Abbasi, Muhannad

ABSTRACT Background Acute heart failure (AHF) exhibits marked heterogeneity in diastolic hemodynamics, yet comprehensive echocardiographic assessment of diastolic function (DF) and filling pressure (FP) is often infeasible. We evaluated whether artificial intelligence–enabled electrocardiography (AI-ECG) could provide scalable DF grading and FP estimation in hospitalized AHF patients. Methods We retrospectively studied adults hospitalized for AHF across Mayo Clinic sites (2013–2023) who received ≥1 dose of intravenous loop diuretic and had paired 12-lead ECG and TTE. The previously validated AI-ECG DF model was applied without retraining to generate four DF grades and a continuous FP probability. Clinical outcomes were all-cause mortality and heart failure rehospitalization. Associations with clinical severity markers and echocardiographic indices were examined. Kaplan–Meier survival analysis and adjusted multivariable Cox proportional hazards models were performed. Exploratory analyses examine the kinetics of change in FP probability and impact on mortality. Results Among 11,513 patients (median age 75 years, 39% female), AI-ECG DF grading was feasible in 100%, whereas echocardiographic DF was indeterminate in 44% of clinically eligible patients. In 2,582 patients with determinate echocardiographic DF, AI-ECG FP probability discriminated TTE Grade 2–3 dysfunction with AUC 0.85 (95% CI 0.83 – 0.86). Higher AI-ECG DF grades were associated with higher comorbidity burden, worse NYHA class, elevated NT-proBNP, higher MAGGIC scores, elevated PCWP, and more advanced structural remodeling. After multivariable adjustment, AI-ECG DF remained independently associated with mortality (hazard ratio [HR] 1.25, 95% CI 1.16–1.35 for Grade 2; HR 1.44, 95% CI 1.33–1.56 for Grade 3 versus Normal/Grade 1). Combining AI-ECG DF with MAGGIC scores yielded ordered risk gradients, with highest mortality in patients with both high MAGGIC and Grade 2–3 DF. Among patients with serial ECGs, improvement in FP probability was independently associated with lower mortality (HR 0.85, 95% CI 0.79–0.91), whereas worsening did not show a consistent adverse gradient beyond baseline DF. Conclusions In a large, geographically diverse AHF cohort, AI-ECG DF grading was universally feasible, correlated with established hemodynamic severity markers, and provided independent prognostic information beyond established risk factors, supporting its role as a pragmatic, scalable diastolic biomarker in AHF. CLINICAL PERSPECTIVE What Is New? In 11,513 hospitalized acute heart failure (HF) patients, artificial intelligence-enabled electrocardiography provided diastolic function grading in 100% of patients from a single 12-lead ECG without requiring additional clinical variables, compared with 56% feasibility for guideline-based echocardiography grading. AI-ECG diastolic function grades correlated with established marker of severity (NYHA functional class, NT-proBNP, MAGGIC risk scores, and pulmonary capillary wedge pressure) and remained independently associated with both mortality and HF rehospitalization after multivariable adjustment. Serial AI-ECG measurements identified post-discharge filling pressure trajectories, with improvement independently associated with 15% lower mortality, a first demonstration that longitudinal ECG assessment can track post-discharge hemodynamic recovery. What Are the Clinical Implications? AI-ECG transforms the universally obtained 12-lead ECG into an actionable hemodynamic biomarker that addresses the critical gap when echocardiographic diastolic function assessment is indeterminate or unavailable in acute HF patients. Despite markedly different hemodynamic severity and long-term outcomes across AI-ECG diastolic function grades, hospitalization length of stay did not differ, suggesting advanced diastolic dysfunction represents occult risk not easily recognized during routine acute care and highlighting the need for improved post-discharge risk stratification. The continuous filling pressure probability metric enables longitudinal monitoring of post-discharge hemodynamic status using serial routine ECGs, potentially identifying patients requiring intensified follow-up or specialist referral.

