Padang, Ratnasari

Abstract Backgrounds Transthoracic echocardiography (TTE) identifies a peculiar hypercontractile phenotype (HP) in patients with heart failure and preserved ejection fraction (HFpEF) with high resting left ventricular (LV) elastance (also called force). Objectives To assess the functional response and its prognosis associated with HP in HFpEF by stress echocardiography (SE). Methods In a prospective, observational, multicenter study, 1213 patients with HFpEF were divided into two groups based on the highest quartile of rest force: non-hypercontractile phenotype group (non-HP, < 5.64 mmHg/mL, Group 1, n= 910), and HP group (≥5.64 mmHg/mL, Group 2, n= 303). All patients underwent SE with at least 4 of the following stress parameters assessed: wall motion score index (WMSI), B-lines (4-site score), force-based LV contractile reserve, coronary flow velocity reserve (CFVR), and heart rate reserve (HRR). The employed stress was exercise (n=687), dobutamine (n=195), or vasodilators (n=331). SE score ranged from 0 (all steps normal) to 1-5, according to the number of abnormal steps. Follow-up was completed in a subset of 260 patients. Results The 2 groups showed similar values of peak stress WMSI but the global functional burden was higher in Group 2 patients: see table. In a subset of 260 patients who finished follow-up, there were 212 non-HP patients and 48 HP patients. During a median follow-up of 15 months (interquartile range: 10-20), 26 deaths, 20 heart failure (HF) rehospitalizations, and 64 major adverse cardiovascular events (MACEs) occurred. The cumulative HF rehospitalization rate and MACEs rate were higher in HP group (log-rank p<0.01): see figure. Rest force (HR, 1.17; 95% CI: 1.06-1.29; P: 0.040), rest SPAP (HR, 1.08; 95% CI: 1.02-1.14; P: 0.007) and ABCDE score (HR, 1.15; 95% CI: 1.01-1.66; P: 0.032) were independently associated with MACEs. Conclusions HFpEF patients with HP are functionally weaker with multiple vulnerabilities during stress and at higher risk of subsequent events compared to non-HP patients.Relation between resting values of force

Abstract Aims Chronotropic incompetence (CI) is a biomarker of cardiac autonomic dysfunction. The aim of the study is to assess the risk stratification value of CI during exercise or pharmacological stress echocardiography in patients with chronic coronary syndromes. Methods and results In a prospective, multicenter, international, observational study, we enrolled 13 445 patients with known or suspected chronic coronary syndromes who underwent stress echocardiography in 19 clinical sites from 10 countries using either exercise (n = 2594), dobutamine (n = 2440), or dipyridamole (n = 8411). Heart rate was automatically measured from the 1-lead ECG in the echocardiography 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 if in permanent atrial fibrillation) for dipyridamole stress. The primary outcome was all-cause death. CI was observed in 5045 patients (38%) and stress-induced regional wall motion abnormalities in 1648 (13%). Over a median follow-up time of 3.4 years (interquartile range, 1.6–9.1 years), there were 2426 (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 increase in 10-year mortality in all age groups ranging from ≤54 years to ≥75 years (P < 0.0001). In addition, it was associated with increased mortality (P < 0.0001) irrespective of β-blocker use. Cox multivariable analysis revealed that CI was an independent predictor of mortality (HR: 1.60, 95% confidence interval: 1.47–1.74; P < 0.0001) together with age, male sex, diabetes mellitus, left ventricular ejection fraction, and resting heart rate. Conclusion In patients with chronic coronary syndromes, CI during exercise or pharmacological stress is a simple and objective predictor of survival.

Abstract Aims Tricuspid valve regurgitation (TR) is common and associated with increased mortality. The interaction between the pulmonary artery (PA) circulation and the right ventricle (RV) and association with outcomes is incompletely understood. The effective PA elastance (PA Ea) is a composite measure of RV afterload that refers to the pulmonary vascular load that the RV must overcome to eject blood. Whether PA Ea discriminates mortality risk in unselected patients with significant TR is unknown. Methods and results In consecutive patients with ≥moderate TR, we compared all-cause mortality at 5 years based on the PA Ea (defined as the RV systolic pressure/stroke volume as measured by transthoracic echocardiography). In a total of 12 682 patients, the median PA Ea was 0.7 mm Hg/mL (interquartile range 0.5, 0.9). Increasing levels of PA Ea were associated with heart failure, liver and kidney disease, and clinical markers of risk such as the Tricuspid Regurgitation Impact on Outcomes score. Increasing levels of PA Ea were associated with larger RVs, worse RV systolic function, higher N-terminal pro-brain natriuretic peptide levels, and greater degrees of right heart failure. After adjusting for age and sex, PA Ea was associated with higher risk of death (hazard ratio 1.55 per 0.5 mm Hg/mL change of PA Ea; 95% confidence intervals 1.51–1.60; P < 0.0001). In multivariable modelling incorporating available clinical variables, PA Ea was independently predictive of outcome compared with other indexes of RV–PA coupling. Conclusion In patients with significant TR, higher PA Ea is progressively associated with RV dysfunction, right heart failure, and worse survival. Incorporating PA Ea into the routine echo assessment may help stratify risk.

