Enriquez‐Sarano, Maurice

Objective To comprehensively explore contemporary differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with chronic haemodynamically significant aortic regurgitation (AR). Methods Consecutive patients with chronic ≥moderate-severe AR from a tertiary referral centre (2006–2017) were included. All-cause mortality, surgical indications and aortic valve surgery (AVS) were analysed. Results Of 798 patients (296 BAV-AR, age 46±14 years; 502 TAV-AR, age 67±14 years, p<0.0001) followed for 5.5 (IQR: 2.9–9.2) years, 403 underwent AVS (repair in 96) and 154 died during follow-up. The 8-year AVS incidence was 60%±3% versus 53%±3% for BAV-AR and TAV-AR, respectively (p=0.014). The unadjusted (real-life) 8-year total survival was 93%±7% versus 71%±2% for BAV-AR and TAV-AR, respectively (p<0.0001), and became statistically insignificant after sole adjustment for age (p=0.14). The within-group relative risk of death in BAV-AR patients demonstrated a large age-dependent increase (two fold at 50–55 years, up to 10-fold at 70 years). The presence of baseline symptoms was significantly associated with death for both BAV-AR (p=0.039) and TAV-AR (p<0.0001), but the strength of the association decreased with age adjustment for BAV-AR (age-adjusted HR 2.43 (0.92–6.39), p=0.07) and not for TAV-AR (age-adjusted HR, 2.3 (1.6–3.3), p<0.0001). As compared with general population, TAV-AR exhibited baseline excess risk which further increased at left ventricular ejection fraction (LVEF) <60% and left ventricular end-systolic dimension index (LVESDi) >20 mm/m2; similar thresholds were observed for BAV-AR patients. Conclusion BAV-AR patients were two decades younger than TAV-AR and underwent AVS more frequently, resulting in a considerable real-life survival advantage for BAV-AR that was determined primarily by age and not valve anatomy. Pragmatically, regardless of valve anatomy, patients with haemodynamically significant AR and age >50–55 years require a low-threshold for surgical referral to prevent symptom development where LVEF <60% and LVESDi >20 mm/m2 seem appropriate referral thresholds.

Objectives Unbiased information regarding the surgical management of patients with mitral regurgitation (MR) at the nationwide level are scarce and mainly US-based. The Programme de Médicalisation des Systèmes d’Information, a mandatory national database, offers the unique opportunity to assess the presentation and outcomes of all consecutive mitral valve (MV) surgeries performed in France in the contemporary era. Methods We collected all MV surgeries performed for MR in France in 2014–2016. MR aetiology was classified as degenerative (DMR), secondary (SMR) or Other (rheumatic or congenital disease and infective endocarditis). Results During the 3-year period, 18 167 MV surgeries were performed in France (55% repair and 45% replacement; 52% isolated). Age was 66±12 years and 59% were male. Aetiology was DMR in 42%, SMR in 16% and other in 42% including 19% with uncertain aetiologies. Overall, in-hospital mortality was 6.5% and increased with age, female gender, Charlson Comorbidity Index, type of surgery (replacement vs repair), associated surgery (combined vs isolated) and MR aetiology (all p<0.01). In-hospital mortality and rate of death/readmission for heart failure (HF) at 1 year were 3.4% and 13%, respectively for DMR (2.4% and 11% for isolated DMR) and 7.8% and 27%, respectively for SMR (5.5% and 23% for isolated SMR). Repair rate was 55% overall, 68% in DMR and 72% for isolated DMR surgery (70% of all DMR). Repair rates decreased with age, Charlson Comorbidity Index and female sex (all p<0.0001). Conclusion In this cross-sectional contemporary prospective nationwide database, in-hospital mortality and 1 year rate of death and HF readmission were considerable overall and in all subsets. Repair rates were suboptimal overall especially in the elderly and women subsets. These results underline the need to develop strategies to improve management and outcomes of patients with both DMR and SMR.

