Prognostic Implications and Alterations in Left Atrial Deformation Following Transcatheter Aortic Valve Implantation.

AIMS: To evaluate the prognostic implications of left atrial reservoir strain-defined diastolic dysfunction (LARS-DD) grade in patients undergoing TAVI for severe aortic stenosis (AS) and to determine if post-TAVI LARS was more closely associated with new-onset atrial fibrillation than pre-TAVI LARS. METHODS AND RESULTS: Pre-TAVI LARS-DD was evaluated by speckle-tracking echocardiography and was assigned as grade 0 to 1 (LARS≥24%), grade 2 (LARS≥19 to <24%) and grade 3 (LARS<19%). Patients were followed-up for the primary endpoint of all-cause mortality from the date of TAVI. For the secondary endpoint, patients with pre- and post-TAVI LARS measurements and no history of atrial fibrillation were evaluated for the occurrence of new-onset atrial fibrillation. A total of 601 patients (median age 81 [76-85] years, 53% male) were included. Overall, 169 patients (28%) were LARS-DD grade 0/1, 96 patients (16%) were LARS-DD grade 2 and 336 (56%) were LARS-DD grade 3. Over a median follow-up of 40 (IQR 26-58) months, a total of 258 (43%) patients died. In a comprehensive multivariable Cox regression model, LARS-DD grade was independently associated with all-cause mortality (adjusted HR 1.28 per one-grade increase, 95%CI 1.07-1.53, P=0.007). For the secondary endpoint of new-onset atrial fibrillation, a total of 285 patients were evaluated. Post-TAVI LARS (SDHR 1.14 per 1%<20%, 95%CI 1.05-1.23, P=0.0009), but not pre-TAVI LARS (P=0.93) was independently associated with new-onset atrial fibrillation. CONCLUSIONS: Increasing LARS-DD grade was independently associated with long-term post-TAVI survival in patients with severe AS. Post-TAVI LARS was closely related to the occurrence of new-onset atrial fibrillation.

Significant Mitral Regurgitation After Permanent Right Ventricular Pacemaker Implantation: Prognostic Implications.

The underlying mechanisms leading to the development of mitral regurgitation (MR) after right ventricular (RV) pacemaker (PM) implantation and its prognostic value have yet to be fully understood. The purpose of this study was to evaluate the prevalence and clinical variables associated with the development of MR after RV pacing and its association with outcomes. A total of 451 patients (mean age 69 ± 15 years, 61% male) who underwent de novo RV PM implantation were included. The development of significant MR, defined as ≥moderate from mild or none/trace at baseline, occurred in 131 (29%) patients at a median of 2.4 years (interquartile range: 1.0 to 3.8 years) after PM implantation. Multivariate logistic regression analysis demonstrated that implantation of a single-chamber PM, left ventricular end-systolic volume index, and the presence of mild MR (vs no MR) at baseline were independently associated with the development of significant MR post-implant. Cardiac events, defined as the composite of all-cause mortality or heart failure hospitalization, occurred in 143 patients (31.7%) during a median follow-up of 5.4 years (interquartile range: 3.0 to 8.1 years). Multivariate Cox regression analysis demonstrated that the development of significant MR was independently related to the occurrence of cardiac events. In conclusion, the development of significant MR after PM implantation is seen in about one-third of recipients and is independently associated with adverse cardiac events.

Cardiac amyloidosis is not a single disease: a multiparametric comparison between the light chain and transthyretin forms.

