Citations

Introduction: Aging and inflammation are associated with risk of atrial fibrillation (AF), to which clonal hematopoiesis of indeterminate potential (CHIP) may contribute. We investigated whether CHIP was associated with AF, inflammatory and cardiac biomarkers and cardiac structural changes. Methods: We ascertained CHIP (variant allele frequency, VAF ≥2%) in the Atherosclerosis Risk in Community Study (ARIC visit-5, n = 4,131) and the UK Biobank (UKBB, n = 195,851) participants. Using multivariable Cox regression models, we studied the association of CHIP and the top three implicated genes (i.e., DNMT3A , TET2 , ASXL1 ) with incident AF and conducted a meta-analysis on both cohorts. We also ascertained high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL6), IL18, high-sensitivity troponin T and I (hs-TnT and hs-TnI), NT-proBNP, and echocardiography indices in ARIC. We first standardized the natural log of all markers (st-ln) and used the adjusted quantile regression to compare the median in those with and without CHIP. Results: In ARIC, the mean ± SD age was 75.8 ± 5.2 years, 41% were men, 23% were Black, 25% had CHIP, and 11.6% had large CHIP (VAF ≥10%). These measures in UKBB were 56.4 ± 8.1 years, 45%, 2%, 5.8%, and 2.6%, respectively. In the meta-analysis, compared to those without CHIP, the hazard ratios (95% confidence interval) for AF were 1.12 (1.01 - 1.25, P =0.035), 1.31 (1.07 - 1.60, P =0.009), and 1.48 (1.05 - 2.08, P =0.026) for Large-CHIP, Large- TET2, and Large- ASXL1 , respectively. hs-CRP and IL18 levels were similar in those with and without CHIP as well as gene-specific subgroups. Large- TET2 and ASXL1 were associated with higher IL6, which was separately associated with AF. Additionally, Large- ASXL1 was associated with increased left ventricle mass index and NT-proBNP (coefficients in Figure 1 ). Conclusion: Large TET2 and ASXL1 but not DNMT3A CHIP is associated with higher IL6 levels, indices of cardiac remodeling, and an increased risk of AF.

Introduction: Right ventricular dysfunction (RVD) is a major prognostic factor in patients with heart failure with preserved ejection fraction (HFpEF), however determinants of RVD in HFpEF are not well described. Although sex-specific mechanisms have been incriminated in the development of HFpEF, it is unclear whether this is also true for RVD. Goals: (1) Assess the prevalence of RVD (defined as a tricuspid annular plane systolic excursion [TAPSE] <1.7 cm, a fractional area change [FAC] <35% or a RV free wall longitudinal strain [RVFWLS] <20%, absolute value) in patients with HFpEF; (2) identify determinants of RVD, overall and according to sex, in patients with HFpEF. Methods: We used data from patients enrolled in the echocardiographic sub-study of the PARAGON-HF trial with adequate image quality (N=809, 53% women, mean age 74±8 years). Determinants of RVD, in the whole study population and according to sex, were identified using a multivariable logistic regression model. Results: There were 461 patients (57%) with RVD. After multivariable adjustment, RVD was cross-sectionally associated with a history of atrial fibrillation of flutter (AFF), older age, higher heart rate, greater LV mean wall thickness and higher NT-proBNP values. Systolic blood pressure and LV global longitudinal strain (absolute value) showed an inverse association ( Figure ). These results were consistent between men and women, except for AFF and LV mean wall thickness, which were associated with a greater likelihood of RVD in men (OR 2.46, 95%CI 1.33-4.56, OR 1.61, 95%CI 1.18-2.21 respectively) but not in women (OR 0.99, 95%CI 0.58-1.68, OR 0.90 95%CI 0.69-1.17 respectively, p-values for interaction=0.028 and 0.006). Conclusions: RVD was highly prevalent in our study population. Determinants of RVD included AFF, LV remodeling and systolic impairment, and increased NT-proBNP levels. Differences between men and women suggest gender-specific mechanisms in the development of RVD in HFpEF.

