A year in heart failure: updates of clinical and preclinical findings.

We witnessed major advances in the management of heart failure (HF) in 2022. Results of recent clinical and preclinical investigations aid preventive strategies, diagnostic efforts, and therapeutic interventions, and collectively, they hold promises for a more effective HF care for the near future. Accordingly, currently available information extends the 2021 European Society of Cardiology guidelines and provides a solid background for the introduction of improved clinical approaches in the number of HF-related cases. Elaboration on the relationships between epidemiological data and risk factors lead to better understanding of the pathophysiology of HF with reduced ejection fraction and HF with preserved ejection fraction. The clinical consequences of valvular dysfunctions are increasingly interpreted not only in their haemodynamic consequences but also in association with their pathogenetic factors and modern corrective treatment possibilities. The influence of coronavirus disease 2019 pandemic on the clinical care of HF appeared to be less intense in 2022 than before; hence, this period allowed to refine coronavirus disease 2019 management options for HF patients. Moreover, cardio-oncology emerges as a new subdiscipline providing significant improvements in clinical outcomes for oncology patients. Furthermore, the introduction of state-of-the-art molecular biologic methods, multi-omic approaches forecast improved phenotyping and precision medicine for HF. All above aspects are addressed in this article that highlights a selection of papers published in ESC Heart Failure in 2022.

Heart failure: an update from the last years and a look at the near future.

In the last years, major progress occurred in heart failure (HF) management. Quadruple therapy is now mandatory for all the patients with HF with reduced ejection fraction. Whilst verciguat is becoming available across several countries, omecamtiv mecarbil is waiting to be released for clinical use. Concurrent use of potassium-lowering agents may counteract hyperkalaemia and facilitate renin-angiotensin-aldosterone system inhibitor implementations. The results of the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trial were confirmed by the Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (DELIVER) trial, and we now have, for the first time, evidence for treatment of also patients with HF with preserved ejection fraction. In a pre-specified meta-analysis of major randomized controlled trials, sodium-glucose co-transporter-2 inhibitors reduced all-cause mortality, cardiovascular (CV) mortality, and HF hospitalization in the patients with HF regardless of left ventricular ejection fraction. Other steps forward have occurred in the treatment of decompensated HF. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload (ADVOR) trial showed that the addition of intravenous acetazolamide to loop diuretics leads to greater decongestion vs. placebo. The addition of hydrochlorothiazide to loop diuretics was evaluated in the CLOROTIC trial. Torasemide did not change outcomes, compared with furosemide, in TRANSFORM-HF. Ferric derisomaltose had an effect on the primary outcome of CV mortality or HF rehospitalizations in IRONMAN (rate ratio 0.82; 95% confidence interval 0.66-1.02; P = 0.070). Further options for the treatment of HF, including device therapies, cardiac contractility modulation, and percutaneous treatment of valvulopathies, are summarized in this article.

COVID-19 and Heart Failure with Preserved and Reduced Ejection Fraction Clinical Outcomes among Hospitalized Patients in the United States.

Heart failure exacerbations impart significant morbidity and mortality, however, large- scale studies assessing outcomes in the setting of concurrent coronavirus disease-19 (COVID-19) are limited. We utilized National Inpatient Sample (NIS) database to compare clinical outcomes in patients admitted with acute congestive heart failure exacerbation (CHF) with and without COVID-19 infection. A total of 2,101,980 patients (Acute CHF without COVID-19 (n = 2,026,765 (96.4%) and acute CHF with COVID-19 (n = 75,215, 3.6%)) were identified. Multivariate logistic regression analysis was utilized to compared outcomes and were adjusted for age, sex, race, income level, insurance status, discharge quarter, Elixhauser co-morbidities, hospital location, teaching status and bed size. Patients with acute CHF and COVID-19 had higher in-hospital mortality compared to patients with acute CHF alone (25.78% vs. 5.47%, adjust OR (aOR) 6.3 (95% CI 6.05-6.62, p < 0.001)) and higher rates of vasopressor use (4.87% vs. 2.54%, aOR 2.06 (95% CI 1.86-2.27, p < 0.001), mechanical ventilation (31.26% vs. 17.14%, aOR 2.3 (95% CI 2.25-2.44, p < 0.001)), sudden cardiac arrest (5.73% vs. 2.88%, aOR 1.95 (95% CI 1.79-2.12, p < 0.001)), and acute kidney injury requiring hemodialysis (5.56% vs. 2.94%, aOR 1.92 (95% CI 1.77-2.09, p < 0.001)). Moreover, patients with heart failure with reduced ejection fraction had higher rates of in-hospital mortality (26.87% vs. 24.5%, adjusted OR 1.26 (95% CI 1.16-1.36, p < 0.001)) with increased incidence of vasopressor use, sudden cardiac arrest, and cardiogenic shock as compared to patients with heart failure with preserved ejection fraction. Furthermore, elderly patients and patients with African-American and Hispanic descents had higher in-hospital mortality. Acute CHF with COVID-19 is associated with higher in-hospital mortality, vasopressor use, mechanical ventilation, and end organ dysfunction such as kidney failure and cardiac arrest.

