Risk of adverse events with liraglutide in heart failure with reduced ejection fraction: A post hoc analysis of the FIGHT trial.

AIM: To perform a post hoc analysis of the FIGHT trial, evaluating the effect of liraglutide (vs. placebo) on the totality of events in patients with heart failure with reduced ejection fraction (HFrEF). MATERIALS AND METHODS: FIGHT was a double-blind randomized controlled trial (RCT) that studied liraglutide versus placebo in 300 recently hospitalized patients with HFrEF followed for 180 days. The main outcome of the present analysis was total events of hospitalizations for heart failure (HF) or all-cause death. Secondary outcomes included total arrhythmic events and prespecified total events of interest (arrhythmias, sudden cardiac death, acute coronary syndrome, worsening HF, cerebrovascular event, venous thromboembolism, lightheadedness, presyncope/syncope or worsening renal function). Treatment effect was evaluated with negative binomial regression. RESULTS: Compared to placebo, there was a trend towards increased risk with liraglutide of total HF hospitalizations or all-cause deaths (96 vs. 143 events, incidence rate ratio [IRR] 1.41, 95% confidence interval [CI] 0.98-2.04; P = 0.064) and total arrhythmias (21 vs. 39, IRR 1.76, 95% CI 0.92-3.37; P = 0.088). Total prespecified events of interest were increased with liraglutide compared to placebo (196 vs. 295, IRR 1.43, 95% CI 1.06-1.92; P = 0.018). The risk of HF hospitalizations or all-cause deaths with liraglutide was higher among patients in New York Heart Association (NYHA) Class III to IV (IRR 1.86, 95% CI 1.21-2.85) than in those in NYHA Class I to II (IRR 0.62, 95% CI 0.31-1.23; interaction P = 0.008), and among patients with diabetes (interaction P = 0.051). The risk of arrhythmic events was higher among those without an implanted cardiac device (interaction P = 0.047). CONCLUSIONS: In patients with HFrEF, liraglutide might increase the risk of cardiovascular adverse effects, an effect possibly driven by excess risk of arrhythmias and worsening HF events. As this was a post hoc analysis, these results should be interpreted as exploratory and hypothesis-generating. Further RCTs must be conducted before drawing definitive conclusions.

Predictive value of cardiac magnetic resonance right ventricular longitudinal strain in patients with suspected myocarditis.

BACKGROUND: Recent evidence underlined the importance of right (RV) involvement in suspected myocarditis. We aim to analyze the possible incremental prognostic value from RV global longitudinal strain (GLS) by CMR. METHODS: Patients referred for CMR, meeting clinical criteria for suspected myocarditis and no other cardiomyopathy were enrolled in a dual-center register cohort study. Ejection fraction (EF), GLS and tissue characteristics were assessed in both ventricles to assess their association to first major adverse cardiovascular events (MACE) including hospitalization for heart failure (HF), ventricular tachycardia (VT), recurrent myocarditis and death. RESULTS: Among 659 patients (62.8% male; 48.1 ± 16.1 years), RV GLS was impaired (> - 15.4%) in 144 (21.9%) individuals, of whom 76 (58%), 108 (77.1%), 27 (18.8%) and 40 (32.8%) had impaired right ventricular ejection fraction (RVEF), impaired left ventricular ejection fraction (LVEF), RV late gadolinium enhancement (LGE) or RV edema, respectively. After a median observation time of 3.7 years, 45 (6.8%) patients were hospitalized for HF, 42 (6.4%) patients died, 33 (5%) developed VT and 16 (2.4%) had recurrent myocarditis. Impaired RV GLS was associated with MACE (HR = 1.07, 95% CI 1.04-1.10; p < 0.001), HF hospitalization (HR = 1.17, 95% CI 1.12-1.23; p < 0.001), and death (HR = 1.07, 95% CI 1.02-1.12; p = 0.004), but not with VT and recurrent myocarditis in univariate analysis. RV GLS lost its association with outcomes, when adjusted for RVEF, LVEF, LV GLS and LV LGE extent. CONCLUSION: RV strain is associated with MACE, HF hospitalization and death but has neither independent nor incremental prognostic value after adjustment for RV and LV function and tissue characteristics. Therefore, assessing RV GLS in the setting of myocarditis has only limited value.

