Kane, Garvan C.

Background: Aortic regurgitation (AR) is a prevalent valve disease with a long latent period to symptoms. Recent data has suggested the role of novel markers of myocardial overload in assessing onset of decompensation. Method: We sought to evaluate the role of unsupervised cluster analyses in identifying different clinical clusters, including clinical status, and a large number of echocardiographic variables including left ventricular (LV) volumes, and their association with mortality. Patients with ≥moderate-severe chronic AR identified using echocardiography at Mayo Clinic, Rochester were retrospectively analyzed. Primary outcome was all-cause mortality censored at aortic valve surgery/last follow-up. Uniform Manifold Approximation and Projection (UMAP) with K -means algorithm was used to cluster patients using clinical and, echocardiographic variables at the time of presentation. Missing data were imputed with the Multiple Imputation by Chained Equations (MICE) method. A supervised approach trained on the training set was used to find cluster membership in a hold-out validation set. Log-rank tests were used to assess differences in mortality rates between the clusters, both in the training and validation sets. Results: Three distinct clusters were identified among 1100 patients (log-rank P for survival <0.001). Cluster 1 (n=337), which included younger males with severe AR but fewer symptoms, showed the best survival, 75.6% (69.5, 82.3). Cluster 2 (n=235), older and more females with elevated filling pressures, showed intermediate survival of 64.2 % (56.8, 72.5). Cluster 3 (n=253), characterized by severe symptomatic AR, demonstrated the lowest survival of 45.3 % (34.4, 59.8) at 5 years. Similar clusters were formed in the internal validation cohort. Conclusion: Distinct clusters with variable echocardiographic features and mortality differences exist within patients with chronic ≥moderate-severe AR. Recognizing these clusters can refine individual risk stratification and clinical decision-making after verification in future prospective studies.

Background: Left ventricular diastolic dysfunction (LVDD) predicts mortality in cardiac intensive care unit (CICU) patients. A novel artificial intelligence enhanced electrocardiogram (AIECG) algorithm can predict LVDD and mortality in general populations but has not been examined in the cardiac intensive care unit (CICU). We aim to assess if LVDD by AI-ECG is associated with in-hospital and one-year mortality in CICU patients. Methods: In this retrospective cohort study, we included consecutive unique adults admitted to the Mayo Clinic CICU from 2007 to 2018 with an admission AIECG, which AI assigned LVDD grade (0 to 3). Medial mitral E/e’ ratio >15 on transthoracic echocardiogram (TTE) defined elevated filling pressures. AIECG and TTE assessment of LVDD were used to assign patients to four groups based on TTE as gold standard: true and false negative, and true and false positive. In-hospital mortality was evaluated using multivariable logistic regression. One-year survival was evaluated using Kaplan-Meier curves and multivariable Cox proportional-hazards. Results: We included 11,868 patients (median age 69.5 years, 37.7% females); 48% had heart failure and 44% had acute coronary syndromes. AIECG LVDD grades were: grade 0 (normal), 33%; grade 1, 7%; grade 2, 39%; grade 3, 21%. In-hospital (adjusted OR) and one-year (adjusted HR) mortality increased in each higher AIECG LVDD grade (Figure A/B), before and after adjustment including TTE measurements. Patients with grade 2-3 LVDD by AIECG and medial mitral E/e’ ratio >15 by TTE (true positive) had the highest in-hospital (adjusted OR 2.5 [1.7-3.9]) and one-year (adjusted HR 1.9 [1.5-2.5]) mortality (Figure C/D), and mortality was elevated similarly in patients with either grade 2-3 LVDD by AIECG (false positive) or medial mitral E/e’ ratio >15 by TTE (false negative). Conclusions: The AIECG LVDD grade was strongly associated with in-hospital and one-year mortality in CICU patients, even after adjusting for clinical variables and TTE measurements. Patients with concordant AIECG and TTE for elevated filling pressures (true positive) were at highest risk.

