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Ischemic stroke (IS) remains one of the most frequent causes of death and disability worldwide. Identifying possible prognosis factors for IS outcomes, including hemorrhagic transformation (HT), could improve patients' recovery. This study aimed to investigate the potential prognosis role of non-specific laboratory data at admission and baseline MMP-2 and MMP-9 serum levels in predicting HT risk, discharge, and 3-month follow-up status of IS patients. Data from 150 successive acute cerebral infarction patients were analyzed in a prospective cohort study. The active group included patients who developed HT during hospitalization (55 persons). There were no significant differences in age, gender distribution, time to admission, or time to blood sample collection for MMPs measurement between patients in the active and control groups. IS patients from the active group had a significantly higher rate of AF (atrial fibrillation) in the past (p=0.003), while differences in other factors such as diabetes, hypertension, myocardial infarction, previous stroke, obesity, smoking, and alcohol were not significant. Admission NIHSS score and mRS (modified Rankin Scale) values (at discharge and 90 days) were significantly worse in the active group (p<0.001). Among the analyzed admission laboratory factors (glycemia, lipid profile, coagulation panel, inflammatory reaction parameters, MMP-2, MMP-9), INR presented an inverse correlation, with lower values in the HT cohort (univariate analysis - p=0.01, OR=0.11; multivariate analysis - p=0.03, OR=0.09). Further research on larger cohorts is warranted to determine the specific laboratory biomarkers for predicting hemorrhagic transformation and ischemic stroke outcomes.

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Background: More than 40% of left atrial appendage closure (LAAC) procedures were combined with atrial fibrillation (AF) ablation in China. Objectives: This study aimed to assess the sex differences in the combined radiofrequency catheter ablation and LAAC procedures. Methods: Data from the LAACablation (Left Atrial Appendage Closure in Combination With Catheter Ablation) registry, which enrolled AF patients who underwent the combined procedure between 2018 and 2021, were analyzed. Procedural complications, long-term outcomes, and quality of life (QoL) were compared between sexes. Results: Of 931 patients, 402 (43.2%) were women. Compared with men, women were older (age 71.3 ± 7.4 years vs 68.7 ± 8.1 years; P < 0.001), presented more often with paroxysmal AF (52.5% vs 42.7%; P < 0.003), and had higher CHA2DS2-VASc scores (4.1 ± 1.5 vs 3.1 ± 1.5; P < 0.001), but received less often linear ablation and had shorter total procedural times and radiofrequency catheter ablation times. Women had similar rates of total and major procedural complications but presented with a higher incidence of minor complications than men (3.7% vs 1.3%; P = 0.027). Follow-up over 1,812 patient-years revealed similar adverse events between women and men, including all-cause death (HR: 0.89; 95% CI: 0.43-1.85; P = 0.754), thromboembolic events (HR: 1.17; 95% CI: 0.54-2.52; P = 0.697), major bleeding (HR: 0.96; 95% CI: 0.38-2.44; P = 0.935), and their composite (HR: 0.85; 95% CI: 0.56-1.28; P = 0.434). The recurrence rates of atrial tachyarrhythmia were also comparable between sexes presenting either paroxysmal or persistent AF. Women were seen with greater QoL impairment at baseline, but the sex gap narrowed at 1-year follow-up. Conclusions: In AF patients who underwent the combined procedure, women had similar procedural safety and long-term efficacy to men and presented greater QoL improvement. (Left Atrial Appendage Closure in Combination With Catheter Ablation [LAACablation]; NCT03788941).

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Proteasome inhibitors (PIs) are the backbone of combination treatments for patients with multiple myeloma and AL amyloidosis, while also indicated in Waldenström's macroglobulinemia and other malignancies. PIs act on proteasome peptidases, causing proteome instability due to accumulating aggregated, unfolded, and/or damaged polypeptides; sustained proteome instability then induces cell cycle arrest and/or apoptosis. Carfilzomib, an intravenous irreversible PI, exhibits a more severe cardiovascular toxicity profile as compared with the orally administered ixazomib or intravenous reversible PI such as bortezomib. Cardiovascular toxicity includes heart failure, hypertension, arrhythmias, and acute coronary syndromes. Because PIs are critical components of the treatment of hematological malignancies and amyloidosis, managing their cardiovascular toxicity involves identifying patients at risk, diagnosing toxicity early at the preclinical level, and offering cardioprotection if needed. Future research is required to elucidate underlying mechanisms, improve risk stratification, define the optimal management strategy, and develop new PIs with safe cardiovascular profiles.