Background: Anemia in Type 2 Myocardial Infarction (T2MI) related hospitalizations has been linked to higher one year mortality along with other causes of hemodynamic stress. We conducted the first ever meta analysis to evaluate the overall global prevalence of Anemia among patients with T2MI with differences by subgroups. Methods: PUBMED, SCOPUS and Google Scholar Databases were systematically reviewed to find studies through January 2023 ascertaining prevalence of Anemia in T2MI. Binary Random Effects models were used to estimate the pooled prevalence and subgroup analysis of anemia in T2MI. Heterogeneity was assessed using I 2 statistics. Leave-One-Out sensitivity analysis was also performed. Results: A total of 16 cohorts with 28,629 patients, hospitalized with T2MI (Mean Age 74; SD13) revealed a 23.3% [95% CI 17.8% - 28.8%, I 2 -98.61%, P<0.001] pooled prevalence of Anemia and a Mean Hb level of 121; SD - 25 in g/L. The prevalence of Anemia was higher among T2MI cohorts with younger Mean Age [Mean <70 vs >70 Years; 24.6% (95% CI 14.1% - 34.1%) vs 21.4% (95% CI 15.6 - 27.2%)]; smaller sample size [ n<500 vs n>500; 26.6% (95% CI 18.4% - 34.8%) vs 18.6% (95%CI 10.4% - 26.8%)]; prospective studies [Prospective vs Retrospective; 26.1% (95%CI 17.4% - 34.7%) vs 18.7% (95%CI 12.7% - 24.7%)] and single center studies [Single Center vs Multi Center; 24.9% (95%CI 17.5% - 32.2%) vs 21.4% (95%CI 12.7% - 30.1%)]. The prevalence of Anemia in T2MI related hospitalizations was also higher in studies from Asia [36.2% (95%CI 24.6% - 47.7%)], Europe [21.9% (95% CI 14.1% - 29.7%)] and Multinational [21.1% (95%CI 11.9%-30.2%)] as compared to North America [16.4% (95%CI 8% - 24.8%)]. Conclusions: The pooled prevalence of Anemia in this worldwide meta analysis of T2MI hospitalized patients was 23.3% with wide variance among subgroups. Further studies should focus on scrutinizing the outcomes and devastating complications of Anemic patients with T2MI among various populations universally.

Introduction: Criteria for aortic valve intervention (AVI) in severe aortic stenosis (AS) rely on symptoms, left ventricular ejection fraction (LVEF) and AS severity. Computed tomography-based aortic valve calcification (CT-AVC) scores associated with severe AS also have prognostic value, but this remains unexplored in patients with non-severe AS. We aimed to assess the prognostic value of AVC in asymptomatic patients with nonsevere AS and preserved LVEF. Methods: We retrospectively identified 395 patients with ≥mild AS but less-than-severe AS by echocardiography, who had CT-AVC assessed within six months. AVCscore was quantified offline by Agatston method (TeraRecon software), and also indexed by LV outflow track area, i.e., AVCdensity. Patients were followed until AVI or death. The primary outcome was all-cause death under medical surveillance. Results: In 395 patients, mean age was 73±12 years, 61% were men, mean aortic valve area 1.2±0.3cm2, mean gradient 28±9 mmHg, peak velocity 3.4±0.5 m/s, LVEF 64±6%. During a follow-up of 2.2[0.74-4.94] years, 220 patients had AVI and 82 patients died. Both AVCscore and AVCdensity were associated with AVI-free survival and the best AVCscore thresholds associated with mortality were 853 in women and 1183 in men by log-rank test (both p<0.001). High AVCscore and high AVCdensity were associated with increased hazard for all-cause death in unadjusted and adjusted analyses (Figure), and after further adjustment for echocardiographic severity (all p ≤0.01). Conclusions: In asymptomatic patients with less-than-severe AS, sex-specific CT-AVC scores differentiate those at higher risk for death versus lower risk. Whether AVI could modify this risk remains to be proven.

