Citations

Abstract Introduction Transthoracic echocardiography (TTE) identifies a hypercontractile phenotype (HP) in chronic coronary syndromes (CCS), characterized by elevated resting left ventricular (LV) elastance (force = systolic blood pressure/end-systolic volume). To evaluate the prognostic significance and functional correlates of HP. Methods In a prospective multicentre study, 10 677 patients with CCS underwent resting TTE to assess LV ejection fraction (EF), stroke volume, and force by quantitative volumetric echocardiography. All patients were followed for the endpoint of all-cause mortality. In a subset of 5834 patients, stress echocardiography (exercise or dobutamine) was performed for LV contractile reserve and heart rate reserve. Results Patients were stratified into Force quintiles (Q1–Q5). Patients with hypercontractile phenotype exhibited lower stroke volume at rest (Q5 = 34.8 ± 12.3 vs Q1–Q4 = 57.4 ± 19.1 mL; P < .01) and higher EF at rest (Q5 = 64.8 ± 6.9% vs Q1–Q4 = 58.1 ± 8.7%, P < .01). During a median follow-up of 24 months (interquartile range = 12–40 months), 509 deaths occurred. The exposure-adjusted death rate was lowest in Q3 (3.53–4.51 mmHg/mL; 1.03 per 100 person/years) and higher in Q1 (≤2.62 mmHg/mL, 2.88), Q2 (2.63–3.52 mmHg/mL, 1.86), Q4 (4.52–6.11 mmHg/mL, 1.56), and Q5 (HP, >6.11 mmHg/mL; 1.88; P < .0001 vs Q1 and Q3). Multivariable analysis identified HP (Q5; HR 1.531 vs Q3, 95% CI 1.116–2.099; P = .006) and EF (HR 0.963, 95% CI 0.953–0.972; P < .0001) as independent predictors of death. During exercise or dobutamine stress, HP showed reduced LV contractile reserve (ΔEF: Q5 = 4.3 ± 9.4% vs Q1–Q4 = 7.0 ± 9.3%; P < .001) and blunted heart rate reserve (Q5 = 1.77 ± 0.33 vs Q1–Q4 = 1.85 ± 0.39; P < .01). All patients with force-based LV contractile reserve >4.1 (present in 185, 3.2% of the population) survived. Conclusion Patients with CCS with HP assessed by resting TTE demonstrate higher mortality and multilayered functional impairment, including reduced LV contractile and chronotropic reserves. Hypercontractile phenotype improved the prediction of mortality by EF. A ‘stronger’ heart is, in fact, functionally and prognostically weaker.

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.

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 Hypercontractile phenotype (HP) of the left ventricle (LV) is an actionable therapeutic target in patients with chronic coronary syndromes (CCS) or heart failure (HF), but its clinical recognition remains difficult. Objectives To assess the clinical variables associated with the HP. Methods In a prospective, observational, multicenter study, we recruited 5,122 patients (age 65 ± 11 years, 2974 males, 58%) with CCS and/or HF with preserved ejection fraction (EF). 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 (SBP/SV), and ventricular-arterial coupling (VAC, as SV/ESV). Univariable and multivariable logistic regression analysis assessed independent factors associated with the highest force sextile. Results For all the studied patients, force was 4.51 ± 2.11 mmHg/ml, with the highest sextile (Group 6) > 6.36 mmHg/ml. By multivariable logistic regression model, the highest sextile of force was associated with age > 65 years (OR 1.62, 95% CI 1.36–1.93, p < 0.001), hypertension (OR 1.76, 95% CI 1.40–2.21, p < 0.001), female sex (OR 4.52, 95% CI 3.77–5.42, p < 0.001), absence of beta-blocker therapy (OR 1.41, 95% CI 1.16–1.68), rest SBP ≥ 160 mmHg (OR 2.81, 95% CI 2.21–3.56, p < 0.001), high heart rate (OR 2.08, 95% CI 1.61–2.67, p < 0.001), and absence of prior myocardial infarction (OR 1.34, 95% CI 1.07–1.68, p = 0.012). Patients in the highest sextile of force showed lower values of WMSI, SV, EDV, and ESV, and higher values of arterial elastance and VAC. Conclusions HP of the LV with high force was clinically associated with advanced age, female sex, high resting SBP, and the absence of 𝛽-blocker therapy. By transthoracic echocardiography, HP was associated with a small heart with reduced EDV, reduced SV despite high EF, and higher arterial elastance.

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021–2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

Background: Two-dimensional volumetric exercise stress echocardiography (ESE) provides an integrated view of left ventricular (LV) preload reserve through end-diastolic volume (EDV) and LV contractile reserve (LVCR) through end-systolic volume (ESV) changes. Purpose: To assess the dependence of cardiac reserve upon LVCR, EDV, and heart rate (HR) during ESE. Methods: We prospectively performed semi-supine bicycle or treadmill ESE in 1344 patients (age 59.8 ± 11.4 years; ejection fraction = 63 ± 8%) referred for known or suspected coronary artery disease. All patients had negative ESE by wall motion criteria. EDV and ESV were measured by biplane Simpson rule with 2-dimensional echocardiography. Cardiac index reserve was identified by peak-rest value. LVCR was the stress-rest ratio of force (systolic blood pressure by cuff sphygmomanometer/ESV, abnormal values ≤2.0). Preload reserve was defined by an increase in EDV. Cardiac index was calculated as stroke volume index * HR (by EKG). HR reserve (stress/rest ratio) <1.85 identified chronotropic incompetence. Results: Of the 1344 patients, 448 were in the lowest tertile of cardiac index reserve with stress. Of them, 303 (67.6%) achieved HR reserve <1.85; 252 (56.3%) had an abnormal LVCR and 341 (76.1%) a reduction of preload reserve, with 446 patients (99.6%) showing ≥1 abnormality. At binary logistic regression analysis, reduced preload reserve (odds ratio [OR]: 5.610; 95% confidence intervals [CI]: 4.025 to 7.821), chronotropic incompetence (OR: 3.923, 95% CI: 2.915 to 5.279), and abnormal LVCR (OR: 1.579; 95% CI: 1.105 to 2.259) were independently associated with lowest tertile of cardiac index reserve at peak stress. Conclusions: Heart rate assessment and volumetric echocardiography during ESE identify the heterogeneity of hemodynamic phenotypes of impaired chronotropic, preload or LVCR underlying a reduced cardiac reserve.