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Stroke risk is currently estimated as part of the composite risk of cardiovascular disease (CVD). We investigated if composite-CVD risk prediction tools QRISK3 and Pooled Cohort Equations-PCE, derived from middle-aged adults, are as good as stroke-specific Framingham Stroke Risk Profile-FSRP and QStroke for capturing the true risk of stroke in older adults. External validation for 10y stroke outcomes was performed in men (60-79y) of the British Regional Heart Study. Discrimination and calibration were assessed in separate validation samples (FSRP n = 3762, QStroke n = 3376, QRISK3 n = 2669 and PCE n = 3047) with/without adjustment for competing risks. Sensitivity/specificity were examined using observed and clinically recommended thresholds. Performance of FSRP, QStroke and QRISK3 was further compared head-to-head in 2441 men free of a range of CVD, including across age-groups. Observed 10y risk (/1000PY) ranged from 6.8 (hard strokes) to 11 (strokes/transient ischemic attacks). All tools discriminated weakly, C-indices 0.63-0.66. FSRP and QStroke overestimated risk at higher predicted probabilities. QRISK3 and PCE showed reasonable calibration overall with minor mis-estimations across the risk range. Performance worsened on adjusting for competing non-stroke deaths. However, in men without CVD, QRISK3 displayed relatively better calibration for stroke events, even after adjustment for competing deaths, including in oldest men. All tools displayed similar sensitivity (63-73 %) and specificity (52-54 %) using observed risks as cut-offs. When QRISK3 and PCE were evaluated using thresholds for CVD prevention, sensitivity for stroke events was 99 %, with false positive rate 97 % suggesting existing intervention thresholds may need to be re-examined to reflect age-related stroke burden.

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Traditional anatomically guided ablation and attempts to perform electrogram-guided atrial fibrillation (AF) ablation (CFAE, DF, and FIRM) have not been shown to be sufficient treatment for persistent AF. Using biatrial high-density electrophysiologic mapping in a canine rapid atrial pacing model of AF, we systematically investigated the relationship of electrogram morphology recurrence (EMR) (Rec% and CLR) with established AF electrogram parameters and tissue characteristics. Rec% correlates with stability of rotational activity and with the spatial distribution of parasympathetic nerve fibers. These results have indicated that EMR may therefore be a viable therapeutic target in persistent AF.

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Analysis of the spatio-temporal distribution of calcium sparks showed a preferential increase in sparks near the sarcolemma in atrial myocytes from patients with atrial fibrillation (AF), linked to higher ryanodine receptor (RyR2) phosphorylation at s2808 and lower calsequestrin-2 levels. Mathematical modeling, incorporating modulation of RyR2 gating, showed that only the observed combinations of RyR2 phosphorylation and calsequestrin-2 levels can account for the spatio-temporal distribution of sparks in patients with and without AF. Furthermore, we demonstrate that preferential calcium release near the sarcolemma is key to a higher incidence and amplitude of afterdepolarizations in atrial myocytes from patients with AF.