[Characteristics and treatment of hospitalized patients with CHF].

The article analyzes some characteristics of hospitalized patients with decompensated chronic heart failure (HF) according to data from Russian and international registries, management of decompensated HF, and tactics for titration of evidence-based disease-modified therapies. The demographic characteristics of the patients from the registers that were used for the research are similar. Yet, the proportion of HF patients with preserved LVEF was greater according to data from several Russian studies. Meanwhile, with the patients that did not receive any loop diuretics and therefore had apparently no congestion signs being excluded from the analysis, the proportion of HF patients with preserved LVEF became similar to that from the international studies. The registers also showed that pulmonary edema and acute left ventricular failure were observed in less than a half of the cases. Nevertheless, patients with mild congestion symptoms still have bad lingering prognosis and require the same amount of medical attention. Up to 40 % of admissions for decompensated CHF resulted from a dietary disorder (excessive sodium consumption), low compliance with therapy and lack of access to primary care providers. Furthermore, the analysis of the outpatient treatment administered prior to the forthcoming hospitalization showed a low prescription rate of evidence-based disease-modifying therapies (ACEi or ARNi, BB, MRA). It is emphasized that in part of patients the administration and/or titration of this therapy can be started during hospitalization. The article also discusses the use of a new class of drugs, angiotensin receptor-neprilysin inhibitors (ARNi), including not only transferring patients from ACEi to ARNi but also the possibility of administering ARNi to stable, hospitalized patients who do not require intravenous diuretics and inotropic drugs.

Permanent Pacemaker Implantation and Long-Term Outcomes of Patients Undergoing Concomitant Mitral and Tricuspid Valve Surgery.

BACKGROUND: Tricuspid valve annuloplasty (TA) during mitral valve repair (MVr) is associated with increased risk of permanent pacemaker (PPM) implantation, but the magnitude of risk and long-term clinical consequences have not been firmly established. OBJECTIVES: This study assesses the incidence rates of PPM implantation after isolated MVr and following MVr with TA as well as the associated long-term clinical consequences of PPM implantation. METHODS: State-mandated hospital discharge databases of New York and California were queried for patients undergoing MVr (isolated or with concomitant TA) between 2004 and 2019. Patients were stratified by whether or not they received a PPM within 90 days of index surgery. After weighting by propensity score, survival, heart failure hospitalizations (HFHs), endocarditis, stroke, and reoperation were compared between patients with or without PPM. RESULTS: A total of 32,736 patients underwent isolated MVr (n = 28,003) or MVr + TA (n = 4,733). Annual MVr + TA volumes increased throughout the study period (P < 0.001, trend), and PPM rates decreased (P < 0.001, trend). The incidence of PPM implantation <90 days after surgery was 7.7% for MVr and 14.0% for MVr + TA. In 90-day conditional landmark-weighted analyses, PPMs were associated with reduced long-term survival among MVr (HR: 1.96; 95% CI: 1.75-2.19; P < 0.001) and MVr + TA recipients (HR: 1.65; 95% CI: 1.28-2.14; P < 0.001). In both surgical groups, PPMs were also associated with an increased risk of HFH (HR: 1.56; 95% CI: 1.27-1.90; P < 0.001) and endocarditis (HR: 1.95; 95% CI: 1.52-2.51; P < 0.001), but not with stroke or reoperation. CONCLUSIONS: Compared to isolated MVr, adding TA to MVr was associated with a higher risk of 90-day PPM implantation. In both surgical groups, PPM implantation was associated with an increase in mortality, HFH, and endocarditis.

Impact of new drug releases on heart failure management and hospitalizations in France: A repeated cross-sectional study between 2014 and 2023.