An audit comparing management of patients with HFrEF at a DGH before and during the COVID-19 pandemic.

This audit compared the management of patients with heart failure with reduced ejection fraction (HFrEF) admitted to a district general hospital (DGH) during comparative eight month periods before and during the COVID-19 pandemic. The periods studied were from 1st February 2019 to 30th September 2019 and between the same dates in 2020. We investigated differences in mortality and patient characteristics (age, gender and new or prior diagnosis). For patients who survived to discharge and who were not referred to palliative care, we also investigated whether there were differences in rates of echocardiography and prescription of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists and beta blockers. We found that the number of cases was lower during the pandemic and there was a lower mortality rate that was not statistically significant. There was a higher proportion of new cases (odds ratio [OR] 2.21, 95% confidence interval [CI] 1.24 to 3.94, p=0.008) and of female patients (OR 2.03, 95%CI 1.14 to 3.61, p=0.019). For survivors, there was a non-significant decrease in prescription rates for ACE inhibitors and angiotensin II receptor antagonists (81.6% vs. 71.4%, p=0.137) that was not seen for beta blockers. The length of stay was increased and there was also an increase in the interval between admission and echocardiography in patients who were newly diagnosed. Regardless of time period, the time before echocardiography was significantly associated with length of stay.

Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study.

BACKGROUND: Heart failure (HF) is a global leading cause of mortality despite implementation of guideline directed therapy which warrants a need for novel treatment strategies. Proof-of-concept clinical trials of anakinra, a recombinant human Interleukin-1 (IL-1) receptor antagonist, have shown promising results in patients with HF. METHOD: We designed a single center, randomized, placebo controlled, double-blind phase II randomized clinical trial. One hundred and two adult patients hospitalized within 2 weeks of discharge due to acute decompensated HF with reduced ejection fraction (HFrEF) and systemic inflammation (high sensitivity of C-reactive protein > 2 mg/L) will be randomized in 2:1 ratio to receive anakinra or placebo for 24 weeks. The primary objective is to determine the effect of anakinra on peak oxygen consumption (VO2) measured at cardiopulmonary exercise testing (CPX) after 24 weeks of treatment, with placebo-corrected changes in peak VO2 at CPX after 24 weeks (or longest available follow up). Secondary exploratory endpoints will assess the effects of anakinra on additional CPX parameters, structural and functional echocardiographic data, noninvasive hemodynamic, quality of life questionnaires, biomarkers, and HF outcomes. DISCUSSION: The current trial will assess the effects of IL-1 blockade with anakinra for 24 weeks on cardiorespiratory fitness in patients with recent hospitalization due to acute decompensated HFrEF. TRIAL REGISTRATION: The trial was registered prospectively with ClinicalTrials.gov on Jan 8, 2019, identifier NCT03797001.

Hyperdynamic left ventricular ejection fraction is associated with higher mortality in COVID-19 patients.

