ESC Heart Failure最新文献

Aims: Left ventricular outflow tract obstruction (LVOTO) drives symptoms and functional limitation in obstructive hypertrophic cardiomyopathy (oHCM). Some patients may only show treatment-qualifying obstruction during exercise echocardiography, yet their clinical profile and response to cardiac myosin inhibition are not well defined. This study compared the characteristics and therapeutic response of patients requiring exercise echocardiography to establish eligibility for mavacamten versus those meeting criteria at rest or during Valsalva.

Methods and results: A single-center retrospective cohort of 56 symptomatic oHCM patients treated with mavacamten was evaluated. LVOTO was assessed at rest, with Valsalva, and during exercise; patients were classified as "exercise" or "non-exercise" LVOTO based on the provocation maneuver eliciting a qualifying gradient (≥50 mmHg). Hemodynamic (Valsalva LVOT gradient) and symptomatic (NYHA class) response were assessed at 12 and 24 weeks. A total of 42.9% qualified for mavacamten exclusively during exercise echocardiography. Although resting and Valsalva gradients were lower by definition, these patients showed similar baseline functional limitation and exercise capacity (pVO2; 17.9±7.4 vs. 16.8±5.5 mL/kg/min, p=0.550). By 24 weeks, most patients in both groups achieved non-obstructive gradients (<30 mmHg; 92.3% vs. 100.0%, p=0.371) and NYHA class improvement (77.3% vs. 92.3%, p=0.377), without significant between-group differences.

Conclusion: Patients requiring exercise echocardiography to document qualifying LVOTO do not exhibit a milder disease phenotype and derive similar treatment benefits from mavacamten compared to those with resting or Valsalva-provoked obstruction. Exercise echocardiography identifies a substantial proportion of symptomatic HCM patients with significant LVOTO missed by resting assessment and is essential for guiding treatment eligibility.

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are currently recommended as one of the four pillars of treatment in heart failure (HF) with reduced ejection fraction (HFrEF). Following the approval of dapagliflozin in 2020, real-world data are relevant for the medical community and payers. This study aimed to characterise the patient population with dapagliflozin initiated for HFrEF in clinical practice in 9 countries from Central Eastern Europe and the Baltic Area (CEE-BA).

Methods: EVOLUTION-HF CEE-BA is a multicentre, multi-country, observational, longitudinal study conducted in 102 centres in Bulgaria, Croatia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, and Slovenia. All treatment decisions were at the discretion of the patient's healthcare providers, based on the locally approved product information and routine clinical practice. Patients with type 1 diabetes, prior treatment with dapagliflozin or other SGLT2i, and initiation of dapagliflozin outside the approved HFrEF indication were excluded. The baseline period covered 12 months prior to dapagliflozin initiation, with prospective follow-up continuing up to 12 months or until loss to follow-up, death, or study discontinuation, whichever occurred first. Descriptive statistics and Kaplan-Meier methods were used.

Results: A total of 1131 patients with HFrEF were included in the full analysis set. Ischemic aetiology was present in 52% of patients. The mean left ventricular ejection fraction was 32%. The most frequent comorbidities were atrial fibrillation (46%), type 2 diabetes (37%), and chronic kidney disease (29%). At the time of dapagliflozin initiation, 93% of patients received any combination of a renin-angiotensin-aldosterone system inhibitor (RAASi), beta-blocker (BB), or mineralocorticoid receptor antagonists (MRA). Of all patients, 60% received concomitantly all three classes plus dapagliflozin for their HFrEF. Except for dapagliflozin, which was administered as 10 mg/day, optimal doses were recorded for 14% for any RAASi, 17% for BB, and 25% for MRA. At 6- and 12-month follow-up, maintenance of dapagliflozin treatment was recorded in 95% and 96% of patients, respectively. The real-world median time to discontinuation of dapagliflozin has not been reached. The percentage of patients receiving all four classes recommended in HFrEF remained stable over the study period. Adverse events were reported spontaneously, as in routine clinical practice in each centre.

Conclusions: This large non-interventional study provides a contemporary perspective of the treatments used in HFrEF over 1-year follow-up. Despite high dapagliflozin persistence rates, a low proportion of patients received complete guideline-directed medical therapy in optimal doses. Improvement of HF management decisions across the CEE-BA region is warranted.

Background and aims: Long-term real-world effects of sacubitril/valsartan (S/V) and the impact of S/V dose reduction or discontinuation are less defined. We assessed longitudinal changes after S/V initiation and the association of dose changes with major adverse cardiovascular events (MACE).

Methods: Multicenter retrospective study of 592 HFrEF outpatients starting S/V (83% men; age 68±10 years; LVEF 32±7%). NT-proBNP, Kansas City Cardiomyopathy Questionnaire (KCCQ) and echocardiography were collected at baseline, 12 months and last follow-up. MACE was analyzed with Kaplan-Meier and Cox models.

