Colonna, Paolo

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 Guidelines recognize the role of exercise stress testing in evaluating functional capacity in patients with asymptomatic severe aortic stenosis (AS). The study aimed to identify the prognostic role of exercise stress echocardiography (ESE) in asymptomatic severe AS. Methods We enrolled 153 asymptomatic patients (70±13 years; 88 male, 57%) with severe AS, aortic valve area (AVA) <1.0 cm2, mean aortic gradient ≥ 40 mmHg, ejection fraction (EF) ≥55%. All were referred for ESE in 7 quality-controlled centers from 5 countries. Rest and ESE assessment also included global longitudinal strain (GLS) and left atrial volume index (LAVI). B-lines were assessed by LUS with the 4-site simplified scan of the third intercostal space. A 4-point ESE score was based on 4 parameters (0 for normal, 1 for abnormal), with the following pre-determined cutoffs of abnormality: ∆-maximal aortic gradient (MAG) ≥20 mmHg; GLS at peak ≤ 19%, according to receiver operating characteristics curve analysis, stress B-lines ≥2; stress LAVI ≥ 34 mL/m2. Follow-up was completed in 142/153 patients (92%). Results At rest, AVA was 0.85±0.14 cm2, maximal aortic gradient: 79±14 mmHg, and peak aortic velocity: 4.42 ± 0.41 m/s. Mean EF at rest: 63.4±5.3% During a median follow-up of 1802 days (IQ range 651-2302), 41 events occurred in 39 patients: 15 all-cause deaths, 17 acute HF, 1 stroke, 1 myocardial infarction, and 7 coronary revascularization. Patients experiencing events displayed a greater increase in MAG during peak ESE, more B-lines with exercise, greater degree of LAVI dilation with exercise and slightly lower GLS compared to those without events (Table). Increase in ESE score was associated with a significant rise (p=0.001) in event incidence from score 0 (n=0/13, 0%) to score 1 (n=2/21, 9.5%), score 2 (n=10/42, 23.8%), and ≥3 (n=27/66, 40.9%), see figure. Conclusions In asymptomatic severe AS cases with preserved LV EF, comprehensive ESE provides early marker of potential cardiac decompensation at follow-up. The composite ESE index, including MAG, GLS, LAVI, and B-lines, holds promise as a prognostic predictor.TableFigure

Abstract Background Guidelines recognize the role of exercise stress testing in evaluating functional capacity in patients with asymptomatic severe aortic stenosis (AS). Exercise stress echocardiography (ESE) allows the detection of pulmonary congestion with B-lines by lung ultrasound (LUS). Aim To identify the prevalence, determinants, and functional correlates of B-lines during ESE in asymptomatic severe AS. Methods We enrolled 35 asymptomatic patients (age= 69±16 years, 69% male) with severe AS, aortic valve area (AVA) <0.6 cm2/m2, mean aortic gradient (MAG) ≥ 40 mmHg, left ventricular ejection fraction ≥55%. All patients were referred for ESE (treadmill in 1, bicycle in 34 patients) in 7 experienced centers from 4 countries between 2021-2022. ESE assessment at rest and peak stress included global longitudinal strain (GLS), left atrial volume index (LAVI) and cardiac output (CO). B-lines were assessed by simplified LUS from 4 lung zones across the third intercostal space (2 on each side). Heart rate reserve (HRR) was measured as the peak/rest heart rate. CO reserve was calculated as the difference between peak stress CO and rest CO. Results B-lines (≥2) were present in 2 patients at rest and in 15 patients during ESE (6% vs 43%, p<0.001). When compared to patients without B-lines during ESE (Group 1, n=20), patients with B-lines during ESE (Group 2, n=15) were older (Group 1= 64±18 vs Group 2=75±8 years, p=0.030) had larger LAVI, higher logNT-pro-BNP and a trend to higher systolic pulmonary artery pressures (SPAP), see Table. The 2 groups showed similar values of resting AVA (Group 1= 0.52±0.11 vs Group 2=0.47±0.15 cm2/m2, p=0.311), stress AVA (Group 1= 0.45±0.09 vs Group 2=0.49±0.13 cm2/m2, p=0.663), resting MAG (Group 1= 45±15 vs Group 2=46±10 mm Hg, p=0.491), and stress MAG (Group 1= 59±19 vs Group 2=58±11 mm Hg, p=0.665). Patients with B-lines during ESE showed lower HRR and CO reserve, with a trend towards lower peak GLS, see Table. Conclusions Exercise-induced pulmonary congestion as evidenced by development of sonographic B- lines on LUS were present commonly (43%) among patients with "asymptomatic" severe AS undergoing ESE. Patients with exercise-induced B-lines have larger resting LAVI, higher NT-pro-BNP levels, lower CO reserve, and blunted HRR. Exercise-induced B-lines might provide an early sign of cardiac decompensation in "asymptomatic" patients with severe AS, which is an important factor to consider in the decision to intervene.TableFigure

