Citations

Introduction: CHIP is associated with CAD and mortality. The prognostic relevance of CHIP for high-risk patients with confirmed CAD is unknown. Hypothesis: CHIP variants are associated with cardiovascular (CV) events and mortality in high-risk patients with known CAD in the ISCHEMIA Trials Biorepository. Methods: 895 ISCHEMIA and ISCHEMIA-CKD (hereafter, ISCHEMIA Trials) participants with moderate-severe ischemia and next-generation sequencing performed for CHIP variant allele fractions of ≥2% (CHIP) and ≥10% (large CHIP) were included. Unadjusted and multivariable adjusted (age, sex, diabetes, eGFR not on HD, HD, and LVEF) associations of CHIP and large CHIP with a) ISCHEMIA Trials initial phase primary endpoint (CV death, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest, RCA) and b) ISCHEMIA Trials combined initial and extended follow-up phase (hereafter, Cumulative) endpoint of all-cause death . Results: Median (IQR) age of sequenced participants was 67 (56 – 79) years, 19% were female, 83% white, and 6% Hispanic. Hypertension (84%), diabetes (45%) and obesity (47%) were common, 26% had an eGFR <60 ml/min/1.73m 2 . The prevalence of CHIP and large CHIP was 23% and 7%, and both increased with age ( Figure 1a ). CHIP mutations in DNMT3A were detected in 106 (12%), TET2 CHIP in 44 (5%), and ASXL1 CHIP in 21 (2%) participants ( Figure 1b ). DNMT3A, TET2, and CREBBP mutations collectively comprised 199 (52%) of overall CHIP mutations, including individuals with multiple mutations in the same gene (N overall = 385); 67 participants (7%) had mutations in >1 gene. Over 3.1 years of RCT follow-up there were 135 (20%), 32 (16%) and 15 (18%) primary endpoints for no CHIP, CHIP and large CHIP, respectively. Over 6.8 years of EXTEND follow-up, there were 126 (18%), 47 (23%) and 24 (29%) deaths in the no CHIP, CHIP and large CHIP groups, respectively. After multivariable adjustment there was no association between CHIP or large CHIP and CV events or mortality ( Figure 1c ). Conclusion: Neither CHIP nor large CHIP was associated with adverse outcomes in 895 high-risk individuals with confirmed CAD, despite a high prevalence of these mutations.

Introduction: Unexplained high-grade AV block (AVB) in patients age <65 years is among the salient features of cardiac sarcoidosis (CS). Guidelines recommend that CS patients with high-grade AVB should receive an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) rather than a permanent pacemaker (PPM). However, in clinical practice, CS may be recognized after PPM implantation for high-grade AVB. Aims: To evaluate the characteristics and outcomes of patients diagnosed with CS after PPM implantation for high-grade AVB and assess the decision-making and rationale for upgrade to ICD/CRT-D. Methods: Retrospective review of the Mayo Clinic Sarcoid Registry (n=848) was performed to identify all patients for which a PPM was implanted for high-grade AVB prior to the diagnosis of CS. Baseline clinical and imaging characteristics were collected during index evaluation at our institution. Decision-making for ICD upgrade, lead management strategy, immunosuppression initiation, and outcomes were assessed. Results: Overall, 29 of 848 (3.4%) of CS patients (62% probable/definite CS; 77% male; median (IQR) age 56 (48-61) years; and median (IQR) LVEF 58% (50-62) received a PPM for high-grade AVB prior to a CS diagnosis. Median (IQR) interval between PPM implant and index evaluation was 10 (3-23) months. Eight of 29 patients underwent upgrade to ICD (n=4) or CRT-D (n=4). Among them, the pacing lead was extracted in 4. All patients were upgraded for primary prevention of sudden cardiac death (SCD), with 3 of them also having LVEF<50% requiring upgrade to CRT-D. Twenty-two (79%) patients in the total cohort were treated with immunosuppression. During median (IQR) follow-up 37 months (11-74), 1 patient in the upgrade group had sustained VT appropriately treated with anti-tachycardia pacing. No events were documented among patients in the non-upgrade group. At last follow-up, 6 (75%) patients in the upgrade group and 12 (57%) in the non-upgrade group were pacemaker dependent. Median LVEF change was 0% in patients who underwent upgrade to CRT-D and –0.2% in those who underwent upgrade to ICD or no upgrade. Conclusions: In this cohort of patients diagnosed with CS several months after a PPM had been implanted for high-grade AVB, incident VT/VF was infrequent with contemporary CS management. In the absence of other SCD risk factors, CS patients who received a PPM for high-grade AVB prior to their CS diagnosis may not require ICD upgrade.