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Background: Few large-scale, real-world studies have compared the efficacy and safety of non-antivitamin K anticoagulants (NOACs) with that of warfarin in catheter ablation (CA) for atrial fibrillation (AF). Methods: This retrospective, cross-sectional study used a nationwide administrative claims database, to compare complication-incidence rates following CA for AF between NOAC-treated patients and warfarin-treated matched cohorts in the real-world. Among the 32,797,540 records between June 2011 and August 2020 from 426 hospitals, 41,347 patients (38,065 on NOACs and 3,282 on Warfarin) were considered eligible. After performing propensity matching, 6,564 patients (3,282 per group) were analyzed. Results: The overall complication incidence was significantly lower in the NOACs group than in the warfarin group (2.3 % vs. 4.0 %; P < 0.001, odds ratio [OR]: 0.55, 95 % confidence interval [CI]: 0.41-0.74). Although no significant differences in the incidence of cardiac tamponade (1.0 % vs. 1.1 %; P = 0.90, OR: 0.97, 95 % CI: 0.60-1.56) and major bleeding (0.6 % vs. 0.7 %; P = 0.54, OR: 0.83, 95 % CI: 0.44-1.52) were noted, blood transfusion requirements (0.6 % vs. 1.2 %; P = 0.02, OR: 0.52, 95 % CI: 0.30-0.88) and vascular complications (0.2 % vs. 0.5 %; P = 0.02, OR: 0.33, 95 % CI: 0.12-0.79) were significantly lower in the NOACs group than in the warfarin group. Furthermore, the thromboembolic event incidence was significantly lower in the NOACs group than in the warfarin group (0.5 % vs. 1.2 %; P < 0.001, OR: 0.36, 95 % CI: 0.19-0.64). Conclusions: NOACs should be considered as a first-line therapy for periprocedural anticoagulation in patients undergoing CA for AF.

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Restrictive physiology, such as cardiac amyloidosis, compromises atrial and ventricular performance, often leading to "atrial" functional valvular regurgitation. While focusing on atrial functional tricuspid regurgitation we aimed at summarizing the pathophysiological characteristics of, and therapeutic options in, cardiac amyloidosis. (Level of Difficulty: Intermediate.).

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Left atrial appendage (LAA) closure may prevent atrial fibrillation (AF)-induced thromboembolism. We describe a rare case of right atrial (RA) thrombus after thoracoscopic left atrial appendectomy and pulmonary vein isolation. Careful evaluation for the presence of RA thrombus in patients with persistent AF after LAA occlusion may be necessary. (Level of Difficulty: Intermediate.).

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An 81-year-old woman with arrhythmogenic right ventricular cardiomyopathy underwent catheter ablation for atrial fibrillation and atrial flutter. Hypoxemia refractory to the administration of oxygen was seen after transseptal puncture. Transthoracic echocardiography revealed right to left shunt via an iatrogenic atrial septal defect (IASD) that was increased by tricuspid regurgitation flow. Her hypoxemia improved after IASD occlusion with the inflation of a venogram balloon catheter. Emergent surgical IASD closure was successfully performed. IASD after transseptal puncture for atrial fibrillation ablation infrequently causes severe complications that require emergent repair. Learning objective: Some cases requiring iatrogenic atrial septal defect (IASD) closure after atrial fibrillation (AF) ablation have been reported. We describe the case of an arrhythmogenic right ventricular cardiomyopathy patient with right to left shunt via an IASD which required emergent surgical repair after AF ablation. Right to left shunt after trans-septal puncture is rare, however it can be an emergent life-threatening complication. IASD occlusion with venogram balloon catheter is helpful for the diagnosis and the short-term solution.

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Objective: To investigate the in-hospital outcomes of acute ischemic stroke in patients with hypertrophic cardiomyopathy (HCM). Patients and Methods: Using weighted discharge data from the National Inpatient Sample, we identified 5804 nonelective hospitalizations for ischemic stroke in adult patients with HCM between 2011 and 2017. For comparison, 58,179 hospitalizations for ischemic stroke in adult patients without HCM were selected as controls using the simple random sampling method. Results: Compared with the patients without HCM, those with HCM had a higher prevalence of hyperlipidemia (62.4% vs 57.5%, respectively, P<.001) and chronic heart failure (25.4% vs 13.6%, respectively, P<.001) but a lower prevalence of diabetes (28.2% vs 34.9%, respectively, P<.001) and hypertension (42.9% vs 53.4%, respectively, P<.001). Atrial fibrillation was documented in 45.1% (n=2617) of the patients with HCM. However, only 28.0% (n=733) of these patients had long-term use of anticoagulants. The in-hospital death rate among the patients with HCM was 6.3% (n=368), which was significantly higher than that in the patients without HCM (4.1%, P<.001). Having HCM (odds ratio [OR], 1.35; P<.001), atrial fibrillation (OR, 2.08; P<.001), and chronic heart failure (OR, 1.65; P<.001) were significant predictors of in-hospital death. In patients with HCM who were discharged alive, 50.0% were transferred to skilled nursing facilities compared with 45.3% of those without HCM (P<.001). Conclusion: The prognosis of acute ischemic stroke is worse in patients with HCM than in those without HCM. These findings emphasize the importance of aggressive treatment of predisposing factors for stroke in patients with HCM, especially atrial fibrillation.