AIMS: Systemic amyloidosis represents a heterogeneous group of diseases resulting from amyloid fibre deposition. The purpose of this study is to establish a differential diagnosis algorithm targeted towards the two most frequent subtypes of CA. METHODS AND RESULTS: We prospectively included all consecutive patients with ATTR and AL evaluated between 2018 and 2022 in two centres in a score derivation cohort and a different validation sample. All patients had a complete clinical, biomarker, electrocardiographic, and imaging evaluation. Confirmation of the final diagnosis with amyloid typing was performed according to the current international recommendations. The study population included 81 patients divided into two groups: ATTR (group 1, n = 32: 28 variant and 4 wild type) and AL (group 2, n = 49). ATTR patients were younger (50.7 ± 13.9 vs. 60.2 ± 7.3 years, P = 0.0001), and significantly different in terms of NT-proBNP [ATTR: 1472.5 ng/L (97-4218.5) vs. AL 8024 ng/L (3058-14 069) P = 0.001], hs-cTn I [ATTR: 10 ng/L (4-20) vs. AL 78 ng/L (32-240), P = 0.0002], GFR [ATTR 95.4 mL/min (73.8-105.3) vs. AL: 68.4 mL/min (47.8-87.4) P = 0.003]. At similar left ventricular (LV) wall thickness and ejection fraction, the ATTR group had less frequently pericardial effusion (ATTR: 15% vs. AL: 33% P = 0.0027), better LV global longitudinal strain (ATTR: -13.1% ± 3.5 vs. AL: -9.1% ± 4.3 P = 0.04), RV strain (ATTR: -21.9% ± 6.2 vs. AL: -16.8% ± 6 P = 0.03) and better reservoir function of the LA strain (ATTR: 22% ± 12 vs. AL: 13.6% ± 7.8 P = 0.02). Cut-off points were calculated based on the Youden method. We attributed to 2 points for parameters having an AUC > 0.75 (NT-proBNP AUC 0.799; hs-cTnI AUC 0.87) and 1 point for GFR (AUC 0.749) and TTE parameters (GLS AUC 0.666; RV FWS AUC 0.649, LASr AUC 0.643). A score of equal or more than 4 points has been able to differentiate between AL and ATTR (sensitivity 80%, specificity 62%, AUC = 0.798). The differential diagnosis score system was applied to the validation cohort of 52 CA patients showing a sensitivity of 81% with specificity of 77%. CONCLUSIONS: CA is a complex entity and requires extensive testing for a positive diagnosis. This study highlights a series of non-invasive checkpoints, which can be useful in guiding the decision-making process towards a more accurate and rapid differential diagnosis.

Association Between Left Ventricular Apical-to-Basal Strain Ratio and Conduction Disorders after Aortic Valve Replacement.

BACKGROUND: The aim of the study was to evaluate whether left ventricular apical-to-basal longitudinal strain differences, representing advanced basal interstitial fibrosis, are associated with conduction disorders after aortic valve replacement (AVR) in patients with severe aortic stenosis. METHODS: Patients with aortic stenosis undergoing AVR were included. The apical-to-basal strain ratio was calculated by dividing the average strain of the apical segments by the average strain of the basal segments. Values >1.9 were considered abnormal, as previously described. All patients were followed up for the occurrence of complete left or right bundle branch block or permanent pacemaker implantation within 2 years after AVR. Subgroup analysis was performed in patients undergoing transcatheter AVR. RESULTS: Two hundred seventy-four patients were included (median age of 74 years [interquartile range, 65, 80], 46.4% male). During a median follow-up of 12.2 months (interquartile range, 0.2, 24.3), 74 patients (27%) developed complete bundle branch block or were implanted with a permanent pacemaker. These patients more often had an abnormal apical-to-basal strain ratio. Cumulative event-free survival analysis showed worse outcome in patients with an abnormal apical-to-basal strain ratio (log rank χ2 = 7.258, P = .007). In multivariable Cox regression analysis, an abnormal apical-to-basal strain ratio was the only independent factor associated with the occurrence of complete bundle branch block or permanent pacemaker implantation after adjusting for other factors previously shown to be associated with conduction disorders after AVR. Subgroup analysis confirmed the independent association of an abnormal apical-to-basal strain ratio with conduction disorders after transcatheter AVR. CONCLUSION: The apical-to-basal strain ratio is independently associated with conduction disorders after AVR and could guide risk stratification in patients potentially at risk for pacemaker implantation.

Mitral regurgitation in atrial fibrillation: Is a simple repair enough to tackle a complex problem?