Background: Sodium-glucose co-transport-2 (SGLT2) inhibitors have been shown to reduce clinical events and improve health status (symptoms, function, and quality of life) in patients with HF across the range of EF. Baseline kidney dysfunction is common in HF, complicates HF management, and is strongly linked to worse health status. Aim: The study objective was to assess whether the treatment effects of dapagliflozin on health status vary based on baseline eGFR. Methods: Patient-level data were pooled from the DEFINE-HF (N = 263 participants with EF < 40%) and PRESERVED-HF trials (N = 324 participants with EF > 45%). Both were double-blind, randomized trials of dapagliflozin vs. placebo, enrolling participants with NYHA class II or higher and elevated natriuretic peptides. The primary endpoint for this analysis was Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CCS) at 12 weeks. Interaction of dapagliflozin effects on KCCQ-CCS by baseline eGFR (mL/min/1.73m 2 ) was assessed as categorical (i.e., eGFR <60 vs. > 60) and continuous variables. Results: Across both trials there were 583 (99.3%) participants with available baseline eGFR. The median (25 th , 75 th ) eGFR was 59 (46,77). Dapagliflozin improved KCCQ-CSS at 12 weeks (placebo-adjusted difference, +5.0 points, 95% Confidence Interval [CI] 2.6-7.5; p-value <0.001), and this was consistent in participants with an eGFR > 60 (+6.0 points, 95% CI 2.4-9.7; p=0.001) and <60 (+4.1 points, 95% CI 0.5-7.7; p=0.025) (p-interaction = 0.46). The benefits of dapagliflozin on KCCQ-CSS were robust across eGFR when modeled continuously (p-interaction = 0.46) ( Figure ). There was no heterogeneity of treatment effects when analyzing other KCCQ domains based on eGFR categorically or continuously (all p-interaction = NS). Conclusion: Treatment with dapagliflozin for 12 weeks led to significant and consistent improvements in health-related quality of life in patients with HF across a wide range of eGFRs.

Purpose: New 2022 European Society of Cardiology/European Respiratory Society PAH guidelines recommend treatment guided by a multi-parameter risk assessment. 1 Patients with low/intermediate risk without cardiopulmonary comorbidities should start dual PAH combination therapy; those with cardiopulmonary comorbidities should be reassessed early for rapid escalation to dual therapy. Initial triple therapy is recommended for high-risk patients. We examined use of dual and triple PAH therapy in the US (before guideline update). Methods: We used the Pulmonary Hypertension Association Registry (PHAR), a prospective US registry of pulmonary hypertension (PH) patients, enrolled within 6 months of their first outpatient visit at one of 54 participating PH care centers in the US, between Sep 2015-Jun 2022. We included adults (≥18 years at enrollment) with incident PAH (newly diagnosed and treated within 6 months of enrollment) and ≥1 follow-up clinic visit post baseline visit. Chronic thromboembolic PH patients were excluded. Results: We analyzed (descriptive statistics) 794 incident patients (baseline characteristics in Table 1). Treatment patterns at baseline (n=794)/last follow-up visit (n=610) were 289 (36.4%)/102 (16.7%) on monotherapy, 419 (52.8%)/314 (51.5%) on dual combination, 83 (10.5%)/179 (29.3%) on triple combination therapy, respectively. Mean time from enrollment to dual and triple combination therapy was 86.1 (standard deviation [SD]: 209.0) and 346.1 days (SD: 430.8), respectively. Conclusions: Among incident PHAR patients, half received initial dual and 10% triple upfront combination therapy. At last follow-up, most (>80%) patients had escalated to dual/triple combination therapies. Clinical Implications: At PH care centers, most incident PHAR patients are escalated to dual and triple therapy (at last follow-up) per current guidelines. Reference 1. Humbert M, et al. Eur Heart J. 2022;43:3618-731.

