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Abstract Background Atrial functional mitral regurgitation (AFMR) is an increasingly recognized cause of functional MR thought to result from left atrial enlargement and myopathy in the setting of preserved left ventricular geometry and function. AFMR mostly occurs in patients with atrial fibrillation (AF) and/or heart failure with preserved ejection fraction. Purpose We investigated whether the use of an artificial intelligence-based electrocardiogram (AI-ECG) can identify patients with new-onset AF and sinus rhythm (SR) who are at highest risk of developing AFMR. Methods Adults with a new diagnosis of AF between 2010 and 2021 who had a transthoracic echocardiogram (TTE) within 1 month after AF diagnosis were identified. Similarly, adults in SR who never had AF diagnosis and had a TTE during the same period were identified. Exclusion criteria from both groups included >mild MR at baseline, primary mitral valve disease, cardiomyopathy, ≥moderate aortic valve disease, current or previous low ejection fraction, enlarged left ventricle, cardiac devices, previous cardiac surgeries, and the absence of follow-up TTE ≥6 months from baseline. Only patients who had ECG within 10 days of the TTE were included. When multiple ECGs were available, the closest was considered. A previously trained AI-ECG algorithm to detect the probability of AF was utilized. Incident AFMR was defined as >mild functional MR in the absence of >mild left ventricle enlargement or dysfunction. Diastolic dysfunction was defined according to ASE/EACVI guidelines. Results Overall, 1,570 patients with new-onset AF (median age 67 years; 34% females) and 16,802 patients in SR (median age 59 years; 46% females) were included. The median AI ECG probability for AF was 43% (IQR 26%-59%) in the new-onset AF group and 2% (0.5%-7%) in the SR group, Figure 1. Incident AFMR occurred in 152 patients in the AF group over median 3.06 (IQR 1.5-5.2) years of follow-up and in 482 patients in the SR group over median 3.0 (1.5-5.6) years of follow-up. The probability of silent AF by the AI-ECG was associated with incident AFMR in the new-onset AF group [hazard ratio 1.19 (95% CI 1.11-1.28) per 10%, p <.001] and the SR group [hazard ratio 1.19 (95% CI 1.12-1.25) per 10%, p <.001]. The AI ECG-derived AF probability remained as an independent risk factor for AFMR in multivariable analysis in both AF and SR, Table 1. Conclusion The AI ECG for AF might be able to reflect the degree of left atrial myopathy and thus the risk of incident AFMR in patients with AF and SR.Distribution of AI ECG probability of AFMultivariable risk factors for AFMR

Abstract Background Cardiac sarcoidosis (CS) is a difficult to diagnose inflammatory heart disease. Certain types of genetic cardiomyopathy have been reported to masquerade as inflammatory cardiomyopathy. The utility of genetic testing in the evaluation of inflammatory cardiomyopathy is not completely explored and data regarding the prevalence of genetic cardiomyopathies in patients with presumed CS is limited. Methods We retrospectively analyzed patients evaluated from May 2020 to October 2022 in our Cardiac Sarcoid Clinic diagnosed with presumed CS as inferred by either fluorodeoxyglucose positron emission tomography (FDG-PET) - computed tomography (CT) or cardiac magnetic resonance (CMR) or both. Pertinent demographic, genetic, electrocardiographic, and imaging data for these patients was extracted from the electronic medical record. Results Genetic testing was obtained in 47 (22%) of the 213 presumed CS patients, among whom 43 (91%) presented with suspected isolated CS, and 4 (9%) with possible cardiac involvement in the setting of systemic sarcoidosis. Among the patients who underwent genetic testing, 10 (21 %) had a pathogenic or likely pathogenic (P/LP) variant(s) in a genetic cardiomyopathy-susceptibility gene, including DSP (n=2), LMNA, FHL1, TPM1, MYBPC3, NRAS, MYH7 (n=2) and TTN (n= 2) genes. All P/LP patients had FDG uptake, and in those with CMR data, 100% had late gadolinium enhancement. The seven patients with P/LP who underwent endomyocardial biopsy had no evidence of granulomatous inflammation. Immunosuppression was initiated in 60% of the P/LP patients before knowledge of genetic results. Conclusion Patients suspected to have CS may have concomitant or primarily genetic cardiomyopathy that may masquerade as an inflammatory phenotype Genetic testing should be considered in these patients, not only to clarify the diagnosis and its prognostic and therapeutic implications, but also to offer cascade screening for the family of patients with P/LP variants who otherwise would not have been considered to have a heritable disease.