Background: Heart failure (HF) is a heterogeneous syndrome with high mortality. Previous work characterizing HF subgroups primarily relied on clinical data to cluster patients, an approach constrained by the boundaries of documented clinical features. Clustering based on biomarker data, such as proteomics, may provide insights into underlying molecular processes. However, few studies have used this approach, and all used targeted cardiovascular proteomics panels and a restricted HF ejection fraction group. Hypothesis: We used unsupervised clustering analysis to characterize molecular phenogroups in a population-based HF cohort using a large-scale array of circulating plasma proteins. We hypothesized that distinct proteomic-defined phenogroups would exhibit differences in clinical characteristics, mortality, and protein expression. Methods: We measured 7151 SOMAmers (Slow off-rate modified aptamers) targeting human proteins via the SomaLogic 7K SomaScan assay in 1351 HF patients. After feature selection, 831 SOMAmers were used in k-means clustering of patients via R package “ConsensusClusterPlus.” Phenogroups were compared for clinical characteristics, all-cause mortality, and protein expression. Results: Three phenogroups were identified, exhibiting different clinical characteristics ( Table 1 ) and survival probabilities (5-year survival probability in phenogroup 1: 65% [61%, 68%], phenogroup 2: 45% [40%, 51%], and phenogroup 3: 26% [22%, 30%]). In covariate-adjusted Cox models, membership in phenogroups 2 and 3 was significantly associated with increased rate of mortality compared to phenogroup 1. Phenogroups did not differ by ejection fraction or New York Heart Association class. Pathway overrepresentation analysis of differentially expressed SOMAmers identified pathways associated with inflammatory response and immune cell trafficking. Conclusions: Unsupervised clustering analysis using large-scale proteomics data identified three HF phenogroups with different proteomic signatures, clinical characteristics, and outcomes. Future work is necessary to elucidate how molecular differences contribute to heterogeneity in HF to improve risk stratification beyond current recommended clinical guidelines.

Background: Individual symptoms are predictors of mortality in adults with heart failure (HF). However, symptom clusters may be more predictive of future risks than isolated symptoms, yet research on these symptom clusters in older adults with HF is limited. Aims: To explore the extent to which symptom cluster profiles predict all-cause mortality among community-dwelling older adults with HF, while adjusting for known risk factors. Methods: We conducted a secondary analysis of data of the 2008 to 2016 surveys of the U.S. Health and Retirement Study using latent class analysis to identify baseline cluster profiles, and survival analysis for time to death with Cox proportional hazard (Cox PH) models, and Kaplan Meier survival analyses. Results: We included 684 participants [mean age=74.9, (SD=10) years, 56.6% female, 16.2% Black/African American]. Three baseline symptom cluster profiles were identified: high-burden (pain, shortness of breath, fatigue, swelling, depressive symptoms, dizziness), low-burden, and cardiopulmonary-depressive (shortness of breath, pain, and dizziness). The estimated median time-to-death was 71 (95% CI=64, 79) months. Of the 364 participants in the cardiopulmonary-depressive profile, 240 (65.9%) died (median time= 65 months, 95% CI= 55, 73) compared to those in the low-burden profile, of which 49% died. Approximately 61% in the high burden profile died (median time=67 months, 95% CI= 51, 90). A significant difference in survival times between the 3 cluster profiles was found (Log-rank= 9.13, p = 0.01). In the adjusted Cox PH model, participants in the high symptom burden and respiratory-depressive distress profiles had adjusted HR of 1.48 (95% CI=1.15, 1.94) and 1.44 (95% CI=1.14, 1.80) compared to those in the low burden symptom cluster profile, after controlling for age, gender, smoking, and comorbidities. Conclusions: The identified symptom cluster profiles predict 8-year all-cause mortality in older adults with HF, after controlling for known risk factors. An evaluation of symptom clusters, rather than individual symptoms, may provide additive prognostic information.

