Gulati, Rajiv

Background: Patients with normal resting left ventricular ejection fraction (LVEF) without either coronary artery disease (CAD) or a hypertensive response can paradoxically develop reduced LVEF during exercise stress echocardiography (ESE). The clinical phenotype and outcomes of these patients is unknown. Hypothesis: Patients who paradoxically develop reduced LVEF during exercise may represent a sub-phenotype of heart failure with preserved LVEF (HFpEF). Aims: To describe the baseline characteristics and clinical outcomes of this unique patient population. Methods: Among all ESE performed between January 2003 and December 2022, patients without a hypertensive response to exercise and without CAD by angiogram within 90 days of ESE, who had a resting LVEF ≥50% with a ≥5% LVEF decrease during ESE were identified. All-cause mortality, HF hospitalization, and atrial fibrillation (AF) outcomes were assessed. Kaplan-Meier and Cox regression methods were used to analyze time-to-event outcomes. Results: Among 213,643 stress echocardiograms performed, 134 patients met eligibility criteria (Table 1). The mean age of the population was 66±10 years, 76% were women, and 16% had AF at baseline. Mean LVEF was 58±4% at rest and 43±4% at peak stress. Stress electrocardiogram met criteria for ischemia in 14%. The 10-year all-cause mortality risk was 12.9% (95% CI 5.5-20.3) with 10 (37%) of 27 deaths due to cancer (Figure 1, Panel A). The 10-year estimated risk of HF hospitalization was 17.6% (95% CI 9.0-26.2) (Figure 1, Panel B). Among 112 patients without AF at baseline, the 10-year risk of developing AF was 23.4% (95% CI 13.4-33.4). Conclusions: Patients with exercise-induced reduced LVEF in the absence of obstructive CAD have a high incidence of HF hospitalizations and AF. Given the preponderance of women, risk for AF, HF hospitalizations, and cancer-related deaths, the possibility that this condition is an early sub-phenotype of HFpEF should be investigated.

Background: Electrocardiography-based artificial intelligence (AI-ECG) validated models that detect cardiac disease are increasingly being applied in clinical practice. The utility of such tools to detect insidious cardiac disease in patients with normal baseline left ventricular ejection fraction (LVEF) who paradoxically develop reduced LVEF during exercise stress echocardiography (ESE), and do not have coronary artery disease (CAD) or hypertension, is unknown. Hypothesis: AI-ECG is useful to diagnose insidious cardiac disease and predict clinical outcomes in patients with exercise-induced cardiomyopathy. Aims: To assess the utility of AI ECG in patients with exercise-induced cardiomyopathy. Methods: Among all ESE performed between January 2003 and December 2022, patients without a hypertensive response to exercise and without CAD (confirmed by coronary angiography within 90 days after ESE), with resting LVEF ≥50% and a paradoxical ≥5% LVEF decrease during ESE were identified. A previously validated AI-ECG algorithm that predicts atrial fibrillation (AF), reduced LVEF, and cardiac amyloidosis (CA) was applied to the baseline ECG closest to the time of ESE. The predicted probability of AF, reduced LVEF, and CA if above the published thresholds, was determined. Results: There were 134 patients with exercise-induced cardiomyopathy who were identified. The mean age of this cohort was 66±10 years, 76% were women and 16% had AF at baseline. Mean LVEF was 58±4% at rest and 43±4% at peak stress. The median follow-up period was 6.8 years (IQR 3.0-12.2). Among patients without a baseline history of AF (n=112), AI-ECG identified 29% with a significant probability of AF, which was associated with a subsequent AF diagnosis at univariable analysis (HR 2.505, 95%CI 1.016-6.177, p=0.046). There were 10 patients with an AI-ECG prediction of reduced LVEF among whom 3 were subsequently hospitalized with HF. AI-ECG was positive for CA in 8 and 3 amongst these had subsequent HF hospitalizations (Table). Conclusions: Baseline AI-ECG may help predict subsequent AF and diagnose preclinical amyloid cardiomyopathy in patients who by resting echocardiography do not seem to have cardiac disease but with exercise develop reduced LVEF.

