ESC Heart Failure最新文献

Aims: Guideline-directed medical therapy (GDMT) is recommended for all patients with heart failure with reduced ejection fraction (HFrEF). Despite this, little data exist describing GDMT use in diverse, real-world populations including the use of vasodilators, prescribed primarily to Black populations. We sought, among a diverse population of HFrEF patients, to determine (1) GDMT use rates and target dosing by medication class and (2) predictors of GDMT use and target dosing by medication class.

Methods: We utilized electronic health records (EHRs) from Kaiser Permanente (KP) Mid-Atlantic States, a large integrated health system. Included patients had heart failure and left ventricular ejection fraction (EF) of ≤40% between 2015 and 2021. GDMT was defined by five medication classes-angiotensin-converting enzyme (ACE) inhibitors (ACEis)/angiotensin receptor blockers (ARBs)/angiotensin receptor-neprilysin inhibitors (ARNis), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), sodium-glucose cotransporter 2 inhibitors (SGLT2is) and vasodilators (Black patients only). Proportions of patients on GDMT and target dose rates were examined. Logistic regression determined, within each class, predictors of medication use and being at ≥80% of the target dose.

Results: A total of 3154 patients were included. Among the 93.8% on some form of GDMT, 82.8%, 81.4%, 23.5%, 3.6% and 13.4% were on ACEis/ARBs/ARNis, BBs, MRAs, SGLT2is and vasodilators (Black patients only), respectively. Among treated patients, 45.8%, 21.4%, 77.6%, 100% and 14.7% were treated at ≥80% of the target dose for ACEis/ARBs/ARNis, BBs, MRAs, SGLT2is and vasodilators, respectively. Overall, increasing age, higher EF, atrial fibrillation/flutter, chronic obstructive pulmonary disease (COPD), prior stroke and dementia were associated with decreased odds of GDMT use. Conversely, higher body mass index (BMI), Black race, higher glomerular filtration rate (GFR), recent echo and cardiac defibrillator were associated with increased odds of GDMT use. Among treated, higher BMI, higher systolic blood pressure, haemoglobin A1C ≥ 6.5% and cardiac defibrillator were associated with higher odds of being at ≥80% of the target dose.

Conclusions: Our study using real-world data from a diverse health system demonstrated gaps in GDMT use among patients with HFrEF, specifically older patients with more comorbidities.

Aims: Heart failure (HF) and erectile dysfunction (ED) share numerous risk factors and pathogenetic mechanisms, resulting in a high prevalence of ED among male patients with HF. This questionnaire-based study aimed to better understand the patient's journey from a patient perspective and that of healthcare professionals (HCPs) regarding communication, education and treatment of ED as a recognized comorbid condition.

Methods: Two independent online surveys were conducted between November 2021 and January 2022 in Germany. Analysis of the first patient-targeting survey comprised 927 male patients with HF. As part of this survey, 176 patients with HF and comorbid ED provided further information about their experiences and ED-related communication with HCPs. The second online survey collected the perspectives of 78 physicians including general practitioners (GPs), cardiologists and internists throughout Germany.

Results: The average age of participating male patients with HF was 55 years. Both patients and HCPs considered sexual life as an important aspect of patients' quality of life (QoL). Fifty-six per cent of all patients with HF rated their sexual life as important, and 43% were unsatisfied with it. Patients' suffering due to ED was reported as moderate to severe by nearly all HCPs (92%) and patients themselves (82%). A communication gap and perceived imbalance in education were identified, with 27% of patients reporting consultations about ED, while 58% of HCPs claimed to proactively address the issue of ED during counselling. Thirty-nine per cent of HCPs felt that their patients were uncomfortable talking about ED, but only 7% of patients reported discomfort. As a possible result, 69% of male HF patients with ED felt left alone, and 74% stated that they would like to talk to an HCP. Due to inadequate education together with patients not considering their HF doctor as a contact for ED management, as few as 20% of patients with ED receive prescription drugs for ED management. HCPs reported that 32% of their patients are non-compliant with HF medication due to ED, highlighting the importance of sexual health for patients' QoL.