Background: Transthyretin cardiac amyloidosis (ATTR-CA) carries an elevated risk of developing ventricular arrhythmias (VA) but there remains limited evidence supporting the role of catheter ablation in this population. Purpose: To assess the safety and efficacy of catheter ablation for VA in ATTR-CA. Methods: An electronic database was used to identify all patients suspected of having ATTR-CA who underwent catheter ablation for VA at our institution between January 2010 and December 2023. Patients who did not meet the diagnosis of ATTR-CA and had a negative workup who underwent catheter ablation for ventricular tachycardia (VT) or premature ventricular contractions (PVCs) were used to form a control group matched for age, sex and left ventricular ejection fraction at a ratio of 2:1. Results: 20 controls and 10 cases of ATTR-CA were identified. Examining the two groups at baseline (Table 1), the mean age at index ablation was 67.7±7.0 and 68.6±8.1 years (p=0.359), mean follow-up time was 4.1±3.1 and 4.2±2.6 years (p=0.494), and the proportion of males was 100% and 90% respectively. The ATTR-CA group had a significantly higher proportion of chronic kidney disease (90% vs. 50%, p=0.032) and prior stroke or thrombotic events compared to the control group (50% vs. 10%, p=0.026) with similar CHA 2 DS 2 VASc scores (4.2±1.6 vs. 3.8±1.3, p=0.233). Both groups had comparable left ventricular ejection fraction (41.4%±14% vs. 46.9%±15.2%, p=0.173), VT/PVCs at presentation (40%/60% vs. 25%/75%, p=0.77), use of antiarrhythmics (70% vs. 60%, p=0.592), and high proportion of atrial fibrillation/flutter (70% vs. 90%, p=0.168). Procedural (261.2±101.2 vs. 265.7±125.6 mins, p=0.449) and total energy delivery time (1442.9±1509.1 vs. 1744.6±956.2 secs, p=0.296) was not significantly different in the two groups. Both groups had a significant decrease in PVC burden postablation with a reduction from 26.8% to 3.8% (p=0.024) and from 27.1% to 13.6% (p=0.028) in the ATTR-CA and control group respectively. A downward trend was seen in antitachycardia pacing events for VT postablation in the ATTR-CA (14.7±9.8 vs. 5.3±6.7, p =0.184) and control (193±387.6 vs. 0.67±1.2. p=0.139) groups. No major complications occurred after ablation (Table 2). Mean time to recurrence post-index ablation was similar between both groups (1620.4±483.8 vs. 1498.8±291.4 days, p=0.987, Figure 1). Conclusions: Catheter ablation appears to be safe and effective for VT and PVCs in patients with ATTR-CA.