Study objective: To compare the characteristics and outcomes of COVID-19 patients with a hyperdynamic LVEF (HDLVEF) to those with a normal or reduced LVEF. Design: Retrospective study. Setting: Rush University Medical Center. Participants: Of the 1682 adult patients hospitalized with COVID-19, 419 had a transthoracic echocardiogram (TTE) during admission and met study inclusion criteria. Interventions: Participants were divided into reduced (LVEF < 50%), normal (≥50% and <70%), and hyperdynamic (≥70%) LVEF groups. Main outcome measures: LVEF was assessed as a predictor of 60-day mortality. Logistic regression was used to adjust for age and BMI. Results: There was no difference in 60-day mortality between patients in the reduced LVEF and normal LVEF groups (adjusted odds ratio [aOR] 0.87, p = 0.68). However, patients with an HDLVEF were more likely to die by 60 days compared to patients in the normal LVEF group (aOR 2.63 [CI: 1.36-5.05]; p < 0.01). The HDLVEF group was also at higher risk for 60-day mortality than the reduced LVEF group (aOR 3.34 [CI: 1.39-8.42]; p < 0.01). Conclusion: The presence of hyperdynamic LVEF during a COVID-19 hospitalization was associated with an increased risk of 60-day mortality, the requirement for mechanical ventilation, vasopressors, and intensive care unit.

A year in heart failure: an update of recent findings.

Major changes have occurred in these last years in heart failure (HF) management. Landmark trials and the 2021 European Society of Cardiology guidelines for the diagnosis and treatment of HF have established four classes of drugs for treatment of HF with reduced ejection fraction: angiotensin-converting enzyme inhibitors or an angiotensin receptor-neprilysin inhibitor, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors, namely, dapagliflozin or empagliflozin. These drugs consistently showed benefits on mortality, HF hospitalizations, and quality of life. Correction of iron deficiency is indicated to improve symptoms and reduce HF hospitalizations. AFFIRM-AHF showed 26% reduction in total HF hospitalizations with ferric carboxymaltose vs. placebo in patients hospitalized for acute HF (P = 0.013). The guanylate cyclase activator vericiguat and the myosin activator omecamtiv mecarbil improved outcomes in randomized placebo-controlled trials, and vericiguat is now approved for clinical practice. Treatment of HF with preserved ejection fraction (HFpEF) was a major unmet clinical need until this year when the results of EMPEROR-Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic HFpEF) were issued. Compared with placebo, empagliflozin reduced by 21% (hazard ratio, 0.79; 95% confidence interval, 0.69 to 0.90; P < 0.001), the primary outcome of cardiovascular death or HF hospitalization. Advances in the treatment of specific phenotypes of HF, including atrial fibrillation, valvular heart disease, cardiomyopathies, cardiac amyloidosis, and cancer-related HF, also occurred. Coronavirus disease 2019 (COVID-19) pandemic still plays a major role in HF epidemiology and management. All these aspects are highlighted in this review.

Understanding the role of left and right ventricular strain assessment in patients hospitalized with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can cause cardiac injury resulting in abnormal right or left ventricular function (RV/LV) with worse outcomes. We hypothesized that two-dimensional (2D) speckle-tracking assessment of LV global longitudinal strain (GLS) and RV free wall strain (FWS) by transthoracic echocardiography can assist as markers for subclinical cardiac injury predicting increased mortality. METHODS: We performed 2D strain analysis via proprietary software in 48 patients hospitalized with COVID-19. Clinical information, demographics, comorbidities, and lab values were collected via retrospective chart review. The primary outcome was in-hospital mortality based on an optimized abnormal LV GLS value via ROC analysis and RV FWS. RESULTS: The optimal LV GLS cutoff to predict death was -13.8%, with a sensitivity of 85% (95% CI 55-98%) and specificity of 54% (95% CI 36-71%). Abnormal LV GLS >-13.8% was associated with a higher risk of death [unadjusted hazard ratio 5.15 (95% CI 1.13-23.45), p = 0.034], which persisted after adjustment for clinical variables. Among patients with LV ejection fraction (LVEF) >50%, those with LV GLS > -13.8% had higher mortality compared to those with LV GLS <-13.8% (41% vs. 10%, p = 0.030). RV FWS value was higher in patients with LV GLS >-13.8% (-13.7 ±â€¯5.9 vs. -19.6 ±â€¯6.7, p = 0.003), but not associated with decreased survival. CONCLUSION: Abnormal LV strain with a cutoff of >-13.8% in patients with COVID-19 is associated with significantly higher risk of death. Despite normal LVEF, abnormal LV GLS predicted worse outcomes in patients hospitalized with COVID-19. There was no mortality difference based on RV strain.

