Michelena, Héctor I.

Background: Cardiac rehabilitation (CR) improves functional capacity after heart valve surgery (HVS), but no survival benefit has yet been described. We hypothesized that attendance at CR after HVS would be associated with improved long-term survival. Methods: In 2013, we surveyed all patients (or a close family member if the patient was deceased) who had isolated HVS between 2006 through 2010 at the Mayo Clinic to assess if they attended CR after their HVS. We assessed survey reliability among local patients by comparing self-reported vs. medical-record verified CR attendance with the kappa statistic. We then performed a propensity-adjusted landmark mortality analysis through October 2014 for the association between CR attendance and long-term all-cause mortality conditional upon surviving the first year after HVS. Results: Survey response rate was 40% (573/1420), with responders more likely to be older, have longer hospitalizations, more aortic valve disease, but have better survival than non-responders. Among local patients, there was “substantial” agreement between reported attendance and medical-record verified CR attendance (agreement at 84%, kappa = 0.62.) A total of 547 patients (age 70 yrs., 62% male, 59% aortic valve surgery) with valid survey responses were included in the propensity analysis, of whom 296 (54.1%) attended CR. There were 100 deaths during a median follow-up of 5.4 years. For all patients, the propensity-adjusted model suggested no impact of CR on mortality (HR 1.03, 95% CI, 0.66 to 1.62). When stratified by procedure type, results suggested a potentially favorable, but non-significant, effect among patients with mitral valve surgery (HR 0.49, 95% CI 0.15 to 1.56), but not among patients with aortic valve surgery (HR 1.00, 95% CI 0.61 to 1.64.) Conclusions: Important improvements in functional capacity from CR have been previously reported after HVS, but, contrary to our hypothesis, we found that CR does not provide long-term survival benefits after HVS. These findings need additional confirmation to better clarify any mortality impact that may exist for CR following HVS, particularly among patients undergoing mitral valve surgery.

Background: Left atrial assessment is complex, particularly in heart failure with reduced ejection fraction due to interactions with functional mitral regurgitation (FMR). Pilot data suggest that left atrial volumetric/mechanical coupling index (LACI) may be useful, but large outcome data are lacking. Methods: We enrolled a comprehensively characterized cohort of patients in sinus rhythm with heart failure with reduced ejection fraction diagnosis at Mayo Clinic from 2007 to 2011. Routinely measured left atrial volume index and tissue-doppler-imaging a’ allowed LACI calculation as (left atrial volume index)/(tissue-doppler-imaging a’). Survival was the outcome measured. Results: The cohort’s 4196 patients (69 [58–77] years, ejection fraction 40 [31–45]%) had mild FMR in 1505 and moderate-severe FMR in 1068. LACI was overall 5.06 (3.50–8.10) and increased with each FMR grade (3.86 [2.94–5.29] without FMR, 5.38 [3.80–8.02] with mild, 5.45 [1.49–8.07] with moderate/severe FMR; P <0.0001). At diagnosis, higher LACI was independently determined by more severe FMR and by higher left ventricular mass index, lower ejection fraction, higher E/e’, and lower glomerular filtration rate (all P <0.0001). During follow-up 1588 (38%) patients died. In spline modeling, excess mortality appeared around LACI=6 and steeply increased thereafter (5-year survival 72±1% with LACI<6 and 49±2% with LACI ≥6, P <0.0001). Multivariable comprehensive adjustment showed LACI strong association with excess mortality (adjusted hazard ratio, 1.41 [1.23–1.61], P <0.0001 for LACI ≥6). Independent link to mortality persistent across FMR grades (adjusted hazard ratio, 1.45 [1.13–1.86], P =0.004 without FMR, 1.42 [1.16–1.77], P =0.0008 with mild FMR, and 1.38 [1.01–1.66], P =0.04 with moderate/severe FMR) without interaction ( P =0.3). LACI independent impact on outcome was incremental to that of left atrial volume index, tissue-doppler-imaging a’, or any other characteristic including the Meta-Analysis Global Group in Chronic-score (least significant P =0.02). Conclusions: In this large cohort, left atrial volumetric/mechanical coupling measured by LACI in routine practice integrates the influence of several morphological/hemodynamic determinants but displays progressive deterioration with increasing FMR severity in heart failure with reduced ejection fraction. About outcome, higher LACI is strongly, independently, and incrementally associated with excess mortality, irrespective of FMR grade and in all subsets. Hence, LACI is a novel and critical measure in heart failure with reduced ejection fraction, quantifiable in routine practice, which should be integrated in prognostication and decision-making.