Over the past decade, stress echocardiography has evolved from a test for assessing epicardial artery stenosis to a comprehensive functional test, targeting multiple cardiovascular parameters. The new approach includes several structured steps: (a) evaluating regional wall motion abnormalities to detect epicardial artery stenosis or vasospasm; (b) assessing pulmonary congestion and diastolic function via B-lines with lung ultrasound; (c) gauging preload and contractile reserve with volumetric echocardiography; (d) measuring coronary microvascular reserve using Doppler-based coronary flow velocity in the middistal left anterior descending artery; and (e) determining cardiac sympathetic reserve by tracking heart rate reserve on an ECG. This evolution was supported extensively by the Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI), which played a key role in five areas: (1) developing the initial, curiosity-driven project; (2) disseminating protocols and results at national and international conferences, supporting logistic infrastructure and publication expenses; (3) establishing a digital platform (customized Redcap) for data entry and storage; (4) facilitating patient recruitment across 19 Italian centers; and (5) offering formal endorsement through six presidencies, adding credibility and reach beyond any single institution. The protocol quickly advanced from concept to high-impact publications, earning inclusion in 2024 specialty guidelines. Initially Italian-led, the study now includes 50 centers across 20 countries (e.g. USA and China). Beyond the 50 peer-reviewed papers published in 2016–2024, this study offers a novel, sustainable approach to cardiac stress testing, providing more information at lower costs, with zero radiation and minimal environmental impact. SIECVI’s endorsement was instrumental in amplifying the study’s rigor and outreach.

Abstract Background Heart failure and preserved ejection fraction (HFpEF) is a heterogeneous entity including patients with different phenotypes of reduced, normal, and supernormal left ventricular (LV) function. Objectives To assess the value of resting LV elastance with transthoracic echocardiography (TTE) to identify HFpEF phenotypes. Methods In a prospective, observational, multicenter study, 2380 HFpEF patients were recruited from July 2016 to May 2024 by 35 certified laboratories of 15 countries. HFpEF was diagnosed according to the European Society of Cardiology (ESC) guidelines. Systolic blood pressure (SBP) was measured. We assessed wall motion score index (WMSI), LV end-diastolic volume (EDV), end-systolic volume (ESV), EF, force (SBP/ESV), stroke volume (SV), arterial elastance (AE, SBP/SV), ventricular-arterial coupling (VAC, as SV/ESV), and left atrial volume index (LAVI). Global longitudinal strain (GLS) was available in 1164 (48.9%) patients. In 271 (11.4%) patients, N-terminal pro-brain natriuretic peptide (NT-proBNP) was assessed. Patients were divided into three groups based on rest force: low rest force group (< 25% percentile, Group 1), median rest force group (≥ 25% percentile & ≤ 75% percentile, Group 2), and high rest force group (> 75% percentile, Group 3). Results 330 (13.9%) patients presented with ischemic RWMA. The 3 groups showed a gradient with descending values (Group 3>2>1) for SBP, EF, GLS, AE, and VAC, with the opposite gradient (Group 1> 2> 3) for EDV, EDVi, ESV, ESVi, SV, SVi, and LAVI values (all P<0.01). Patients in Group 3 have higher NTproBNP level and higher percentage of B-line compared to groups 1 and 2 (P<0.05). The 3 groups were similar for values of coronary flow velocity, systolic pulmonary artery pressure, and E/e’ (see table). Univariable linear regression analysis showed that NTproBNP was correlated with force (r = 0.271, p < 0.001), VAC (r = 0.194, p = 0.001), LAVI (r = 0.327, p < 0.001), LVEDV (r = -0.245, p < 0.001), LVEDVi (r = -0.261, p < 0.001), LVESVi (r = -0.190, p = 0.002) and LVESV (r = -0.187, p = 0.002) (see figure). However, multivariable linear regression analysis showed that NTproBNP was independently associated with LAVI (β= 0.211, p < 0.001) and force (β= 1.804, p = 0.002). Conclusions HFpEF patients present with different LV contractile phenotypes, easily identified with resting LV force and volumetric TTE. LV force is linearly correlated with cardiac natriuretic peptide levels. The dominant hemodynamic feature of hypocontractile phenotype is a preload recruitment with dilation of LV EDV and normal SV, while the hypercontractile phenotype is characterized by a small LV with reduced SV. heat map