History of heart failure in patients with coronavirus disease 2019: Insights from a French registry.

BACKGROUND: Although cardiovascular comorbidities seem to be strongly associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19), data regarding patients with preexisting heart failure are limited. AIMS: To investigate the incidence, characteristics and clinical outcomes of patients with COVID-19 with a history of heart failure with preserved or reduced ejection fraction. METHODS: We performed an observational multicentre study including all patients hospitalized for COVID-19 across 24 centres in France from 26 February to 20 April 2020. The primary endpoint was a composite of in-hospital death or need for orotracheal intubation. RESULTS: Overall, 2809 patients (mean age 66.4±16.9years) were included. Three hundred and seventeen patients (11.2%) had a history of heart failure; among them, 49.2% had heart failure with reduced ejection fraction and 50.8% had heart failure with preserved ejection fraction. COVID-19 severity at admission, defined by a quick sequential organ failure assessment score>1, was similar in patients with versus without a history of heart failure. Before and after adjustment for age, male sex, cardiovascular comorbidities and quick sequential organ failure assessment score, history of heart failure was associated with the primary endpoint (hazard ratio [HR]: 1.41, 95% confidence interval [CI]: 1.06-1.90; P=0.02). This result seemed to be mainly driven by a history of heart failure with preserved ejection fraction (HR: 1.61, 95% CI: 1.13-2.27; P=0.01) rather than heart failure with reduced ejection fraction (HR: 1.19, 95% CI: 0.79-1.81; P=0.41). CONCLUSIONS: History of heart failure in patients with COVID-19 was associated with a higher risk of in-hospital death or orotracheal intubation. These findings suggest that patients with a history of heart failure, particularly heart failure with preserved ejection fraction, should be considered at high risk of clinical deterioration.

Changing to remote management of a community heart failure population during COVID-19 - Clinician and patient perspectives'.

BACKGROUND: The COVID pandemic has challenged the traditional methods used in care of patients with heart failure (HF). Remote management of HF patients has been recommended in order to maintain routine standards of care, but satisfaction with this platform of care is unknown. We set out to address the physician and patient opinion of remote management of HF during COVID-19. METHODS AND RESULTS: An observational report of the use of a Structured Telephonic assessment (STA) in stable outpatient HF patients. Physician grading of the STA was complemented by 100 randomly chosen patients to ascertain patient satisfaction and comment. 278 patients underwent a STA. Patient preference for STA was noted in 66%. Convenience was the single most cited reason for this preference (83.3%). The STA was deemed satisfactory by clinicians in 67.6%. The two-leading reasons for clinician dissatisfaction were data gaps providing a barrier to titration (55.6%) and need for clinical exam (18.9%). The annual review appointment visit subtype possessed the highest levels of satisfaction congruence amongst both clinicians and patients. CONCLUSION: In summary, this report demonstrates reasonable patient / physician satisfaction with STA, and provides some direction on how this care platform might be sustained beyond the COVID crisis.

Dynamic Regulation of SARS-Cov-2 Binding and Cell Entry Mechanisms in Remodeled Human Ventricular Myocardium.

Using serial analysis of myocardial gene expression employing endomyocardial biopsy starting material in a dilated cardiomyopathy cohort, we show that mRNA expression of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) cardiac myocyte receptor ACE2 is up-regulated with remodeling and with reverse remodeling down-regulates into the normal range. The proteases responsible for virus-cell membrane fusion were expressed but not regulated with remodeling. In addition, a new candidate for SARS-CoV-2 cell binding and entry was identified, the integrin encoded by ITGA5. Up-regulation in ACE2 in remodeled left ventricles may explain worse outcomes in patients with coronavirus disease 2019 who have underlying myocardial disorders, and counteracting ACE2 up-regulation is a possible therapeutic approach to minimizing cardiac damage.