Journal of the American Heart Association最新文献

Studies have established the safety and benefits of exercise training in patients admitted with acute heart failure, yet heterogeneity in exercise delivery patterns exists. Hence, a scoping review was undertaken to map the evidence on early exercise-based interventions (early mobilization with/without exercise training) in patients recovering from acute heart failure (admission to up to 2 weeks post-hospitalization), for geographic distribution, exercise prescription, and exercise initiation time. A systematic search was conducted across 5 databases until September 2024. Studies, including protocols, providing early exercise-based intervention anytime between admission and up to 2 weeks from discharge, in any setting, were included. Data were extracted from 30 included studies, and the obtained evidence was mapped. This study uses the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-Extension for Scoping Reviews. The review included 1,54 980 participants with acute heart failure, and 26.6% (8 of 30) of the studies focused on the older adult population. Early exercise-based interventions, ie, early mobilization (n=12), exercise training (n=5), or combined (n=13), were limited to higher- (n=23) and upper-middle-income (n=6) countries and were primarily observational (n=19) in design. The median (Q1-Q3) initiation time to exercise was 3.8 days (2.8-5.5), with a dose of eight sessions (4.7-21). The intensity ranged from very low to moderate intensity, with the duration per session ranging from 10 to 60 minutes. The use of pre-specified, well-developed initiation, monitoring, and termination criteria was not common. Early exercise-based interventions were comprehensive, multi-modal, and of low-moderate intensity, initiated within 4 days of admission.

Background: Despite recent advances in pharmacotherapy, heart failure (HF) remains a major cause of hospitalization and death, particularly among aging populations. Sodium-glucose cotransporter 2 inhibitors have reduced hospitalization for HF and cardiovascular death. However, the mechanisms underlying these cardioprotective effects, particularly in the absence of diabetes, remain unclear. Therefore, we aimed to define the cardiac-specific effects of sodium-glucose cotransporter 2 inhibitors and the mechanism by which they improve HF prognoses.

Methods: We investigated the cardioprotective properties of empagliflozin in mouse models of HF induced by transverse aortic constriction. Empagliflozin was administered daily for 2 weeks, starting 2 weeks after transverse aortic constriction, and then cardiac function was evaluated.

Results: Empagliflozin preserved cardiac function and markedly reduced myocardial fibrosis and HF markers. Empagliflozin decreased cardiac C-C chemokine receptor type 2-positive macrophages, suggesting attenuated inflammation. Empagliflozin also reduced C-C motif chemokine ligand 2 expression in cardiac fibroblasts, indicating direct modulation of fibroblast behavior under mechanical stress and inhibited recruitment of proinflammatory macrophages.

Conclusions: We propose a novel antifibrotic mechanism in which empagliflozin acts directly on mechanically stressed cardiac fibroblasts to reduce chemokine signaling and macrophage-mediated inflammation. This mechanosensitive, fibroblast-targeted action might represent a paradigm shift in understanding sodium-glucose cotransporter 2 inhibitor cardioprotection and lead to new therapeutic strategies to mitigate HF progression.

Background: Triptan medications are proposed as an association of cerebral ischemic stroke in patients with migraine, but population-based data on this are lacking.

Methods: A retrospective, observational, cohort study was performed using computerized claims data from a proprietary, insurance-based registry-Marketscan (by Merative). Patients with at least 1 claim related to a migraine diagnosis were included. The primary exposure was initiation of any triptan medication defined by at least 1 prescription fill. The primary end point was time to cerebral ischemic stroke. Secondary end points included time to retinal stroke (central retinal artery occlusion, other retinal artery occlusion), intracranial hemorrhage, and myocardial infarction. The association between triptan initiation and study end points was modeled using a propensity score-overlap weighted Cox model. Adjusted hazard ratios (HR) and corresponding 95% CIs were computed.

Results: In total, 869 092 patients (median age 40.0 years [Q1-Q3, 30.0-50.0]; 77.5% female) met study selection criteria of whom 287 629 initiated a triptan and 581 463 did not. Median follow-up was 2555 days in the entire cohort. Initiation of a triptan was associated with higher hazard of cerebral ischemic stroke (adjusted HR, 2.37 [95% CI, 1.65-3.51]; absolute risk difference of 0.17% per year). Of 4 secondary end points, 2 were associated with triptan use: intracranial hemorrhage (adjusted HR, 2.37 [95% CI, 1.65-3.41]) and myocardial infarction (adjusted HR, 2.06 [95% CI, 1.60-2.66]).

Conclusions: In a population-based cohort study, initiation of a triptan was independently associated with risk of subsequent cerebral ischemic stroke.

Background: Radiomic and transcriptomic analyses have independently identified features linked to mechanical thrombectomy (MT) outcomes. Here, we integrated paired radiomics/transcriptomics of stroke clots to identify neutrophil extracellular trap (NET) enrichment as a predictor of first-pass MT success, assessing the potential to noninvasively detect NET enrichment using prethrombectomy computed tomography imaging.