Abstract Background Conflicting evidence exists regarding the functional and prognostic significance of hypertensive response to exercise (HRE), commonly defined as peak systolic blood pressure (SBP) >210 mmHg in males and >190 mmHg in females. No study yet has explored the impact of sex-specific, workload-indexed HRE in patients at different stages of the heart failure (HF) spectrum, as defined by the American College of Cardiology/American Heart Association HF staging system. Purpose We evaluated the SBP/Workload slope during exercise across the HF spectrum and investigated the hemodynamic, functional and prognostic correlates of HRE. Methods Fifty-eight healthy controls, 201 subjects at risk of developing HF (HF Stages A-B), and 369 patients with a definite diagnosis of HF (Stage C) were enrolled; among the latter, 143 had preserved (HFpEF) and 226 reduced (HFrEF) left ventricular ejection fraction. All patients underwent a combined cardiopulmonary-exercise stress echocardiography test. For each patient, we recorded at least two BP measurements during exercise: the first within the first minute of exercise and the last at peak effort. The SBP/Workload slope was calculated as the difference in SBP over the corresponding increment in watts (W): (SBPpeak – SBPfirst)/(Wpeak – Wfirst). In each ACC/AHA HF Stage, we divided patients according to SBP/Workload slope tertiles; HRE was defined as the highest sex-specific SBP/Workload slope tertile. A composite of all-cause mortality and hospitalization for cardiovascular reasons was chosen as the primary outcome. Results The median SBP/Workload slope was 0.53 (interquartile range 0.36-0.72) mmHg/W and was steeper in women than in men in all subgroups (p<0.0001). After adjusting for age and sex, SBP/Workload slope was significantly higher in Stages A-B (0.61, 0.47-0.75 mmHg/W) and HFpEF (0.63, 0.42-0.86 mmHg/W) compared to controls (0.43, 0.35-0.57 mmHg/W) and HFrEF (0.47, 0.30-0.63 mmHg/W, Figure 1). In all subgroups, patients with HRE showed significantly lower peak oxygen consumption and peripheral oxygen extraction (Table). After a median follow-up of 16 months, HRE was an independent predictor of adverse outcomes (Hazard Ratio 2.05, 95% confidence interval 1.81-5.18), while rest and peak absolute SBP values did not. Kaplan-Meier analysis confirmed a worse survival probability for patients with HRE in Stages A-B and HFpEF but not in HFrEF. After adjusting for confounding factors, the patients with the highest SBP/Workload slope had a 47% higher risk of the primary outcome than subjects in the lowest tertile (Figure 2). Conclusions Across the HF spectrum, patients with HRE, as evaluated by the SBP/Workload slope, present with peculiar pathophysiological features and impaired functional capacity. This is especially true for those in Stages A-B and patients with HFpEF. In these subgroups, HRE may portend an increased risk of adverse cardiovascular outcomes.SBP/workload slopesKaplan-Meier curves and Hazard Ratios

