Maor, Elad

Abstract Background Mitral regurgitation (MR) and tricuspid regurgitation (TR) are prevalent valvular heart diseases associated with significant morbidity and mortality. Traditional echocardiography faces limitations in availability, cost, consistency, and reliability, leading to misdiagnosis and undertreatment. The application of artificial intelligence (AI) to echocardiographic scans has the potential to address these challenges. Methods This study evaluates the performance of an AI algorithm on an external population. The algorithm utilizes deep learning networks to analyze echocardiographic exams for diagnosing atrioventricular valve disorders. We tested the algorithm on transthoracic echocardiography data collected from a single center between 2013 and 2023. The model's performance was compared to ground truth values using two classification schemes: distinguishing between normal-mild and moderate-severe regurgitation, and categorizing results into four groups: normal, mild, moderate, and severe. Results The MR cohort included 280 patients, while the TR cohort comprised 298 patients. The model demonstrated a robust ability to identify clinically significant (moderate and above) atrioventricular valve regurgitation. The MR model achieved an area under the curve (AUC) of 0.98 (95% CI: 0.97–0.99), with 91% accuracy, 95% sensitivity, and 89% specificity. In comparison, the TR model exhibited an AUC of 0.96 (95% CI: 0.94–0.98), with 84% accuracy, 91% sensitivity, and 80% specificity. Conclusion The model demonstrated high diagnostic accuracy and reliability in assessing atrioventricular valve regurgitation severity, highlighting its potential as a valuable clinical tool. The findings underscore the role of AI in complementing expert evaluations and improving access to effective diagnostics, with future applications potentially including point-of-care diagnosis and monitoring of disease progression.

Abstract Background Many patients with atrial fibrillation (AF) suffer life-limiting symptoms and heart failure. Although enormous advances in rhythm control have been made, device-based therapies for treating recurrent episodes are limited. Using pulsed electric fields (PEF) to induce reversible electroporation of cardiac tissue may effectively terminate AF. Purpose To assess the feasibility of PEF delivery for converting atrial arrhythmias via reversible electroporation. Methods Four swine models were used in this acute study. Custom-made decapolar catheters for PEF delivery were deployed with the following configurations: 1. Endocardial right atrium (RA) and coronary sinus (CS), n=2; 2. Endocardial RA and epicardial left atrium (epiLA), n=2. AF and atrial flutter (AFL) were induced with programmed stimulation. PEF delivery was performed using the BTX 830 generator. For each attempt, a single monophasic pulse at 10 or 20µs pulse width was administered, with voltage varied across attempts (range 750-3000V). Successful (type 1 and 2 breaks) and unsuccessful conversion attempts were recorded. Post-PEF signal changes and arrhythmias were identified. Results A total of 58 AF/AFL (28 and 30 respectively) episodes were induced. Of the 37 successful conversion attempts, 33 (89.1%) were type 1 breaks. Conversion success probabilities generally increased with higher voltages for both configurations. >70% conversion success was seen with ≥1500V for the RA/CS configuration and ≥2000V for the RA/epiLA configuration. Arrhythmias including intra-atrial delay and high-grade atrioventricular block were seen, usually following successive PEF deliveries. Significant muscle stimulation was provoked with the current experimental setup. Conclusion Termination of atrial arrhythmias with PEF delivery is feasible, although further work is required to optimize its efficacy and safety.

Abstract Background Ventricular fibrillation (VF) is a leading cause of sudden cardiac death worldwide. Defibrillation via direct current shocks is effective but associated with significant pain and morbidity, prompting the need for alternative approaches. Reversible electroporation of cardiac tissue with pulsed electric fields (PEF) may be an effective means of terminating VF. Purpose To assess the feasibility of PEF delivery for terminating VF. Methods 5 acute swine models were used. Mechanical circulatory support with peripheral veno-arterial extracorporeal membrane oxygenation +/- percutaneous left ventricular assist device (Impella 5.5 L) was implemented and titrated to a mean arterial pressure ≥65 mmHg. Decapolar catheters were introduced into the endocardial right and/or left ventricle as well as epicardium. VF was induced with R on T shocks or rapid ventricular pacing. PEF was delivered with the endocardial catheter as the cathode and epicardial catheter as the anode; monophasic pulses (5-10) at 3000V, 100µs, and 200ms inter-pulse intervals were used. If VF persisted post-PEF, catheters were repositioned into regions of intact voltages for repeat delivery. Results 10 VF episodes were induced, 7 of which were successfully terminated with PEF delivery (70.0%). The median number of attempts to achieve VF termination was 2 (range 1-5). The post-VF rhythm was complete heart block with ventricular asystole in all successful defibrillation attempts, with no recovery after 30 minutes of observation. Significant muscle stimulation was seen with the utilized PEF parameters and catheter configurations. Conclusion Termination of VF using PEF – pulsed field defibrillation – is possible. However, further study is required to optimize delivery parameters/configurations to improve effectiveness and avoid muscle stimulation as well as conduction abnormalities.