Abstract Background Heart failure (HF) and atrial fibrillation (AF) are intertwined, sharing common risk factors and influencing each other in a reciprocal manner. While left ventricular diastolic dysfunction (LVDD) stands as a hallmark of HF's hemodynamic profile, its direct correlation with heightened AF risk remains uncertain. Our recent validation of an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm for LVDD detection has opened new avenues. Yet, whether AI-ECG-detected LVDD correlates with long-term AF risk remains unexplored. Methods We performed a retrospective study among all patients with a comprehensive LVDD assessment from the test population of the AI-ECG LVDD study between September 2001 and June 2022. Patients with prior documented AF according to health records or previous ECG were excluded. Patients were classified by AI-ECG as normal diastolic function (DF), grade 1 (G1), grade 2 (G2), or grade 3 (G3) LVDD. We assessed the risk of AF across AI-ECG LVDD grade, with normal DF as reference, with competing risk models. Results Of 97,023 patients free of AF at baseline, 63,533 (65.4%), 10,776 (11.1%), 18,940 (19.5%), and 3,774 (3.9%) were classified as normal DF, G1-LVDD, G2-LVDD, and G3-LVDD, respectively. Worse AI-ECG LVDD was associated with older age, lower left ventricular ejection fraction (LVEF), and higher rates of HF, diabetes, hypertension, chronic pulmonary disease, renal failure, and cardiovascular disease (p-of-trend&lt;0.001 for all). Over a median follow-up of 4.8 years (interquartile range 1.8-9.2 years), new-onset AF occurred in 6,795 (7.0%) patients. In multivariable survival analysis, adjusted to multiple risk factors including LVEF and clinical HF, G2 and G3 LVDD, representing patients with high filling pressures, were independently associated with a higher AF-risk [G2-LVDD: adjusted hazard ratio (aHR) 1.64 (95% confidence interval (95%CI) 1.52-1.73), G3-LVDD: aHR 2.24 (95%CI 2.02-2.48)]. Conclusion The AI-ECG LVDD algorithm independently predicts long-term AF risk, regardless of LVEF and clinical HF status, highlighting its potential for identifying high-risk populations and guiding proactive monitoring and management.

Abstract Background The determination of left ventricular diastolic dysfunction (LVDD) and filling pressure in patients with significant (&gt;moderate) mitral regurgitation (MR) poses a complex challenge. We recently validated an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm to detect LVDD and estimate LV filling pressures. Methods This retrospective study sought to examine the risk of all-cause mortality across AI-ECG LVDD grades. Patients from the AI-ECG LVDD study test cohort who underwent transthoracic echocardiography confirming significant MR and an ECG within fourteen days of each other at Mayo Clinic between 09/2001 and 06/2022 were included. LVDD status was determined based on the index ECG, and patients were categorized into groups representing normal diastolic function (NDF) or LVDD grades 1 (G1), 2 (G2), or 3 (G3). Results Of 4,019 patients with significant MR (mean age 69.8, 49.0% women), 1,175 (29.2%), 1,881 (46.8%), and 963 (24.0%) were classified by AI-ECG as NDF/G1-LVDD, G2-LVDD, and G3-LVDD, respectively. The median mitral effective regurgitant orifice area was 26 mm² (interquartile range 20-36 mm²). Over a median follow-up of 3.5 years, 1,636 (40.7%) patients died. In multivariable survival analysis adjusted for multiple risk factors, a worse AI-ECG LVDD grade was independently associated with an increased death risk [G2DD: adjusted hazard ratio (aHR) 1.98 (95% confidence interval (95% CI) 1.63-2.40), G3DD: aHR 2.59 (95% CI 2.09-3.20)]. These findings were consistent when accounting for mitral valve intervention and among patients with &gt;moderate MR or after mitral valve intervention. Conclusion In patients with significant MR, the grading of LVDD by AI-ECG is independently associated with all-cause mortality.

Cardiac sonographers are frequently exposed to ergonomic risks such as postural stress and high levels of physical exertion while performing scanning tasks, contributing to work-related pain, and discomfort among cardiac sonographers. Passive exoskeletons are a potential ergonomic intervention with the potential to mitigate some of the risks associated with scanning. This study examined the effectiveness of a passive upper body exoskeleton in reducing the levels of work-related pain, discomfort, and workload in cardiac sonographers while performing transthoracic echocardiograms (TTE). Twelve cardiac sonographers were asked to use the HAPO FRONT exoskeleton while performing TTEs during a full workday. Participants were asked to rate their body part discomfort and workload throughout the day, both with and without the exoskeleton. The exoskeleton did not significantly decrease discomfort or workload associated with performing TTEs, except for a slight reduction in the discomfort at the left hand/wrist. This result indicates that the HAPO FRONT was not effective or appropriate for use by cardiac sonographers. Future development and study of purpose-designed exoskeletons for healthcare applications may provide greater benefits to cardiac sonographers.