Results: NT-proBNP decreased from 1,000 (494-2,333) to 751 (304-1,726) and 735 (215-1,980) pg/mL (p<0.001). KCCQ improved from 53±15 to 62±14 and 66±15 (p<0.001). LVEF increased from 32±7 to 36±8 and 37±9% (p<0.001) and GLS improved from -10.8±3.2 to -12.3±3.1 and -14.0±2.9% (p<0.001). During a median follow-up of 3.72 years, 225 patients (38%) experienced MACE (36 deaths; 134 HF hospitalizations). MACE incidence was higher in patients with S/V discontinuation and with dose reduction (log-rank p=0.013 and p=0.014). In multivariable Cox analysis, S/V discontinuation (HR 1.52, 95% CI 1.28-1.97; p=0.040), change in GLS (HR 0.81, 95% CI 0.67-0.98; p=0.028) and change in KCCQ (HR 0.95, 95% CI 0.92-0.98; p=0.001) were independently associated with MACE.

Conclusions: S/V initiation was associated with sustained improvements in NT-proBNP, quality of life and cardiac remodeling. S/V discontinuation or dose reduction identified patients at higher MACE risk.

Background: Left ventricular reverse remodeling (LVRR) is a key objective of contemporary heart failure (HF) therapies and is characterized by reversal of left ventricular (LV) dilation and dysfunction.

Objectives: To report the incidence and clinical impact of early (30-day) LVRR patients with primary (PMR) and secondary mitral regurgitation (SMR) treated with mitral transcatheter edge-to-edge repair (M-TEER), and to identify independent associations with early LVRR.

Methods: The EXPANDed cohort includes 2205 patients treated with M-TEER from the EXPAND and EXPAND G4 studies. Patients were classified as having early LVRR if they demonstrated a >10% reduction in LV dimension or volume from baseline to 30 days. All LV measurements were assessed by independent echocardiographic core laboratories.

Results: Among 527 SMR patients, 338 patients (64.1%) experienced early LVRR after M-TEER. At 1 year, SMR patients with early LVRR had significantly lower rates of death or HF hospitalizations compared to those without (early LVRR: 24.7% vs no early LVRR: 35.9%, p=0.009), despite similar MR reduction (both ≥93% in both groups) and comparable improvements in functional status (NYHA≤II ≥78%) and quality of life (∼20-points improvement per KCCQ-OS). Independent associations with early LVRR included hypertension (OR=1.96, p=0.004), absence of prior cardiac surgeries (OR=0.51, p=0.002), and smaller LV end-systolic volume (OR=0.81, p=0.002).Among 536 PMR patients, 391 (73.0%) experienced early LVRR at 30 days. At 1 year, PMR patients with early LVRR group had similar clinical (composite all-cause mortality or HF hospitalization: early LVRR: 14.5% vs no early LVRR: 17.1%, p=0.47) and symptomatic outcomes (≥83% NYHA≤II; ∼19-point improvement per KCCQ-OS) compared to those without. However, among PMR patients with dilated ventricles, early LVRR group was associated with significantly lower all-cause mortality (early LVRR: 3.8%, no Early LVRR: 14.0%, p=0.028).

Conclusions: Regardless of etiology, most patients experienced early LVRR after M-TEER with significant MR reduction and symptom relief. In SMR patients, early LVRR was associated with lower rates of HF hospitalization and death.

Aims: Circulating dipeptidyl peptidase 3 (cDPP3) is implicated in cardiocirculatory failure and elevated concentrations predict poor outcomes in shock states. Its role in acute heart failure (AHF) is unexplored. We assessed the clinical relevance of cDPP3 in AHF.

Methods: Analysis were performed using two prospective AHF trials, STRONG-HF and CORTAHF. cDPP3 was measured at baseline and follow-up (day 90 in STRONG-HF; day 30 in CORTAHF). Associations with 180-day (STRONG-HF) and 90-day (CORTAHF) outcomes were evaluated according to baseline concentrations. Longitudinal changes during guideline-directed medical therapy (GDMT) optimization and predictors of elevated cDPP3 were analysed.

Results: In STRONG-HF, 222/973 patients (23%) had cDPP3 ≥40 ng/mL. These patients were younger (58 ± 15 vs. 65 ± 13 years, p < 0.0001), more frequently female (47.7% vs. 35.8%, p = 0.0013) and Black (42.8% vs. 14.4%, p < 0.0001), with lower NT-proBNP concentrations (p<0.0001). Baseline cDPP3 ≥40 ng/mL was not associated with 180-day outcomes. Over 90 days, cDPP3 decreased by -15% with high-intensity care and -8% with usual care (p=0.078). Changes in cDPP3 were not associated with NT-proBNP reduction (continuous p=0.797; ≥30% responder p=0.990). In pooled multivariable analysis, MRA use was independently associated with cDPP3 ≥40 ng/mL (OR 3.83; 95% CI 1.47-9.96; p = 0.006), whereas non-Black ethnicity was associated with lower odds (OR 0.43; 95% CI 0.29-0.64; p < 0.0001).

Conclusion: In AHF, cDPP3 was mildly elevated and was not associated with clinical outcomes or congestion relief during GDMT optimization. Elevated cDPP3 identified a distinct clinical phenotype but did not confer adverse prognosis.