Case Description: A 68-year-old man with end-stage renal disease on dialysis, peripheral vascular disease with metatarsal amputations, atrial fibrillation and type 1 diabetes was admitted for foot osteomyelitis secondary to MSSA bacteremia. Transesophageal echocardiogram revealed mobile mitral valve vegetations up to 1.8cm on the atrial aspect of the posterior mitral valve leaflet which prolapsed through the mitral valve during diastole. Ejection fraction was 60% and there was trivial-mild mitral regurgitation without valvular destruction or peri-annular extension into the mitral annulus. MRI brain showed bilateral cerebral and cerebellar hemispheric infarcts, consistent with acute embolic stroke. He was at high risk for both recurrent embolism and operative mortality (STS risk score 51%) due to his comorbidities and risk of hemorrhagic conversion of stroke. After shared decision making, percutaneous aspiration of the mitral vegetation was performed with AngioVac (Fig). Cerebral embolism protection devices were deployed prior to AngioVac evacuation of the mass. There was no residual mitral regurgitation and only a small vegetation strand remained (Fig). Surgical pathology confirmed MSSA endocarditis. Blood cultures remained negative, and the patient did not suffer from recurrent embolic events. The patient underwent revision metatarsal amputation and was discharged with a 6-week course of IV cefazolin. Discussion: Infective endocarditis with high embolic risk is life-threatening and challenging to treat in patients with high surgical risk. We illustrate a case of percutaneous vegetation aspiration using the AngioVac device in our patient who suffered from embolic strokes due to MSSA mitral valve endocarditis. Meta-analyses have shown clinically successful debulking in 90% of cases, with 82% of patients able to clear bacteremia with AngioVac. Although most commonly used in right-sided lesions, percutaneous debulking of left-sided endocarditis with AngioVac and cerebral protection can be considered as a treatment strategy in select patients with prohibitive surgical risk.

Background: In the landscape of organ transplantation, heart transplantation stands as a life-saving procedure for patients with end-stage heart failure. Comprehensive analyses of transplant programs are imperative to optimize outcomes and understand the complexities. Hypothesis: This study hypothesizes that an increasing trend of heart transplant service and short-term mechanical circulatory support (STMCS) is the bridge to transplant; the UNOS (United Network for Organ Sharing) guideline positively impacts STMCS utilization. Even with the standard of care, there might be a disparity in receiving care in terms of gender and race. Goal/ Aims: By examining this center's collective experience, this research provides valuable insights into the evolving landscape of heart transplantation, ultimately contributing to advancements in patient care and transplant policy. Methods: This retrospective cohort study includes heart transplant patients in a single large transplant center. For statistical analysis, Cox regression, Mann-Whitney test, Kruskal Wallis, and Chi-Square test were used in IBM SPSS 25. Result: Trends: This retrospective study covering 2010 to 2022 comprehensively analyzed 1513 heart transplant patients. The cohort consisted of 1071 (70.78%) males and 442 (29.21%) females, 31.9% were bridged through STMCS. 76.7% of Caucasian and 16.1% were African American.The mean utilization of STMCS was 20.08% before the UNOS policy change, increasing to 53.81% after that (p < 0.001). Disparity Analysis: There was a statistically significant difference in STMCS utilization between white and black patients (p= 0.008) but no difference in between obese and non-obese cohorts (P=0.362).Wait time was similar among the genders (p=0.161) and different races (p=0.302). Survival Analysis: There is a significant survival discrepancy between patients bridged through MCS and those without STMCS(p< 0.001). However, yearly trend analysis showed an evolving survival trajectory favoring STMCS users. There are statistically significant survival differences among whites and blacks (P =0.008) but similar among the genders (p=0.589). Summary: The study reveals significant changes in the trend of transplants regarding STMCS utilization since the UNOS guideline. There are substantial differences in survival between STMCS vs. non-STMCS groups and among the races.There was a significant difference in STMCS utilization among the races.