Conclusions: The results of our surveys suggest that most of the male HF patients may be receiving incomplete ED management also affecting HF treatment, most likely due to impaired communication with their HCPs with barriers from both sides. HCPs giving patients advice on this topic are urgently needed to improve patients' QoL, reduce patient suffering and avoid discontinuation of HF medications for fear of side effects.

Purpose: Vericiguat, a soluble guanylate cyclase (sGC) stimulator, has been demonstrated effective in improving prognosis of patients with heart failure with reduced ejection fraction. However, there are limited data concerning the effect of vericiguat in patients with doxorubicin (DOX)-induced cardiomyopathy (DIC). In this study, we investigated the effects of vericiguat on cardiac structure and function in rats with DIC as well as their potential mechanisms of action.

Methods: DIC rats were established by intraperitoneal injection of DOX (1 mg/kg) twice a week for 6 weeks, followed by intragastric administration of vericiguat 1 mg/kg/day or an equal volume of normal saline for 8 weeks. Cardiac histology and function, circulating levels of amino-terminal pro-B-type natriuretic peptide (NT-proBNP), nitric oxide (NO), and oxidative indices, as well as myocardial cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signalling, oxidative and apoptosis-associated protein were measured.

Results: Compared with the control group, rats treated with DOX exhibited significantly increased heart size, reduced systolic function and elevated plasma levels of NT-proBNP. Histological findings revealed myocardial cell atrophy, fibrosis and apoptosis. Vericiguat treatment effectively reversed DOX-induced cardiac remodelling and improved systolic function. Mechanistically, Vericiguat attenuated the inhibitory effects of DOX on the myocardial cGMP-PKG axis and nuclear factor erythroid 2-related factor 2 (Nrf2) protein, thereby alleviating oxidative stress and apoptosis.

Conclusions: Vericiguat improved cardiac remodelling and contractile function in rats with DIC through upregulation of cGMP-PKG signalling and inhibition of oxidative stress and myocardial apoptosis.

Aims: Patients with heart failure with preserved ejection fraction represent half of the heart failure patients nowadays, an at least steady trend due to the aging of the population. We investigated whether the parameters obtained from cardiopulmonary exercise testing (CPET) correlated with the prognosis of these patients. This prospective observational cohort study assesses the relationship between the CPET parameters peakVO₂ and VE/VCO₂ slope and the number of heart failure hospitalizations or cardiovascular death of these patients.

Methods and results: From August 2016 until May 2019, 99 patients from our outpatient unit with newly diagnosed heart failure with preserved ejection fraction underwent CPET. Median follow-up was 30 months [interquartile range, 24-38.5]. We selected peakVO₂ < 14 mL/min/kg and a VE/VCO₂ slope > 34 as threshold values for our primary clinically relevant endpoint, a composite of hospitalization for heart failure or cardiovascular death. Mean age was 75.07 ± 7.31 years, 49% were women, 75% were at NYHA class II and median NTproBNP was 511 pg/mL. Mean peakVO₂ was 15.09 ± 4.75, and mean VE/VCO₂ was 36.05 ± 6.60. During follow-up, there were 207 all-cause hospitalizations, 126 cardiovascular hospitalizations, 58 heart failure hospitalizations and 4 deaths. Over a median follow-up of 30 months, the primary clinically relevant endpoint occurred in 5 of 40 patients (12.5%) with a VE/VCO₂ slope ≤ 34 and in 19 of 59 patients (32.2%) with a VE/VCO₂ slope > 34 [hazard ratio, 2.69; 95% confidence interval (CI), 1.00-7.21; P = 0.04]. On multivariate analysis, VE/VCO₂ slope was independently associated with heart failure hospitalization or cardiovascular death as a terminal event.

Conclusions: In patients with heart failure with preserved ejection fraction, a VE/VCO₂ slope > 34 predicts heart failure hospitalizations and cardiovascular death.

