Thapa, Prabin

BACKGROUND: Degenerative mitral regurgitation (DMR) due to valve prolapse predominates in men, but sex-specific differences are poorly understood due to a lack of quantitative and sex-stratified studies. METHODS: The international MIDA-Q (Mitral Regurgitation International Database-Quantitative) registry enrolled 3274 men and 2331 women with greater than or equal to mild DMR prospectively quantified, comprehensively characterized, and long-term follow-up. RESULTS: Women were more symptomatic despite lower effective regurgitant orifice (ERO, 27±18 versus 38±22 mm 2 , standardized mean difference 0.54; P <0.0001) and regurgitant volume (46±26 versus 61±31 mL/beat, standardized mean difference 0.52; P <0.0001), even for similar mitral lesions. With increasing ERO, women showed lower regurgitant volume, higher heart rate, lower blood pressure, but left ventricular size response in women was smaller in absolute measures while larger when body surface area normalized, with higher ejection fraction and cardiac index (all P <0.0001). Incidence of mitral valve surgery was similar in symptomatic women and men, but lower in asymptomatic women versus men (adjusted hazard ratio, 0.80 [0.69–0.94]; P =0.008) for similar ERO, linked to smaller left ventricular diastolic absolute diameter ( P <0.0001). Excess mortality under medical management (of severe versus mild ERO) was similar in women (adjusted hazard ratio, 1.67 [1.24–2.24]; P =0.0007) and men (adjusted hazard ratio, 1.63 [1.27–2.09]; P <0.0001) and versus expected survival (2.12 [1.51–2.98] in women and 2.27 [1.75–2.94] in men). However, moderate ERO (20–39 mm 2 ) was associated with significant excess mortality in women (1.47 [1.19–1.77] versus mild). In men, the corresponding hazard ratio did not reach statistical significance. Postoperative survival was similar in men and women. CONCLUSIONS: Women with DMR present with lower ERO and regurgitant volume than men and with considerable adaptive differences to increasing DMR severity versus men. Asymptomatic women are less referred to surgery than men of similar DMR severity, linked to smaller absolute left ventricular size. Severe DMR by similar quantitative thresholds causes similar excess mortality in men and women; moderate quantitative DMR shows a trend for higher excess mortality versus expected in women than men, requiring further confirmation. These data emphasize the importance of quantitative DMR and left ventricular remodeling assessment in men and women for appropriate clinical management.

Background Left ventricular (LV) end‐systolic enlargement in severe degenerative mitral‐regurgitation (MR) is a class I surgical trigger. Whether it occurs disproportionately to less‐than‐severe MR due to mitral valve prolapse and is associated with mortality are unknown. We aimed to analyze prevalence and association with survival of disproportionate LV enlargement in less‐than‐severe MR. Methods A multicenter cohort international study enrolled 2848 consecutive patients (52% women, 69±16 years) with degenerative MR prospectively quantified and graded mild or moderate. Primary end point was survival under medical management. Secondary outcome was survival throughout follow‐up stratified by performance of early mitral surgery within 3 months postdiagnosis. Results Among LV remodeling parameters (abnormal end‐diastolic diameter, LV end‐systolic diameter [LVESD] absolute and indexed), LVESD ≥40 mm (present in 12.4%) was the sole independent associate of reduced survival (5‐year 70±3 versus 76±9%; P =0.009). LVESD ≥40 mm was independently linked to larger body surface area, effective regurgitant orifice, and left atrium, and to male sex and diabetes. With multivariable comprehensive adjustment, LVESD ≥40 mm (adjusted hazard ratio [aHR], 1.25 [95% CI, 1.005–1.53]; P =0.04) remained associated with excess mortality under medical management, even after adjustment for lowered ejection fraction (aHR, 1.49 [95% CI, 1.13–1.95]; P =0.004) and in all patient subsets. Among patients with moderate degenerative MR and LVESD ≥40 mm, 22% underwent mitral surgery within 3 months, which was associated with superior survival, even after comprehensive adjustment (aHR, 0.11 [95% CI, 0.005–0.51]; P =0.002). Conclusions Disproportionate LV enlargement in patients with less‐than‐severe degenerative MR is common, particularly with larger bodies, regurgitation, and overall cardiac remodeling. LVESD ≥40 mm is associated with worse survival independent of all baseline characteristics, even lowered ejection fraction, and represents a marker for risk stratification of patients who are generally not yet considered for medical or surgical/interventional treatment.