Methods: We performed radiomic/transcriptomic analyses of 32 stroke clots retrieved by MT. Clots were segmented from pre-MT computed tomography angiography and noncontrast computed tomography scans, and radiomic features (RFs) were extracted using PyRadiomics. Differentially expressed genes were identified between modified first-pass effect (mFPE) success and failure using the criteria of log(fold-change) ≥1.5 and q <0.05. RFs significantly different between mFPE outcomes were identified. A NET enrichment score was computed from expression data, and RFs that differed significantly between low- and high-NET-enriched clots were selected to construct an RF signature predictive of NET enrichment. Immunofluorescence was completed on clots to provide ground truth NET labeling.

Results: A total of 44 differentially expressed genes were identified between mFPE outcomes. NET formation, neutrophil degranulation, and the NET signaling pathway were among the most enriched gene ontologies in the mFPE failure group, with related genes downregulated in the mFPE success group. Forty RFs were significantly different between mFPE outcomes. Of these, 4 were found to be predictive of clot NET enrichment. Immunofluorescence validated that transcriptomic NET signatures accurately reflected NET presence within clot tissues.

Conclusions: NET enrichment in clots is associated with reduced mFPE success. With further validation, RFs extracted from prethrombectomy computed tomography imaging may serve as noninvasive biomarkers of clot NET content to aid in preprocedural MT decision-making.

Background: The competing risk of nonstroke mortality may limit the potential benefit of stroke prophylaxis therapy in patients with atrial fibrillation or atrial flutter AF.

Methods: Using a Medicare 20% sample, we identified a cohort of beneficiaries diagnosed with atrial fibrillation or atrial flutter from 2006 to 2019 using International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes. Fine and Gray regression analysis determined the hazard of stroke with a competing risk of nonstroke mortality, and Cox proportional hazard analysis determined risk of nonstroke mortality. A scoring tool stratified patients into low or high potential benefit for thromboembolic prophylaxis.

Results: Among a total of 1 883 759 Medicare beneficiaries, 330 136 patients were included with median age of 79.7 years. 54% of patients had prior bleeding episodes. The median CHA₂DS₂-VASc score was 5. Of these patients, 211 791 (64%) died and 77 717 (24%) experienced an embolic stroke over median follow-up of 7.3 years. In the high potential benefit group (26.1%), the risk of stroke was much higher than the risk of nonstroke mortality at 1 year (12.2% versus 7.1%); 3 years (22.7% versus 16.9%); 5 years (31.9% versus 26.1%). In the low potential benefit group (73.9%), the risk of stroke was much lower than the risk of nonstroke mortality at 1 year (11.5% versus 39.2%); 3 years (23.2 versus 57.2%); and 5 years (34.3% versus 69.4%).

Conclusions: We propose a scoring tool to identify the potential benefit of thromboembolic prophylaxis therapy in older patients diagnosed with atrial fibrillation or atrial flutter. This tool can be used in shared decision-making settings. Further studies to improve and validate this scoring tool are warranted.

Background: Cardiac troponin T is associated with mortality in heart transplantation recipients, but the association between its longitudinal measurements and clinical outcomes has not been evaluated. This study aimed to determine whether 3 parameterizations of serial hs-cTnT (high-sensitivity cardiac troponin T)-instantaneous concentration, temporal trend, and cumulative exposure-are associated with clinical outcomes in this population.

Methods: In a retrospective analysis, 222 heart transplantation recipients (median age 50 years, 86% men) who survived >30 days post transplant were included. Joint models were used to analyze the association between longitudinal hs-cTnT and the primary outcome of all-cause mortality and the secondary outcome of major adverse cardiac events.

Results: Over a median follow-up of 2.3 years, 32 deaths and 41 major adverse cardiac events occurred. Both instantaneous hs-cTnT concentration (hazard ratio [HR], 1.85 [95% CI, 1.48-2.31]; P<0.001) and cumulative hs-cTnT exposure (HR, 1.80 [95% CI, 1.38-2.37]; P<0.001) were strongly associated with mortality. The temporal trend of hs-cTnT was significantly associated with mortality after adjustment for donor and recipient factors. Similarly, instantaneous concentration and cumulative exposure were associated with major adverse cardiac events incidence (both P<0.05). In contrast, baseline hs-cTnT lost its significant association with outcomes after multivariable adjustment.

Conclusions: Longitudinally measured hs-cTnT is independently associated with mortality and major adverse cardiac events in heart transplant recipients.

