood. METHODS: The cohort of all Mayo Clinic patients from 2003 to 2011 diagnosed with heart failure stage B-C and ejection fraction<50%, with FTR grading and systolic pulmonary artery pressure estimation by Doppler echocardiography was identified and outcomes were analyzed. Patients with pacemakers/defibrillators, organic valve disease, or previous valve surgery were excluded. The primary outcome measure was overall mortality (censored at implantation of a defibrillator, ventricular assist device, or cardiac transplantation), adjusting for clinical and echocardiographic associates with mortality and major comorbidities. RESULTS: Among 13 026 patients meeting inclusion criteria, FTR was detected in 88% (N=11 507: 33% trivial, 32% mild, 17% moderate, and 6% severe), aged 68±14 years, 35% women, ejection fraction 36±10%, systolic pulmonary artery pressure 41±14 mm Hg with 20% atrial fibrillation. Covariates independently associated with FTR included elevated systolic pulmonary artery pressure, older age, female sex, lower ejection fraction, mitral regurgitation, and atrial fibrillation (all P<0.0001). FTR was independently associated with more dyspnea, impaired kidney function, and lower cardiac output ( P<0.003 for all). For long-term outcome, higher FTR degree compared with trivial tricuspid regurgitation was independently associated with higher mortality (adjusted hazard ratios 1.09 [1.01-1.17] for mild FTR, 1.21 [1.11-1.33] for moderate FTR and 1.57 [1.39-1.78] for severe FTR); hence, 5-year survival was substantially lower with increasing severity of functional FTR, 68±1% for trivial FTR, 58±2% for mild FTR, 45±2% for moderate FTR, and 34±4% for severe FTR. CONCLUSIONS: In this large cohort of patients with heart failure with reduced ejection fraction, FTR was common and independently associated with pulmonary hypertension, atrial fibrillation, and more severe heart failure presentation. Long-term, higher FTR severity is associated with considerably worse survival, independently of baseline characteristics. Given these untoward outcomes associated with FTR in patients with heart failure with reduced ejection fraction, clinical trials should be directed at testing FTR treatment.

[Cardiomyopathy in a 22-year-old man with a long history of methamphetamine abuse]. / Kardiomyopathie bei einem 22-Jährigen mit langjährigem Methamphetaminkonsum.

This article presents the case of a 22-year-old male patient with cardiomyopathy associated with a long history of methamphetamine abuse. Echocardiography revealed a dilated cardiomyopathy with highly reduced systolic pump function and severe mitral valve regurgitation. Inotropic treatment and MitraClip® (Abbott Vascular, Santa Clara, CA, USA) implantation resulted in enhancement of hemodynamics. The rising prevalence of methamphetamine abuse should give reason to raise awareness for the diagnostic work-up and patient history particularly in cases of unexplained cardiomyopathy in young patients.

Age and Outcomes of Primary Prevention Implantable Cardioverter-Defibrillators in Patients With Nonischemic Systolic Heart Failure.