Introduction: Spontaneous coronary artery dissection (SCAD) is a poorly understood cause of acute coronary syndrome (ACS), predominantly affecting young women and frequently related to acute stressors. It has been suggested that stress induced cardiomyopathy can cause dissection via mechanical distortion of the vessel at wall-motion hinge points. Whether specific coronary anatomic configurations also predispose to distortion and hence SCAD remains unknown. Hypothesis: Patients with left anterior descending (LAD) SCAD have a higher frequency of a “wrap around” (type IV - perfuses >25% of the inferior wall) LAD. Methods: Coronary angiograms of patients in the Mayo Clinic SCAD Registry were reviewed. Patients from functional angiogram registry with similar characteristics were used as controls. Patients with an LAD SCAD were compared to patients who never had an LAD SCAD. For identifying predictors of LAD SCAD, patients who never had an LAD SCAD were compared to patients that had an LAD SCAD as a recurrent event, but not as the initial presentation. Results: A total of 456 patients with SCAD (46±6 years; 96% women) were included. The control group consisted of 178 patients (44±7 years, 97% women). Type IV LAD was more common in the SCAD cohort (Figure 1), and patients in the LAD SCAD group had a higher proportion of type IV LAD when compared to non-LAD SCAD (47.6% vs 23.0% p < 0.001). Bifurcation involvement was also more frequent (48.6 vs 25.8%, p <0.001). Individual predictors of an LAD SCAD during follow-up were diagnosis of hypertension, peripartum SCAD, involvement of a bifurcation and type IV LAD. After multivariate analysis, only bifurcation involvement (OR 2.49, p = 0.01) and type IV LAD (OR 2.26, p = 0.02) remained as predictors of LAD SCAD during follow-up. In patients in whom the PDA perfused the apex (LAD I and II), PDA was more likely to be involved by SCAD (OR 6.17, p<0.001). There were no other differences in coronary distribution after stratifying by LAD types. Conclusions: Type IV LAD variant is more common in patients with LAD SCAD. This finding suggests that coronary anatomic variants predispose to SCAD and lend further support to the mechanical distortion hypothesis.

Abstract Background Concern for acute kidney injury (AKI) after percutaneous coronary intervention (PCI) is a major determinant in the decision to pursue cardiac catheterization if otherwise indicated. A bedside AKI risk prediction model derived from the National Cardiovascular Data Registry (NCDR), most recently updated in 2023, employs relatively complex parameters for AKI prediction. Purpose To test the efficacy of a simplified pre-procedural 5-variable bedside score for post-PCI AKI prediction based on the NCDR model. Methods We analyzed our institution’s NCDR-reported catheterization laboratory registry between Q2 2022 and Q1 2023. Inclusion criteria, variable selection, and definitions were based on the NCDR model. A bedside prediction model was validated, including 5 pre-procedural variables: anemia (hemoglobin &lt;10 mg/dl), history of heart failure, stage 4 or 5 chronic kidney disease (glomerular filtration rate &lt;30 mg/dl), cardiac arrest, and shock status. Results We included 840 patients, of which 593 (70.6%) were men. Mean age was 69 (±12.5). Most procedures were performed on an urgent basis (444, 52.9%). AKI developed in 107 (12.7%) patients. Compared to the non-AKI group, patients who developed AKI were older (age 74±11.5 vs 68.3 ±12.5), and more frequently had anemia (23.6% vs 7.4%), diabetes (51.4% vs 35.2%), severe frailty (45.8% vs 23.7%), heart failure (62.6% vs 29.7%), cardiac arrest (13.1% vs 2.9%), CKD (30.8% vs 6%), shock (12.1% vs 1.5%), and mechanical circulatory support (7.5% vs 2.9%), p&lt;0.001. Utilizing integer scores, the simplified bedside model employing 5 pre-procedural variables demonstrated discrimination similar to the bedside NCDR model, with a C-statistic of 0.77 (0.60-0.88) and excellent calibration (intercept of 0.31 and slope of 1.03) (Figure), indicating the robust performance of the model (compared to bedside NCDR model with a C-statistic 0.793, intercept of -0.197, and slope of 0.957). Conclusion A simplified NCDR-based bedside score using 5 pre-procedural variables is an effective tool for predicting AKI as a complication of PCI, with comparable performance to the 2023 updated bedside NCDR AKI risk model.