Background Although US recent data suggest that mitral regurgitation (MR) is severely undertreated and carries a poor outcome, population‐based views on outcome and management are limited. We aimed to define the current treatment standards, clinical outcomes, and costs related to MR at the nationwide level. Methods and Results In total, 107 412 patients with MR were admitted in France in 2014 to 2015. Within 1 year, 8% were operated and 92% were conservatively managed and constituted our study population (68% primary MR and 32% secondary MR). The mean age was 77±15 years; most patients presented with comorbidities. In‐hospital and 1‐year mortality rates were 4.1% and 14.3%, respectively. Readmissions were common (63% at least once and 37% readmitted ≥2 times). Rates of 1‐year mortality or all‐cause readmission and 1‐year mortality or heart failure readmission were 67% and 34%, respectively, and increased with age, Charlson index, heart failure at admission, and secondary MR etiology; however, the event rate remained notably high in the primary MR subset (64% and 28%, respectively). The mean costs of hospital admissions and of readmissions were 5345±6432 and 10 080±10 847 euros, respectively. Conclusions At the nationwide level, MR was a common reason for admission and affected an elderly population with frequent comorbidities. Less than 10% of patients underwent a valve intervention. All subsets of patients who were conservatively managed incurred high mortality and readmissions rates, and MR represented a major societal burden with an extrapolated annual cost of 350 to 550 million euros (390–615 million US dollars). New strategies to improve the management and outcomes of patients with both primary and secondary MR are critical and warranted.

Abstract Background The majority of patients with of Mitral-valve-prolapse (MVP) have a excellent prognosis. Until recently most cases of mortality were thought to be related to mitral regurgitation and left ventricular dysfunction. The concept of the arrhythmic MVP emerged to describe cases of sudden cardiac death (SCD) in the presence of isolated MVP yet it’s phonotype remains incompletely and inconsistently defined. Purpose To analyze the prevalence, severity and characteristics of ventricular-arrhythmia (VA), to determine it’s phenotypical context and independent impact on outcome in patients with MVP. Methods A cohort of 595 (65 ± 16 years, 278 female) consecutive patients with MVP and comprehensive clinical, arrhythmia (24hour-Holter) and Doppler-echocardiographic characterization, was identified and long-term outcome analyzed. Results VA was frequent, present in 43% of patients with at least ventricular ectopy≥5%, but was most often moderate (ventricular-tachycardia—VT 120-179bpm) in 27% and rarely severe (VT≥180/min) in 8.6%. Presence of VA was associated with older age, male sex, bileaflet-prolapse, marked leaflet redundancy, mitral-annulus-disjunction (MAD), larger left-atrium and left ventricular end-systolic diameter, and T-wave-inversion/ST-depression (all P ≤ 0.001). Severe VA was independently associated with presence of MAD, leaflet-redundancy and T-wave-inversion/ST-depression (all P &lt; 0.0001) but not with mitral regurgitation severity or ejection-fraction. Outcome primary endpoint of overall survival after arrhythmia diagnosis (8-year 87 ± 2%) was strongly associated with arrhythmia-severity (8-year 90 ± 2% for no/trivial arrhythmia, 85 ± 3% for mild/moderate and 76 ± 7% for severe arrhythmia. P = 0.02, Figure). Excess-mortality was substantial for severe-arrhythmia (univariate-hazard-ratio 2.70[1.27-5.77], P = 0.01 vs. no/trivial arrhythmia), even adjusted comprehensively including for MVP-characteristics (adjusted-hazard-ratio 2.94[1.36-6.36], P = 0.006) ). Conclusions This large cohort of isolated consecutive MVP characterized with 24-hour-Holter monitoring, clinical and Echocardiographic assessment, demonstrates that VA are frequent with MVP but rarely severe. The arrhythmic MVP was independently and strongly associated with specific ECG and morphologic patterns, particularly ST-T changes, MAD presence and marked leaflet redundancy, suggestive of a specific arrhythmic MVP phenotype, independently of MR-severity. Arrhythmia, particularly severe, is associated with long-term excess-mortality, independently of any other characteristics, including MR severity and LVEF. These findings lay the foundation for novel risk-stratification of MVP for the conduct of prospective controlled studies evaluating the management of MVP high-risk patients. Figure – Impact on survival of ventricular arrhythmia Overall survival of MVP stratified by ventricular arrhythmia (Panel A) or ventricular arrhythmia severity (Panel B) throughout follow-up. Abstract Figure.