Real-life data on the impact of sacubitril-valsartan and sodium-glucose cotransporter type 2 (SGLT-2) inhibitors on heart failure (HF) in France is lacking. Using French health insurance databases, we examined the ten-year evolution in HF medication use, focusing on SGLT-2 inhibitors and sacubitril/valsartan, and incidence of HF hospitalizations during the same period. We conducted a repeated cross-sectional study using medical-administrative data from French health insurance databases between 2014 and 2023. These included "OpenMedic" for outpatient medication reimbursements and "ScanSanté" for annual hospitalization data. Medications were classified using ATC codes, and hospitalizations were identified using ICD-10 codes. Statistical analyses encompassed annual rates of users and boxes dispensed for HF medications, along with HF, ischemic heart disease and ischemic stroke hospitalization rates. Prevalence of SGLT-2 inhibitors and sacubitril-valsartan use was also studied regionally, with direct standardization by age and sex, with the French population as the standard population. Between 2014 and 2023, HF drug use increased significantly, with beta-blockers and ACE inhibitors/ARBs leading in prevalence of use. ARNi and SGLT-2 inhibitors, introduced later, showed remarkable rises: +506% and +3766% in users since their market introduction, respectively. Meanwhile, HF hospitalizations slightly increased by +3.6% between 2016 and 2019, followed by a notable decline of -12.5% during 2019-2023, coinciding with the introduction of SGLT-2 inhibitors. In contrast, hospitalizations for ischemic heart disease rose by 11.6% over the period 2016-2019 and by +5.2% over the period 2019-2023, and hospitalizations for ischemic stroke rose by 8.2% over the period 2016-2019 and declined by -0.6% over the period 2019-2023. We observed regional disparities in SGLT-2 inhibitors use, with prevalence ranging from 0.9% in Bretagne to 1.5% in Hauts-de-France. The data suggests a temporal correlation between the increase in SGLT-2 inhibitors use and the decline in HF hospitalizations since 2019. More studies are needed to measure real life effectiveness of SGLT-2 inhibitors in heart failure.

Implantable Hemodynamic Monitors Improve Survival in Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND: Trials evaluating implantable hemodynamic monitors to manage patients with heart failure (HF) have shown reductions in HF hospitalizations but not mortality. Prior meta-analyses assessing mortality have been limited in construct because of an absence of patient-level data, short-term follow-up duration, and evaluation across the combined spectrum of ejection fractions. OBJECTIVES: The purpose of this meta-analysis was to determine whether management with implantable hemodynamic monitors reduces mortality in patients with heart failure and reduced ejection fraction (HFrEF) and to confirm the effect of hemodynamic-monitoring guided management on HF hospitalization reduction reported in previous studies. METHODS: The patient-level pooled meta-analysis used 3 randomized studies (GUIDE-HF [Hemodynamic-Guided Management of Heart Failure], CHAMPION [CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients], and LAPTOP-HF [Left Atrial Pressure Monitoring to Optimize Heart Failure Therapy]) of implantable hemodynamic monitors (2 measuring pulmonary artery pressures and 1 measuring left atrial pressure) to assess the effect on all-cause mortality and HF hospitalizations. RESULTS: A total of 1,350 patients with HFrEF were included. Hemodynamic-monitoring guided management significantly reduced overall mortality with an HR of 0.75 (95% CI: 0.57-0.99); P = 0.043. HF hospitalizations were significantly reduced with an HR of 0.64 (95% CI: 0.55-0.76); P < 0.0001. CONCLUSIONS: Management of patients with HFrEF using an implantable hemodynamic monitor significantly reduces both mortality and HF hospitalizations. The reduction in HF hospitalizations is seen early in the first year of monitoring and mortality benefits occur after the first year.

Effect of intravenous iron replacement on recurrent heart failure hospitalizations and cardiovascular mortality in patients with heart failure and iron deficiency: A Bayesian meta-analysis.