Background and objectives: Initially described as a benign acute cardiomyopathy, Takotsubo syndrome has been linked to elevated mortality rates. Emerging evidence suggests that unresolved myocardial inflammation may contribute to this adverse prognosis. This study aimed to evaluate the incremental prognostic utility of C-reactive protein (CRP) in conjunction with the InterTAK prognosis score for stratifying long-term mortality in Takotsubo syndrome.

Methods: A retrospective analysis was conducted from a multicentre registry encompassing 307 patients diagnosed with Takotsubo syndrome between 2008 and 2020. Patients were stratified into quartiles based on the InterTAK prognosis score. The discriminatory potential of CRP in predicting long-term mortality was assessed. The primary endpoint was defined as all-cause mortality within 1 year.

Results: A stepwise increase of CRP at discharge that corresponds to INTERTAK quartiles was observed: 9.5 mg/L (25th percentile) in the first quartile, 15.8 mg/L (median) in the second quartile, 25.3 mg/L (75th percentile) in the third quartile and 41.2 mg/L (maximum) in the fourth quartile. Receiver operating-characteristic curves analysis revealed that CRP value at discharge was predictive of 1 year mortality (area under the curve = 0.81; 95% confidence interval = 0.68-0.90) with an optimal threshold set at 33 mg/L (sensitivity: 65%; specificity: 87%). When considering the InterTAK score, the incorporation of CRP at discharge with a cut-off of 33 mg/L exhibited a significant enhancement in the prediction of 1 year mortality in 'intermediate' risk (25% vs. 1%; P = 0.008) or 'very high' risk (40% vs. 10%; P = 0.02) patients.

Conclusions: In Takotsubo syndrome, the persistence of inflammatory burden at hospital discharge emerged as an independent predictor of 1 year mortality, augmenting the predictive capacity of the conventional InterTAK prognosis score.

Aims: This study aimed to conduct a phase 2 proof-of-concept and safety study to evaluate the effect of ENIBARCIMAB (EN), a non-neutralizing humanized monoclonal antibody targeting the N-terminus of adrenomedullin (ADM), administered immediately after stabilization with standard of care (SoC) treatment, in patients hospitalized for acute heart failure (AHF).

Methods and results: This prospective, open-label, controlled, interventional, multicenter, dose-escalation study was conducted at two cardiology sites in Indonesia. Patients were divided into two interventional groups sequentially receiving 0.5 mg/kg (SoC + EN 0.5 mg/kg, n = 10; first cohort) and 2 mg/kg (SoC + EN 2 mg/kg, n = 10; second cohort) of EN via 1-h intravenous (IV) infusion within 48 h after admission for AHF. The control group (n = 10) was treated with SoC therapy for AHF therapy. All patients were monitored continuously within 24 h post-infusion and subsequent daily until discharge. Treatment-related serious adverse events (SAEs) were recorded during hospitalization and up to 90 days after discharge. Both EN dosages were well-tolerated, and no significant safety issues were identified during hospitalization and up to 90 days of follow up. SAEs occurred in 10% of patients in each EN group but were deemed not related to treatment. No significant differences in the occurrence of SAEs were found between the groups. Five deaths occurred: three (30%) in the control group as compared with two deaths (20%) in the SoC + EN 2 mg/kg group. EN led to a significant increase in plasma bio-ADM levels within 24 h post-infusion, with the SoC + 2 mg/kg group showing the highest increase. Within 1 h from IV EN infusion, SoC + EN 2 mg/kg compared with 0.5 mg/kg, resulted in a significant percentage reduction in systolic, diastolic blood pressure, and mean arterial pressure. However, it did not result in severe hypotension and the need for drug discontinuation.

Conclusions: In this pilot safety study of patients hospitalized for AHF, IV infusion of EN 0.5 and 2 mg/kg increased circulating plasma bio-ADM levels and was well-tolerated without treatment-related SAEs occurring during hospitalization and up to 90 days after discharge.

Aims: This study aimed to investigate potential biomarkers for predicting incident heart failure (HF) in patients with atrial fibrillation and flutter (AF and AFL), utilizing proteomic data from the UK Biobank Pharma Proteomics Project (UKB-PPP).