BACKGROUND: The DANISH study (Danish Study to Assess the Efficacy of ICDs [Implantable Cardioverter Defibrillators] in Patients With Non-Ischemic Systolic Heart Failure on Mortality) did not demonstrate an overall effect on all-cause mortality with ICD implantation. However, the prespecified subgroup analysis suggested a possible age-dependent association between ICD implantation and mortality with survival benefit seen only in the youngest patients. The nature of this relationship between age and outcome of a primary prevention ICD in patients with nonischemic systolic heart failure warrants further investigation. METHODS: All 1116 patients from the DANISH study were included in this prespecified subgroup analysis. We assessed the relationship between ICD implantation and mortality by age, and an optimal age cutoff was estimated nonparametrically with selection impact curves. Modes of death were divided into sudden cardiac death and nonsudden death and compared between patients younger and older than this age cutoff with the use of χ2 analysis. RESULTS: Median age of the study population was 63 years (range, 21-84 years). There was a linearly decreasing relationship between ICD and mortality with age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.003-1.06; P=0.03). An optimal age cutoff for ICD implantation was present at ≤70 years. There was an association between reduced all-cause mortality and ICD in patients ≤70 years of age (HR, 0.70; 95% CI, 0.51-0.96; P=0.03) but not in patients >70 years of age (HR, 1.05; 95% CI, 0.68-1.62; P=0.84). For patients ≤70 years old, the sudden cardiac death rate was 1.8 (95% CI, 1.3-2.5) and nonsudden death rate was 2.7 (95% CI, 2.1-3.5) events per 100 patient-years, whereas for patients >70 years old, the sudden cardiac death rate was 1.6 (95% CI, 0.8-3.2) and nonsudden death rate was 5.4 (95% CI, 3.7-7.8) events per 100 patient-years. This difference in modes of death between the 2 age groups was statistically significant (P=0.01). CONCLUSIONS: In patients with systolic heart failure not caused by ischemic heart disease, the association between the ICD and survival decreased linearly with increasing age. In this study population, an age cutoff for ICD implantation at ≤70 years yielded the highest survival for the population as a whole. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00542945.

Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo-controlled, dose-ranging hemodynamic study.

BACKGROUND: Pulmonary hypertension caused by systolic left ventricular dysfunction is associated with significant morbidity and mortality; however, no treatment is approved for this indication. We hypothesized that riociguat, a novel soluble guanylate cyclase stimulator, would have beneficial hemodynamic effects in patients with pulmonary hypertension caused by systolic left ventricular dysfunction. METHODS AND RESULTS: Overall, 201 patients with heart failure resulting from pulmonary hypertension caused by systolic left ventricular dysfunction were randomized to double-blind treatment with oral placebo or riociguat (0.5, 1, or 2 mg 3 times daily) for 16 weeks in 4 parallel arms. The primary outcome was the placebo-corrected change from baseline at week 16 in mean pulmonary artery pressure. Although the decrease in mean pulmonary artery pressure in the riociguat 2 mg group (-6.1±1.3 mm Hg; P<0.0001 versus baseline) was not significantly different from placebo (P=0.10), cardiac index (0.4 L·min(-1)·m(-2); 95% confidence interval, 0.2-0.5; P=0.0001) and stroke volume index (5.2 mL·m(-2); 95% confidence interval, 2.0-8.4; P=0.0018) were significantly increased without changes in heart rate or systemic blood pressure compared with placebo. Both pulmonary (-46.6 dynes·s(-1)·cm(-5); 95% confidence interval, -89.4 to -3.8; P=0.03) and systemic vascular resistance (-239.3 dynes·s(-1)·cm(-5); 95% confidence interval, -363.4 to -115.3; P=0.0002) were significantly reduced with riociguat 2 mg. Riociguat reduced the Minnesota Living With Heart Failure score (P=0.0002). Discontinuation of treatment was similar between treatment groups. CONCLUSIONS: Although the primary end point of the study was not met, riociguat was well tolerated in patients with pulmonary hypertension caused by systolic left ventricular dysfunction and improved cardiac index and pulmonary and systemic vascular resistance. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01065454.

Treating iron deficiency in patients with heart failure: what, why, when, how, where and who.

For patients with heart failure and reduced or mildly reduced left ventricular ejection fraction, iron deficiency is common and associated with more severe symptoms, worse quality of life and an increased risk of hospitalisations and death. Iron deficiency can be swiftly, effectively and safely treated by administering intravenous iron, either as ferric carboxymaltose or ferric derisomaltose, which improves patient well-being and reduces the risk of hospitalisations including those for heart failure. However, the current definition of iron deficiency in heart failure has serious flaws. A serum ferritin <100 µg/L does not identify patients more likely to respond to intravenous iron. In contrast, patients with transferrin saturations <20%, most of whom are also anaemic, are more likely to have a beneficial response to intravenous iron. In this review, we summarise the available evidence for use of intravenous iron in heart failure and provide recommendations for targeted future research and practical considerations for the general cardiologist.