Background and aims: We have previously shown an association between metabolic syndrome (MS) and heart failure (HF) outcomes in patients with implanted defibrillators (ICD) or cardiac resynchronization therapy (CRT-D). However, the role of MS in predicting outcomes was not assessed in non-obese patients. We aimed to examine how the presence of MS and its components predicts the risk of HF/death in non-obese ICD or CRT-D patients.

Methods: We included obese and non-obese patients, enrolled in Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT). Patients needed at least 2 of the 3 criteria, dyslipidemia, diabetes, or hypertension, to be considered for having MS. Kaplan-Meier analyses were used to assess the rate of HF/death by MS. Multivariate Cox-proportional analyses were performed to assess the risk of HF/death by MS.

Results: From 1,180 (65%) non-obese patients in MADIT-CRT, 672 (57%) presented with MS. Among non-obese patients with MS, 284 (42%) had diabetes mellitus. Non-obese MS patients had a significantly higher, 34% cumulative probability of HF/death at 3 years, as compared to the 20% of non-obese patients without MS (log-rank p<0.001) (Hazard Ratio: 1.64, 95% CI: 1.15-2.32, p=0.006). Within non-obese MS patients, those with diabetes had a significantly higher rate of HF/death with 28% vs. 20% in non-diabetics at 2.5 years (log-rank p<0.001). Reverse remodeling was similar in all subgroups.

Conclusions: Metabolic syndrome in non-obese ICD or CRT-D patients is associated with a higher risk of HF/Death, most prominent in those with diabetes, necessitating early intervention.

Background: Accurate assessment of left ventricular ejection fraction (LVEF) is crucial for heart failure (HF) diagnosis but requires skilled sonographers. Artificial intelligence-enabled point-of-care (AI-POC) devices may enable novices to assess LVEF, potentially reducing healthcare costs. We conducted a cost-minimization analysis comparing conventional sonographer-performed echocardiography versus novice-operated AI-POC devices.

Methods: Using a decision tree model, we compared the costs of diagnosing LVEF <50% in patients with suspected heart failure across two pathways: novice-operated AI-POC devices versus standard transthoracic echocardiogram (TTE) performed by sonographers. The model incorporated LVEF<50% prevalence, diagnostic accuracy metrics, and comprehensive cost data for both approaches. We conducted a probabilistic sensitivity analysis to test the robustness of our findings under varying assumptions.

Results: The AI-POC pathway demonstrated substantial cost savings, averaging S$1,185 [US$1,422] per patient compared to S$1,403 [US$1,684] for conventional TTE. In a single tertiary referral centre in Singapore, implementing AI-POC devices for LVEF assessment in 100 patients resulted in savings of S$21,669 [US$26,013]. Probabilistic sensitivity analysis suggested a 99.9% probability that the AI-POC approach would be cost-saving compared to standard TTE.

Conclusion: This study provides economic evidence that task-shifting echocardiographic assessment of LVEF to novices using AI-POC devices is likely cost-saving compared to standard TTE. This task-shifting strategy offers a cost-saving alternative to conventional sonographer-led TTE.

Background and aims: Peripartum cardiomyopathy (PPCM) is an idiopathic form of heart failure occurring in the peripartum phase. Elevated circulating levels of the senescence-associated-secretory-phenotype (SASP) factor Activin-A have been associated with heart failure severity in acute PPCM patients at baseline diagnosis. Here, we investigated Activin-A serum levels in the German PPCM registry in acute PPCM and during left ventricular (LV) recovery.

Methods and results: Clinical data including LV ejection fraction (LVEF) and Activin-A serum levels were assessed at initial diagnosis (baseline [BL]) and during follow-up (FU) at 3 months (M) and 6M in PPCM patients from the German PPCM Registry (n = 151, mean age 33 ± 5 years) compared to postpartum healthy controls (n = 27, mean age 32 ± 5 years). Activin-A serum levels at BL were elevated (404 pg/ml; interquartile range [IQR]: 197-815, n = 151) compared to healthy postpartum controls (240 pg/ml, IQR:148-446, n = 27; P < .01) and remained persistently elevated above postpartum healthy controls at 3 M (418 pg/ml, IQR: 169-806, n = 100) and 6M-FU (520 pg/ml, IQR: 214-1131, n = 104). Activin-A levels at BL did not correlate with LVEF (Spearman r  = 0.10, P = .2416, n = 139), NT-proBNP (r  = 0.096, P = .2766, n = 131), CRP (r  = -0.0008, P = .9933; n = 110) or PPCM biomarker plasminogen-activator-inhibitor-1 (PAI-1) (r  = 0.095, P = .3273, n = 109). The majority of PPCM patients showed LV recovery 6M after initial diagnosis, indicated by improved LVEF (PPCM BL: 25%, IQR: 20-33, n = 152; 6M-FU: 52% IQR: 45-56, n = 128, P < .0001). Activin-A levels did not differ between full or incomplete LV recovery, or between patients with hypertensive pregnancy disorders.

Conclusions: In PPCM patients from the German PPCM registry Activin-A serum levels were elevated at diagnosis, remained persistently high after 3M- and 6M-FU but were not associated with LV recovery.