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Rationale and objectives: Selecting region of interest (ROI) for left atrial appendage (LAA) filling defects assessment can be time consuming and prone to subjectivity. This study aimed to develop and validate a novel artificial intelligence (AI), deep learning (DL) based framework for automatic filling defects assessment on CT images for clinical and subclinical atrial fibrillation (AF) patients. Materials and methods: A total of 443,053 CT images were used for DL model development and testing. Images were analyzed by the AI framework and expert cardiologists/radiologists. The LAA segmentation performance was evaluated using Dice coefficient. The agreement between manual and automatic LAA ROI selections was evaluated using intraclass correlation coefficient (ICC) analysis. Receiver operating characteristic (ROC) curve analysis was used to assess filling defects based on the computed LAA to ascending aorta Hounsfield unit (HU) ratios. Results: A total of 210 patients (Group 1: subclinical AF, n = 105; Group 2: clinical AF with stroke, n = 35; Group 3: AF for catheter ablation, n = 70) were enrolled. The LAA volume segmentation achieved 0.931-0.945 Dice scores. The LAA ROI selection demonstrated excellent agreement (ICC ≥0.895, p < 0.001) with manual selection on the test sets. The automatic framework achieved an excellent AUC score of 0.979 in filling defects assessment. The ROC-derived optimal HU ratio threshold for filling defects detection was 0.561. Conclusion: The novel AI-based framework could accurately segment the LAA region and select ROIs while effectively avoiding trabeculae for filling defects assessment, achieving close-to-expert performance. This technique may help preemptively detect the potential thromboembolic risk for AF patients.

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Pacemaker insertion incurs significant costs for fluoroscopy machines and operator-related musculoskeletal injuries from long-term use of radiation protection equipment. Moreover, there are small potential risks to patients from pneumothorax, lead dislodgment, and cardiac perforation. We report a first-in-human case report of successful pacemaker insertion performed entirely with ultrasound. (Level of Difficulty: Advanced.).

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Introduction: Rheumatic heart disease (RHD), is a common cause of mitral stenosis (MS) in developing nations. As per current recommendation, Percutaneous Transvenous Mitral Commissurotomy (PTMC) is advised as a Class IA (I-Class Of Recommendation, COR; A-Level Of Evidence, LOE) indication in patients with symptomatic severe mitral stenosis. We aim to examine the clinical profile and in-hospital results of PTMC for mitral stenosis. Methods: A cross-sectional retrospective study was conducted at Manmohan Cardiothoracic Vascular and Transplant Center from April 2020 to May 2022. A structured questionnaire was used to collect the data and ethical approval for conducting the study was taken from the Institutional Review Committee (IRC) of Institute of Medicine (IOM). The data was collected in Microsoft Excel (Ver. 2013). For statistical analysis, SPSS 21 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.) Association was measured using a parametric and non-parametric test (depending upon the distribution of data) and p value < 0.05 was considered significant. Results: A total of 104 patients who met the inclusion criteria underwent PTMC during the study period. The mean age group of the patient was 41.7 ± 12.5 years, of which 23 (22.1%) were males and 81 (78.9%) were females. Mean mitral valve area prior to PTMC was 0.98 ± 0.19 mm2 that increased to 1.69 ± 0.19 mm2 after the procedure and it was statistically significant (p=<0.001). The post PTMC MVA varied with PTMC Wilkin's score with less than or equal to 8 having favorable outcomes. Conclusion: Successful PTMC is highly influenced by the patients' increasing age, valve morphology (calcification, thickness, mobility), Left atrial dimensions, Pre PTMC mitral valve area, Degree of Baseline mitral regurgitation. Post procedure development of MR is usually well tolerated but rarely be severe enough requiring surgical valve replacement.