BACKGROUND: Clinical and echocardiographic results of valve repair for mitral regurgitation in the setting of atrial fibrillation are poorly studied. METHODS: Between January 2008 and December 2020, 89 patients underwent valve repair for mitral regurgitation in the setting of atrial fibrillation. Clinical and echocardiographic follow-up data were collected and studied. The primary composite endpoint consisted of all-cause mortality or hospitalization for heart failure. RESULTS: Valve repair with true-sized annuloplasty was performed in 83 (93 %) and restrictive annuloplasty in 6 (7 %) patients. Early mortality occurred in 3 (3 %) and residual mitral regurgitation in 1 (1 %) patient. During a median follow-up of 5.4 years (interquartile range 3.4-9.5), 25 patients died, 6 due to end-stage heart failure. Ten patients were hospitalized for heart failure. The estimated event-free survival rate at 10 years was 48.2 % (95 % CI 33.5 %-62.9 %). Recurrent mitral regurgitation was observed in 14 patients and most often caused by leaflet tethering. When analyzed as a time-dependent variable, recurrent regurgitation was related to the occurrence of the primary endpoint (hazard ratio 3.192, 95 % CI 1.219-8.359, p = 0.018). On exploratory sub-analyses, no recurrent regurgitation was observed after restrictive annuloplasty or in patients with paroxysmal atrial fibrillation. Moreover, recurrent regurgitation was observed more often when signs of left ventricular impairment were present preoperatively. CONCLUSIONS: Despite good initial results, recurrent regurgitation was a frequent observation after valve repair for mitral regurgitation in atrial fibrillation and had an effect on heart failure related morbidity and mortality. Refinements in the timing of surgery and surgical technique might help improve outcomes.

The value of serial echocardiography in risk assessment of patients with paroxysmal atrial fibrillation.

Progression from paroxysmal to persistent atrial fibrillation (AF) is associated with increased morbidity and mortality. We examined the association of left atrial (LA) remodeling by serial echocardiography, and AF progression over an extended follow-up period. Two-hundred ninety patients (mean age 61  ±  11 years, 73% male) who underwent transthoracic echocardiography performed at first presentation for non-valvular paroxysmal AF (PAF) and repeat echocardiogram 1-year later, were followed for progression to persistent AF. LA and left ventricular (LV) dimensions, volumes, LA reservoir, conduit and booster pump strains, LV global longitudinal systolic strain (GLS) assessed by 2D speckle tracking, and PA-TDI (time delay between electrical and mechanical LA activation- reflecting the extent of LA fibrosis) were compared on serial echocardiography. Sixty-nine (24%) patients developed persistent AF over a mean follow-up period of 6.3 years. At baseline, patients with subsequent persistent AF had larger LA dimensions (46 mm vs. 42 mm, p < 0.001), indexed LA volumes (41 ml/m2 vs. 34 ml/m2, p < 0.001), lower LA reservoir and conduit strain (17.6% vs. 27.6%, p < 0.001; 10.5% vs. 16.3%, p < 0.001; respectively) and longer PA-TDI (155 ms vs. 132 ms, p < 0.001) compared to the PAF group. Patients with subsequent persistent AF showed over time significant enlargement in LA volumes (from 37.7 ml/m2 to 42.4 ml/m2, p < 0.001), lengthening of PA-TDI (from 142.2 ms to 162.2 ms, p = 0.002), and decline in LA reservoir function (from 21.9% to 18.1%, p = 0.024) after adjusting for age, gender, diabetes and LV GLS. There were no changes in LA diameter, LA conduit or booster pump function. Conversely, the PAF group showed no decline in LA function. Patients who developed persistent AF had larger LA size and impaired LA function and atrial conduction times at baseline, compared to patients who remained PAF. Over the 1-year time course of serial echocardiographic evaluation, there was progression of LA remodeling in patients who subsequently developed persistent AF, but not in patients who remained in PAF.