Methods: This study analysed data from AF and AFL patients, split into discovery (n = 1050) and replication (n = 305) cohorts. Plasma biomarkers were screened using a multivariable-adjusted Cox proportional hazards model. Kaplan-Meier survival analysis and area under the receiver operating characteristic (ROC) curve assessments were conducted to evaluate predictive performance.

Results: Over a follow-up of 14.2 years, 222 cases (21.1%) of HF were documented in the discovery cohort, while 117 cases (38.4%) occurred over 13.8 years in the replication cohort. Out of 2923 proteins measured, only pro-adrenomedullin (pro-ADM) consistently showed a significant association with incident HF in both cohorts. In the discovery cohort, each unit increase in pro-ADM was linked to an increased risk of HF (HR = 2.78, 95% CI 1.64-4.71, P < 0.001, FDR = 0.026), which was confirmed in the replication cohort (HR = 3.95, 95% CI 1.97-7.94, P < 0.001, FDR = 0.012). Kaplan-Meier analysis demonstrated that patients with higher pro-ADM levels had significantly shorter time to HF onset, with median times ranging from 2306 to 3183 days across quartiles (P < 0.001). The cumulative incidence of HF ranged from 15.3% to 42.7% across quartiles of pro-ADM (log-rank P < 0.001). Adding pro-ADM to a model with traditional risk factors, including NT-proBNP, significantly improved predictive accuracy for 3-year (AUC = 0.783; integrated discrimination improvement [IDI] = 0.010 and net reclassification index [NRI] = 0.206, both P = 0.002) and 5-year (AUC = 0.749, IDI = 0.013, NRI = 0.179, P = 0.001) risk of HF. In sensitivity analyses, the association between pro-ADM and incident HF remained consistent after excluding participants with self-reported AF and AFL, with each unit increase in pro-ADM being associated with an increased risk of HF (HR = 1.77, 95% CI 1.02-3.04, P = 0.041) and across subgroups of paroxysmal AF (HR = 2.80, 95% CI 1.11-7.07, P = 0.029) and persistent AF (HR = 4.36, 95% CI 1.41-13.43, P = 0.010).

Conclusions: Pro-ADM is identified as an independent biomarker for predicting incident HF in AF and AFL patients. Its inclusion in risk prediction models enhances the ability to stratify HF risk beyond traditional biomarkers, demonstrating its potential utility in clinical practice.

Background: The optimal strategy for modern chemotherapy should be based on a comprehensive approach for cancer patients with cardiovascular diseases. Therefore, cardio-oncology has received increasing attention owing to the cardiotoxic effects of anti-cancer therapies.

Objectives: We aimed to evaluate the clinical characteristics and outcomes of patients with heart failure (HF) who received chemotherapy compared with those of a matched cohort with HF who did not receive chemotherapy, using real-world HF data.

Methods: This study was based on the Diagnosis Procedure Combination (DPC) database of the Japanese Registry of All Cardiac and Vascular Diseases (JROAD). We identified 1 328 113 patients who were hospitalized for HF between April 2012 and March 2021. The propensity score (PS) was estimated using a logistic regression model, with chemotherapy as the dependent variable, and a clinically score-matched analysis of 11 532 patients with HF with or without chemotherapy. The primary endpoint was readmission.

Results: Colon, lung, breast and prostate cancers accounted for >60% of all cancer types. After PS matching, readmission was significantly more frequently observed in patients with chemotherapy than those without [odds ratio (OR), 1.26; 95% confidence interval (CI) 1.17-1.36, P < 0.01]. In particular, treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) (OR, 1.69; 95% CI 1.39-2.07), taxane (OR, 2.95; 95% CI 2.11-4.12), anthracyclines (OR, 1.86; 95% CI 1.19-2.90) and fluorouracil agents (OR, 1.65; 95% CI 1.18-2.30) caused a higher risk of readmission.

Conclusions: Medical providers need to monitor and follow-up patients with HF, depending on the characteristics of the anti-cancer agents and types of cancer.