Abstract Funding Acknowledgements Type of funding sources: None. Background Pulmonary hypertension is a frequent complication of severe degenerative mitral regurgitation (DMR) associated with major outcome implications. However, whether pulmonary hypertension is linked with worse outcome in less that severe MR is uncertain and even more unsubstantiated is the link of elevated systolic pulmonary artery pressure (sPAP) &lt; 50mmHg with clinical presentation and outcome. Purpose To assess the outcome implication of sPAP elevation, even moderate, among mitral regurgitation severity subgroups. Methods The MIDA-Quantitative (MIDA-Q) unprecedented registries included 7373 consecutive patients (age 64 ± 17 years, 45% women, follow-up 5.5 ± 3.4 years) with isolated DMR diagnosed at tertiary (European/North-American/Middle East) centers in which systolic pulmonary artery pressure (sPAP) was measured prospectively at baseline. Long-term survival overall, under medical management and post-mitral surgery was analyzed. Results Elevated pulmonary pressure (sPAP &gt;50mmHg) was observed in 1371 patients (19%, mean 63 ± 13mmHg) and moderate increase in pulmonary pressure (35&lt; sPAP &lt; 50mmHg) in 1874 patients (25%, mean 41 ± 14mmHg), with no/mild MR in 4067 (50%), moderate in 2073 (25%), and severe or above in 2047 (25%), mean ERO 0.24 ± 24cm2, RVol 37 ± 35mL and posterior leaflet prolapse in 34%. sPAP severe but also moderate both strongly and independently linked to more severe clinical presentation, with more dyspnea, more AFib, and impaired renal function (P ≤ 0.0001). &lt;SPAP&lt; &gt;By sPAP categories, 35 &lt; sPAP&lt; 50mmHg (vs. 35mmHg) was independently associated with worse outcome under medical management adjusted-HR 1.62[1.40-1/87], with considerable excess-mortality for sPAP &gt; 50mmHg (vs. &lt;35mmHg) adjusted-HR 2.54[2.17-2.96], all P &lt; 0.0001. As continuous variable, sPAP was associated with worse outcome adjusted-HR 1.25[1.21-1.29], P &lt; 0.0001 per 10mmHg-increase. Mitral valve surgery (performed in 2378 patients, 32%) improved outcome without alleviating completely higher mortality associated with sPAP &gt; 50mmHg (P &lt; 0.0001). Conclusion In this very large international cohort of patients with DMR of all range and prospective sPAP grading, higher sPAP is associated at diagnosis with more severe clinical presentation. Long term, sPAP &gt; 50mmHg but also 35-50mmHg is independently of all confounders, associated with worse mortality. Thus careful assessment and consideration for mitral surgery/transcatheter therapy is warranted even in patients with sPAP &lt;50mmHg.&lt;/SPAP&lt; &gt; Abstract Figure. Survival stratified by sPAP Categories Abstract Figure. Postop survival by sPAP Categories

Abstract Aims Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of &gt;2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder. Methods and results We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors. Conclusion We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-β signalling molecules and spectrin β. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention.

AbstractObjectivesTo compare all‐cause mortality in patients with mitral annulus calcification (MAC) and severe mitral valve dysfunction (MVD) who received standard mitral intervention versus no intervention.BackgroundPatients with MAC often have high surgical risk due to advanced age, comorbidities, and technical challenges related to calcium. The impact of a mitral intervention on outcomes of patients with MAC and severe MVD is not well known.MethodsRetrospective review of patients with MAC by transthoracic echocardiography (TTE) in 2015 at a single institution. Patients with severe mitral stenosis (MS) or regurgitation (MR) were analyzed and stratified into two groups: surgical or transcatheter intervention performed <1 year after the index TTE, and no or later intervention. The primary endpoint was all‐cause mortality.ResultsOf 5502 patients with MAC, 357 had severe MVD (MS = 27%, MR = 73%). Of those, 108 underwent mitral intervention (surgery = 87; transcatheter = 21). They were younger (73 ± 11 vs. 76 ± 11 years, p < 0.01) and less frequently had cardiovascular diseases compared with no‐intervention. Frequency in women was similar (45% vs. 50%, p = 0.44). During median follow‐up of 3.2 years, the intervention group had higher estimated survival than those without intervention (80% vs. 72% at 1 year and 55% vs. 35% at 4 year, p < 0.01). Adjusted for age, eGFR, LVEF < 50%, and pulmonary hypertension, mitral intervention was an independent predictor of lower mortality (hazard ratio = 0.66, 95% confidence interval 0.43–0.99, p = 0.046).ConclusionPatients with MAC and severe MVD who underwent mitral intervention <1 year from index TTE had lower mortality than those without intervention. Mitral intervention was independently associated with lower mortality.

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.