Abstract Aims The increasing adoption of transcatheter tricuspid valve replacement (TTVR) offers a promising therapeutic option for patients with severe tricuspid regurgitation. However, many of these patients have pre-existing cardiac implantable electronic devices (CIEDs), raising concerns about potential lead-related complications. Despite these concerns, limited data exist on the impact of TTVR on CIED integrity and function. This study aimed to evaluate the impact of TTVR on CIED lead function, including pacing thresholds, sensing, and impedance, in patients undergoing TTVR with the EVOQUE valve system. Methods and results A retrospective observational study was conducted at Mayo Clinic Rochester, including 32 consecutive patients who underwent TTVR with pre-existing CIEDs. A total of 32 patients were included, with a mean age of 79.2 ± 8.4 years; 59% were female. A total of 62.5% had a permanent pacemaker, 12.5% had an implantable cardioverter-defibrillator, 15.6% had a cardiac resynchronization therapy pacemaker, and 9.4% had a cardiac resynchronization therapy defibrillator. Following TTVR, 10 (31%) of patients developed lead function changes during a median device follow-up of 210 days (IQR: 43–307 days). The right ventricular lead was primarily affected, with only one case involving an atrial lead. Neither the Ottawa score nor the anatomical lead position reliably predicted lead abnormality (P = 0.86 and P = 0.53, respectively). R-wave sensing changes were the most common lead change observed, affecting 55% of cases. In 67% of these cases, R-wave sensing alterations occurred as an isolated finding, with no significant change in impedance or thresholds, and were managed conservatively without any need for device reprogramming. Four patients (13%) had findings concerning for a lead insulation breach, in which one (3%) required a lead revision. Among five patients with follow-up exceeding 600 days, two patients exhibited a statistically significant gradual decline in impedance without other lead dysfunction, suggesting potential subclinical lead degradation. Conclusion Transcatheter tricuspid valve replacement with the EVOQUE system in the setting of cardiac device leads is associated with lead function changes in 31%. The majority of lead-related changes were managed conservatively, but 13% of patients had findings concerning for an insulation breach. Future studies should focus on refining implantation techniques and defining optimal strategies for managing device-lead interactions in this population.

Background: CD19 CAR T-cell therapy is a novel cancer treatment for B-cell malignancies. Systemic inflammation due to Cytokine Release Syndrome (CRS) can occur. Elevated levels of cytokines have been linked to valve damage. Hypothesis: Evaluate changes in valve morphology or progression of valvular heart disease in adult patients after CD19 CAR T-cell therapy and by clinical CRS grade. Methods: Patients that underwent CD19 CAR T-cell therapy with both a baseline and a post-treatment transthoracic echocardiogram (TTE) were included. Patient characteristics and outcomes were abstracted from the electronic medical record. CRS was categorized as CRS<2 and CRS ≥2 for all patients using the ASTCT 2019 criteria. Valve thickening was graded as a dichotomous variable. Valve disease (regurgitation or stenosis) was ranked on a 1-to-6-point numeric scale (none, mild, mild-moderate, moderate, moderate-severe, severe) and grade point value difference was calculated. Variables were compared by Chi Squared and Student’s t tests. Results: 114 patients were included with a median TTE follow-up of 44 days, 54% developed CRS ≥2 (Table 1a). Overall, no statistically significant changes in valve morphology and valve disease progression were observed in the cohort (Figure 1a, 1b). Among CRS groups, valve morphology changes and valve disease progression were similarly distributed (21% in CRS <2 vs 19% in CRS ≥2, p=0.623 and 28% in CRS <2 vs 24% in CRS ≥2, p=0.62 respectively) (Fig. 1a). In the cases that progression was observed, it was mostly mild, and regurgitation was the most common pattern (Fig. 1c). Conclusions: This is the first study to evaluate the incidence of cardiac valve disease progression or thickening in patients treated with CD19 CAR T therapies. We can conclude that no progression of valve disease or changes in valve morphology were observed in its entirety or by CRS groups. Longer follow up is needed to validate these findings.

1. Background: We sought to determine acute and subacute changes in cardiac function after proton beam (PBT) and photon beam (PhT) radiotherapy (RT) using conventional and two-dimensional speckle tracking echocardiography (2D-STE) in patients with malignant breast and thoracic tumors. 2. Methods: Between March 2016 and March 2017, 70 patients with breast or thoracic cancer were prospectively enrolled and underwent transthoracic echocardiography with comprehensive strain analysis at pretreatment, mid-treatment, end of treatment, and 3 months after RT. 3. Results: PBT was used to treat 44 patients; PhT 26 patients. Mean ± SD age was 55 ± 12 years; most patients (93%) were women. The median (interquartile range) of the mean heart dose was lower in the PBT than the PhT group (47 [27–79] vs. 217 [120–596] cGy, respectively; p < 0.001). Ejection fraction did not change in either group. Only the PhT group had reduced systolic tissue Doppler velocities at 3 months. 2D-STE showed changes in endocardial and epicardial longitudinal, radial, and circumferential early diastolic strain rate (SRe) in patients undergoing PhT (global longitudinal SRe, pretreatment vs. end of treatment (p = 0.04); global circumferential SRe, pretreatment vs. at 3-month follow-up (p = 0.003); global radial SRe, pretreatment vs. at 3-month follow-up (p = 0.02) for endocardial values). Epicardial strain values decreased significantly only in patients treated with PhT. Patients in the PhT group had a significant decrease in epicardial global longitudinal systolic strain rate (GLSRs) (epicardial GLSRs, at baseline vs. at end of treatment [p = 0.009]) and in GCSRe and GRSRe (epicardial GCSRe, at baseline vs. at 3-month follow-up (p = 0.02); epicardial GRSRe, at baseline vs. at 3-month follow-up (p = 0.03)) during treatment and follow-up. No changes on 2D-STE were detected in the PBT group. 4. Conclusions: Patients who underwent PhT but not PBT had reduced tissue Doppler velocities and SRe values during follow-up, suggesting early myocardial relaxation abnormalities. PBT shows promise as a cardiac-sparing RT technology.