Hemodynamic implications of mitral annular calcification in patients undergoing transcatheter aortic valve implantation for severe aortic stenosis.

PURPOSES: Predicting hemodynamic changes of stenotic mitral valve (MV) lesions with mitral annular calcification (MAC) following transcatheter aortic valve implantation (TAVI) may inform clinical decision-making. This study aimed to investigate the association between the MAC severity quantified by computed tomography (CT) and changes in mean transmitral gradient (mTMG), mitral valve area (MVA) and stroke volume index (SVi) following TAVI. METHODS AND RESULTS: A total of 708 patients (median age 81, 52% male) with severe aortic stenosis (AS) underwent pre-procedural CT and pre- and post-TAVI transthoracic echocardiography. According to the classification of MAC severity determined by CT, 299 (42.2%) patients had no MAC, 229 (32.3%) mild MAC, 102 (14.4%) moderate MAC, and 78 (11.0%) severe MAC. After adjusting for age and sex, there was no significant change in mTMG following TAVI (Δ mTMG = 0.07 mmHg, 95% CI -0.10 to 0.23, P = 0.92) for patients with no MAC. In contrast, patients with mild MAC (Δ mTMG = 0.21 mmHg, 95% CI 0.01 to 0.40, P = 0.018), moderate MAC (Δ mTMG = 0.31 mmHg, 95% CI 0.02 to 0.60, P = 0.019) and severe MAC (Δ mTMG = 0.43 mmHg, 95% CI 0.10 to 0.76, P = 0.0012) had significant increases in mTMG following TAVI, with greater changes associated with increasing MAC severity. In contrast, there was no significant change in MVA or SVi following TAVI. CONCLUSION: In patients with severe AS undergoing TAVI, MAC severity was associated with greater increases in post-procedural mTMG whereas MVA or SVi remained unchanged. MAC severity should be considered for potential subsequent MV interventions if TAVI does not improve symptoms.

Imaging in patients with cardiovascular implantable electronic devices: part 1-imaging before and during device implantation. A clinical consensus statement of the European Association of Cardiovascular Imaging (EACVI) and the European Heart Rhythm Association (EHRA) of the ESC.

More than 500 000 cardiovascular implantable electronic devices (CIEDs) are implanted in the European Society of Cardiology countries each year. The role of cardiovascular imaging in patients being considered for CIED is distinctly different from imaging in CIED recipients. In the former group, imaging can help identify specific or potentially reversible causes of heart block, the underlying tissue characteristics associated with malignant arrhythmias, and the mechanical consequences of conduction delays and can also aid challenging lead placements. On the other hand, cardiovascular imaging is required in CIED recipients for standard indications and to assess the response to device implantation, to diagnose immediate and delayed complications after implantation, and to guide device optimization. The present clinical consensus statement (Part 1) from the European Association of Cardiovascular Imaging, in collaboration with the European Heart Rhythm Association, provides comprehensive, up-to-date, and evidence-based guidance to cardiologists, cardiac imagers, and pacing specialists regarding the use of imaging in patients undergoing implantation of conventional pacemakers, cardioverter defibrillators, and resynchronization therapy devices. The document summarizes the existing evidence regarding the use of imaging in patient selection and during the implantation procedure and also underlines gaps in evidence in the field. The role of imaging after CIED implantation is discussed in the second document (Part 2).

Imaging in patients with cardiovascular implantable electronic devices: part 2-imaging after device implantation. A clinical consensus statement of the European Association of Cardiovascular Imaging (EACVI) and the European Heart Rhythm Association (EHRA) of the ESC.

Cardiac implantable electronic devices (CIEDs) improve quality of life and prolong survival, but there are additional considerations for cardiovascular imaging after implantation-both for standard indications and for diagnosing and guiding management of device-related complications. This clinical consensus statement (part 2) from the European Association of Cardiovascular Imaging, in collaboration with the European Heart Rhythm Association, provides comprehensive, up-to-date, and evidence-based guidance to cardiologists, cardiac imagers, and pacing specialists regarding the use of imaging in patients after implantation of conventional pacemakers, cardioverter defibrillators, and cardiac resynchronization therapy (CRT) devices. The document summarizes the existing evidence regarding the role and optimal use of various cardiac imaging modalities in patients with suspected CIED-related complications and also discusses CRT optimization, the safety of magnetic resonance imaging in CIED carriers, and describes the role of chest radiography in assessing CIED type, position, and complications. The role of imaging before and during CIED implantation is discussed in a companion document (part 1).

