ESC Heart Failure最新文献

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.

Background: Unexplained exertional dyspnoea without significant elevation of natriuretic peptides is common. One of the causes might be early heart failure with preserved ejection fraction (HFpEF).

Aims: This study aimed to characterize patients with exertional dyspnoea and normal/near-to-normal N-terminal pro-brain natriuretic peptide (NT-proBNP) levels with regard to early stages of HFpEF and non-cardiac causes.

Method and results: Sixty-six patients (age 62 ± 7 years old, 85% women) with dyspnoea assessed using the Multidimensional Dyspnea Profile (MDP) questionnaire and NT-proBNP level of <125 pg/mL for patients <75 years old or <300 pg/mL for patients >75 years old were recruited. Patients with known significant heart disease, lung disease (abnormal respiratory function tests) or renal insufficiency stage ≥ 4 were excluded. In 11 patients (16.7%), HFpEF was confirmed according to the European Society of Cardiology Heart Failure Association (ESC HFA) criteria, 31 patients (47%) presented isolated deconditioning and 5 patients (7.6%) had idiopathic hyperventilation. In the remaining 19 patients (28.8%) with normal echocardiography and cardiopulmonary exercise testing (CPX), no objective cause of dyspnoea could be found. Compared with patients without HFpEF, those with HFpEF were older, more often hypertensive and diabetic, with higher NT-proBNP levels. They had higher E/e' ratios during exercise echocardiography and lower volume of oxygen uptake (VO₂) peaks and steeper minute ventilation (VE)/volume of carbon dioxide produced (VCO₂) slopes during CPX. Psychological impact measured on the Short Form-36 (SF-36) questionnaire was less important in HFpEF patients than in other patients.

Conclusions: The most common causes of unexplained exertional dyspnoea in patients without significant elevation of natriuretic peptides are peripheral deconditioning, HFpEF and hyperventilation. Studying patients during exercise allows for getting more data about pathophysiology and improving patient phenotyping and management. Early unmasking of HFpEF using exercise echocardiography and/or CPX and initiation of treatment could prevent hospitalizations for acute heart failure. Although using exercise testing, many patients could not be classified according to their diagnosis, and this reinforces the need to better define exercise diagnostic criteria.

Aims: Knowledge of the effects of sex in cardio-oncology is limited, particularly in patients treated with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukaemia (CML). This study aims to evaluate the influence of gender differences on the incidence of cardiovascular toxicity in patients with CML.

Methods: The study population consisted of 148 patients (45% women, mean age: 58 ± 14.2 years) diagnosed with CML treated with TKIs. The HFA-ICOS score estimated cardiovascular risk. The HFA-ICOS score revealed that 12% of men and 6% of women were categorized as very high risk while 45% of men and 50% of women fell into the high-risk group. Myocardial ischaemia, peripheral artery disease, venous thromboembolism, pulmonary hypertension and new-onset arterial hypertension during treatment with TKIs were recorded.

Results: The incidence of global events between men and women was comparable (35% vs 32%, P = 0.68). There were 33% who experienced a cardiovascular event during TKI therapy, with a significant sex difference in arterial thrombosis incidence (P = 0.02) and venous thrombosis incidence (P = 0.02). Patients treated with ponatinib had a 41% event rate, followed by nilotinib (32%) and imatinib (32%). The HFA-ICOS score demonstrated greater predictive efficacy for events in the female group [area under the curve (AUC) = 0.797] compared with the male group (AUC = 0.537). Very high [hazard ratio (HR) 3.07; confidence interval (CI) 1.11, 8.47 P = 0.03] and high (HR 3.29; CI 1.17, 9.26 P = 0.02) HFA-ICOS scores were associated with increased event risk, particularly in women. Diabetes was women's strongest predictor of events (HR 5.40; CI 1.37, 21.3 P = 0.01).

Conclusions: Our study showed a similar frequency of cardiovascular events between men and women. Accurate cardiovascular risk stratification with HFA-ICOS score in cancer patients is crucial. Diabetes and the HFA-ICOS score were significant predictors of events in the female groups. A sex approach in clinical practice could be pursued to improve the appropriateness of care.

Aims: Patients with cardiomyopathies are a heterogeneous group of patients who experience high morbidity and mortality. Early cardiac assessment and intervention with access to genetic counselling in a multidisciplinary Cardiomyopathy Clinic may improve outcomes and prevent progression to advanced heart failure.