Characterisation of the octogenarians presenting to the diagnostic heart failure clinic: SHEAF registry.

INTRODUCTION: Heart failure (HF) incidence is increasing in older adults with high hospitalisation and mortality rates. Treatment is complicated by side effects and comorbidities. We investigated the clinical characteristics of octogenarians presenting to the HF clinic. METHODS: Data were collected on octogenarians (80-89 years) referred to the HF clinic in two periods. The data included demographics, HF phenotype, comorbidities, symptoms and treatment. We investigate the temporal changes in clinical characteristics using χ2 test. We aimed to determine the clinical characteristics which were associated with optimisation of HF pharmacological intervention in the clinic, conducting multivariate regression analysis. Statistical significance is determined at p<0.05. RESULTS: Data were collected in April 2012 to January 2014 and in June 2021 to December 2022. In this cross-sectional study of temporal data, 571 octogenarians were referred to the clinic in the latter period, in whom the prevalence of HF was 68.48% (391 patients). HF with preserved ejection fraction (HFpEF) was the most common phenotype and increased significantly compared with the first period (46.3% and 29.2%, p<0.001). Frailty, chronic kidney disease and ischaemic heart disease increased significantly versus the first period (p<0.001). During the second period, and following the consultation, of the patients with HF with reduced ejection fraction (HFrEF), 86.4% and 82.7% were on a beta blocker and on an ACE inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, respectively. Clinical characteristics associated with further optimisations of HF pharmacological therapy in the HF clinic were: New York Heart Association (NYHA) functional class III and the presence of HFrEF phenotype CONCLUSIONS: With a prevalence of HF at 68% among the octogenarians referred to the HF clinic, HFpEF incidence is rising. The decision to optimise HF pharmacological treatment in octogenarians is driven by NYHA functional class III and the presence of HFrEF phenotype.

Effects of trimetazidine on heart failure with reduced ejection fraction and associated clinical outcomes: a systematic review and meta-analysis.

BACKGROUND: Despite maximal treatment, heart failure (HF) remains a major clinical challenge. Besides neurohormonal overactivation, myocardial energy homoeostasis is also impaired in HF. Trimetazidine has the potential to restore myocardial energy status by inhibiting fatty acid oxidation, concomitantly enhancing glucose oxidation. Trimetazidine is an interesting adjunct treatment, for it is safe, easy to use and comes at a low cost. OBJECTIVE: We conducted a systematic review to evaluate all available clinical evidence on trimetazidine in HF. We searched Medline/PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov to identify relevant studies. METHODS: Out of 213 records, we included 28 studies in the meta-analysis (containing 2552 unique patients), which almost exclusively randomised patients with HF with reduced ejection fraction (HFrEF). The studies were relatively small (median study size: N=58) and of short duration (mean follow-up: 6 months), with the majority (68%) being open label. RESULTS: Trimetazidine in HFrEF was found to significantly reduce cardiovascular mortality (OR 0.33, 95% CI 0.21 to 0.53) and HF hospitalisations (OR 0.42, 95% CI 0.29 to 0.60). In addition, trimetazidine improved (New York Heart Association) functional class (mean difference: -0.44 (95% CI -0.49 to -0.39), 6 min walk distance (mean difference: +109 m (95% CI 105 to 114 m) and quality of life (standardised mean difference: +0.52 (95% CI 0.32 to 0.71). A similar pattern of effects was observed for both ischaemic and non-ischaemic cardiomyopathy. CONCLUSIONS: Current evidence supports the potential role of trimetazidine in HFrEF, but this is based on multiple smaller trials of varying quality in study design. We recommend a large pragmatic randomised clinical trial to establish the definitive role of trimetazidine in the management of HFrEF.