Background: Etripamil nasal spray (NS) is a fast acting, self-administered calcium channel blocker in development for the termination of AV-nodal-dependent supraventricular tachycardia (SVT). Prior randomized, placebo-controlled and open-label studies have demonstrated favorable safety and efficacy of etripamil in converting paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm (SR) self-administered without direct medical supervision. Research Question/Hypothesis: To assess patterns and annualized PSVT episode frequency among patients opting to self-administer acute treatment with etripamil. Methods: NODE-303 was an event-driven, multi-center, open-label Phase 3 study, conducted in North and South America to evaluate the safety and efficacy of etripamil in patients with documented PSVT over multiple episodes. Test dosing was not performed prior to at-home use. Enrolled patients, upon perceiving symptoms of PSVT: applied an ambulatory ECG monitor, performed a previously trained vagal maneuver and, if symptoms persisted, self-administered etripamil NS 70 mg. During the study, the protocol was amended to allow a repeat dose (70 mg) if symptoms persisted 10 min after the first dose. Each patient could self-treat up to 4 episodes. Results: Of 1,116 enrolled patients, 503 (45.1%) treated ≥1 perceived PSVT episode (safety population). Etripamil achieved conversion to SR in 60% of patients by 30 minutes and 70% by 60 minutes. A total of 220, 118, 62, and 103 patients completed the study with 1, 2, 3, and 4 etripamil-treated perceived episodes of PSVT, respectively, with an average time on study of 440 days. Among these patients, the average number of annualized etripamil-treated PSVT episodes was 3.2 (standard deviation 3.8). Annualized use: etripamil was self-administered for 0-2 PSVT episodes per year, 2-6 episodes, 6-12 episodes, and >12 episodes, in 54%, 32%, 10%, and 4% of patients, respectively (Figure). Conclusions: This analysis aimed to assess the annualized use of etripamil NS in a real-world setting, by analyzing how often patients would self-administer the drug for PSVT episodes. Of patients that self-administered etripamil (n=503), the majority treated >1 episode and the annualized frequency of episodes treated with etripamil was 3.2 episodes/yr.

Background: Pulsed field ablation (PFA) and high-power short-duration radiofrequency ablation (HPSD) are emerging techniques for treating atrial fibrillation (AF), offering promising results compared to cryoballoon ablation (CBA). This network meta-analysis aims to evaluates the efficacy and safety of PFA, HPSD, and CBA. Method: PubMed, Embase, Cochrane Central Register of Controlled Trials, and EBSCO Information Services were systematically searched for relevant studies until April 2024. The primary outcome is freedom from atrial arrhythmia. A random-effects model was used for data synthesis, and P-scores were employed for outcome ranking. Point estimation (odd ratios) was calculated for comparisons. Results: Fifteen studies were included in our network meta-analysis, involving 5,093 atrial fibrillation patients: 812 (16%), 2,659 (52%), and 1,622 (32%) patients underwent PFA, CBA, and HPSD, respectively. PFA demonstrated the highest efficacy (P-scores 99.3%). Point estimation between PFA and HPSD, and PFA and CBA, were 1.394 (95% CI: 1.047-1.858) and 1.479 (95% CI: 1.134–1.929), respectively. PFA had higher complications compared to HPSD (OR=4.44, 95% CI: 1.405-14.031) and CBA (OR=2.581, 95% CI: 0.992–6.720). HPSD had the shortest fluoroscopic time (P-scores 100%), while CBA had the longest (P-scores 0%). PFA had the shortest procedural time compared to CBA and HPSD with P-scores of 100% 50% and 0%, respectively. Conclusion: PFA showed higher efficacy but higher complication risk than HPSD and CBA. HPSD and CBA demonstrated similar efficacy and safety.

AbstractThis critical review summarizes the current state of omics‐based biomarkers in the alcohol research field. We first provide definitions and background information on alcohol and alcohol use disorder (AUD), biomarkers, and “omic” technologies. We next summarize using (1) genetic information as risk/prognostic biomarkers for the onset of alcohol‐related problems and the progression from regular drinking to problematic drinking (including AUD), (2) epigenetic information as diagnostic biomarkers for AUD and risk biomarkers for alcohol consumption, (3) transcriptomic information as diagnostic biomarkers for AUD, risk biomarkers for alcohol consumption, and (4) metabolomic information as diagnostic biomarkers for AUD, risk biomarkers for alcohol consumption, and predictive biomarkers for response to acamprosate in subjects with AUD. In the final section, the clinical implications of the findings are discussed, and recommendations are made for future research.