Methods and results: Our prospective cohort study was conducted at a multidisciplinary Cardiomyopathy Clinic with 421 patients enrolled (42.5% female, median age 58 years), including 224 patients with dilated cardiomyopathy (DCM, 42.9% female, median age 57 years), 72 with hypertrophic cardiomyopathy (HCM, 43.1% female, median age 60 years), 79 with infiltrative cardiomyopathy (65.8% female, median age 70 years) and 46 who were stage A/at risk for genetic cardiomyopathy (54.3% female, median age 36 years). Patients were seen in follow-up at a median of 18 months. A pathogenic/likely pathogenic variant was identified in 28.5% of the total cohort, including 33.3% of the DCM cohort (28% TTN mutations) and 34.1% of the HCM cohort (60% MYBPC3 and 20% MYH7) who underwent genetic testing. The use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitor (48.3-69.5% of total cohort, P < 0.001), β-blockers (58.4-72.4%, P < 0.001), mineralocorticoid receptor antagonists (33.9-41.4%, P = 0.0014) and sodium/glucose cotransporter-2 inhibitors (5.3-27.9%, P < 0.001) all increased at follow-up. Precision-based therapies were also implemented, including tafamidis for transthyretin amyloidosis (n = 21), enzyme replacement therapy for Fabry disease (n = 14) and mavacamten (n = 4) for HCM. Optimization of medications and devices resulted in improvements in left ventricular ejection fraction (LVEF) from 27% to 43% at follow-up for DCM patients with reduced LVEF at baseline (P < 0.001) and reduction in left ventricular mass index (LVMI) from 156 g/m² to 128 g/m² at follow-up for HCM patients with abnormal LVMI at baseline (P = 0.009). Optimization of therapies was associated with stable plasma biomarkers in stage B patients while lowering levels of BNP (619-517.5 pg/mL, P = 0.048), NT-proBNP (777.5-356 ng/L, P < 0.001) and hsTropT (31-22 ng/L, P = 0.005) at follow-up relative to baseline values for stage C patients. Despite stage B patients having overt cardiomyopathy at baseline, stage A and B patients had a similarly high probability of survival (χ2 = 0.204, P = 0.652). The overall cardiovascular mortality rate was low at 1.7% for the cohort (0.5% for stage B and 3.3% for stage C) over a median of 34-month follow-up.

Conclusion: Our study demonstrates that a multidisciplinary cardiomyopathy clinic can improve the clinical profiles of patients with diverse genetic cardiomyopathies.

Aims: Biomarkers are pivotal in the management of heart failure (HF); however, their lack of cardiac specificity could limit clinical utility. This study aimed to investigate the transcoronary changes and intracardiac production of these biomarkers.

Methods: Transcoronary gradients for B-type natriuretic peptide (BNP) and five novel biomarkers-galectin-3 (Gal-3), soluble suppression of tumourigenicity 2 (sST2), tissue inhibitor of metalloproteinase 1 (TIMP-1), growth differentiation factor 15 (GDF-15) and myeloperoxidase (MPO)-were determined using femoral artery (FA) and coronary sinus (CS) samples from 30 HF patients and 10 non-HF controls. Intracardiac biomarker production was assessed in an HF canine model using real-time quantitative PCR (qPCR) and western blot (WB) analysis.

Results: Compared with the control group, levels of all detected biomarkers were significantly elevated in the HF group, while transcoronary gradients were only observed for BNP, Gal-3 and TIMP-1 levels in the HF group (BNP: FA: 841.5 ± 727.2 ng/mL vs. CS: 1132.0 ± 959.1 ng/mL, P = 0.005; Gal-3: FA: 9.5 ± 3.0 ng/mL vs. CS: 19.7 ± 16.4 ng/mL, P = 0.002; and TIMP-1: FA: 286.7 ± 68.9 ng/mL vs. CS: 377.3 ± 108.9 ng/mL, P = 0.001). Real-time qPCR and WB analysis revealed significant elevation of BNP, Gal-3 and TIMP-1 in the cardiac tissues of the HF group relative to other groups.

Conclusions: This study provided evidence of transcoronary changes in BNP, Gal-3 and TIMP-1 levels in HF patients, offering insights into their intracardiac production. These findings enhance the understanding of the biology of these biomarkers and may inform their clinical application.

