Journal of cardiology最新文献

Thrombosis is a potentially fatal condition for which various anticoagulant therapies have been used for prevention and treatment. However, bleeding events remain a concern with all anticoagulant drugs. Recent evidence suggests that inhibiting coagulation factor XI (FXI) and activated FXI (FXIa) plays a greater role in the formation of pathological thrombi in thrombosis than in normal hemostatic thrombi, allowing for the potential to address these two events separately. Consequently, FXI/XIa inhibition has become the focus of anticoagulant drug research, leading to the development of numerous FXI-targeting compounds with diverse mechanisms of action. Herein, we aimed to review FXI/FXIa inhibitors under development, discussing the role of FXI in the coagulation reaction and the advantages and disadvantages associated with its deficiency. The results of a Phase II study showed that FXI/XIa inhibitors provide efficacy comparable to that of low molecular weight heparin therapy while reducing clinically significant bleeding events. Additionally, in a study of patients with atrial fibrillation, FXI/XIa inhibitors reduced bleeding events compared to those with direct oral anticoagulants. Furthermore, when combined with antiplatelet therapy, FXI/XIa inhibitors did not significantly increase bleeding risk in non-cardioembolic stroke or acute coronary syndrome. However, conflicting trial results have also been reported, highlighting the difficulty in assessing the clinical benefit of FXI/XIa inhibitors in different clinical settings, such as atrial fibrillation and acute myocardial infarction. Future large, well-designed Phase III studies are needed to evaluate the safety and efficacy of FXI/XIa inhibitors across diverse populations requiring antithrombotic therapy.

Cognitive impairment (CI) is a significant comorbidity in individuals with heart failure (HF). A substantial number of patients with HF may experience CI, which can present as deficits in attention, memory, executive function, and processing speed. HF patients with CI tend to have reduced functional independence, self-care capabilities, medication adherence and decision-making ability, along with more frequent rehospitalizations, and an increased risk of mortality. Currently, there is no established gold standard diagnostic tool or follow-up strategy for assessing CI in patients with HF. There has been an increasing recognition of the complex bidirectional relationship between HF and CI. However, the exact pathological mechanisms of CI in HF need further in-depth investigation. This review aims to explore the current epidemiological status of CI in patients with HF, the relationship between HF and cognitive dysfunction, the pathological mechanisms involved, as well as the early screening, diagnosis, and management issues for HF patients with CI. It also discusses prevention and intervention strategies. The objective is to provide a scientific basis for the clinical diagnosis, management, and treatment of CI in HF, while proposing future research directions to advance this field.

Background: Ventricular arrhythmia (VA) is an ominous manifestation of cardiac sarcoidosis (CS). Hence, identifying specific characteristics associated with VA in imaging modalities may enhance risk stratification.

Methods: Fifty-nine patients diagnosed with CS were retrospectively studied and grouped based on presenting symptoms as the VA group (sustained ventricular tachycardia and ventricular fibrillation) and the non-VA group (atrioventricular block, heart failure, and other symptoms). Thirty-nine patients underwent comprehensive evaluation by cardiac magnetic resonance imaging and ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) for comparing cardiac involvement distribution.

Results: The VA group (n = 15) showed higher prevalence of right bundle branch block, basal interventricular thinning, and left ventricle wall motion abnormality. In Cox analysis, VA at baseline (hazard ratio 4.75, p = 0.008) was associated with poor outcomes. The VA group showed a larger extent of late gadolinium enhancement than the non-VA group, especially in the left ventricular mid inferoseptal, right ventricular (RV) basal lateral to mid lateral, and RV apical anterior lesions. FDG-PET accumulation was prominent in the RV basal lateral to basal inferior, and mid anterior lesions in the VA group.

Conclusions: Patients who presented with VA had worse outcomes and a larger cardiac involvement predominant to the RV and ventricular septum; RV predominant scar pattern may serve as a surrogate in patients with CS and explain possible correlation with electrophysiological abnormalities.

Background: In the era of high-sensitivity troponin assays, overdiagnosis of acute coronary syndrome (ACS) has become increasingly common, overriding underdiagnosis and carrying a burden of healthcare issues. This study aimed to assess the incidence, predictors, and sex differences in ACS overdiagnosis among patients presenting with chest pain (CP) to the emergency department (ED).