Introduction: Valve-in-valve transcatheter mitral valve replacement (ViV-TMVR) and redo surgical mitral valve replacement (redo-SMVR) are two treatment strategies for patients with bioprosthetic mitral valve dysfunction. We conducted a systematic review and meta-analysis to compare the outcomes of ViV-TMVR versus redo-SMVR. Methods: We searched PubMed, EMBASE, Cochrane, and Google Scholar for studies comparing outcomes of ViV-TMVR versus redo-SMVR in degenerated bioprosthetic mitral valves. We used a random effects model to calculate risk ratios (RRs) with 95% confidence intervals (CIs). Outcomes included in-hospital, 30-day, 1-year, and 2-year mortality, stroke, bleeding and vascular complications, acute kidney injury (AKI), arrhythmias, and hospital length of stay (LOS). Results: Six observational studies with a total of 1,339 subjects were included. Median follow-up was 2 years. Compared to redo-SMVR, ViV-TMVR was associated with significantly lower in-hospital (RR 0.42; 95% CI 0.25-0.70; p=0.001) and 30-day mortality (RR 0.49; 95% CI 0.24-0.98; p=0.04) but similar 1-year (RR 0.97; 95% CI 0.64-1.47; p=0.89) and 2-year mortality (RR 1.14; 95% CI 0.71-1.81; p=0.59). Stroke, bleeding, AKI, and arrhythmias were less frequent and hospital LOS was shorter with ViV-TMVR, however vascular complications were similar between both strategies. Conclusion: In patients with degenerated bioprosthetic mitral valves, ViV-TMVR is associated with better outcomes compared to redo-SMVR including lower in-hospital and 30-day mortality, lower complication rates, and shorter hospital LOS. Given these findings and the ongoing advances in transcatheter therapeutics, ViV-TMVR may be preferred over redo-SMVR, particularly in individuals at intermediate-to-high surgical risk.

Background: To identify factors that increase the specificity of the treadmill exercise test (TMET), and develop a novel scoring system which accounts for functional capacity to aid in determining the need for further testing. Methods: We retrospectively evaluated the electronic health records of 600 patients who had positive TMET results and follow-up stress echocardiography from 1-January-2004, through 31-December-2016. Correlations between clinical and aerobic variables and multivessel disease (MVD) were determined. Duke Treadmill Score (DTS) was calculated and compared with a novel scoring system titled the Intermediate-High-Workload Treadmill Score (IHWTS) that used variables associated with MVD. Results: In total, 124 of 600 patients (21%) had coronary catheterization, and 51 of these patients (41%) had MVD. Mean (SD) DTS was –2.10 (6.3) among patients with MVD vs –0.16 (5) among patients without MVD (p = 0.06). Mean (SD) functional aerobic capacity (FAC) was 76% (20%) among patients with MVD vs 90% (21%) among patients without MVD (p < 0.001). Mean (SD) metabolic equivalent (MET) was 7 (2) among patients with MVD vs 8 (2) among patients without MVD (p = 0.002). Only 6 (12%) of patients with MVD achieved 9 MET or greater on TMET. DTS less than 4 did not distinguish between patients with and without MVD (p = 0.67). Age, hypertension and FAC were independently associated with MVD (all p < 0.05). Conclusions: Our novel scoring system IHWTS utilized age, hypertension, and FAC appeared comparable to DTS to risk-stratify patients regardless of baseline symptoms. Clinical parameters such as hypertension along with exercise functional capacity should be considered when evaluating a positive TMET result in patients that achieve an intermediate-high workload >5 Metabolic Equivalents (METs).