Abstract Aims Mitral and tricuspid regurgitation (MR and TR) are common in older adults and associated with substantial morbidity and mortality. While transthoracic echocardiography (TTE) is the diagnostic gold standard, access remains limited in many care settings. Artificial intelligence (AI)–based echocardiographic analysis may help address this diagnostic gap. Methods and results We externally validated a deep learning algorithm developed by Aisap.ai using TTE studies from the Mayo Clinic Health System (2013–23). The model analyses echocardiographic images to classify atrioventricular regurgitation severity and was evaluated against cardiologist interpretations. Performance was assessed using binary (normal–mild vs. moderate–severe) and ordinal (normal, mild, moderate, severe) classification schemes. Among 1541 eligible TTEs, the model returned predictions for 578 studies (38%). Performance analysis was limited to these cases. The MR cohort included 280 studies and the TR cohort 298. For MR, the model achieved an area under the receiver operating characteristic curve (AUC) of 0.98 [95% confidence interval (CI): 0.97–0.99], with 91% accuracy, 95% sensitivity, and 89% specificity. For TR, the AUC was 0.96 (95% CI: 0.94–0.98), with 84% accuracy, 91% sensitivity, and 80% specificity. Conclusion In cases where a prediction was generated, the model demonstrated high diagnostic performance in identifying clinically significant atrioventricular regurgitation. These findings support the feasibility of AI-assisted echocardiography in diverse populations, while underscoring the need for technical alignment between model requirements and local acquisition practices to ensure real-world applicability.

Background: Previous animal studies have shown no significant vascular injury from pulsed electrical field (PEF) ablation. We sought to assess the effect of PEF on swine coronary arteries. Methods: We performed intracoronary and epicardial (near the coronary artery) PEF ablations in swine pretreated with dual antiplatelet and antiarrhythmic therapy. Intracoronary PEF was delivered using MapiT catheters (Biotronik, Berlin), whereas epicardial PEF was delivered using EPT catheters (Boston Scientific, MA). PEF pulse duration was microseconds (Nanoknife 3.0, Angio Dynamics, NY) or nanoseconds (CellFX, Pulse Biosciences, CA). Results: We performed 39 intracoronary ablations in 10 swine and 20 epicardial-pericoronary ablations in 4 separate swine. Intracoronary PEF was delivered at higher energy compared with epicardial PEF (46 [interquartile range, IQR 20–85] J versus 10 [IQR 10–11] J, P < 0.01). Reversible coronary spasm occurred in 49% intracoronary ablations and 45% epicardial ablations ( P =0.80). At the end study, fixed coronary stenosis was demonstrated in 44% intracoronary ablations (80% for microsecond PEF and 18% for nanosecond PEF) and 0% epicardial ablations. Visible hemorrhagic and/or fibrotic myocardial lesions were observed at necropsy with similar frequency between intracoronary and epicardial PEF (45% versus 50%, P =0.70). Nanosecond PEF (49 ablations in 11 swine), when compared with microsecond PEF (10 intracoronary ablations in 3 swine), resulted in lower energy delivery (21 [IQR 10–46] J versus 129 [IQR 24–143] J, P =0.03) and less incidence of fixed coronary stenosis (18% versus 80%, P =0.04). Conclusions: In the swine model, intracoronary PEF resulted both in significant coronary spasm and fixed coronary stenosis. Epicardial PEF, delivered at lower energy, resulted in reversible spasm but no fixed coronary stenosis.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P &amp;lt; .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P &amp;lt; .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P &amp;lt; .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Abstract Pulsed electric fields (PEFs) have emerged as an ideal cardiac ablation modality. At present numerous clinical trials in humans are exploring PEF as an ablation strategy for both atrial and ventricular arrhythmias, with early data showing significant promise. As this is a relatively new technology there is limited understanding of its principles and biophysics. Importantly, PEF biophysics and principles are starkly different to current energy modalities (radiofrequency and cryoballoon). Given the relatively novel nature of PEFs, this review aims to provide an understanding of the principles and biophysics of PEF ablation. The goal is to enhance academic research and ultimately enable optimization of ablation parameters to maximize procedure success and minimize risk.