Methods: Consecutive CP patients presenting at the ED were included. Patients with other causes of CP, non-suspicious for ACS, were excluded. Six-month ACS rate was assessed in discharged patients. In ACS hospitalized patients, clinical records were analyzed to evaluate true-ACS incidence. Patients inappropriately hospitalized for ACS (ACS-overdiagnosis, false-positives) were compared to correctly discharged (true-negatives) and actual ACS patients (true-positives and false-negatives).

Results: From 7040 CP patients, a random sample of 1025 was included. ACS was initially diagnosed in 237 (23.1 %) patients who were hospitalized, while 788 (76.9 %) were discharged from the ED. ACS misdiagnosis occurred in 30 (2.9 %) patients: 8 (1 %) discharged patients experienced ACS at follow-up (false-negatives) while 22 (9.3 %) hospitalized for ACS were considered not to have ACS (ACS-overdiagnosis). True incident ACS at 6 months was 223 (21.8 %). Independent predictors of ACS overdiagnosis were electrocardiographic alterations, troponin T > 99° percentile, and male sex, while women were older with lower pre-test likelihood of ACS according to ED physicians, with a higher rate of early discharge but similar outcomes.

Conclusions: ACS overdiagnosis is more frequent than underdiagnosis, carrying potential issues for the healthcare system. Patients with ACS overdiagnosis were more commonly men with elevated high-sensitivity troponin, often indistinguishable from true-ACS patients according to standard care.

Background: Donor-recipient size matching is an important consideration for heart allocation, of which predicted heart mass (PHM) ratio has been found to be the most optimal metric. However, the PHM formula has not been validated in a cohort that included obese recipients. Therefore, our study seeks to add further granular data on this topic by investigating acute survival in PHM categories across multiple body mass index (BMI) groups.

Methods: Adult heart transplant recipients were analyzed using the United Network for Organ Sharing database. BMI groups included: normal (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), obese class I (30.0-34.9 kg/m²), and obese class II+ (≥35.0 kg/m²). PHM ratio (PHMR) categories were: severely undersized (U2): <0.85, undersized (U1): 0.85-0.95, approximately equally sized (R): 0.95-1.05, oversized (O1): 1.05-1.25, and severely oversized (O2): ≥1.25. All-cause acute mortality was the primary outcome of interest.

Results: A total of 46,141 recipients were included in our analysis. The percentage of obese patients and donors increased over the years, from 21.5 % and 17.2 % in 2000 to 34.4 % and 33.1 % in 2022, respectively. Survival analysis found a stepwise reduction in mortality risk for severely undersized grafts as BMI increased (normal: HR = 1.59, p < 0.001; overweight: HR = 1.20, p = 0.029), until ultimately reaching insignificant levels in obese groups across all PHMR categories.

Conclusion: Patients with a normal to overweight BMI were susceptible to increased mortality with a severely undersized graft. Conversely, obese groups appeared to be resistant to the hazards of organ size mismatching by PHMR. The clinical implications of this study may enable recruitment from a larger donor pool and improve challenges in transplantation for obese patients.

The type 2 ryanodine receptor (RyR2) is a giant Ca²⁺ (Ca)-releasing channel on the sarcoplasmic reticulum (SR) membrane, with subunits composed of 5000 amino acids constituting a homotetrameric channel. The N-terminal (1-220) and central (2300-2500) domain interactions (inter-subunit zipping interfaces) within RyR2 are located in close proximity to each other between different neighboring subunits and play an important "cornerstone" role in maintaining the tetrameric structure of RyR2. External stress such as oxidative stress causes Ca leak by destabilizing RyR2 (instability of the tetrameric structure) due to domain unzipping between N-terminal (1-220) and central (2300-2500) domains, followed by dissociation of calmodulin (CaM: binds to the RyR2 and stabilize RyR2) from RyR2. Ca leak from SR causes arrhythmias and myocardial dysfunction. RyR2 is also present in the endoplasmic reticulum (ER), thus it is not surprising that undesired Ca release from RyR2 on the ER is closely associated with various diseases involving ER dysfunction such as neurodegenerative diseases, diabetes, metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, and autoimmune diseases. Pharmacological or genetic (point mutations within RyR2 that increase CaM-RyR2 affinity: knock-in RyR2-V3599K) RyR2 structural stabilization has shown potential therapeutic effects not only for SR failure-related diseases (malignant hyperthermia, arrhythmia, and heart failure) but also for ER failure-related disease. RyR2-stabilizers may function as a panacea for aging-related diseases.