AIMS: Iron deficiency is common in patients with heart failure (HF) and reduced ejection fraction (HFrEF) and is associated with a poor prognosis. Whether intravenous iron replacement improves recurrent HF hospitalizations and cardiovascular mortality of these patients is uncertain although several trials were conducted. Moreover, none of the trials were powered to assess the effect of intravenous iron in clinically important subgroups. Therefore, we conducted a Bayesian analysis to derive precise estimates of the effect of intravenous iron replacement on recurrent HF hospitalizations and cardiovascular mortality in iron-deficient HFrEF patients using consistent subgroup definitions across trials. METHODS AND RESULTS: Individual participant data were used from the FAIR-HF (n = 459), CONFIRM-HF (n = 304) and AFFIRM-AHF (n = 1108) trials. These data were re-analysed following as closely as possible the approach taken in the analyses of IRONMAN (n = 1137), for which study level data were used. Definitions of outcomes and subgroups from the FAIR-HF, CONFIRM-HF and AFFIRM-AHF were matched with those used in IRONMAN. The primary endpoint was recurrent HF hospitalizations and cardiovascular mortality. The analysis of recurrent events was based on rate ratios (RR) derived from the Lin-Wei-Yang-Ying model, and the data were pooled using Bayesian random-effects meta-analysis. Compared with placebo, intravenous iron significantly reduced the rates of recurrent HF hospitalizations and cardiovascular mortality (RR 0.73, 95% credible interval [CI] 0.48-0.99; between-trial heterogeneity tau = 0.16). The pooled treatment effects did not provide evidence for any differential effects for subgroups based on sex (ratio of rate ratios [RRR] 1.49 [95% CI 0.95-2.37], age <69.4 vs. ≥69.4 years) (RRR 0.68 [0.40-1.15]), ischaemic versus non-ischaemic aetiology of HF (RRR 0.73 [0.42-1.33]), transferrin saturation <20% vs. ≥20% (RRR 0.75 [0.40-1.34]), estimated glomerular filtration rate ≤60 versus >60 ml/min/1.73 m2 (RRR 0.97 [0.56-1.68]), haemoglobin <11.8 versus ≥11.8 (RRR 0.95 [0.53-1.60]), ferritin <35 versus ≥35 µg/L (RRR 1.26 [0.72-2.48]) and New York Heart Association class II versus III/IV (RRR 0.91 [0.54-1.56]). CONCLUSIONS: Treatment of iron-deficient HFrEF patients with intravenous iron - namely with ferric carboxymaltose or ferric derisomaltose - results in significant reduction in recurrent HF hospitalizations and cardiovascular mortality. Results were nominally consistent across the subgroups studied, but for several of these subgroups uncertainty remains present.

Differences in Demographics, in-Hospital Management and Short-Term Prognosis in Admissions for Acutely Decompensated Heart Failure to Cardiology vs. Internal Medicine Departments: A Prospective Study.

Heart failure (HF) is among the leading causes of unplanned hospital admissions worldwide. Patients with HF carry a high burden of comorbidities; hence, they are frequently admitted for non-cardiac conditions and managed in Internal Medicine Departments (IMD). The aim of our study was to investigate differences in demographics, in-hospital management, and short-term outcomes of HF patients admitted to IMD vs. cardiology departments (CD). A prospective cohort study enrolling consecutive patients with acutely decompensated HF either as primary or as secondary diagnosis during the index hospitalization was conducted. Our primary endpoint was a combined endpoint of in-hospital mortality and 30-day rehospitalization for HF. A total of 302 patients participated in the study, with 45% of them admitted to IMD. Patients managed by internists were older with less pronounced HF symptoms on admission. In-hospital mortality was higher for patients admitted to IMD vs. CD (21% vs. 6%, p < 0.001). The composite endpoint of in-hospital death and heart failure hospitalizations at 30 days post-discharge was higher for patients admitted to IMD both in univariate [OR: 3.2, 95% CI (1.8-5.7); p < 0.001] and in multivariate analysis [OR 3.74, 95% CI (1.72-8.12); p = 0.001]. In addition, the HF rehospitalization rate at 6 months after discharge was higher in IMD patients [HR 1.65, 95% CI (1.1, 2.4), p = 0.01]. Overall, HF patients admitted to IMD have worse short-term outcomes compared to patients admitted to CD.

Association of Pioglitazone With Major Adverse Cardiovascular Events, All-Cause Mortality, and Heart Failure Hospitalizations: A Systematic Review.

Modern diabetic treatment has gone beyond glycemic control, with the choice of different medications to attain therapeutic targets also affected by the risk of long-term outcomes and safety profiles. The effect of diabetes on increased morbidity and mortality and its relationship to cardiovascular outcomes and coronary artery diseases have driven recent diabetes studies toward medications that improve cardiovascular outcomes and reduce all-cause mortality. This is attained by holistically treating cardiovascular complications in type 2 diabetic patients beyond glycemic control. Moreover, both diabetes and pre-diabetes are considered risk factors for both microvascular and macrovascular cardiac events. Despite the fact that initial research acknowledged fluid retention as a safety issue in pioglitazone use, clinical trial data have not presented conclusive proof of a positive or negative impact on cardiac function. This comprehensive literature review aims to evaluate the effect of pioglitazone on all-cause mortality, hospitalizations for heart failure, and major adverse cardiovascular outcomes, including the individual outcomes of non-fatal stroke, non-fatal myocardial infarction, and cardiovascular mortality.

