Mantovani, Francesca

Abstract Background Obese patients often exhibit a clustering of cardiovascular risk factors and are frequently referred for noninvasive cardiac imaging. Coronary microvascular dysfunction (CMD) represents an early indicator of cardiovascular disease that can be noninvasively diagnosed using coronary flow velocity reserve (CFVR) measurements obtained during stress echocardiography (SE) in patients without evidence of obstructive coronary artery disease (CAD). Purpose This study aimed to evaluate the prognostic significance of CFVR in overweight and obese patients within a prospective multicenter cohort. Methods 2273 patients (mean age 65 ± 11 years; 51% women) classified as overweight or obese (for definition see Table) were included in 27 sites from 11 countries. All patients had normal left ventricular ejection fraction (EF ≥ 50%), no prior history of CAD, and underwent exercise or pharmacological SE, which was negative for inducible ischemia. CFVR of the left anterior descending coronary artery was assessed, with CMD defined as CFVR >2.0. Patients were divided into two groups based on the presence (Group 1) or absence (Group 2) of CMD. The primary endpoint was overall mortality. Results CMD was identified in 492 patients (22%), with a mean CFVR of 2.3 ± 0.5 across the study population. Group 1 patients (CMD) were older, with a greater prevalence of diabetes and metabolic syndrome compared to group 2 (no CMD) (Table). During a median follow-up period of 2.1 years (IQR: 1.2-3.7 years), 103 patients (5%) died. Patients with CMD had significantly worse late survival compared to those without CMD (3-year survival: 96 ± 1% vs. 96 ± 1%, p=ns; 6-year survival: 79 ± 4% vs. 93 ± 1%, p < 0.0001): see Figure. Multivariate analysis adjusting for age, sex, EF, body mass index, smoking habits, diabetes, dyslipidemia, arterial hypertension, and type of stress confirmed CMD as an independent predictor of mortality (hazard ratio: 1.8 [95% CI: 1.1–2.8], p = 0.01). Conclusions CMD, assessed via CFVR during SE, was a robust and independent prognostic marker of long-term mortality in obese patients with preserved EF and no evidence of inducible ischemia. These findings underscore the pivotal role of noninvasive assessment of CMD in refining risk stratification and guiding clinical decision-making in this high-risk population.

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 Aims Operating on patients with severe degenerative mitral regurgitation (DMR) is based on ACC/AHA or ESC/EACTS guidelines. Doubts persist on best surgical indications and their potential association with postoperative survival loss. We sought to investigate whether guideline-based indications lead to late postoperative survival loss in DMR patients. Methods and results We analysed outcome of 2833 patients from the Mitral Regurgitation International Database registry undergoing surgical correction of DMR. Patients were stratified by surgical indications: Class I trigger (symptoms, left ventricular end-systolic diameter ≥ 40 mm, or left ventricular ejection fraction < 60%, n = 1677), isolated Class IIa trigger [atrial fibrillation (AF), pulmonary hypertension (PH), or left atrial diameter ≥ 55 mm, n = 568], or no trigger (n = 588). Postoperative survival was compared after matching for clinical differences. Restricted mean survival time (RMST) was analysed. During a median 8.5-year follow-up, 603 deaths occurred. Long-term postoperative survival was lower with Class I trigger than in Class IIa trigger and no trigger (71.4 ± 1.9, 84.3 ± 2.3, and 88.9 ± 1.9% at 10 years, P < 0.001). Having at least one Class I criterion led to excess mortality (P < 0.001), while several Class I criteria conferred additional death risk [hazard ratio (HR): 1.53, 95% confidence interval (CI): 1.42–1.66]. Isolated Class IIa triggers conferred an excess mortality risk vs. those without (HR: 1.46, 95% CI: 1.00–2.13, P = 0.05). Among these patients, isolated PH led to decreased postoperative survival vs. those without (83.7 ± 2.8% vs. 89.3 ± 1.6%, P = 0.011), with the same pattern observed for AF (81.8 ± 5.0% vs. 88.3 ± 1.5%, P = 0.023). According to RMST analysis, compare to those operated on without triggers, operating on Class I trigger patients led to 9.4-month survival loss (P < 0.001) and operating on isolated Class IIa trigger patients displayed 4.9-month survival loss (P = 0.001) after 10 years. Conclusion Waiting for the onset of Class I or isolated Class IIa triggers before operating on DMR patients is associated with postoperative survival loss. These data encourage an early surgical strategy.

