Kane, G C

Abstract Background Exercise stress echocardiography (ESE) is recommended in patients with mitral regurgitation (MR) when resting echocardiographic findings and symptoms do not align. However, the role of MR assessment in patients undergoing ESE for any indication remains uncertain. Purpose This study aimed to investigate whether the assessment of MR during ESE provides prognostic value beyond the evaluation of inducible regional wall motion abnormalities (RWMA) in patients undergoing ESE for any clinical indication, including suspected coronary artery disease (CAD). Methods Data were analyzed from a large multicenter and multinational prospective study. Current analysis included patients who underwent ESE for any indication and had MR (from 0= absent, to 3= severe) assessed at rest and peak exercise with an integrated qualitative, semi-quantitative, and (in selected cases) quantitative assessment. The primary endpoint was all-cause mortality. Results Of 1,351 included patients (age 56±16 years; 66% women; 30% with known CAD). MR score increased during exercise (rest=0.74±0.7 vs. peak=0.89±0.8, p<0.001), with severe MR present in 2% of patients at rest and 7% at peak ESE. Patients with severe MR during exercise (n=96, Group 1) compared to those with non-severe MR during exercise (n=1255, Group 2) showed more B-lines, lower left ventricular contractile and chronotropic reserve, and trend (p=0.09) to more frequent decrease in ejection fraction during ESE (Table 1). After a median follow-up of 2.1 years (IQR 1.0–6.9), 99 patients (7%) had died. Severe MR at rest was associated with increased mortality (log-rank p<0.001). Patients with severe MR at peak ESE had a higher risk of death compared to the other patients (log-rank p 0.035) (Figure 1). After adjusting for age, CAD, and inducible RWMA, severe MR with exercise remained strongly associated with an increased risk of death (adjusted-HR: 2.2, 95%CI 1.3-3.8, p=0.002). Similar results were seen with further adjustment for rest MR severity (adjusted-HR:1.9, 95%CI 1.02-3.5, p=0.004). Conclusion Patients, with and without CAD, with severe MR during ESE have greater functional impairment expressed by more pulmonary congestion, blunted heart rate reserve, and lower left ventricular contractile reserve. The assessment of MR during ESE provides significant prognostic information, independent of resting RWMA or inducible ischemia. Incorporating MR evaluation into routine ESE protocols may improve clinical decision-making and patient outcomes.Fig 1 Survival by MR at peak exercise Table 1

Abstract Background Chronotropic incompetence (CI) is a biomarker of cardiac autonomic dysfunction. Aim To assess the risk stratification value of CI during physical or pharmacological stress echocardiography in patients with chronic coronary syndromes. Methods In a prospective, multicenter, international, observational study design, we enrolled 13,445 patients with known or suspected chronic coronary syndromes who underwent stress echo in 19 sites from 10 countries using either exercise (n=2,594), dobutamine (n=2,440), or dipyridamole (n=8,411). Heart rate was automatically measured from the 1-lead ECG in the echo monitor. We considered CI as failure to reach 85% of the maximal predicted (220-age) heart rate for exercise and dobutamine, and heart rate reserve (peak/rest heart rate) <1.22 (<1.17 in permanent atrial fibrillation) for dipyridamole. All-cause death was the outcome measure. Results Heart rate reserve was available in all patients; there was no extra imaging or analysis time, and no intra- and inter-observer variability. CI was observed in 5,045 patients (38%); abnormal regional wall motion abnormality in 1,648 (13%). Over a median follow-up time of 3.5 years, there were 2,426 (18%) deaths. The 10-year mortality was 39% in patients with and 21% in patients without CI (p<0.0001). CI was associated with a significant (p<0.0001) increase in 10-year mortality in all age groups ranging from <54 years to >75 years. In addition, it was associated with increased mortality (p<0.0001) irrespective of β-blocker use (Figure). Cox multivariable analysis revealed that CI was a significant predictor of mortality (HR 1.60, 95% confidence interval 1.47-1.74; p<0.0001) together with age, male sex, diabetes mellitus, ejection fraction, and resting heart rate. Conclusion In patients with chronic coronary syndromes, CI during physical or pharmacological stress is a simple, inexpensive, quantitative, and objective predictor of survival.