Abstract Background Cardiovascular abnormalities have been observed in half of all COVID-19 patients in the acute phase of the infection. Additionally, 10-35% of these patients have various long-term symptoms diagnosed with post-acute sequelae of COVID-19 (PASC). Aim of this study was to evaluate the role of exercise stress echocardiography (ESE) with an integrated approach, inclusive of Speckle-Tracking Echocardiography (STE) with Myocardial Work (MW) analysis in the evaluation of patients after COVID infection. Methods We prospectively recruited a population of 370 post-COVID 19 patients (Group 1) (225 males; 55.8 ±8.3 years), and of 250 age- and sex-comparable healthy controls (Group 2). In Standard Doppler echocardiography, STE and MW analyses and lung ultrasound at rest and at peak supine-bicycle ESE were performed. Results Left ventricular (LV) wall thickness, diameters and mass index were comparable between the two groups. Both LV ejection fraction (EF) and right ventricular (RV) functional indexes (TAPSE and Tissue Doppler S’ wave) at rest did not show differences between the two groups. Conversely, baseline LV GLS (-16.2±2.8 vs. –20.4±3.3 %; p<0.01), MW efficiency (88.8±3.2 vs. 93.2±3.3 %; p<0.001), and RV strain (-16.4±2.8 vs. –20.4±4.3 %; p<0.01), were significantly reduced in Group 1. Also pulmonary artery systolic pressures (PASP) (33.5±3.8 vs. 24.6±3.1 mmHg; p<0.001), and LV E/e’ ratio were significantly increased in COVID group, while B-lines ( ≥ 2) at rest were found in 25.3% of Group 1 and 5.1% of Group 2 (p < 0.001). During effort, COVID patients showed reduced exercise time and exercise capacity (<0.001). Values of LVEF, RV strain and LV GLS (all with p value <0.01) and MWE (p<0001) were much lower in COVID patients when compared to Group 2. Additionally, COVID patients showed at peak effort an increased LV E/e’ ratio, pulmonary pressures and B-lines by lung ultrasound (all p <0.001). Multivariable analysis detected independent associations of baseline GLS and MWE with maximal workload (watts reached), LV E/e’ ratio and B-lines during effort (p<0.001), stronger than the association of LVEF with the same functional parameters (p<0.01). What’s more, RV strain (p<0.001) was significantly associated with PASP levels at peak effort. Conclusions In post-COVID patients, biventricular involvement with impairment of LV and RV systolic function is frequent, missed by conventional indices such as EF or TAPSE, and detected by more sensitive STE indices such as LV-GLS, ME, and RV-strain. These alterations are functionally significant and associated with shorter exercise -time, more pulmonary hypertension, and greater pulmonary congestion during stress.

Background: Left atrial (LA) myopathy with paroxysmal and permanent atrial fibrillation (AF) is frequent in chronic coronary syndromes (CCS) but sometimes occult at rest and elicited by stress. Aim: This study sought to assess LA volume and function at rest and during stress across the spectrum of AF. Methods: In a prospective, multicenter, observational study design, we enrolled 3042 patients [age = 64 ± 12; 63.8% male] with known or suspected CCS: 2749 were in sinus rhythm (SR, Group 1); 191 in SR with a history of paroxysmal AF (Group 2); and 102 were in permanent AF (Group 3). All patients underwent stress echocardiography (SE). We measured left atrial volume index (LAVI) in all patients and LA Strain reservoir phase (LASr) in a subset of 486 patients. Results: LAVI increased from Group 1 to 3, both at rest (Group 1 = 27.6 ± 12.2, Group 2 = 31.6 ± 12.9, Group 3 = 43.3 ± 19.7 mL/m2, p < 0.001) and at peak stress (Group 1 = 26.2 ± 12.0, Group 2 = 31.2 ± 12.2, Group 3 = 43.9 ± 19.4 mL/m2, p < 0.001). LASr progressively decreased from Group 1 to 3, both at rest (Group 1 = 26.0 ± 8.5%, Group 2 = 23.2 ± 11.2%, Group 3 = 8.5 ± 6.5%, p < 0.001) and at peak stress (Group 1 = 26.9 ± 10.1, Group 2 = 23.8 ± 11.0 Group 3 = 10.7 ± 8.1%, p < 0.001). Stress B-lines (≥2) were more frequent in AF (Group 1 = 29.7% vs. Group 2 = 35.5% vs. Group 3 = 57.4%, p < 0.001). Inducible ischemia was less frequent in SR (Group 1 = 16.1% vs. Group 2 = 24.7% vs. Group 3 = 24.5%, p = 0.001). Conclusions: In CCS, rest and stress LA dilation and reservoir dysfunction are often present in paroxysmal and, more so, in permanent AF and are associated with more frequent inducible ischemia and pulmonary congestion during stress.

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.