Abstract Background While the Medtronic Micra pacemaker provided a small device for leadless pacemaker implantation, the Aveir device allows chronic retrievability and mapping prior to fixation. We present the first Aveir leadless pacemaker implantations in a pediatric population. Purpose To describe the first retrievable leadless pacemaker implants in children. Methods Retrospective review of pediatric Aveir implants occurred between November 2022 and December 2022. All patients were implanted via internal jugular vein insertion utilizing the Aveir sheath and catheter deployment system with mid-atrial approach taken prior to insertion of the catheter across the tricuspid valve. All patients had initial mapping of capture threshold, impedance and R-wave noted prior to deployment. Indications for pacing included sinus pauses and intermittent atrioventricular block. Results Three patients underwent Aveir leadless pacemaker implantation with weights of 32.3kg, 44kg, and 51kg. Capture thresholds were all 0.75Volts@0.2 milliseconds with impedance range of 370-1110 ohms, and R-waves of 8-14 millivolts (mV). Follow-up at 3 months ranged from 0.5V@0.2ms to 1V@0.2ms with impedances ranging 400-700 ohms, and R-wave 7-14 mV. At VVI 50-55bpm, with pacing ranged from 5% to 14%, predicted longevities ranged from 20 to 24.5 years at 3 months follow-up. Conclusion(s) Retrievable leadless pacemaker implantation is feasible in children and may offer good longevities for intermittent pacing need.Aveir Leadless Pacemaker in RVAveir Leadless Pacemaker in RV

Abstract Background Atrial fibrillation (AF) is associated with increased risk of incident tricuspid regurgitation (TR), but types of incident TR in AF versus sinus rhythm (SR) are not well-defined. Purpose We aimed to compare the risk of the different types of incident ≥moderate TR in AF and SR. Methods Adults first diagnosed with AF (2010-2021) who had a transthoracic echocardiogram (TTE) within 30 days after AF and adults with no diagnosis of AF who had a TTE in the same period were identified. Patients with previous cardiac surgeries, congenital heart disease, cardiomyopathy, cardiac devices, primary valve disease, previous or current ejection fraction (EF) <50%, severe diastolic dysfunction (SDD), ≥moderate left-sided valve disease (LVD), right ventricular systolic pressure (RVSP) ≥50 mmHg, ≥moderate TR, any tricuspid stenosis, or with no follow-up TTE ≥6 months from baseline were excluded. Patients were followed for the development of ≥moderate TR, the type of which was identified in a hierarchal order: 1) pacemaker-associated TR, 2) LVD-associated TR in the setting of ≥moderate LVD, 3) low EF or SDD-related TR, 4) pulmonary hypertension (PH)-associated TR if RVSP was ≥50 mmHg, 5) other ventricular functional TR (VFTR) if there was >mild RV enlargement or dysfunction, and 6) atrial functional TR (AFTR) when none of the previous was present. Patients were also followed for the occurrence of risk factors for TR (pacemaker insertion, ≥moderate LVD, low EF or SDD, PH, >mild RV enlargement or dysfunction) in a hierarchal order, and both the prevalence and future risk of the corresponding type of ≥moderate TR was determined at the onset of these conditions in AF and SR. Results Overall, 1,360 patients with new-onset AF (median age 67 years, 34% females) and 20,438 patients in SR (median age 60 years; 54% females) were included. Over median 3.8 (IQR 1.8-6.6) years, incident ≥moderate TR occurred in 110 patients with new-onset AF [2.13 per 100-person years] compared to 378 patients in SR [0.41 per 100-person years, p <.001]. All types of incident ≥moderate TR occurred more frequently in AF (p <.001 for all). The distribution and incidence of each type of TR in AF and SR are shown in Figure 1. The incidence of risk factors associated with the development of TR was higher in the AF group, except for pre-capillary PH, Figure 2A. At time of diagnosis or occurrence of these conditions, the prevalence of the corresponding TR types was higher in AF, except for pacemaker-TR, Figure 