Aims: The prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) as a biomarker in patients with cardiac sarcoidosis (CS) has yet to be fully determined, especially when compared with B-type natriuretic peptide (BNP).

Methods and results: In this post-hoc analysis of the ILLUMINATE-CS (ILLUstration of the Management and prognosIs of JapaNese pATiEnts with Cardiac Sarcoidosis), which is a multicentre retrospective observational study, we analysed 103 patients (62.2 ± 10.9 years old, 31.1% male) diagnosed as CS and with available data for hs-cTnT measured at the time of diagnosis. The primary outcome was the combined outcomes of all-cause death, fatal ventricular arrhythmia events and heart failure hospitalization. During a median follow-up period of 2.6 (inter-quartile range, 1.6-5.7) years, 24 primary outcomes were observed. Patients with a high hs-cTnT level, defined as a level above the median value (>0.016 ng/mL), were associated with a higher incidence of adverse events than those with a low hs-cTnT level (log-rank, P = 0.017). In Cox regression analysis, a high log-transformed hs-cTnT level and a high log-transformed BNP level were significant risk factors for primary outcome [hazard ratio (HR), 4.368 (95% confidence interval, CI, 1.032-18.480), P = 0.045. and HR, 3.127 (95% CI, 1.029-9.499), P = 0.044, respectively]. Patients with both high hs-cTnT and high BNP (>140 pg/mL: above the median value) levels had a 3.49 (95% CI, 1.23-9.88)-fold increased risk of the primary outcome compared with patients with both low hs-cTnT and low BNP levels.

Conclusions: In patients with CS, a high hs-cTnT level is a useful predictor of adverse events, and combined measurement of hs-cTnT and BNP further improves the prognostic value.

Aims: Cardiac resynchronization therapy (CRT) is guideline recommended for the treatment of symptomatic heart failure (HF) with reduced left ventricular ejection fraction and prolonged QRS. However, patients with common comorbidities, such as persistent/permanent atrial fibrillation (AF), are often under-represented in clinical trials.

Methods: The Strategic Management to Optimize Response to Cardiac Resynchronization Therapy (SMART) registry (NCT03075215) was a global, multicentre, registry that enrolled de novo CRT implants, or upgrade from pacemaker or implantable cardioverter defibrillator to CRT-defibrillator (CRT-D), using a quadripolar left ventricular lead in real-world clinical practice. The primary endpoint was CRT response between baseline and 12 month follow-up defined as a clinical composite score (CCS) consisting of all-cause mortality, HF-associated hospitalization, New York Heart Association (NYHA) class and quality of life global assessment.

Results: The registry enrolled 2035 patients, of which 1558 had completed CCS outcomes at 12 months. The patient cohort was 33.0% female, mean age at enrolment was 67.5 ± 10.4 years and the mean left ventricular ejection fraction was 29.6 ± 7.9%. Notably, there was a high prevalence of mildly symptomatic patients (NYHA class I/II 51.3%), non-left bundle branch block (LBBB) morphology (38.0%), AF (37.2%) and diabetes mellitus (34.7%) at baseline. CCS at 12 months improved in 58.9% (n = 917) of patients; 20.1% (n = 313) of patients stabilized and 21.0% (n = 328) worsened. Several patient characteristics were associated with a lower likelihood of response to CRT including older age, ischaemic aetiology, renal dysfunction, AF, non-LBBB morphology and diabetes. Higher HF hospitalization (P < 0.001) and all-cause mortality (P < 0.001) were observed in patients with AF. These patients also had lower percentages of ventricular pacing than patients in sinus rhythm at baseline and follow-up (P < 0.001, both). A further association between AF and non-LBBB was observed with 81.4% of AF non-LBBB patients experiencing an HF hospitalization compared with 92.5% of non-AF LBBB patients (P < 0.001). Mortality between subgroups was also statistically significant (P = 0.019).

Conclusions: This large, global registry enrolled a CRT-D population with higher incidence of comorbidities that have been historically underrepresented in clinical trials and provides new insight into factors influencing response to CRT. As defined by CCS, 58.9% of patients improved and 20.1% stabilized. Patients with AF had particularly worse clinical outcomes, higher HF hospitalization and mortality rates and lower percentages of ventricular pacing. High incidence of HF hospitalization in patients with AF and non-LBBB in this real-world cohort suggests that ablation may play an important role in increasing future CRT response rates.