ImportanceGreater splanchnic nerve ablation may improve hemodynamics in patients with heart failure and preserved ejection fraction (HFpEF).ObjectiveTo explore the feasibility and safety of endovascular right-sided splanchnic nerve ablation for volume management (SAVM).Design, Setting, and ParticipantsThis was a phase 2, double-blind, 1:1, sham-controlled, multicenter, randomized clinical trial conducted at 14 centers in the US and 1 center in the Republic of Georgia. Patients with HFpEF, left ventricular ejection fraction of 40% or greater, and invasively measured peak exercise pulmonary capillary wedge pressure (PCWP) of 25 mm Hg or greater were included. Study data were analyzed from May 2023 to June 2024.InterventionSAVM vs sham control procedure.Main Outcomes and MeasuresThe primary efficacy end point was a reduction in legs-up and exercise PCWP at 1 month. The primary safety end point was serious device- or procedure-related adverse events at 1 month. Secondary efficacy end points included HF hospitalizations, changes in exercise function and health status through 12 months, and baseline to 1-month change in resting, legs-up, and 20-W exercise PCWP.ResultsA total of 90 patients (median [range] age, 71 [47-90] years; 58 female [64.4%]) were randomized at 15 centers (44 SAVM vs 46 sham). There were no differences in adverse events between groups. The primary efficacy end point did not differ between SAVM or sham (mean between-group difference in PCWP, −0.03 mm Hg; 95% CI, −2.5 to 2.5 mm Hg; P = .95). There were also no differences in the secondary efficacy end points. There was no difference in the primary safety end point between the treatment (6.8% [3 of 44]) and sham (2.2% [1 of 46]) groups (difference, 4.6%; 95% CI, −6.1% to 15.4%; P = .36). There was no difference in the incidence of orthostatic hypotension between the treatment (11.4% [5 of 44]) and sham (6.5% [3 of 46]) groups (difference, 4.9%; 95% CI, −9.2% to 18.8%; P = .48).Conclusions and RelevanceResults show that SAVM was safe and technically feasible, but it did not reduce exercise PCWP at 1 month or improve clinical outcomes at 12 months in a broad population of patients with HFpEF.Trial RegistrationClinicalTrials.gov Identifier: NCT04592445

Abstract Aims Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as they often have increased high-sensitivity cardiac troponin T (hs-cTnT) concentrations. Methods and results Observational US cohort study of emergency department patients undergoing hs-cTnT measurement. Cases with ≥1 hs-cTnT increase &gt; 99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2 h hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (estimated glomerular filtration rate &lt; 60 mL/min/1.73 m2). The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 75 (15%) and 350 (70%) patients with CKD and 80 (5%) and 351 (24%) without CKD who had acute MI and myocardial injury. In CKD patients with baseline hs-cTnT thresholds of ≥52, &gt;100, &gt;200, or &gt;300 ng/L, positive predictive values (PPVs) for MI were 36% (95% CI 28–45), 53% (95% CI 39–67), 73% (95% CI 50–89), and 80% (95% CI 44–98), and in those without CKD, 61% (95% CI 47–73), 69% (95% CI 49–85), 59% (95% CI 33–82), and 54% (95% CI 25–81). In CKD patients with a 2 h hs-cTnT delta of ≥10, &gt;20, or &gt;30 ng/L, PPVs were 66% (95% CI 51–79), 86% (95% CI 68–96), and 88% (95% CI 68–97), and in those without CKD, 64% (95% CI 50–76), 73% (95% CI 57–86), and 75% (95% CI 58–88). Conclusion Diagnostic performance of standard baseline and serial 2 h hs-cTnT thresholds to rule-in MI is suboptimal in CKD patients. It significantly improves when using higher baseline thresholds and delta values.

Introduction: We aim to elucidate the incidence of major complications related to right heart catheterization (RHC) and ascertain if there are unique risks with right ventricular biopsy. Methods: Diagnostic RHC procedures from 1/1/2002 through 12/31/2013 were identified using the clinical scheduling system at Mayo Clinic, Rochester. Major complications were identified through electronic records using International Classification of Diseases, Ninth Revision billing codes. All events were recorded and adjudicated. Analysis was performed on four separate patient categories (RHC/RV angiography alone, RV biopsy alone, multiple RHC procedures, and concurrent RHC/LHC procedures) and the overall group. Primary outcomes are described in Table 1. Outcomes were measured within 7 days of the procedure, except for death (same day events) and tricuspid regurgitation (variable time endpoints). Results: There were 17,696 RHC procedures (5,556 RHC/RV angiography, 3,846 RV biopsy alone, 776 multiple RHC procedures, and 7,518 combined RHC/LHC). Patient population had a mean age of 56.5 years (15.3) and was predominantly male (58.5%). Same-day death related to RHC procedure occurred in 1 procedure or 0.6 of 10,000 RHCs. There was no significant difference in the risk of complications across RHC procedure categories except for worsening tricuspid regurgitation, which was significantly (p<0.001) more prevalent with RV biopsy (392 cases, 6.0%) than without (136 cases, 1.2%). Conclusion: The incidence of major complications related to right heart catheterization is rare. Worsening tricuspid regurgitation is the most frequently identified change with a significantly higher prevalence with biopsies.