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Background: More than 90% of thromboses originate from the left atrial appendage (LAA) in patients with nonvalvular atrial fibrillation (NVAF). Objectives: This study was designed to investigate the safety and efficacy of LAA closure with the Leftear device (Pulse Scientific) in NVAF patients. Methods: A prospective, multicenter, registry-based study was conducted in 200 NVAF patients with CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack, vascular disease, female sex) scores ≥2. The primary safety endpoint was defined as any serious adverse events. Efficacy was assessed by a primary composite endpoint of hemorrhagic or ischemic stroke, systemic embolism, and cardiac or unexplained death at 1 year of follow-up. Results: The device was implanted in 196 patients, with 1-stop LAA closure combined with atrial fibrillation ablation implemented in 133 patients. The immediate success rate was 100%. There were serious adverse events in 9 patients (4.5%; 95% CI: 1.6%-7.4%), which mainly occurred in 1-stop LAA closure. All pericardial tamponades occurred in 6 patients with 1-stop LAA closure. No patient experienced a major bleeding event or acute device-related thrombus. During the 12-month follow-up period, the risk of the primary composite endpoint was 1.6% (95% CI: 0.3%-4.5%), and statistical noninferiority was achieved (the upper bound of 95% CI: 4.5% < the prespecified maximum annual incidence of 8.0%). Ischemic stroke occurred in 1 patient, 3 patients had incomplete LAA sealing, and no delayed device-related thrombus was found. Conclusions: LAA closure with the novel disc-like occluder shows high procedural success, satisfactory safety, and encouraging efficacy for stroke prevention in patients with NVAF. Compared with 1-stop LAA closure, single LAA closure may be more tolerable. (A multicenter, single-arm clinical trial to evaluate the efficacy and safety of left atrial appendage system for left atrial appendage occlusion in patients with non-valvular atrial fibrillation; ChiCTR1900023035).

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Background: There is an absence of clinical evidence on what factors modify the effect of heart rate (HR)-reducing treatment on mortality and morbidity in symptomatic heart failure patients with reduced ejection fraction (HFrEF). We performed a Bayesian meta-analysis and meta-regression to identify predictive factors that interact with HR-reducing therapy. Methods: A systematic review was performed to identify randomized placebo-controlled trials that enrolled symptomatic HFrEF patients. The primary objective was to evaluate how different predictive factors modify the efficacy of HR-reducing therapy on clinical outcomes. Secondary objectives included the evaluation of subgroups stratified by a HR reduction threshold of 10 bpm. Results: Data from 20 studies were synthesized and HR-reducing therapy was responsible for 16.7 %, 16.4 %, and 21.1 % risk reductions in all-cause mortality, cardiovascular (CV)-related mortality, and rehospitalization due to worsening HF (WHF), respectively. Empirical Bayes meta-regression showed that type 2 diabetes mellitus (T2DM) significantly modified the efficacy of HR-reducing therapy on all-cause mortality (slope = 0.012 in log risk ratio (RR) per 1 %-unit [95 % credible interval (CrI) 0.004, 0.021]) and CV-related mortality (0.01 in log RR per 1 %-unit [95 % CrI 0.0003, 0.0200]). There were insufficient studies to perform a meta-regression when stratifying by a HR reduction threshold of 10 bpm; however, when including all studies, we observed a significant effect modification for rehospitalization due to WHF (p = 0.004). Conclusions: This meta-analysis focused on the central tenet of HR-reducing therapy and revealed that T2DM is a predictor of HR-reducing treatment effect on all-cause mortality and CV-related mortality in HFrEF patients.

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Atrial fibrillation is the most common sustained cardiac arrhythmia and is associated with substantial increases in the risk of stroke and systemic thromboembolism. With the successful introduction of the first non-vitamin K antagonist direct oral anticoagulant (NOAC) in 2009, the role of vitamin K antagonists has been replaced in most clinical settings except in a few conditions when NOACs are contraindicated. Data for the use of NOACs in different clinical scenarios have been accumulating in the recent decade, and a more sophisticated strategy for atrial fibrillation patients is now warranted. JACC: Asia recently appointed a working group to summarize the most updated information regarding stroke prevention in AF. This statement aimed to provide possible treatment option in daily practice. Local availability, cost, and patient comorbidities should also be considered. Final decisions may still need to be individualized and based on clinicians' discretion. This is the part 1 of the whole statement.