Corrigendum: The atrial secondary tricuspid regurgitation is associated to more favorable outcome than the ventricular phenotype.

[This corrects the article DOI: 10.3389/fcvm.2022.1022755.].

Pacing burden and clinical outcomes after transcatheter aortic valve replacement-A real-world registry report.

INTRODUCTION: Conflicting data exist on the prognostic significance of permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR). OBJECTIVE: The purpose of this study was to evaluate whether PPM implantation after TAVR is associated with adverse outcomes. METHODS: A retrospective analysis of a cohort comprised patients enrolled in a prospective registry between 2008 and 2019. Participants were allocated into 3 groups: patients without a prior pacemaker (n = 930 [75%]), those with previous pacemaker implantation (n = 118 [10%]), and those with pacemaker implantation after TAVR (n = 191 [15%]). The primary outcome included death and heart failure hospitalizations at 1 year. Secondary outcomes included death and heart failure hospitalizations stratified by pacing burden. RESULTS: A total of 1239 patients underwent TAVR with a median follow-up period of 2.3 years (interquartile range 1-4 years). Patients with previous and new pacemaker implantation were older (84 [80-88], 84 [80-88], and 82 [78-86] years; P = .009) and had lower baseline left ventricular ejection fraction (50% ± 15%, 55% ± 12%, and 56% ± 12%; P < .001). Patients who underwent new pacemaker implantation had higher combined outcome of death and heart failure hospitalizations (21%,12%, and 14%; P = .01). New pacemaker implantation was associated with almost twice the risk of 1-year mortality (odds ratio 1.85; 95% confidence interval 1.13-3.02; P = .014). Pacing burden, however, was not associated with the primary outcome. Furthermore, no significant difference was observed at long-term follow-up (cumulative probability to develop the primary end point at 3 years was 57% ± 2% [without PPM], 57% ± 6% [prior PPM], 54% ± 4% [new PPM]; P = .52). CONCLUSION: Pacemaker implantation after TAVR is associated with higher 1-year adverse outcome, but this attenuates over time, suggesting that competing factors may play a role. Interestingly, pacing burden is not associated with adverse clinical course.

Left Ventricular Remodeling and Heart Failure Predictors in Acute Myocardial Infarction Patients with Preserved Left Ventricular Ejection Fraction after Successful Percutaneous Intervention in Western Romania.

(1) Acute myocardial infarction (AMI) patients are at risk of left ventricular (LV) remodeling and heart failure (HF), even after successful revascularization by percutaneous coronary intervention (PCI). We wanted to assess the independent predictors of these outcomes in AMI patients. (2) Methods: The study enrolled patients with a LVEF ≥50% after a successful PCI for their first AMI. After 24 months, patients were separated into two groups based on whether their LVEF remained ≥50% (group I), or decreased to <50% (group II). (3) Outcomes: 26% of the patients experienced a decrease in LVEF below 50%, 41% showed LV remodeling, and 8% had experienced HF hospitalizations. HF hospitalizations were significantly more frequent in group II patients (p < 0.0001). The Killip class at admission >2, infarct-related longitudinal strain ≤−12.5%, and the presence of LV remodeling were identified as independent predictors of HF hospitalizations. (4) Conclusions: About 26% of AMI patients with normal LV function after a successful PCI developed HF. More sensitive techniques are required that allow for a more efficient risk-stratification and preventive therapy to reduce LV remodeling and HF in AMI patients with LVEF ≥50% after a successful PCI. The detection of abnormal ventricular deformation patterns after PCI by speckle-tracking echocardiography might be a valuable method in this approach.

The atrial secondary tricuspid regurgitation is associated to more favorable outcome than the ventricular phenotype.