Tissue inhibitor of metalloproteinase (TIMP)-1 predicts failure of recovery of ejection fraction in acute heart failure with reduced ejection fraction.

BACKGROUND: Heart failure (HF) with improved ejection fraction (HFimpEF) is a recently identified phenotype of HF, which had better cardiovascular outcomes compared with persistent HF with reduced ejection fraction (HFrEF). The present study aimed to investigate the predictive value of tissue inhibitor of metalloproteinase (TIMP)-1 and matrix metalloproteinases-9 (MMP-9) in the recovery of left ventricular ejection fraction (LVEF). METHODS: Subjects who presented with acute decompensated HF and reduced LVEF of ≤40% were eligible for this study. HFimpEF was defined by a follow-up LVEF >40% and a ≥10% improvement in LVEF. Overnight fasting N-terminal pro-brain natriuretic peptide (NT-proBNP), MMP-9 and TIMP-1 were measured within 24 hours before discharge. The study participants were followed for up to 5 years. RESULTS: Among a total of 91 participants (70.1±16.2 years, baseline LVEF 28.9±7.6%), 19 (20.8%) of them had HFimpEF and 72 (79.2%) had persistent HFrEF at 6 months. The receiver operating characteristic curve analyses showed the area under curve measures for TIMP-1, MMP-9 and NT-proBNP in the prediction of HFimpEF were 0.69, 0.52 and 0.65, respectively. TIMP-1 was negatively correlated with HFimpEF as continuous variables (OR per 1-SD and 95% CI 0.99 (0.98 to 1.00)) and categorical variables (cut-off value 200.68 ng/mL, OR and 95% CI 0.16 (0.05 to 0.54)) after adjustment of confounding factors. During a mean follow-up duration 34.8 months, patients with HFimpEF will have better long-term survival than those with persistent HFrEF. CONCLUSIONS: In subjects with decompensated HFrEF, TIMP-1, but not MMP-9 was associated with the reverse remodelling in LVEF. In addition, patients with HFimpEF would have better long-term survival.

Colchicine in acute myocardial infarction: cardiovascular events at 1-year follow up.

OBJECTIVE: In the COVERT-MI randomised placebo-controlled trial, oral administration of high-dose colchicine at the time of reperfusion and for 5 days in acute ST-elevated myocardial infarction did not reduce infarct size but was associated with a significant increase in left ventricular thrombus (LVT) in comparison to placebo. We aimed to assess the 1-year clinical outcomes of the study population. METHODS: This study is a follow-up analysis of the COVERT-MI study on prespecified secondary clinical endpoints at 1 year. The primary endpoint of this study was a composite of major adverse cardiovascular events (MACEs), including all-cause death, acute coronary syndromes, heart failure events, ischaemic strokes, sustained ventricular arrhythmias and acute kidney injury at 1-year follow-up. The quality of life (QOL) and the drug therapy prescription were also assessed. RESULTS: At 1 year, 192 patients (101 patients in the colchicine group, 91 in the placebo group) were followed up. Seventy-six (39.6%) MACEs were reported in the study population. There was no significant difference regarding the number of MACEs between groups: 36 (35.6%) in the colchicine group and 40 (44.1%) in the placebo group (p=0.3). There were no differences in the occurrence of ischaemic strokes between the colchicine group and the control group (3 (3%) vs 2 (2.2%), respectively, p=0.99). There was a trend towards fewer heart failure events in the colchicine group compared with the placebo group (12 (11.9%) vs 18 (19.8%), p=0.20). There was no significant difference in QOL scores at 1 year (75.8±15.7 vs 72.7±16.2 respectively, p=0.18). CONCLUSIONS: There was no significant difference between the colchicine and placebo groups at 1 year regarding MACEs, especially concerning deaths or ischaemic strokes. No excess of ischaemic adverse events was observed despite the initial increase in LVT in the colchicine group. TRIAL REGISTRATION NUMBER: NCT0315681.