Coronary angiography is the gold standard for the diagnosis and treatment of epicardial coronary artery disease. Further, it is an essential tool for conduction of translational cardiac research on large animal models, in the development of novel cardiac therapies. While in humans coronary angiography has an exceedingly low mortality rate; in pigs, procedural mortality has been reported as high as 15%, likely due to unsuitable variations in angiographic techniques. Porcine models are used due to the resemblance of cardiac function and anatomy to humans. However, procedural guidelines delineating proper equipment to be used for angiography in this model has yet to be systematically assessed. Aims: To evaluate clinically common catheters for their utility in the safe engagement of the coronary vessels in pigs. Establish optimal workflow and fluoroscopy views for safe coronary artery engagement and angiography. Method/Results: Percutaneous superficial femoral artery access was acquired via ultrasound guidance and subsequent cardiac catheterization was performed in sus domesticus weighing 35-50 kg. Catheters that were tested included the JL 2.5, JL3.0, JR 3.0, AR1, AL1, MPA1, Champ1, 3DRC, hockey stick and RCB (5-7 french) operated over a standard .035 J tip wire. AP views were optimum to engage both the left and right coronary vessels. Only AR1, 3DRC, and hockey stick catheters successfully engaged the RCA, while all catheters tested could successfully engage the LCA. AR1 was noted to be the best for RCA engagement and AL1 for Left system engagement. AR1 was also the most succesful in engagement of both LM and RCA in same pig. AL1 provided the most stable engagement for Left coronary system. AR1/JL were better for LAD intervensions. AL1 is best for LCX intervensions Conclusion: We present a systematic description of percutaneous coronary angiographic procedures highlighting that AL for the LCA and AR for the RCA are the best choice of catheters for fastest and safest engagement of the coronary arteries limiting both radiation time and contrast use. While variations in anatomy can mandate changes in angiographic angles and catheter techniques, AP visualization and use of AL and AR catheters provided the most consistent and effective approach for porcine angiography.

For patients in cardiogenic shock, percutaneous mechanical circulatory support devices (MCSD) have emerged as critical tool to improve hemodynamics and optimize end-organ perfusion; successfully bridging patients to recovery, decision or transplantation. The most commonly utilized MCSD is the femoral intra-aortic balloon pump (IABP). However, femoral access hampers the patient's mobility, quality of life, and capacity to participate in rehabilitation. The advent of the axillary artery approach has served to circumvent limitations associated with the femoral artery approach. However, optimum anatomical placement of IABP within the axillary artery (axIABP) is a topic of debate considering its proximity to the brachial plexus. Here, we report our experince with percutaneous access of the third poriton of the axillary artery which showed promising results with minimal device related complications or adverse events. Methods/Results: Between 2017-2023, a total of 89 patients in cardiogenic shock underwent percutaneous axIABP placement at the Mayo Clinic, MN. All demographic, clinical, and periprocedural data were obtained from hospital chart review and recorded in a database under IRB approval. Indications for axIABP support was determined by multidisciplinary assessment. Complications encountered in the cohort included infection at site 6.7% (n=6), device malfunction [rupture, fracture, leak] 8.98%(n=8), and balloon migration 5.61% (n=5). One patient developed local erythema, 4 (4.49%) patients developed significant vascular complications, including access site bleeding in two patients 2.24%, arterial thrombosis in three patients 3.37%, and self-limited intracranial bleeding in one patient 1.12%. Of note, no nerve injury or damage was observed in the entire patient cohort. Conclusion: Our study highlights the feasibility of percutaneous axIABP in the third portion of the axillary artery, while assessing safety profile and ease of removal. Notably in our review, we did not encounter any brachial nerve damage. Ultrasound was pivotal in identifying and avoiding nerves and nerve bundles during initial access. In conclusion, this approach of axIABP insertion is feasible and can be leveraged for delivery of future innovation in MCSD