Introduction: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of acute coronary syndrome. While most patients are managed conservatively, some patients may require percutaneous or surgical revascularization. Limited data exist on SCAD patients referred for coronary artery bypass graft (CABG) surgery. Hypothesis: Examine the clinical characteristics, management, and outcomes of SCAD patients referred for CABG. Methods: Retrospective study of patients enrolled in the Mayo Clinic SCAD Registry between 2010-2020 who underwent CABG during the initial management of acute SCAD episode. Results: Among the 81 patients with SCAD referred for CABG, 3 (4%) were men, mean age was 40.6 +/- 8.4 years; the majority were white (91%), and 24 (30%) had pregnancy-associated SCAD (P-SCAD). The most common presenting symptom was chest pain 80 (99%); 57 (70%) presented with ST elevation myocardial infarction (STEMI), and 21 (26%) presented with non-ST elevation MI. Multivessel dissection occurred in 40 (49%), left anterior descending artery (LAD) involvement occurred in 66 (81%) and left main (LM) in 32 (40%). Left ventricular ejection fraction was <50% in 40 patients (49%) at time of initial SCAD. The most common reasons for CABG were the presence of high-risk anatomy (56%), hemodynamic instability/active ischemia (7%), failed PCI (9%), and other/unknown (12%). Most patients received venous plus arterial bypass grafts 42 (52%), saphenous vein grafts in 20 (25%), and left internal mammary artery in 17 (21%). Screening for underlying arteriopathy was performed in 50 (62%) of whom 29 (36%) had fibromuscular dysplasia. Recurrent SCAD occurred in 10 (12%) after an average of 6.2 +/- 5 years after initial SCAD. Of those with recurrent SCAD, none required repeat surgical revascularization and 6 required percutaneous intervention (PCI). There were no deaths. Conclusions: Patients undergoing CABG for SCAD commonly present with STEMI, LM, or multivessel dissection, and failed percutaneous intervention attempts. In addition, CABG for P-SCAD was more frequent than expected and may relate to the increased prevalence of multivessel dissection. CABG was associated with low mortality, but recurrent SCAD may still occur.

Introduction: Survivorship needs to be comprehensively evaluated amongst older adults. We examined follow-up mortality in patients referred to cardiac catheterization laboratory by prospectively examining frailty. Methods: Frailty in 923 patients ≥55 years was determined using Rockwood’s deficit index. The frailty deficit was based on symptoms, signs, disabilities, diseases, and laboratory measurements. The number of deficits was expressed as a proportion of the total measured deficits. Frailty index was grouped into <0.10 (control), 0.10-<0.20, 0.20-<0.30, 0.30+ and age- and gender-adjusted follow-up mortality was determined using a Cox proportional hazards model. Results: There were 180 (20%) with frailty index <0.10, 348 (38%) in 0.10-<0.20, 215 (23%) in 0.20-<0.30 and 177 (19%) with an index of 0.30 or higher. Patients with a frailty index of 0.30+ were significantly older than those with an index <0.10 (75 ± 10 vs 67 ± 8 years; p<0.001) and more likely to be women (50% vs 20%; p<0.001). Patients with frailty index ≥0.20 and ≥0.30 had a significantly higher mortality risk (HR 3.95, 95% CI 1.51-10.3 and HR: 10.3, 95% CI 4.11-25.7, respectively) on follow-up which remained significant following adjustment for age and gender (HR 3.20, 95% CI 1.21-8.45 and HR: 7.99, 95% CI 3.13-20.4). Conclusions: Among older adults refereed to catheterization laboratory, frailty deficit index predicts follow-up mortality.