2B. The incidence of the corresponding TR type after occurrence of TR risk factors was higher in the AF group for LVD-TR and low EF/SDD-associated TR (p ≤0.03); although numerically higher in AF, the association was only borderline for PH-TR (p =0.05), Figure 2C. Conclusion Incident ≥moderate TR of all types occurred more frequently in patients with AF vs. SR and the distribution of TR types differed by rhythm. Patients with AF may benefit from a closer follow-up.Distribution and incidence rates of TRIncidence of TR risk factors & TR after

Abstract Background Antitachycardia pacing (ATP) found in most implantable cardioverter defibrillators (ICDs) is an important therapy for painless termination of ventricular tachycardias (VT). In ICDs programmed to guideline-recommended detection and therapy settings typical ATP success rates are 50-70%.[1-3] The first closed-loop, automated ATP (AATP) algorithm, introduced in 2021, applies an S1 train derived from the detected VT, followed by an S2 derived initially from a refractory period estimator and then adjusted using analysis of the post-pacing interval if ATP fails. The termination efficacy of AATP in the real-world population is unknown. Purpose To assess the effectiveness AATP in a large real-world population. Methods A database of de-identified ICD transmissions from subjects in the United States, Australia, Canada, and New Zealand was queried for AATP treated episodes. ICDs were randomly sampled, biased toward ICDs with multiple treated VT episodes. For rhythms classified as monomorphic ventricular tachycardia, each AATP pulse train was reviewed for: rhythm at delivery, effect of ATP, and any non-capturing pulses. Acceleration was defined as a post-ATP decrease in MVT cycle length (VTCL) of at least 10% and at least 30ms. Acceleration to polymorphic VT or ventricular fibrillation (PVT/VF) was assessed. Rates of termination and acceleration were calculated for all MVT and dichotomized using a 320ms VTCL cutoff. The method of generalized estimating equations (GEE) was used to correct event rates for multiple episodes from a single patient. Results There were 2281 episodes of MVT in 340 patients; 63% of patients had 2 or more episodes. There were 724 episodes with initial VTCL <320ms and 1557 episodes with VTCL ≥320ms. The rate of termination of MVT by AATP was 78% for all VTCL [95% CI: 74%-81%]. In 300 patients (88%) AATP terminated at least one MVT. For MVT with VTCL ≥320ms the termination rate was 80% [95% CI: 75%-83%] and for VTCL <320ms the termination rate was 75% [95% CI: 69%-80%]. The rate of acceleration was 3.6% [95% CI: 2.7%-4.9%], with a 0.8% rate of acceleration to PVT/VF [95% CI: 0.4%-1.8%]. Acceleration led to shock therapy in 63% of accelerated episodes. All MVT accelerated to PVT/VF either spontaneously terminated (4/14) or were successfully converted by a single shock therapy (10/14). All accelerations that remained MVT were successfully treated by the device with either subsequent ATP (35%) or shock therapy (61%), or spontaneously terminated (4%). Conclusion In this large, real-world cohort analysis, automated ATP’s termination rate exceeded the typical success rate of burst ATP, particularly for MVT <320ms. Acceleration to PVT/VF was low and effective first-shock defibrillation was consistent. Subsequent ATP for accelerated MVT had incremental benefit, leading to successful termination one-third of the time. Additional data are currently being prospectively collected in a separate post-approval study.