Abstract Background Left ventricular diastolic function (LVDF) and left bundle branch block (LBBB) are both linked with increased risk of LV systolic dysfunction, heart failure, and mortality. Assessing LVDF, which is typically done through echocardiography, becomes challenging in the presence of LBBB due to the intraventricular conduction delay that disrupts the reliability of tissue Doppler imaging. Recently, we validated an artificial intelligence-enabled electrocardiogram (AI-ECG) model to assess LVDF and filling pressures. Methods We performed a retrospective study among patients with ECG-confirmed LBBB who also underwent comprehensive echocardiography within 14 days of the index ECG between September 2001 and June 2022. Using multivariable survival models, we assessed the risk of all-cause mortality across AI-ECG-derived LVDF grades. Results Of 2,554 patients with LBBB (mean age 72.0+12.6, 54.6% women), 252 (9.8%), 656 (25.7%), and 1,436 (56.2%), and 210 (8.2%) had normal LVDF, G1 LVDF, G2 LVDF, and G3 LVDF, respectively. The median LV ejection fraction (LVEF) was 54% and 49.3% of the patients had heart failure. Worse LVDF was associated with older age, lower LVEF, and higher rates of diabetes, hypertension, chronic pulmonary disease, renal failure, cardiovascular disease, and heart failure (p-of-trend<0.001 for all). During a median follow-up of 2.6 years (interquartile range 0.5-4.0 years), 847 (33.2%) patients died. In multivariable survival analysis, adjusted to multiple risk factors including baseline LVEF and heart failure, worse LVDF was independently associated with a higher risk of death [G1 LVDF: adjusted hazard ratio (aHR) 2.15 (95% confidence interval (95%CI) 0.75-1.77), G2 LVDF: aHR 2.25 (95%CI 1.50-3.38) G3 LVDF: aHR 2.96 (95%CI 1.88-4.65); p<0.001 for both)]. These findings were consistent also in a subgroup of patients with baseline LVEF > 50%. Conclusion Among patients with LBBB, worse LVDF, as derived by a dedicated AI-ECG algorithm is independently associated with all-cause mortality beyond baseline LVEF and clinical heart failure.survival across AI-ECG LVDF grades

Abstract Background Ischemic mitral regurgitation (IMR) is a common complication of coronary artery disease (CAD), often occurring after myocardial infarction (MI). Even when moderate in severity, IMR is associated with adverse outcomes, including a twofold increase in mortality rates. Aim To assess the functional correlates of resting IMR during stress echocardiography (SE) in patients with CAD. Methods This prospective multicenter study included 192 patients with CAD (143 males; mean age 65 ± 10 years) from eight cardiology institutions. Exclusion criteria included a history of coronary artery bypass surgery, more than moderate IMR, and other significant valvular diseases. Patients were divided into two groups based on semiquantitative- quantitative assessment at rest based on EACVI-ASE criteria: Group 1: Patients with moderate IMR, Group 2: Patients without IMR or with trivial IMR. All patients underwent stress echocardiography (SE) using the ABCE protocol. Patients underwent exercise tests, if execise echocardiography was not possible, dobutamine stress tests were performed. At rest and peak SE, we assessed: Left atrial volume index (LAVi), Left ventricular end-diastolic (LV EDV) and end-systolic volumes (LV ESV), ejection fraction (EF), wall motion score index (WMSI), global longitudinal strain (GLS), B-lines (4-site simplified scan), tricuspid annular plane systolic excursion (TAPSE), systolic pulmonary artery pressure (SPAP), LV contractile reserve (LVCR) and heart rate reserve (HRR). Results Despite similar EF at rest, Group 1 patients showed more pronounced functional impairment at rest, which increased during stress. Stress-induced functional worsening affected indices of MR (more frequently becoming severe), ischemic burden (WMSI), diastolic function (LAVI and LVEDV dilation), LV systolic function (LVCR), pulmonary congestion (B-lines), cardiac sympathetic reserve (reduced HRR) and right ventricular/pulmonary artery coupling (reduced TAPSE/SPAP): table 1. Conclusion Compared to CAD patients with absent-to-trivial resting IMR, patients with moderate IMR at rest show a constellation of functional vulnerabilities during SE involving more frequent exercise-induced worsening of MR, blunted LV diastolic and systolic reserve, more pulmonary congestion, impaired cardiac autonomic reserve, and worse right ventricular-pulmonary artery coupling. The individual patient's functional response heterogeneity can be identified with comprehensive exercise SE, possibly a roadmap to personalized and targeted therapeutic interventions.