Background Racial and ethnic disparities in outcomes exist following many cardiac procedures. Transcatheter mitral valve replacement (TMVR) has grown as an alternative to mitral valve surgery for patients at high surgical risk. The outcomes of TMVR by race and ethnicity are unknown. We aimed to evaluate racial and ethnic disparities in the outcomes of TMVR. Methods and Results We analyzed the National Inpatient Sample database from 2016 to 2020 to identify hospitalizations for TMVR. Racial and ethnic disparities in TMVR outcomes were determined using logistic regression models. Between 2016 and 2020, 5005 hospitalizations for TMVR were identified, composed of 3840 (76.7%) White race, 505 (10.1%) Black race, 315 (6.3%) Hispanic ethnicity, and 345 (6.9%) from other races (Asian, Pacific Islander, American Indian or Alaska Native, Other). Compared with other racial and ethnic groups, Black patients were significantly younger and more likely to be women (both P <0.01). There were no significant differences between White, Black, and Hispanic patients in in‐hospital mortality (5.2% versus 5.0% versus <3.5%; P =0.89) and procedural complications, including heart block ( P =0.91), permanent pacemaker ( P =0.49), prosthetic valve dysfunction ( P =0.45), stroke ( P =0.37), acute kidney injury ( P =0.32), major bleeding ( P =0.23), and blood transfusion ( P =0.92), even after adjustment for baseline characteristics. Adjusted vascular complications were higher in Black compared with White patients ( P =0.03). Trend analysis revealed a significant increase in TMVR in all racial and ethnic groups from 2016 to 2020 ( P trend <0.05). Conclusions Between 2016 and 2020, Black and Hispanic patients undergoing TMVR had similar in‐hospital outcomes compared with White patients, except for higher vascular complications in Black patients. Further comparative studies of TMVR in clinically similar White patients and other racial and ethnic groups are warranted to confirm our findings.

The field of malignant hematology is transforming with novel immunotherapeutic approaches. Unfortunately, quality of life, treatment efficacy, and life expectancy are negatively affected by cardiotoxic side effects of treatment. To date, the exact mechanism and incidence of cardiotoxicity associated with these therapies is unclear. These events are believed to be triggered or occur concurrently with cytokine release syndrome. Furthermore, there are no formal guidelines to provide evaluation, treatment, and surveillance. We aim to synthesize available literature with updates on the cardiotoxic effects of novel therapies used in malignant hematologic disorders, with a focus on chimeric antigen receptor T-cell therapy and bispecific T-cell engager therapy, along with a proposed algorithm that may guide pretreatment evaluation, monitoring during treatment, and post-treatment surveillance.

Background: Four-dimensional (D) flow magnetic resonance imaging (MRI) is limited by time-consuming and nonstandardized data analysis. We aimed to test the efficiency and interobserver reproducibility of a dedicated 4D flow MRI analysis workflow. Materials and Methods: Thirty retrospectively identified patients with bicuspid aortic valve (BAV, age=47.8±11.8 y, 9 male) and 30 healthy controls (age=48.8±12.5 y, 21 male) underwent Aortic 4D flow MRI using 1.5 and 3 T MRI systems. Two independent readers performed 4D flow analysis on a dedicated workstation including preprocessing, aorta segmentation, and placement of four 2D planes throughout the aorta for quantification of net flow, peak velocity, and regurgitant fraction. 3D flow visualization using streamlines was used to grade aortic valve outflow jets and extent of helical flow. Results: 4D flow analysis workflow time for both observers: 5.0±1.4 minutes per case (range=3 to 10 min). Valve outflow jets and flow derangement was visible in all 30 BAV patients (both observers). Net flow, peak velocity, and regurgitant fraction was significantly elevated in BAV patients compared with controls except for regurgitant fraction in plane 4 (91.1±29.7 vs. 62.6±19.6 mL/s, 37.1% difference; 121.7±49.7 vs. 90.9±26.4 cm/s, 28.9% difference; 9.3±10.1% vs. 2.0±3.4%, 128.0% difference, respectively; P <0.001). Excellent intraclass correlation coefficient agreement for net flow: 0.979, peak velocity: 0.931, and regurgitant fraction: 0.928. Conclusion: Our study demonstrates the potential of an efficient data analysis workflow to perform standardized 4D flow MRI processing in under 10 minutes and with good-to-excellent reproducibility for flow and velocity quantification in the thoracic aorta.