Abstract Objectives A new standard of practice in stress echocardiography (SE) was founded with the development of the ABCDE protocol, which added functional information to conventional ischemia diagnosis. Each step showed to provide incremental prognostic information: step A, regional wall motion abnormalities; step B, B lines; step C, left ventricular contractile reserve; step D, Doppler-based coronary flow velocity reserve in the left anterior descending coronary artery; and step E, electrocardiogram-based heart rate reserve. However, the utility of SE and ABCDE protocol in patients with atrial fibrillation (AF) has never been tested. Background A growing body of evidence suggests that AF patients have a significant residual risk of myocardial infarction despite anticoagulant treatment; furthermore, they have an increased risk of heart failure and all-cause death. However, ABCDE-SE has never been applied in this population. Methods Of the 3965 patients who completed clinically indicated ABCDE-SE and with available information on rhythm stored in the shared data bank and enrolled from 13 certified centers, 3891 were in sinus rhythm (SR, Group 1) and 50 in permanent AF (Group 2) at the time of the test. ABCDE-SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). The employed stress was an exercise in 1626 (41%), vasodilator in 1864 (47%), and dobutamine in 475 (12%). Results Group 2 pts were older than Group 1 patients, more frequently hypertensives and diabetics, with lower ejection fraction, and with more signs of pulmonary congestion at rest. During stress, differences were magnified, and Group 2 patients showed more peak stress B-lines and higher values of peak WMSI compared with Group 1 (see Table). In addition, patients with AF had higher ABCDE scores (Group 1= 1.5 ±1.4 vs. Group 2= 2.6±1.6, p<0.0001). The distribution of the score in patients in SR and AF is shown in Figure. Conclusions Patients with AF are scarcely represented among patients undergoing SE. Patients with AF showed a higher prevalence of positivity in each step and a higher ABCDE score. More specifically, AF patients are more vulnerable than patients in SR to coronary microvascular dysfunction and chronotropic incompetence during stress.TableFigure

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.

Stress echo (SE) 2030 study is an international, prospective, multicenter cohort study that will include >10,000 patients from ≥20 centers from ≥10 countries. It represents the logical and chronological continuation of the SE 2020 study, which developed, validated, and disseminated the “ABCDE protocol” of SE, more suitable than conventional SE to describe the complex vulnerabilities of the contemporary patient within and beyond coronary artery disease. SE2030 was started with a recruitment plan from 2021 to 2025 (and follow-up to 2030) with 12 subprojects (ranging from coronary artery disease to valvular and post-COVID-19 patients). With these features, the study poses particular challenges on quality control assurance, methodological harmonization, and data management. One of the significant upgrades of SE2030 compared to SE2020 was developing and implementing a Research Electronic Data Capture (REDCap)-based infrastructure for interactive and entirely web-based data management to integrate and optimize reproducible clinical research data. The purposes of our paper were: first, to describe the methodology used for quality control of imaging data, and second, to present the informatic infrastructure developed on RedCap platform for data entry, storage, and management in a large-scale multicenter study.

The need for multiple transducer positions, especially from right parasternal windows, is consistently mentioned in the recommendations for the accurate measurement of peak velocities across a stenotic aortic valve, but yet poorly adopted. We performed a subanalysis of the largest prospective series on the right parasternal acoustic windows in patients with aortic stenosis (330 consecutive) to calculate the degree of misalignment and estimate the potential outcome implication of this often-forgotten approach. The right parasternal view was highly feasible with an average estimated misalignment from the apical view of 14 ± 16 degree; in 10 cases, an estimated misalignment >40 degree. Right parasternal assessment (vs. apical alone) provided a significant reclassification from moderate to severe or even very-severe aortic valve stenosis. Considering a wellestablished survival benefit provided by either percutaneous or surgical valve replacement in patients with severe aortic stenosis the reclassification would result in approximately 1 life-year saved for every 30–35 patients in whom parasternal view were effectively utilized.