Background The prevalence and impact of right ventricular dysfunction (RVD) in degenerative mitral regurgitation (DMR) is unknown. We aimed to determine whether RVD assessed by echocardiography in routine clinical practice is independently associated with mortality in patients with DMR. Methods and Results We used data from the MIDA‐Q (Mitral Regurgitation International DAtabase‐Quantitative) registry, which included patients with isolated DMR due to mitral valve prolapse from January 2003 to January 2020 from 5 tertiary centers across North America, Europe, and the Middle East. A cohort of 2917 (mean age: 66 years, 70.8% male patients, follow‐up: 5.2 [3.3–8.3] years) consecutive patients with severe DMR was included and long‐term mortality was analyzed. RVD, identified in 426 (14.6%) patients, was associated with reduced 8‐year survival (55%±3% versus 77%±1%; P <0.001), overall and in all subgroups of patients, even after comprehensive adjustment including left ventricular dilatation and dysfunction, DMR severity, pulmonary pressures, and surgery (adjusted hazard ratio, 1.44 [95% CI, 1.17–1.77]; P <0.001). This excess mortality was observed under medical management (adjusted hazard ratio, 1.57 [95% CI, 1.20–2.05]; P =0.001) and after surgical correction of mitral regurgitation (adjusted hazard ratio, 1.45 [95% CI, 1.02–2.05]; P =0.039). Patients with RVD undergoing surgery within 3 months of diagnosis experienced a better 8‐year survival (73%±4% versus 43%±4%; P <0.001), even after adjustment (adjusted hazard ratio, 0.44 [95% CI, 0.29–0.67]; P <0.001) despite an increase of 1‐month postoperative mortality (7.1% versus 0.5% for patients without RVD; P <0.001). Conclusions RVD is observed in 14.6% of severe DMR and exhibits a powerful and independent association with excess mortality partially attenuated by mitral surgery. Therefore, assessment of right ventricular systolic function should be included in routine DMR evaluation and in the clinical decision‐making process.

Abstract Aims Degenerative mitral stenosis (DMS) is due to degenerative mitral annular calcification (MAC) and valvular calcification. However, DMS impacts on the outcome, and therefore, potential treatment needs are poorly known. We aimed at evaluating survival after DMS diagnosis by Doppler echocardiography in routine practice. Methods and results A cohort of 2937 (75 ± 12 years, 67% women) consecutive patients were diagnosed between 2003 and 2014 with DMS (diastolic mean gradient ≥ 5 mmHg), with analysis of short- and long-term survival. All patients had overt mitral annular/valvular degenerative calcification without rheumatic involvement. Mean gradient was 6.5 ± 2.4 mmHg, and DMS was considered mild in 50%, moderate in 44%, and severe in 6%. DMS was associated with left atrial enlargement (52 ± 23 mL/m2) and elevated pulmonary pressure (49 ± 16 mmHg) despite generally normal ejection fraction (61 ± 13%). DMS was associated with frequent comorbid conditions (74% hypertension, 58% coronary disease, and 52% heart failure) and humoural alterations (haemoglobin 11.3 ± 1.8 g/dL and creatinine 1.5 ± 1.4 mg/dL). One-year mortality was 22%, most strongly related to older age, higher comorbidity, and abnormal haemoglobin/creatinine but only weakly to DMS severity (with anaemia 42% irrespective of DMS severity, P = 0.99; without anaemia 18, 23, and 28% with mild, moderate, and severe DMS, respectively, P &lt; 0.0004). Long-term mortality was high (56% at 5 years) also mostly linked to aging and weakly to DMS severity [with anaemia P = 0.90; without anaemia: adjusted-hazard ratio: 1.30 (1.19–1.42), P &lt; 0.0001, for moderate vs. mild DMS and 1.63 (1.34–1.98), P &lt; 0.0001, for severe vs. mild DMS]. Conclusion DMS is a condition of the elderly potentially resulting in severe mitral obstruction and haemodynamic alterations. However, DMS is frequently associated with severe comorbidities imparting considerable mortality following diagnosis, whereas DMS severity is a weak (albeit independent) determinant of mortality. Hence, patients with DMS should be carefully evaluated and interventional/surgical treatment prudently considered in those with limited comorbidity burden, particularly without anaemia. Keywords: Degenerative Mitral Stenosis; Outcome; Natural history; Ecocardiography; Mitral Stenosis.