Aim: We sought to evaluate the differences in prognosis between the atrial (A-STR) and the ventricular (V-STR) phenotypes of secondary tricuspid regurgitation. Materials and methods: Consecutive patients with moderate or severe STR referred for echocardiography were enrolled. A-STR and V-STR were defined according to the last ACC/AHA guidelines criteria. The primary endpoint was the composite of all-cause death and heart failure (HF) hospitalizations. Results: A total of 211 patients were enrolled. The prevalence of A-STR in our cohort was 26%. Patients with A- STR were significantly older and with lower NYHA functional class than V-STR patients. The prevalence of severe STR was similar (28% in A-STR vs. 37% in V-STR, p = 0.291). A-STR patients had smaller tenting height (TH) (10 ± 4 mm vs. 12 ± 7 mm, p = 0.023), larger end-diastolic tricuspid annulus area (9 ± 2 cm2 vs. 7 ± 6 cm2/m2, p = 0.007), smaller right ventricular (RV) end-diastolic volumes (72 ± 27 ml/m2 vs. 92 ± 38 ml/m2; p = 0.001), and better RV longitudinal function (18 ± 7 mm vs. 16 ± 6 mm; p = 0.126 for TAPSE, and -21 ± 5% vs. -18 ± 5%; p = 0.006, for RV free-wall longitudinal strain, RVFWLS) than V-STR patients. Conversely, RV ejection fraction (RVEF, 48 ± 10% vs. 46 ± 11%, p = 0.257) and maximal right atrial volumes (64 ± 38 ml/m2 vs. 55 ± 23 ml/m2, p = 0.327) were similar between the two groups. After a median follow-up of 10 months, patients with V-STR had a 2.7-fold higher risk (HR: 2.7, 95% CI 95% = 1.3-5.7) of experiencing the combined endpoint than A-STR patients. The factors related to outcomes resulted different between the two STR phenotypes: TR-severity (HR: 5.8, CI 95% = 1, 4-25, P = 0.019) in A-STR patients; TR severity (HR 2.9, 95% CI 1.4-6.3, p = 0.005), RVEF (HR: 0.97, 95% CI 0.94-0.99, p = 0.044), and RVFWLS (HR: 0.93, 95% CI 0.85-0.98, p = 0.009) in V-STR. Conclusion: Almost one-third of patients referred to the echocardiography laboratory for significant STR have A-STR. A-STR patients had a lower incidence of the combined endpoint than V-STR patients. Moreover, while TR severity was the only independent factor associated to outcome in A-STR patients, TR severity and RV function were independently associated with outcome in V-STR patients.

Rationale and design of the AFFIRM-AHF trial: a randomised, double-blind, placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalisations and mortality in iron-deficient patients admitted for acute heart failure.

AIMS: Iron deficiency (ID) is a common co-morbidity in heart failure (HF), associated with impaired functional capacity, poor quality of life and increased morbidity and mortality. Treatment with intravenous (i.v.) ferric carboxymaltose (FCM) has shown improvements in functional capacity, symptoms and quality of life in stable HF patients with reduced ejection fraction. The effect of i.v. iron supplementation on morbidity and mortality in patients hospitalised for acute HF (AHF) and who have ID has yet to be established. The objective of the present article is to present the rationale and design of the AFFIRM-AHF trial (ClinicalTrials.gov NCT02937454) which will investigate the effect of i.v. FCM (vs. placebo) on recurrent HF hospitalisations and cardiovascular (CV) mortality in iron-deficient patients hospitalised for AHF. METHODS: AFFIRM-AHF is a multicentre, randomised (1:1), double-blind, placebo-controlled trial which recruited 1100 patients hospitalised for AHF and who had iron deficiency ID defined as serum ferritin <100 ng/mL or 100-299 ng/mL if transferrin saturation <20%. Eligible patients were randomised (1:1) to either i.v. FCM or placebo and received the first dose of study treatment just prior to discharge for the index hospitalisation. Patients will be followed for 52 weeks. The primary outcome is the composite of recurrent HF hospitalisations and CV mortality. The main secondary outcomes include the composite of recurrent CV hospitalisations and CV mortality, recurrent HF hospitalisations and safety-related outcomes. CONCLUSION: The AFFIRM-AHF trial will evaluate, compared to placebo, the effect of i.v. FCM on morbidity and mortality in iron-deficient patients hospitalised for AHF.