Background: In women with low to intermediate risk of coronary artery disease (CAD), prognostic detection strategies have been controversial. We present the follow-up data of the SMART trial in peri/postmenopausal women at low to intermediate risk of CAD. Objectives: To determine the value of contrast stress echocardiography (CSE), stress electrocardiogram (sECG), and serum biomarkers for prediction of cardiovascular events (CE) in peri/postmenopausal women at low to intermediate risk of CAD. Materials and Methods: From January 2004 to August 2007, 400 peri/postmenopausal women were prospectively enrolled. All women had detailed risk factor assessment, and underwent simultaneous CSE (Definity ® , Lantheus Medical Imaging) and sECG. Laboratories included brain natriuretic peptide (BNP), atrial natriuretic peptide, endothelin, and high sensitivity C-reactive protein. Wall motion score index was based on a 16-segment model. Abnormal CSE was defined as new or worsening wall motion abnormality at stress, while abnormal sECG was ≥1 mm horizontal/downsloping ST segment depression/elevation (80 mseconds duration). Self-reported outcome data were collected from a mailed Women's Heart Clinic Questionnaire. CE outcomes included all-cause mortality, nonfatal myocardial infarction (MI), heart failure, chest pain hospitalization or development of typical angina (CP), and revascularization (REVASC). Adjusted Cox proportional hazard ratios (HR; 95% confidence intervals) were reported. Results: A total of 366 women (54.4 ± 5.5 years, Framingham risk 6.5% ± 4.4%) completed simultaneous CSE and sECG. Forty-two (11.5%) had abnormal CSE, while sECG was abnormal in 22 (6%) women. Follow-up (4.4 ± 1.2 years) was available in 315/366 (86%) women (78% exercise-CSE, 22% dobutamine-CSE). In those who completed follow-up, CSE was abnormal in 33 women (10.5%) and sECG was abnormal in 21 (6.7%). In 33 women with abnormal CSE, sECG was abnormal in 7 (21.2%) and normal in 26 (79%), p = 0.0004. CE occurred in 27 (8.6%) women: 8 all-cause mortality, 2 nonfatal MI, 13 CP, and 4 REVASC. CE occurred in 21% versus 7% of women with abnormal versus normal CSE, p = 0.014 and 38% versus 6% of women with abnormal versus normal sECG, p < 0.0001. Rest BNP was higher in women with CE versus those without ( p = 0.018). Abnormal sECG and abnormal CSE were associated with CE, while only abnormal sECG was an independent predictor of CE (adjusted HR 10.3 [1.9–61.4], p = 0.007). Of the laboratory results, only BNP was associated with CE (adjusted HR 2.9 [1.1–7.3], p = 0.028). Conclusions: sECG and rest BNP were independent predictors of subsequent CE within 5 years in peri/postmenopausal women at low to intermediate risk of CAD.

Despite its high prevalence, little is known about mechanisms of mitral regurgitation in degenerative mitral valve disease apart from the leaflet prolapse itself. Mitral valve is a complex structure, including mitral annulus, mitral leaflets, papillary muscles, chords, and left ventricular walls. All these structures are involved in physiological and pathological functioning of this valvuloventricular complex but up to now were difficult to analyze because of inherent limitations of 2-dimensional imaging. The advent of 3-dimensional echocardiography, computed tomography, and cardiac magnetic resonance imaging overcoming these limitations provides new insights into mechanistic analysis of degenerative mitral regurgitation. This review will detail the contribution of quantitative and qualitative dynamic analysis of mitral annulus and mitral leaflets by new imaging methods in the understanding of degenerative mitral regurgitation pathophysiology.