Abstract Background and Aims Severe aortic stenosis (AS) is the guideline-based indication for aortic valve replacement (AVR), which has markedly increased with transcatheter approaches, suggesting possible increasing AS incidence. However, reported secular trends of AS incidence remain contradictory and lack quantitative Doppler echocardiographic ascertainment. Methods All adults residents in Olmsted County (MN, USA) diagnosed over 20 years (1997–2016) with incident severe AS (first diagnosis) based on quantitatively defined measures (aortic valve area ≤ 1 cm2, aortic valve area index ≤ 0.6 cm2/m2, mean gradient ≥ 40 mmHg, peak velocity ≥ 4 m/s, Doppler velocity index ≤ 0.25) were counted to define trends in incidence, presentation, treatment, and outcome. Results Incident severe AS was diagnosed in 1069 community residents. The incidence rate was 52.5 [49.4–55.8] per 100 000 patient-year, slightly higher in males vs. females and was almost unchanged after age and sex adjustment for the US population 53.8 [50.6–57.0] per 100 000 residents/year. Over 20 years, severe AS incidence remained stable (P = .2) but absolute burden of incident cases markedly increased (P = .0004) due to population growth. Incidence trend differed by sex, stable in men (incidence rate ratio 0.99, P = .7) but declining in women (incidence rate ratio 0.93, P = .02). Over the study, AS clinical characteristics remained remarkably stable and AVR performance grew and was more prompt (from 1.3 [0.1–3.3] years in 1997–2000 to 0.5 [0.2–2.1] years in 2013–16, P = .001) but undertreatment remained prominent (&gt;40%). Early AVR was associated with survival benefit (adjusted hazard ratio 0.55 [0.42–0.71], P &lt; .0001). Despite these improvements, overall mortality (3-month 8% and 3-year 36%), was swift, considerable and unabated (all P ≥ .4) throughout the study. Conclusions Over 20 years, the population incidence of severe AS remained stable with increased absolute case burden related to population growth. Despite stable severe AS presentation, AVR performance grew notably, but while declining, undertreatment remained substantial and disease lethality did not yet decline. These population-based findings have important implications for improving AS management pathways.

Abstract Background Randomized clinical trials demonstrated transcatheter edge-to-edge repair (TEER) efficacy in improving outcome vs. medical management for functional mitral regurgitation, but limited randomized data are available for the treatment of degenerative mitral regurgitation (DMR). We aimed to compare the outcome of older patients treated with TEER vs. unoperated DMR. Methods and results Registries including consecutive patients ≥65 years with symptomatic severe DMR treated with TEER (MitraSwiss and Minneapolis Heart Institute registries) or unoperated (MIDA registry) were analysed. Survival was compared overall and after matching for age, sex, EuroSCORE II, and ejection fraction. The study included 1187 patients (872 treated with TEER and 315 unoperated). During 24 ± 17 months of follow-up, 430 patients died, 18 ± 1% at 1 year and 50 ± 2% at 4 years. Patients undergoing TEER had similar age (82 ± 6 vs. 82 ± 7 years) and sex to unoperated patients, but higher surgical risk/comorbidity (EuroSCORE II 3.98 ± 4.28% vs. 2.77 ± 2.46%), more symptoms, and atrial fibrillation (P &lt; 0.0001). Transcatheter edge-to-edge repair was associated with lower mortality accounting for age, sex, EuroSCORE II, New York Heart Association class, atrial fibrillation, and ejection fraction [hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.37–0.58; P &lt; 0.0001]. After propensity matching (247 pairs of patients), TEER consistently showed better survival compared with unoperated patients (49 ± 6% vs. 37 ± 3% at 4 years, P &lt; 0.0001) even in comprehensive multivariable analysis (HR: 0.60, 95% CI: 0.40–0.91; P = 0.03). Procedural failure was infrequent but post-procedural mitral regurgitation, remaining moderate-to-severe in 66 (7.6%) patients, was associated with excess mortality vs. trivial residual regurgitation (30 ± 6% vs. 11 ± 1% at 1 year, P &lt; 0.0001). Conclusion Amongst older patients with severe symptomatic DMR at high surgical risk, mitral TEER was associated with higher survival vs. unoperated patients. Successful control of mitral regurgitation was key to survival improvement with mitral TEER, which should be actively considered in patients deemed inoperable.