Abstract Background Intracranial aneurysm (IA) has been associated with bicuspid aortic valve (BAV) with prevalence of 6–10% which has led some to recommend routine surveillance for IA in BAV patients. Higher incidence of IA in BAV could signal towards systemic arteriopathy beyond the thoracic aorta. With CoA as an independent risk factor for IA formation, it is currently uncertain if the association between IA and BAV reflects the association of BAV and CoA, or the result of BAV-related systemic arterial changes. Purpose Despite this association, 2 small studies suggest no increased risk of the most important patient outcome: aneurysmal sub-arachnoid hemorrhage (aSAH). Our primary aim was identifying the prevalence of BAV in aSAH patients and compare it with that of a control group without aSAH. Secondary aims included neurologic outcomes of aSAH and anatomical characteristics of IA in BAV, and final disposition and outcome. Methods Patients (&gt;18 years age) with an accurate diagnosis of aSAH and at least one echocardiogram in the system between January 2000-December 2019 were identified from a prospectively maintained registry of aSAH admissions. Controls, without a diagnosis of SAH ever, were age- and gender-matched (1:2 cases:controls). BAV prevalence was echocardiographically-confirmed in all patients. Severity of aSAH was categorized using the modified Fisher (mFisher) and the World Federation of Neurological Scale (WFNS). Results A total of 488 aSAH cases and 990 controls were included in the final analysis with confirmed aortic valve status. The prevalence of BAV in aSAH patients was 1.2% (6/488) vs 3.5% (35/990) in controls, p=0.01. None of the aSAH cases were noted to have CoA, whereas 3 (0.3%; p=0.12) control patients had presence of both BAV and CoA. Within aSAH patients, BAV+aSAH were noted to be younger than tricuspid aortic valve (TAV)+aSAH (56±11 vs 68±14; p=0.03). Aneurysm size was smaller in the BAV+aSAH group (5±2 vs 7±4 in TAV+aSAH; p=0.31). The severity of the bleed was lesser in BAV+aSAH than TAV+aSAH (mFisher grade &gt;2 50% vs 74%; p=0.19, WFNS grade &gt;3 17% vs 36%; p=0.43) which is clinically significant. The BAV+aSAH group had higher disposition rate to home (67% vs 39%; p=0.21) with no difference in in-hospital mortality rates (17% vs 18%; p=0.93). BAV had lower odds on univariate and multivariate analyses adjusted for age/sex/body mass index (OR 0.33 [CI 0.14–0.81]; p=0.01, OR 0.23 [CI 0.08–0.65]; p=0.01) of presenting with aSAH. Conclusion Within a large prospective registry with accurate aSAH diagnoses, we found 3-times lower prevalence of echocardiographically-confirmed BAV as compared to non-aSAH controls. We observed 3-times higher prevalence of BAV in controls than among aSAH cases. In addition, size of intracranial aneurysms was clinically smaller in BAV patients, and the severity of SAH was significantly lesser in BAV from a clinical standpoint. Our findings argue against routine surveillance for IA in BAV patients without CoA. Funding Acknowledgement Type of funding sources: None.

Abstract Background The Mitral Regurgitation International Database (MIDA) score is a validated tool for Degenerative Mitral Regurgitation (DMR) management, being able to position a given patient within a continuous spectrum of short and long term mortality. However, whether this score may be applicable and incremental in the entire span of Floppy Mitral Valves (FMV), regardless of DMR severity, remains unsubstantiated. Methods The MIDA-Quantitative (MIDA-Q) unprecedented registries include 8187 consecutive patients (age 64±17 years, 45% women, follow-up 5.5±3.4 years) with isolated degenerative mitral valve disease diagnosed at tertiary (European/ North-American/ Middle Eastern) centers in whom DMR severity used both integrative and quantitative grading. The MIDA-Q Score ranged from 0 to 15 depending on accumulating risk factors. Long-term survival overall, under medical management and post-mitral surgery was analysed. Results By quantitative grading, MR was no/trivial in 1938 (24%), mild in 1423 (17%), moderate in 2027 (25%) and severe in 2799 (34%), with ERO 0.24±24cm2, RVol 37±35mL, and posterior leaflet prolapse in 49%. MIDA-Q Scores stratified in 8 categories were 0 (score 0, n=851), 1 (score 1–2, n=1301), 2 (score 3–4, n=2043), 3 (score 5–6, n=1581), 4 (score 7–8, n=1273), 5 (score 9–10, n=718), 6 (score 11–12, n=331) and 7 (score 13–15, n=89). In the whole MIDA-Q population (n=8187 patients), 5-year survival under medical management with Scores categories 0–1, 2–4, and 5–7 was 96±1%, 73±1%, and 61±3% respectively (P&lt;0.0001). Five-year mortality ranged from 3% with MIDA Q-score 0 to 95% with MIDA Q-score 13–15 (P&lt;0.0001). After mitral surgery, 1-year mortality with Scores categories 0–1, 2–4, and 5–7 was 0%, 1%, and 6% respectively and 5-year post-operative survival was 99±1%, 94±1%, and 82±2% (all P&lt;0.0001). In models including age, sex and all guideline-provided prognostic markers, the EuroScoreII and the MIDA Score without DMR severity, the MIDA-Q Score provided incremental prognostic information (P&lt;0.001). Conclusion This unheard international cohort of patients with FMV and prospective mitral severity quantitative grading, enables for the first time the calculation of a MIDA-Q Score, highly determinant of survival after diagnosis of FMV with any degree of DMR, that may be very useful for mitral valve prolapse management. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Mayo Fundation Figure 1