Introduction: The predictive value of left atrial (LA) volume and reservoir function (ResF) post-atrial fibrillation (AF) ablation has been scarcely studied. Hypothesis: Abnormal LA volume and ResF post-ablation are associated with adverse cardiovascular events. Methods: We analyzed LA maximum (LAVImax) and minimum (LAVImin) volume index, and 2 measures of ResF, emptying fraction (LAEF) and expansion index (LAEI), prospectively measured at 3-month post-procedure in patients in sinus rhythm who underwent AF ablation between 2007-2016. Composite endpoint (CE) at follow up was all-cause mortality, cardiac hospitalization (heart failure or acute ischemic event) and stroke. Results: 792 patients were studied ( age 60±10 years, 25% women ; Table 1) . Over 7.5 years [IQR 3.0-9.7], 96 (12%) patients experienced CE, which was more prevalent in patients with enlarged LA and reduced ResF. Impaired LA volumes and ResF were each independently associated with CE ( Fig.1 ), even after adjustment for clinical, demographic and echo characteristics (Model A, Fig.2 ) (LAVImax ≥35 ml/m 2 : HR 2.15 [95% CI, 1.35-3.43], p=0.001; LAVImin≥20.5 ml/m 2 : HR 2.88 [1.77-4.69], p<0.0001; LAEF<39%: HR 2.00 [1.31-3.05], p=0.001; LAEI<65%: HR 1.95 [1.27-3.01], p=0.003). ResF measures (LAEF and LAEI) were incremental to LAVImax (all p<0.05), but not LAVImin (all p>0.05; Fig.2 ). In patients with normal LA (LAVImax <35 ml/m 2 ; n=408), increased LAVImin (≥20.5 ml/m 2 ) remained associated with CE (HR 3.11 [1.45-6.67], p=0.004) and cardiac hospitalization (HR 5.81 [1.87-18.01], p=0.002). These findings were independent of AF recurrence. Conclusions: In these patients, enlarged LA and impaired ResF at 3-month post-ablation were strongly associated with adverse cardiovascular outcomes, regardless of AF recurrence. Measures of LA ResF were incremental to LAVImax. Notably, LAVImin showed the strongest associations and even identified a high-risk subgroup among patients with non-dilated LA.

Background: A community based, cross-sectional echo survey demonstrated that pulmonary artery systolic pressure (PASP) increases with age and that PASP is associated with systemic arterial stiffness, Doppler estimated left ventricular (LV) filling pressures and lung function. Longitudinal assessment of PASP is needed to confirm cross-sectional observations. Objectives: To assess the whether PASP changes over time in longitudinally studied subjects and determine whether changes in PASP are associated with changes in systemic vascular stiffness, LV filling pressures or lung function. Methods: A random sample (n=2042) of the Olmsted County, MN population over age 40 underwent echo, record review and spirometry between 1997-2000 (Exam 1). A subset (n=1402) underwent repeat studies four years later (2001-2004; Exam 2). The current analysis includes the 723 subjects with paired PASP measurements. Changes ([[Unable to Display Character: ▵]]) in PASP, systemic arterial stiffness (pulse pressure; PP), LV filling pressure (E/e’) and lung function (% age/sex expected forced expiratory volume, %FEV1) were assessed. Results: At Exam 1, the median (interquartile range) age was 62 (69-70) years (62% female). Median time between exams was 48 (47-49) months. PASP increased from 26.1 (24.4-30.0) mmHg at Exam 1 to 28.0 (24.4-32.0) mmHg at Exam 2 (p<0.0001 by paired t test) for an average (SD) [[Unable to Display Character: ▵]] of 1.2 ± 5.5 mmHg. Adjusting for age and PASP at Exam 1, [[Unable to Display Character: ▵]]PASP was associated with [[Unable to Display Character: ▵]] age with an increase (parameter estimate (pe) ± standard error (se)) of 1.4±0.7 mmHg per year increase in age (p=0.046). [[Unable to Display Character: ▵]]PASP was not associated with sex and there was no age-sex interaction. Adjusting for age and PASP at Exam 1, [[Unable to Display Character: ▵]] age and Exam 1 values for PP, E/e or %FEV1 as appropriate, [[Unable to Display Character: ▵]]PASP was associated with [[Unable to Display Character: ▵]] PP (pe±se = 0.03±0.01 mmHg; p=0.01) [[Unable to Display Character: ▵]]E/e’ (pe±se = 0.21±0.06 mmHg, p=0.001) and [[Unable to Display Character: ▵]]%FEV1 (-0.09±0.02 mmHg, p<0.0001) suggesting that increases in PASP were related to increases in vascular stiffening, increases in LV filling pressures and declining lung function. Conclusions: In this longitudinal, population based study we find that PASP increases with aging and that increases in PASP over time are related to increases in systemic vascular stiffness and LV filling pressures and decreases in lung function.