Abstract Introduction Lipoprotein(a) [Lp(a)] is associated with an increased incidence of aortic stenosis. Bioprosthetic aortic valve degeneration and native aortic stenosis share similar pathological mechanisms. Evidence regarding the role of serum Lp(a) concentrations in bioprosthetic aortic valve degeneration is lacking. Purpose To evaluate the association between serum Lp(a) concentrations and bioprosthetic aortic valve degeneration. Methods In this retrospective multicenter study, consecutive patients who underwent a bioprosthetic aortic valve replacement between Jan-2010 and Dec-2020 and had a preoperatory serum Lp(a) measurement were included. A baseline transthoracic echocardiography (TTE) was performed following the aortic valve replacement and a follow-up TTE was performed at least 24 months after the baseline study to determine the presence of bioprosthetic valve degeneration. Significant degeneration was defined as: (a) an increase >10 mmHg in mean bioprosthetic aortic valve gradient from baseline status + a decrease in effective orifice area + a decrease in Doppler velocity index + exclusion of clinically thrombotic leaflet thickening, OR (b) new moderate or severe prosthetic aortic regurgitation (if the main component was periprosthetic, then it was not considered). Lp(a) concentrations were compared between patients with and without degeneration and regression analysis was conducted to investigate the association between bioprosthetic valve degeneration and Lp(a) levels. Results In total, 211 cases were included (mean age 74.1 ±9.4 years, 72.0% males, 29.9% transcatheter aortic valve replacements) (Figure 1). Median time between baseline and follow-up TTE was 5.0 (IQR 3.7) years. Bioprostheses degeneration was observed in 33 (15.6%) patients at follow-up. Median serum levels of Lp(a) were significantly higher in the patients affected by degeneration versus non-affected cases (50.0 vs 15.7 mg/dl, p=0.003). In the regression analysis, high Lp(a) levels (≥30 mg/dl) were associated with degeneration both in a univariate analysis (OR 4.8, 95%CI 2.2-10.9, p<0.001) and multivariate analysis adjusted by other risk factors for bioprostheses degeneration (age, sex, hypertension, smoking, patient prosthesis mismatch, creatinine levels, and body surface area) (OR 5.2, 95%CI 2.1-12.8, p<0.001). Conclusion Serum Lp(a) concentrations seem to be a risk factor for bioprosthetic aortic valve degeneration (Figure 2). There is an increasing need to accurately predict bioprosthetic aortic valve degeneration and to develop novel methods and treatments to increase their durability. Prospective studies are needed to confirm these findings and to investigate whether lowering Lp(a) could slow bioprostheses degradation.Population characteristicsLp(a) and bioprostheses degeneration

Abstract Background There are no robust data addressing the United States (US) experience with the 0/2 hours (h) European Society of Cardiology (ESC) algorithm using high-sensitivity cardiac troponin T (hs-cTnT). Purpose To evaluate the diagnostic performance of the 0/2h ESC-recommended absolute deltas in a US population. Methods Observational US cohort study of ED patients undergoing 0 and 2 h hs-cTnT measurements. The 99th percentiles upper reference limits (URL) used were 10 ng/L for women and 15 ng/L for men. Diagnostic outcomes were the adjudicated diagnoses of acute myocardial infarction (MI, type 1 or 2). Results A total of 1084 patients met inclusion criteria, amongst which 49% were women. Chest discomfort was reported in 521 (48%) patients. Among patients with a baseline hs-cTnT≤99th URL (n=434), 4 MIs occurred. To rule-out MI, an absolute 0-2h delta change <4 ng/L resulted in a sensitivity of 100% (95% CI: 39.8, 100) and a negative predictive value (NPV) of 100% (95% CI: 99.1, 100). To rule-in MI, an absolute 0-2h delta ≥10 ng/L had a specificity of 99.8 % (95% CI: 98.7, 99.9) and positive predictive value (PPV) of 75% (95% CI: 19.4, 99.4). Among patients with a baseline hs-cTnT >99th URL (n=650), 110 MIs occurred. In these patients, both rule-out (sensitivity 65%, NPV 91%) and rule-in (specificity 7.2%, PPV 11%) were poor using the ESC-recommended absolute deltas. Among patients with modest hs-cTnT increases (99th URL to 100 ng/L) neither the ESC-recommended absolute nor the Fourth Universal Definition of MI (UDMI)-recommended relative deltas provided acceptable performance. Among patients with marked hs-cTnT increases at presentation (>100 ng/L), a relative delta change >20% as recommended by the UDMI resulted in a superior rule-in performance, with a specificity of 92.0% (95% CI 74.0, 99.0) and PPV of 84.6% (57.4, 95.7). Conclusions In our unselected US-cohort of patients undergoing hs-cTnT, the 0/2h ESC algorithm had a good diagnostic performance in patients without myocardial injury at presentation. Conversely, in patients with myocardial injury at baseline, the ESC-recommended absolute deltas performed poorly to determine who had MI. In patients with marked hs-cTnT increases >100 ng/L at presentation, the UDMI recommended 20% relative change showed good rule-in performance.