Multimodality imaging for patient selection, procedural guidance, and follow-up of transcatheter interventions for structural heart disease: a consensus document of the EACVI Task Force on Interventional Cardiovascular Imaging: part 1: access routes, transcatheter aortic valve implantation, and transcatheter mitral valve interventions.

Transcatheter therapies for the treatment of structural heart diseases (SHD) have expanded dramatically over the last years, thanks to the developments and improvements of devices and imaging techniques, along with the increasing expertise of operators. Imaging, in particular echocardiography, is pivotal during patient selection, procedural monitoring, and follow-up. The imaging assessment of patients undergoing transcatheter interventions places demands on imagers that differ from those of the routine evaluation of patients with SHD, and there is a need for specific expertise for those working in the cath lab. In the context of the current rapid developments and growing use of SHD therapies, this document intends to update the previous consensus document and address new advancements in interventional imaging for access routes and treatment of patients with aortic stenosis and regurgitation, and mitral stenosis and regurgitation.

Changes in Computed-Tomography-Derived Segmental Left Ventricular Longitudinal Strain After Transcatheter Aortic Valve Implantation.

Patients with severe aortic stenosis (AS) may show left ventricular (LV) apical longitudinal strain sparing. Transcatheter aortic valve implantation (TAVI) improves LV systolic function in patients with severe AS. However, the changes in regional longitudinal strain after TAVI have not been extensively evaluated. This study aimed to characterize the effect of the pressure overload relief after TAVI on LV apical longitudinal strain sparing. A total of 156 patients (mean age 80 ± 7 years, 53% men) with severe AS who underwent computed tomography before and within 1 year after TAVI (mean time to follow-up 50 ± 30 days) were included. LV global and segmental longitudinal strain were assessed using feature tracking computed tomography. LV apical longitudinal strain sparing was evaluated as the ratio between the apical and midbasal longitudinal strain and was defined as an LV apical to midbasal longitudinal strain ratio >1. LV apical longitudinal strain remained stable after TAVI (from 19.5 ± 7.2% to 18.7 ± 7.7%, p = 0.20), whereas LV midbasal longitudinal strain showed a significant increase (from 12.9 ± 4.2% to 14.2 ± 4.0%, p ≤0.001). Before TAVI, 88% of the patients presented with LV apical strain ratio >1% and 19% presented with an LV apical strain ratio >2. After TAVI, these percentages significantly decreased to 77% and 5% (p = 0.009, p ≤0.001), respectively. In conclusion, LV apical sparing of strain is a relatively common finding in patients with severe AS who underwent TAVI and its prevalence decreases after the afterload relief after TAVI.

Coronary Volume to Left Ventricular Mass Ratio in Patients With Hypertension.