(1) Introduction: Most studies rely on in-hospital data to predict cardiovascular risk and do not include prehospital information that is substantially important for early decision making. The aim of the study was to define clinical parameters in the prehospital setting, which may affect clinical outcomes. (2) Methods: In this population-based study, we performed a retrospective analysis of emergency calls that were made by patients to the largest private emergency medical services (EMS) in Israel, SHL Telemedicine Ltd., who were treated on-site by the EMS team. Demographics, clinical characteristics, and clinical outcomes were analyzed. Mortality was evaluated at three time points: 1, 3, and 12 months’ follow-up. The first EMS prehospital measurements of the systolic blood pressure (SBP) were recorded and analyzed. Logistic regression analyses were performed. (3) Results: A total of 64,320 emergency calls were included with a follow-up of 12 months post index EMS call. Fifty-five percent of patients were men and the mean age was 70.2 ± 13.1 years. During follow-up of 12 months, 7.6% of patients died. Age above 80 years (OR 3.34; 95% CI 3.03–3.69, p < 0.005), first EMS SBP ≤ 130 mm Hg (OR 2.61; 95% CI 2.36–2.88, p < 0.005), dyspnea at presentation (OR 2.55; 95% CI 2.29–2.83, p < 0001), and chest pain with ischemic ECG changes (OR 1.95; 95% CI 1.71–2.23, p < 0.001) were the highest predictors of 1 month mortality and remained so for mortality at 3 and 12 months. In contrast, history of hypertension and first EMS prehospital SBP ≥ 160 mm Hg were significantly associated with decreased mortality at 1, 3 and 12 months. (4) Conclusions: We identified risk predictors for all-cause mortality in a large cohort of patients during prehospital EMS calls. Age over 80 years, first EMS-documented prehospital SBP < 130 mm Hg, and dyspnea at presentation were the most profound risk predictors for short- and long-term mortality. The current study demonstrates that in prehospital EMS call settings, several parameters can be used to improve prioritization and management of high-risk patients.

Abstract Background Heart failure (HF) is a debilitating disease and is associated with significant morbidity and mortality, and costs to health care systems. Monitoring the impact of therapy remotely holds the potential to reduce HF-related hospitalizations, improve quality of life, and optimize the use of the limited resources. Voice signal is an emerging non-invasive biomarker that has been associated with a number of disease states. We previously identified a significant relationship between specific vocal biomarkers and coronary artery disease, and recently extended these observations by showing that a pre-specified voice biomarker was associated with increased mortality and re-hospitalization in patients with HF. Purpose In the current study, we evaluated the association between a vocal biomarker derived from voice signal analysis and invasively measured indices of pulmonary hypertension (PH). We hypothesized that the pre-specified voice biomarker might be associated with hemodynamic indices reflective of PH that are known to be linked to HF-severity, and that predict outcomes such as HF-related hospitalization and death. Methods The study population included patients referred for an invasive cardiac hemodynamic study between January 2017 and December 2018. Subjects had their voice signal recorded to their smartphone on three separate occasions prior to the cardiac study. A pre-established numeric vocal biomarker was derived from each recording, and the mean vocal biomarker calculated for each patient. Patients were a priori divided into two groups: those with high pulmonary arterial pressure (PAP) defined as ≥35 mmHg consistent with moderate or greater PH, versus those with a lower PAP. Results Eighty three patients, mean age 61.6±15.1 years, 37 (44.6%) male, were included in the study. The intraclass correlation coefficient for the vocal biomarker in all patients was 0.83 implying very good agreement between values. Patients with a high mean PAP (≥35 mmHg) had significantly higher values of the voice biomarker compared to those with a lower mean PAP (0.74±0.85 vs. 0.43±0.86, p=0.008). Patients with a high pulmonary vascular resistance (PVR) defined as a PVR ≥1.7 Wood Units had significantly higher values of the voice biomarker compared to those with a lower PVR (0.62±0.83 vs. 0.33±0.90, p=0.026). Multivariable logistic regression showed that an increase in the voice biomarker by 1 unit was significantly associated with a high PAP, odds ratio (OR) 2.31, 95% CI 1.05–5.07, p=0.038, and with borderline significance with a high PVR, OR 2.14, 95% CI 0.94–4.87, p=0.07. Conclusion The current study shows a relationship between a noninvasive vocal biomarker derived from voice signal analysis and invasively derived hemodynamic indices related to PH obtained during cardiac catheterization. These results may have important and practical clinical implications for telemedicine and remote monitoring of patients with HF and PH. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Mayo Foundation; Beyond Verbal Communications

Background The purpose of this article is to evaluate the association of voice signal analysis with adverse outcome among patients with congestive heart failure ( CHF ). Methods and Results The study cohort included 10 583 patients who were registered to a call center of patients who had chronic conditions including CHF in Israel between 2013 and 2018. A total of 223 acoustic features were extracted from 20 s of speech for each patient. A biomarker was developed based on a training cohort of non‐ CHF patients (N=8316). The biomarker was tested on a mutually exclusive CHF study cohort (N=2267) and was evaluated as a continuous and ordinal (4 quartiles) variable. Median age of the CHF study population was 77 (interquartile range 68–83) and 63% were men. During a median follow‐up of 20 months (interquartile range 9–34), 824 (36%) patients died. Kaplan–Meier survival analysis showed higher cumulative probability of death with increasing quartiles (23%, 29%, 38%, and 54%; P <0.001). Survival analysis with adjustment to known predictors of poor survival demonstrated that each SD increase in the biomarker was associated with a significant 32% increased risk of death during follow‐up (95% CI, 1.24–1.41, P <0.001) and that compared with the lowest quartile, patients in the highest quartile were 96% more likely to die (95% CI , 1.59–2.42, P <0.001). The model consistently demonstrated an independent association of the biomarker with hospitalizations during follow‐up ( P <0.001). Conclusions Noninvasive vocal biomarker is associated with adverse outcome among CHF patients, suggesting a possible role for voice analysis in telemedicine and CHF patient care.