Background: Impact of right ventricular (RV) overload on left ventricular (LV) performance has been demonstrated in Ebstein’s anomaly (EA). We have shown that LV radial strain (RS) in 83 EA patients was significantly less than in controls. We subsequently sought to evaluate LV strain after EA surgery. Methods: Systolic strain, strain rate (SR) and early diastolic strain rate (SRe) were retrospectively performed, using velocity vector imaging, in 24 repaired EA patients (age 35 ±12 years; 67% women) with LV ejection fraction >50%, preoperatively (median 5 days [1-145 days]) and postoperatively within 5 years at sequential follow-up (6 months-3 years). Repair of EA included tricuspid valve repair, valve replacement and bidirectional cavopulmonary anastomosis. A slope of change postoperatively was estimated for each subject using linear regression. A one-sample t-test of the mean slope=0 assessed average change per year. Results: Mean (standard deviation) and median (range) of preoperative LV RS was 36.5 +/- 11.4% and 36.3% (16.8-59.8) respectively. LV strain analyses are summarized in tables 1 and 2. Conclusions: LV RS improved significantly after EA surgery whereas circumferential strain (CS), SR and radial SR did not. This may reflect the change in RV and subsequently LV geometry after resolution of tricuspid regurgitation with EA surgery. Ongoing evaluation with deformational imaging may help to characterize if these changes are compensatory or maladaptive and may determine optimal timing for surgery. In the subgroup with the lowest RS, significant improvement postoperatively was not seen. This may suggest that surgery was performed too late to allow favorable remodeling.

Background: Non-cardiac surgery (NCS) in patients with severe aortic stenosis has traditionally been associated with high perioperative mortality. Aortic valve replacement is recommended prior to elective NCS, but the impact of this strategy has not been systematically assessed. Methods: A retrospective review was performed of all patients with severe aortic stenosis undergoing major NCS at Mayo Clinic between 2000 and 2013. Patients undergoing aortic valve intervention (AVI) prior to NCS were compared to those undergoing surgery without prior AVI (control). Patients undergoing emergency surgery were excluded. Primary endpoint was occurrence of major adverse cardiac events (MACE; combination of death, stroke, myocardial infarction, new/worsening heart failure, ventricular arrhythmia) within 30 days of NCS; secondary endpoints were mortality at 30 days and 1 year after NCS. Results: 180 patients (age 74.5 ± 10.5 years, 64% male) who underwent NCS within 12 months after AVI, were compared to 232 patients (age 76.6 ± 10.7 years, 56% male) in the control group. Patients undergoing AVI were more often symptomatic than controls (41% vs 26%, p = 0.002). MACE was significantly higher in the control group (21.6% vs 5.6%, p < 0.001), mainly due to the increased risk of heart failure in the postoperative period in this group (18.5% vs 2.2%, p < 0.001). There was no significant difference in the rate of myocardial infarction (1.7% vs 0.6%, p = 0.39), ventricular arrhythmia (0.9 % vs 0 %, p = 0.51) or stroke (0.9 % vs 0 %, p = 0.51). Kaplan-Meier assessment demonstrated no significant difference at 30 days but a reduction in 1 year mortality in the AVI group compared to the control group (Figure). Conclusions: Pre-operative AVI for severe aortic stenosis results in reduced heart failure and improved 1 year survival. However, other MACE and 30 day mortality appears unchanged. Pre-operative AVI should be considered in symptomatic patients, where the benefit of AVI is demonstrated to be greatest.

Introduction: Creation of an atrial septal defect via atrial septostomy (AS) is a therapeutic option traditionally utilized for PAH in settings where medical therapy was unavailable. Its utility in the context of progressive disease despite medical therapy remains incompletely understood. Hypothesis: AS may be a useful option in patients with symptomatic PAH despite medical therapy and may improve functional class. Methods: Single center retrospective study of all adult PAH patients receiving AS at a tertiary PAH referral center. Results: Eleven atrial septostomy procedures were performed in 8 patients who were refractory to maximal medical management. All patients were WHO functional class III or IV and average patient age was 40 ± 13 years with a female predominance (89%). Mean RA pressure was 18 ± 4 mm Hg with cardiac index of 2.28 ± 0.82 L/min/m 2 prior to AS. Mean pulmonary artery pressure was 63 mm Hg with a pulmonary artery saturation of 48% and average systolic blood pressure of 97 mm Hg. Baseline NT-proBNP was 5573 ± 4589 pg/ml with a mean 6 minute walk distance (6MWD) of 311 ± 131 meters. Five of the 11 procedures resulted in functional class improvement. Functional class change did not relate to change in 6MWD or NT-pro BNP level. Three patients had repeat AS due to spontaneous narrowing of the original septostomy, with a mean duration of 220 ± 135 days between procedures. One patient died within 30 days of the procedure and another at day 88 while one patient received a heart/lung transplant at day 42 post AS. Mean follow up was 243 ± 183 days. The REVEAL risk scores ranged from 10 to 15, with predicted 1 year survival from pre-septostomy clinical data ranging from 22% to 80% (mean predicted survival of 57%). Actual transplant free survival at 1 year was 63%. Conclusions: Selected patients at high risk for 1 year mortality may receive symptomatic benefit from atrial septostomy. One year mortality remains high, and not significantly different from that predicted by the REVEAL score. Atrial septostomy may be a palliative treatment option for patients who are refractory to maximal medical therapy but further long term investigation is necessary.