The coronary vascular volume to left ventricular mass (V/M) ratio assessed by coronary computed tomography angiography (CCTA) is a promising new parameter to investigate the relation of coronary vasculature to the myocardium supplied. It is hypothesized that hypertension decreases the ratio between coronary volume and myocardial mass by way of myocardial hypertrophy, which could explain the detected abnormal myocardial perfusion reserve reported in patients with hypertension. Individuals enrolled in the multicenter ADVANCE (Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care) registry who underwent clinically indicated CCTA for analysis of suspected coronary artery disease with known hypertension status were included in current analysis. The V/M ratio was calculated from CCTA by segmenting the coronary artery luminal volume and left ventricular myocardial mass. In total, 2,378 subjects were included in this study, of whom 1,346 (56%) had hypertension. Left ventricular myocardial mass and coronary volume were higher in subjects with hypertension than normotensive patients (122.7 ± 32.8 g vs 120.0 ± 30.5 g, p = 0.039, and 3,105.0 ± 992.0 mm3 vs 2,965.6 ± 943.7 mm3, p <0.001, respectively). Subsequently, the V/M ratio was higher in patients with hypertension than those without (26.0 ± 7.6 mm3/g vs 25.3 ± 7.3 mm3/g, p = 0.024). After correcting for potential confounding factors, the coronary volume and ventricular mass remained higher in patients with hypertension (least square) mean difference estimate: 196.3 (95% confidence intervals [CI] 119.9 to 272.7) mm3, p <0.001, and 5.60 (95% CI 3.42 to 7.78) g, p <0.001, respectively), but the V/M ratio was not significantly different (least square mean difference estimate: 0.48 (95% CI -0.12 to 1.08) mm3/g, p = 0.116). In conclusion, our findings do not support the hypothesis that the abnormal perfusion reserve would be caused by reduced V/M ratio in patients with hypertension.

Prognostic implications of left ventricular inward displacement assessed by cardiac magnetic resonance imaging in patients with myocardial infarction.

Risk stratification of patients with ischemic heart disease (IHD) still depends mainly on the left ventricular ejection fraction (LVEF). LV inward displacement (InD) is a novel parameter of LV systolic function, derived from feature tracking cardiac magnetic resonance (CMR) imaging. We aimed to investigate the prognostic impact of InD in patients with IHD and prior myocardial infarction. A total of 111 patients (mean age 57 ± 10, 86% male) with a history of myocardial infarction who underwent CMR were included. LV InD was quantified by measuring the displacement of endocardially tracked points towards the centreline of the LV during systole with feature tracking CMR. The endpoint was a composite of all-cause mortality, heart failure hospitalization and arrhythmic events. During a median follow-up of 142 (IQR 107-159) months, 31 (27.9%) combined events occurred. Kaplan-Meier analysis demonstrated that patients with LV InD below the study population median value (23.0%) had a significantly lower event-free survival (P < 0.001). LV InD remained independently associated with outcomes (HR 0.90, 95% CI 0.84-0.98, P = 0.010) on multivariate Cox regression analysis. InD also provided incremental prognostic value to LVEF, LV global radial strain and CMR scar burden. LV InD, measured with feature tracking CMR, was independently associated with outcomes in patients with IHD and prior myocardial infarction. LV InD also provided incremental prognostic value, in addition to LVEF and LV global radial strain. LV InD holds promise as a pragmatic imaging biomarker for post-infarct risk stratification.

Managing Patients With Moderate Aortic Stenosis.

Current guidelines recommend that clinical surveillance for patients with moderate aortic stenosis (AS) and aortic valve replacement (AVR) may be considered if there is an indication for coronary revascularization. Recent observational studies, however, have shown that moderate AS is associated with an increased risk of cardiovascular events and mortality. Whether the increased risk of adverse events is caused by associated comorbidities, or to the underlying moderate AS itself, is incompletely understood. Similarly, which patients with moderate AS need close follow-up or could potentially benefit from early AVR is also unknown. In this review, the authors provide a comprehensive overview of the current published reports on moderate AS. They first provide an algorithm that helps to diagnose moderate AS correctly, especially when discordant grading is observed. Although the traditional focus of AS assessment has been on the valve, it is increasingly acknowledged that AS is not only a disease of the aortic valve but also of the ventricle. The authors therefore discuss how multimodality imaging can help to evaluate the left ventricular remodeling response and improve risk stratification in patients with moderate AS. Finally, they summarize current evidence on the management of moderate AS and highlight ongoing trials on AVR in moderate AS.

Extensive aortic root endocarditis with extension into the intervalvular fibrous body: an updated report of a mitral valve sparing approach.