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Background: Atrial fibrillation (AF) is a complex disease associated with comorbidities and adverse outcomes. The Atrial fibrillation Better Care (ABC) pathway has been proposed to streamline the integrated and holistic approach to AF care. Objectives: This study sought to evaluate patients' characteristics, incidence of adverse events, and impact on outcomes with ABC pathway-adherent management. Methods: The study included consecutive AF patients enrolled in the nationwide, ChioTEAF registry (44 centers, 20 Chinese provinces from October 2014 to December 2018), with available data to evaluate the ABC criteria and on the 1-year follow-up. Results: A total of 3,520 patients (mean age 73.1 ± 10.4 years, 43% female) were included, of which 1,448 (41.1%) were managed as ABC pathway adherent. The latter were younger and had comparable CHA2DS2-VASc and lower HAS-BLED (mean 71.7 ± 10.3 years of age vs 74.1 ± 10.4 years of age; P < 0.01; 3.54 ± 1.60 vs 3.44 ± 1.70; P = 0.10; and 1.95 ± 1.10 vs 2.12 ± 1.20; P < 0.01, respectively) scores compared with ABC-nonadherent patients. At 1-year follow-up, patients managed adherent to the ABC pathway had a lower incidence of the primary composite outcome of all-cause death or any thromboembolic event (1.5% vs 3.6%; P < 0.01) as compared with ABC-nonadherent patients. On multivariate analysis, ABC pathway-adherent care was independently associated with a lower risk of the composite endpoint (OR: 0.51; 95% CI: 0.31-0.84). Conclusions: Adherence to the ABC pathway for integrated care in a contemporary nationwide cohort of Chinese AF patients was suboptimal. Clinical management adherent to the ABC pathway was associated with better outcomes.

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Mirror syndrome is the phenomenon of fetal hydrops causing maternal edema and weight gain. Here, we report a case of arrhythmia as the primary maternal symptom. A 36-year-old woman, G2P1001, at 34.5 weeks of gestation presented with new-onset fetal hydrops combined with maternal weight gain and edema. She developed atrial fibrillation with rapid ventricular response; cardiac workup was unremarkable. Rate control was achieved with diltiazem. She underwent delivery and reverted to normal sinus rhythm on post-operative day 1. Volume overload causes atrial wall stress and neurohormonal changes that may trigger atrial fibrillation. Optimization with rate control facilitated good maternal and fetal outcomes in this case.

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Background: Atrial fibrillation (AF) is common in heart failure with preserved ejection fraction (HFpEF). Objectives: This study aimed to investigate the prognostic value of echocardiographic markers of congestion that can be applied to both AF and patients without AF with HFpEF. Methods: We conducted a multicenter study of 505 patients with HFpEF admitted to hospitals for acute decompensated heart failure. The ratio of early diastolic transmitral flow velocity to mitral annulus velocity (E/e'), the tricuspid regurgitation peak velocity, and the collapsibility of the inferior vena cava were obtained at discharge. Congestion was determined by echocardiography if any one of E/e' ≥14 (E/e' ≥11 for AF), tricuspid regurgitation peak velocity ≥2.8 m/s, or inferior vena cava collapsibility <50% was positive. We classified patients into grade A, grade B, and grade C according to the number of positive congestion indices. The primary endpoint was the composite of cardiovascular death and heart failure hospitalization. Results: During the follow-up period (median: 373 days), 162 (32%) patients experienced the primary endpoint. Grade C patients had a higher risk for the primary endpoint than grade A (HR: 2.98; 95% CI: 1.97-4.52) and grade B patients (HR: 1.92; 95% CI: 1.29-2.86) (log-rank P < 0.0001). Echocardiographic congestion grade improved the predictive value when added to the age, sex, New York Heart Association functional class, and N-terminal pro-B-type natriuretic peptide, not only in sinus rhythm (Uno C-statistic: 0.670 vs 0.655) but in AF (Uno C-statistic: 0.667 vs 0.639). Conclusions: Echocardiographic congestion grade has prognostic value in patients with HFpEF with and without AF.