Mantovani, Francesca

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.

Background— Fibro-elastic deficiency (FED) and diffuse myxomatous degeneration (DMD) are phenotypes of degenerative mitral valve disease defined morphologically. Whether physiological differences in annular and valvular dynamics exist between these phenotypes remains unknown. Methods and Results— We performed triple quantitation of cardiac remodeling and of mitral regurgitation severity and of annular and valvular dimensions by real-time 3-dimensional-transesophageal-echocardiography. Forty-nine patients with degenerative mitral valve disease classified as FED (n=31) and DMD (n=18) by surgical observation showed no difference in age (65±10 versus 59±13; P =0.5), body surface area (2.0±0.2 versus 2.0±0.2 m 2 ; P =0.5), left ventricular and atrial dimensions (all P >0.55), and mitral regurgitation regurgitant orifice ( P =0.62). On average, annular dimensions were larger in DMD versus FED, but height was similar resulting in lower saddle shape. Dynamically, annular DMD versus FED display poorer contraction and saddle-shape accentuation in early systole and abnormal enlargement, particularly intercommissural, in late-systole (all P <0.05). Valvular dynamics showed stable valvular area in systole in FED versus considerable systolic increased area in DMD ( P <0.001). Prolapse height and volume increased little throughout systole in FED versus marked increase in DMD ( P <0.001). Conclusions— Our novel observations show that FED and DMD, although both labeled myxomatous, display considerable physiological phenotypic differences. In DMD, the annular increased size and profoundly abnormal dynamics demonstrate DMD-specific annular degeneration compared with the enlarged but relatively normal FED annulus. DMD does not incur more severe mitral regurgitation, despite larger prolapse and valve redundancy, underscoring potential compensatory role of tissue redundancy of DMD (or aggravating role of tissue paucity of FED) on mitral regurgitation severity.

Objectives Cleft-like indentations (CLI) are deep separations between scallops of the mitral posterior leaflet observed in myxomatous mitral valve disease (MMVD), but their diagnosis, mechanisms and implications are unknown. Using 3D transoesophageal echocardiography (3DTOC), we aimed at assessing diagnostic accuracy and defining mechanisms of CLI in patients undergoing surgery for MMVD. Methods 3DTOC of mitral valve was acquired in 49 patients with MMVD and severe regurgitation prior to valve repair. Qualitative review compared 3DTOC diagnosis of CLI with surgical inspection. Mitral, annular and leaflet dimensions were quantified with dedicated software and compared between those with and without CLI. Results Diagnosis of CLI was made by 3DTOC in 17 (35%) while none was identified by 2D and was confirmed in 15 (88%) by surgical inspection. Mechanistically, LV diameters and mitral regurgitant volume (RVol) were similar with and without CLI (p>0.49). Conversely, mitral annulus was smaller with CLI (anteroposterior diameter 42.2±7.1 vs 47.0±7.5 mm, p=0.04; circumference 133±16 vs 148±19 mm, p=0.009; area 1289±326 vs 1619±427 mm2, p=0.008). Prolapse volume tended to be smaller with CLI (1.9±1.2 vs 4.0±4.3 mL, p=0.06) involving single posterior scallop at surgery (82% vs 44%, p=0.007) with smaller 3DTOC leaflet area (1574±409 vs 2019±652 mm2, p=0.01). During valve repair, surgical closure of all surgically diagnosed CLI was required. Conclusions Posterior leaflet CLI are frequent in MMVD, are identified by 3DTOC with high accuracy and require closure during valve repair. CLI are mechanistically not related to excess annular enlargement or excess prolapse. Conversely, CLI occur in the context of single scallop prolapse with tissue paucity causing excess separation of scallops. These 3DTOC data enhance diagnostic and mechanistic comprehension of the diversity of MMVD phenotypical presentation.

Background— Ejection fraction (EF) as a marker of left ventricular (LV) dysfunction and the appropriate thresholds for diagnosing severe or mild/moderate LV dysfunction in mitral regurgitation are doubted and poorly followed in clinical practice. We aimed at assessing the role of EF in a large registry of organic mitral regurgitation to objectively establish thresholds for various degrees of LV dysfunction and to analyze whether mitral surgery remains beneficial in those subsets of patients. Methods and Results— We investigated the relation between EF and mortality in 1875 patients with mitral regurgitation due to flail leaflets in sinus rhythm (65±13 years; median EF, 66% [60%–71%]) enrolled in the Mitral Regurgitation International Database (MIDA) registry. With EF <60%, mortality after diagnosis increased precipitously under medical management (adjusted hazard ratio [HR], 1.59 [1.19–2.12]) and during the entire follow-up (adjusted HR, 1.51 [1.22–1.87]). Severe LV dysfunction, if defined by EF <30%, would affect a minuscule number of patients (0.3%). Conversely, EF <45% was more frequent (2.9%) and was associated with considerable mortality under medical management (adjusted HR, 2.43 [1.50–3.95]) and during the entire follow-up (adjusted HR, 2.46 [1.67–3.61]). The group with EF of 45% to 60% represented a large proportion of patients (23%), exhibited rarely overt symptoms, and had higher mortality compared with EF >60%. Above 60%, no EF threshold further determined survival. The benefit of surgery remained considerable in the groups with EF <45% (adjusted HR, 0.28 [0.17–0.56]) and with EF of 45% to 60% (adjusted HR, 0.34 [0.21–0.64]). Conclusions— EF is valuable in defining presence and severity of LV dysfunction in organic mitral regurgitation. Patients with EF <45% have severe LV dysfunction, catastrophic outcome under medical management, and should not be denied surgery. Although there is no survival gain with EF ranges >60%, with EF dropping <60%, mortality increases precipitously and prompt surgical referral is critical to outcome.