Despite advances in drug and device technology, health care delivery, and research infrastructure, cardiogenic shock (CS) continues to have nearly 50% in-hospital mortality. In patients with CS, both the initial severity of Society for Cardiovascular Angiography and Intervention CS and its subsequent trajectory predicts the clinical outcomes. Accordingly, delayed initial recognition and failure to escalate or deescalate treatment can significantly affect the outcomes of CS. Traditional assessment methods, with the exception of blood pressure measurement, require a high index of suspicion and frequent reassessment by the clinical team. Electronic medical record-based detection has been successfully implemented in acute and critical care patients with septic shock and acute kidney injury. In CS, electronic medical record-based studies have largely focused on using models to predict outcomes in patients with CS, with limited data on electronic medical record-based tools to assist with either predicting CS or providing real time alerts when escalation or de-escalation might be indicated. Early detection of CS may be associated with detection of earlier Society for Cardiovascular Angiography and Intervention stages of CS and potentially prevent deterioration to higher stages. In this review, we seek to highlight a blueprint for electronic medical record-based detection of CS that focuses on reproducibility, convenience, clinical decision support, and research aspects.

Background: Catheter ablation of atrial fibrillation (AF) is an effective treatment to achieve left atrial (LA) and left ventricular (LV) reverse remodeling in patients with systolic dysfunction. However, the relationship between LA and LV reverse remodeling (LARR and LVRR) and their clinical implications remains unclear.

Methods: Among 5287 consecutive patients undergoing first-time AF ablation, 620 with baseline LV ejection fraction <50% were evaluated. They underwent multidetector computed tomography at baseline and 3 months after ablation. LARR and LVRR were defined as ≥15% reductions in the LA and LV end-systolic volume, respectively. The relationship between LARR and LVRR and their impact on clinical outcomes was investigated.

Results: AF ablation reduced the LA and LV end-systolic volumes, with reduction rates of 24%±16% and 39%±24%, respectively (r=0.54, P<0.001). During a follow-up of 50.4 months, patients with LARR-/LVRR- (n=86) showed the highest incidence of AF recurrence (50.0%) and composite of heart failure hospitalization or cardiovascular death (25.6%). Patients with LARR+/LVRR- (n=43) exhibited similar AF recurrence but the second highest incidence of the composite outcomes (16.3%) compared with those with LARR-/LVRR+ (n=95) and LARR+/LVRR+ (n=396). Age- and sex-adjusted Cox regression analysis revealed that LARR-/LVRR- alone was associated with AF recurrence (hazard ratio [HR], 2.01 [95% CI, 1.42-2.85], P<0.001), whereas LARR-/LVRR- (HR, 6.73 [95% CI, 3.48-13.0]) and LARR+/LVRR- (HR, 4.58 [95% CI, 1.86-11.3]) were associated with the composite end point.

Conclusions: LARR and LVRR were moderately correlated after AF ablation in patients with systolic dysfunction. Their combined assessment delineated distinct postablation trajectories and may improve individual risk stratification.

Background: Patients with atrial fibrillation (AF) often complain of dyspnea, raising the question that symptoms could be related to unrecognized heart failure (HF) with preserved ejection fraction (HFpEF).

Methods: We used the HFpEF-age, body mass index and history of AF algorithm to estimate the probability of undiagnosed HFpEF in CABANA (Catheter Ablation vs. Antiarrhythmic Drug Therapy), and its interaction with catheter ablation on quality of life (QOL). Probable HFpEF was defined as patient-reported dyspnea with HFpEF-age, body mass index and history of AF probability≥75%. Absence of dyspnea or HFpEF-age, body mass index and history of AF probability<75% was considered to reflect patients without HFpEF. The effect of randomization to catheter ablation on QOL (Mayo Atrial Fibrillation-Specific Symptom Inventory questionnaire and EuroQol-5 Dimension-3 Level score) was assessed using mixed models.

Results: Of participants without known HF, 70% (n=1225) had probable HFpEF and the remaining 30% (n=522) did not. Those with probable HFpEF had worse New York Heart Association class, EuroQol-5 Dimension-3 Level score, Mayo Atrial Fibrillation-Specific Symptom Inventory severity, and Mayo Atrial Fibrillation-Specific Symptom Inventory frequency scores (P<0.0001 for all), with higher risk of HF hospitalization (hazard ratio [HR], 2.19 [95% CI, 1.11-4.31], P=0.01). Ablation resulted in greater improvement in EuroQol-5 Dimension-3 Level and Mayo Atrial Fibrillation-Specific Symptom Inventory severity/frequency scores in probable HFpEF (interactions P=0.005, P=0.05, and P=0.04 respectively). In probable HFpEF, catheter ablation was associated with lower risk of cardiovascular hospitalization (HR, 0.78 [95% CI, 0.66-0.92], P=0.003, interaction P=0.03) but not HF hospitalization (HR, 0.94 [95% CI, 0.55-1.64], P=0.84).

Conclusions: Nearly three quarters of CABANA participants had potentially undiagnosed HFpEF, with worse QOL and risk of HF hospitalization. Catheter ablation in probable HFpEF resulted in greater improvement in QOL, but residual QOL impairment and HF risk remained elevated despite ablation. These data reinforce the importance of diligent consideration of HFpEF among patients with symptomatic AF to ensure optimal use of foundational treatments for HF.