Abstract Background Inflammation plays a potential role in heart failure (HF) etiology and prognosis. Neutrophil-to-Lymphocyte ratio (NLR) is a simple, routinely available lab criteria. In this meta-analysis, we sought to investigate the role of NLR on HF outcomes which remains unexplored. Methods PubMed, Embase and Scopus were systematically screened to find studies through August 2022, reporting data on association of HF related outcomes [all-cause mortality (ACM), cardiovascular (CV) death, in-hospital, HF readmissions and composite events] and NLR. Random effects models and I2 statistics were used to estimate pooled odds of outcomes and heterogeneity. Leave one out sensitivity analysis was performed. Results A total of 11 studies (6 retrospective and 5 prospective, 4 studies from Asia and Europe each, 2 from the US and 1 multicenter study) including 12954 patients (mean age: 69 years, Males 57.2%) from 2011 to 2022 with an average follow up duration of 54.8 months were included. Elevated NLR was significantly associated with ACM (aOR 1.80, 95%CI 1.46-2.22, p<0.01, Table 1), HF readmissions (aOR 2.53, 95% CI 1.60-3.99), in-hospital mortality (aOR 3.26, 95% CI 1.76- 6.02), CV mortality (aOR 1.84, 95%CI 1.03-3.31) and composite CV outcome including heart transplant (OR 2.07, 95% CI 1.32-3.25), p<0.001. Conclusion Elevated NLR was significantly associated with worse outcomes in HF patients. The NLR test might potentially be useful in identifying high-risk HF patients and curtail worse outcomes.

Abstract Background/Introduction Over the last decade, epidemiology and pathology studies have suggested that gamma-glutamyl transferase (GGT) has an independent role in the pathogenesis and clinical evolution of cardiovascular diseases associated with atherosclerosis. Recently, machine learning (ML) algorithms have identified pre-procedural GGT as a significant predictor of long-term mortality after coronary revascularization in the SYNTAX trial. Purpose The aim of this study is to investigate the impact of pre-procedural GGT on 10-year all-cause mortality in patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) following revascularization. Methods The SYNTAX trial was a randomized trial comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in 1,800 patients with complex CAD. The present report is a post-hoc sub-analysis of the SYNTAXES study, an investigator-driven extended 10-year follow-up of the SYNTAX trial. Before revascularization, blood samples were taken for GGT as well as other biological markers and analyzed by an independent central chemistry laboratory. The primary endpoint was all-cause mortality at 10-years. The changes in hazard for all-cause mortality in GGT over time were modelled using restricted cubic spline functions in a Cox regression model adjusted by age and sex. Subsequently, we compared survival in four groups defined by gender specific GGT thresholds of <32 IU and ≥32 IU for females and <64 IU and ≥64 IU for males, in accordance with prior studies. Results Out of 1,800 patients enrolled in the SYNTAX study, 167 (9.3%) did not have a GGT available at baseline and 1,633 (90.7%) patients were included in the present study. The mean values of GGT for males and females were 43.5±48.5 and 36.4±46.1 U/L, respectively. In the overall population a 10 U/L increase in GGT was significantly associated with 10-year all-cause death (adjusted hazard ratio [HR] 95% confidence interval [CI]: 1.03 [1.02–1.04], p <0.001, Figure A). For Kaplan–Meier analysis, patients were stratified into four groups according to previously reported sex related GGT thresholds. Ten-year mortality was numerically higher in males (adjusted HR 1.31, 95% CI: 0.90–1.91), and significantly higher in females (adjusted HR 1.88, 95% CI: 1.16–3.05) among patients with higher versus lower GGT (Figure B). Furthermore, GGT was significantly associated with CRP, a surrogate-marker of inflammation, as well as established cardiovascular risk biomarkers such as TG, total cholesterol, and glucose. Conclusions Preprocedural GGT is an independent predictor of 10-year mortality following coronary revascularization in patients with 3VD and/or LMCAD. This long-term association has been identified using ML algorithms and should be corroborated using data from large biobanks.Figure AFigure B