Introduction: Data on clinical outcomes of percutaneous closure of iatrogenic atrial septal defect (PC-ASD) in patients undergoing transcatheter edge-to-edge repair (TEER) or mitral valve replacement (TMVR) remains limited. We used a real-world USA database to evaluate the differences in the in-hospital outcomes between both groups. Hypothesis: Is there a clinical significance for PC-ASD in patients undergoing TEER or TMVR? Methods: We used the National Inpatient Sample (2015-2020) by utilizing ICD-10 codes to identify all patients who underwent TEER or TMVR with or without PC-ASD. Multivariate logistic regression was used for adjusted outcomes (adjusted odds ratio [aOR]). Results: A total of 44,065 eligible weighted hospitalizations were included: 39,625 (89.9%) of the patients underwent TEER and 4,440 (10.1%) underwent TMVR. Rates of PC-ASD were higher in TMVR group compared to TEER group (10.7% vs. 2.0%, p<0.01). In patients who underwent TEER without PC-ASD, PC-ASD was more associated with acute heart failure (AHF) (aOR 1.42 [1.19-1.68], p<0.01) and longer hospitalizations (aOR 1.64 [1.41-1.89], p<0.01), without significant difference in inpatient mortality (aOR 0.97 [0.61-1.54], p<0.01), cardiogenic shock (aOR 1.13 [0.85-1.51], p=0.21), need for mechanical circulatory support (MCS) (aOR 0.98 [0.61-1.54], p=0.18), and stroke. Compared to patients who underwent TMVR without PC-ASD, PC-ASD was associated with higher inpatient morality (aOR 1.65 [1.13-2.4], p<0.01), need for MCS (aOR 1.91 [1.33-2.73], p<0.01) without significant difference in AHF (aOR 1.19 [0.94-1.51], p=0.18] and cardiogenic shock (aOR 0.83 [0.56-1.22], p=0.43). Remarkably, PC-ASD was less associated with stroke (aOR 0.27 [0.10-0.72], p<0.01). Conclusions: Rates of PC-ASD after TEER were lower than after TMVR and were associated with worse in-hospital mortality and need for MCS in TMVR but not in TEER. Also, PC-ASD was less associated with stroke after TMVR.

Background: The incidence and causes of sudden cardiac death (SCD) among young competitive athletes impact prevention strategies yet remain incompletely understood. Methods: National Collegiate Athletic Association (NCAA) athlete deaths from 7/1/2002-6/30/2022 were identified through 4 independent databases/search strategies. Autopsy reports and medical history were reviewed by an expert panel to adjudicate causes of SCD. Poisson regression was used to calculate incidence rate ratios (IRR) for 5-year intervals over the 20-year study. Results: A total of 143 SCD cases were identified among 1102 athlete deaths and 9,106,516 athlete-years (AYs). The incidence of SCD among NCAA athletes was 1:63,682 AYs [95% CI 1:54,065, 1:75,010]. Incidence was higher in males compared to females (1:43,348 vs. 1:164,504 AYs) and Black compared to White athletes (1:27,217 vs. 1:74,581 AYs). The highest incidence of SCD was among Division 1 male basketball players (1:8,188; White 1:5,848; Black 1:7,696 AYs). The incidence rate for SCD decreased over the study period (5-year IRR 0.71 [95% CI 0.61,0.82]), whereas the rate of non-cardiovascular deaths remained stable (5-year IRR 0.98 [95% CI 0.94,1.04]; Figure 1A ). Autopsy-negative sudden unexplained death (AN-SUD, 19.5%) was the most common post-mortem exam finding, followed by idiopathic left ventricular hypertrophy/possible cardiomyopathy (CM, 16.9%) and hypertrophic CM (12.7%) in cases with enough information for adjudication (118/143, Figure 1B ). There were 8 cases of myocarditis, with none attributed to COVID-19 infection. SCD events occurred most commonly during exertion among athletes with coronary artery anomalies (100%) and arrhythmogenic CM (83%), whereas AN-SUD and hypertrophic CM had a higher proportion of non-exertional SCD (44% and 40%, respectively). Conclusions: The incidence of SCD in college athletes has decreased. Male sex, Black race, and basketball are associated with a higher incidence of SCD.