OBJECTIVES: Aortic root abscess can spread to include adjacent cardiac structures, including the central or intervalvular fibrous body and mitral valve. After radical debridement, complex surgical correction is needed. We describe the results of our mitral valve sparing approach. METHODS: Between January 2004 and December 2020, 60 patients underwent operation for infective endocarditis of the aortic root with extension towards the mitral valve at 2 centres in the Netherlands. Early and late clinical and echocardiographic outcomes were studied. RESULTS: Prosthetic valve endocarditis was present in 42 (70%) patients and emergent or salvage surgery was performed in 8 (13%) patients. After radical debridement of all infected tissue, mitral valve repair was feasible in 48 (80%) patients. Early mortality occurred in 11 (18%) patients while mechanical circulatory support was needed in 8 (13%) patients. At 10 years after surgery, the estimated reintervention-free survival rate was 51.9% (95% confidence interval 37.0-66.8%). Eight patients underwent reintervention; this was more common in patients who underwent aortic valve rather than root replacement and in patients in whom mitral valve repair was performed without ring annuloplasty. For 48 patients who underwent mitral valve repair, the estimated freedom from recurrent mitral regurgitation rate was 64.4% (95% confidence interval 40.1-88.7%) at 10 years after surgery. CONCLUSIONS: Surgical intervention for extensive infective endocarditis of the aortic root is related to reasonable perioperative morbidity and mortality. Optimal surgical technique is crucial to lower the risk of late reintervention. Mitral valve repair is feasible in the majority of patients with satisfactory durability.

Factors influencing post-surgical survival in degenerative mitral regurgitation.

AIMS: Indications for surgery in patients with degenerative mitral regurgitation (DMR) are increasingly liberal in all clinical guidelines but the role of secondary outcome determinants (left atrial volume index ≥60 mL/m2, atrial fibrillation, pulmonary artery systolic pressure ≥50 mmHg and moderate to severe tricuspid regurgitation) and their impact on post-operative outcome remain disputed. Whether these secondary outcome markers are just reflective of the DMR severity or intrinsically affect survival after DMR surgery is uncertain and may have critical importance in the management of patients with DMR. To address these gaps of knowledge the present study gathered a large cohort of patients with quantified DMR, accounted for the number of secondary outcome markers and examined their independent impact on survival after surgical correction of the DMR. METHODS AND RESULTS: The Mitral Regurgitation International DAtabase-Quantitative registry includes patients with isolated DMR from centres across North America, Europe, and the Middle East. Patient enrolment extended from January 2003 to January 2020. All patients undergoing mitral valve surgery within 1 year of registry enrolment were selected. A total of 2276 patients [65 (55-73) years, 32% male] across five centres met study eligibility criteria. Over a median follow-up of 5.6 (3.6 to 8.7) years, 278 patients (12.2%) died. In a comprehensive multivariable Cox regression model adjusted for age, EuroSCORE II, symptoms, left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LV ESD) and DMR severity, the number of secondary outcome determinants was independently associated with post-operative all-cause mortality, with adjusted hazard ratios of 1.56 [95% confidence interval (CI): 1.11-2.20, P = 0.011], 1.78 (95% CI: 1.23-2.58, P = 0.002) and 2.58 (95% CI: 1.73-3.83, P < 0.0001) for patients with one, two, and three or four secondary outcome determinants, respectively. A model incorporating the number of secondary outcome determinants demonstrated a higher C-index and was significantly more concordant with post-operative mortality than models incorporating traditional Class I indications alone [the presence of symptoms (P = 0.0003), or LVEF ≤60% (P = 0.006), or LV ESD ≥40 mm (P = 0.014)], while there was no significant difference in concordance observed compared with a model that incorporated the number of Class I indications for surgery combined (P = 0.71). CONCLUSION: In this large cohort of patients treated surgically for DMR, the presence and number of secondary outcome determinants was independently associated with post-surgical survival and demonstrated better outcome discrimination than traditional Class I indications for surgery. Randomised controlled trials are needed to determine if patients with severe DMR who demonstrate a cardiac phenotype with an increasing number of secondary outcome determinants would benefit from earlier surgery.