Abstract Background/Introduction Tricuspid valve regurgitation (TR) is a common valvular disease associated with increased mortality. There is a need for tools to assess the interaction between the pulmonary artery (PA) circulation and the right ventricle (RV) in patients with TR and to investigate their association with outcomes. Various echo parameters have emerged that assess RV-PA coupling, including the ratio of TAPSE to RV systolic pressure (RVSP) and the PA pulsatility index (PAPi). The effective PA elastance (PA Ea) is a composite measure of RV afterload that refers to the measure of the pulmonary vascular load that the RV must overcome to eject blood into the PA. PA Ea is simple to estimate by echo and found to be an independent haemodynamic risk measure in various left heart and pulmonary hypertension (PH) diseases. Whether PA Ea discriminates risk in unselected patients with significant TR and how it compares to other measures of RV-PA coupling is untested. Purpose To ascertain the prognostic value of PA Ea in patients with TR. Methods In consecutive patients with a first diagnosis of ≥ moderate TR (regardless of aetiology), we compared all-cause mortality at five years based on the PA Ea (defined as the RVSP/stroke volume as measured by transthoracic echocardiography). As stroke volume was measured by Doppler at the left ventricular (LV) outflow tract, patients with > moderate aortic valve regurgitation were excluded. The Tricuspid Regurgitation Impact on Outcomes (TRIO) score was calculated as previously described. PA Ea was separated into 4 groups for comparison based on the separation of quartiles of PA Ea rounded to one decimal place. Results In the 13,608 patients studied, PA Ea could be calculated in 12,682 patients (94.4%). The median PA Ea was 0.68 mmHg/mL (IQR 0.50, 0.92). Increasing levels of PA Ea were associated with clinical comorbidities including heart failure, liver and kidney disease and clinical markers of risk such as the TRIO score. Increasing levels of PA Ea were also associated with larger RVs, worse RV systolic function, higher NT-pro BNP levels, and greater degrees of right heart failure (Table). Each quartile of PA Ea was associated with a significant increase in all-cause mortality (Figure). After adjusting for age and sex, PA Ea was associated with higher risk of death (HR 2.41 (2.28-2.56); p<.0001). While worsening degrees of PA Ea correlated with both declining levels of TAPSE/PASP and PAPi (Table), PA Ea was independently predictive of outcome in a combined model: PA Ea HR 1.65 (1.51-1.80, Chi-squ 120, p<.0001); PAPi HR 0.84 (0.80-0.89, Chi-squ 48, p<.0001) and TAPSE/PASP HR 0.32 (017-0.60, Chi-squ 12, p=.0004). Conclusion(s) In patients with significant TR, PA Ea is highly feasible and higher PA Ea is progressively associated with RV dysfunction, right heart failure, and worse survival. Incorporating PA Ea into the routine echo assessment may help stratify disease severity in patients with significant TR. Table Assoc. of PA Ea with mortality in TR

Introduction: Tricuspid regurgitation (TR) is a common complication of right ventricle lead extraction (RVLE) in 5 to 10% of cases. This study aims to identify clinical outcomes such as predictors of heart failure hospitalization, need for tricuspid valve intervention, and death among patients with new severe TR after device lead removal (DLR). Methods: Patients who underwent DLR (pacemaker/ICD) between 3/1997 and 3/2024 were identified. Those who had an echocardiogram before and after RVLE with evidence of new severe TR were included. Cox univariable regression controlling for current age was used to assess association with death. Prentice Williams Peterson total time (PWPTT) Cox univariable regression was used to determine the rate of heart failure hospitalization up to three events per subject. Bivariable cox regression was used to control for ejection fraction for ICD and coil removal. Analysis was conducted using Stata IC16. Results: We identified 2,122 people who underwent RVLE, of whom 90 (4.24%) developed new severe TR and were included in the analysis. There were 68 hospitalizations among 38 people at a median of 2 years following lead extraction (IQR 0.57 to 4.5 years). The rate of hospitalization was 11.60 [9.14 to 14.71] per 100 person-years. Removal of an ICD was associated with increased hospitalization (HR 5.48 p<0.001) but not mortality (HR 1.21, p=0.707). Removal of a single coil ICD lead was associated with increased hospitalization rate (HR 3.01, p=0.031) but not mortality (HR =0.51, p=0.380). Removal of dual coil ICD lead was associated with more than a tenfold increase in hospitalization rate (HR 11.55, p=0.001) and four times the mortality rate (HR 4.05, p=0.031) (Figures 1&2). The presence of an abandoned (pacemaker/ICD) lead was associated with increased hospitalization (HR 5.75, p=0.004) and mortality (HR4.95, p=0.034). There was no change in hospitalization rate following tricuspid valve replacement (HR 1.33, p=0.716, n=18). Conclusion: Among people with new severe TR following DLR, the characteristics of the leads are strongly correlated with morbidity and mortality.