Abstract Aims More evidence is needed to quantify the association between tricuspid regurgitation (TR) and mortality in patients with heart failure (HF). Methods and results Between 2008–2017, using the Optum longitudinal database, a patient-level database that integrates multiple US-based electronic health and claim records from several health care providers, we identified 435 679 patients with new HF diagnosis and both an assessment of the left ventricular ejection fraction and at least 1 year of history. TR was graded as mild, moderate or severe and classified as prevalent (at the time of the initial HF diagnosis) or incident (subsequent new cases thereafter). For prevalent TR, the analysis was performed using a Cox proportional hazards model with adjustment for patient covariates. Incident TR was modelled as a time-updated covariate, as were other non-fatal events during follow-up. Prevalence of mild, moderate and severe TR at baseline was 10.1%, 5.1% and 1.4%, respectively. Over a median follow-up of 1.5 years, 121 273 patients (27.8%) died and prevalent TR was independently associated with survival. Compared to patients with no TR at baseline, the adjusted hazard ratios for mortality were 0.99 [95% confidence interval (CI) 0.97–1.01], 1.17 (95% CI 1.14–1.20) and 1.34 (95% CI 1.28–1.39) for mild, moderate and severe TR, respectively. In the 363 270 patients free from TR at baseline, incident TR (at least mild, at least moderate, or severe) developed during follow-up in 12.1%, 5.1% and 1.1%, respectively. Adjusted mortality hazard ratios for such new cases were 1.48 (95% CI 1.44–1.52), 1.92 (95% CI 1.86–1.99) and 2.44 (95% CI 2.32–2.57), respectively. Findings were consistent across all patient subgroups based on age, gender, rhythm, associated comorbidities, prior cardiac surgery, B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide, and left ventricular ejection fraction. Conclusions In this large contemporary patient-level database of almost half-million US patients with HF, TR was associated with a marked increases in mortality risk overall and in all subgroups. Future randomized controlled trials will evaluate the impact of TR correction on clinical outcomes and the causal relationship between TR and mortality.

Abstract Aims To assess functional tricuspid regurgitation (FTR) determinants, consequences, and independent impact on outcome in degenerative mitral regurgitation (DMR). Methods and results All patients diagnosed with isolated DMR 2003–2011, with structurally normal tricuspid leaflets, prospective FTR grading and systolic pulmonary artery pressure (sPAP) estimation by Doppler echocardiography at diagnosis were identified and long-term outcome analysed. The 5083 DMR eligible patients [63 ± 16 years, 47% female, ejection fraction (EF) 63 ± 7%, and sPAP 35 ± 13 mmHg] presented with FTR graded trivial in 45%, mild in 37%, moderate in 15%, and severe in 3%. While pulmonary hypertension (PHTN-sPAP ≥ 50 mmHg) was the most powerful FTR severity determinant, other strong FTR determinants were older age, female sex, lower left ventricle EF, DMR, and particularly atrial fibrillation (AFib) (all P ≤ 0.002). Functional tricuspid regurgitation moderate/severe was independently linked to more severe clinical presentation, more oedema, lower stroke volume, and impaired renal function (P ≤ 0.01). Survival (95% confidence interval) throughout follow-up [70% (69–72%) at 10 years] was strongly associated with FTR severity [82% (80–84%) for trivial, 69% (66–71%) for mild, 51% (47–57%) for moderate, and 26% (19–35%) for severe, P &lt; 0.0001]. Excess mortality persisted after comprehensive adjustment [adjusted hazard ratio 1.40 (1.18–1.67) for moderate FTR and 2.10 (1.63–2.70) for severe FTR, P ≤ 0.01]. Excess mortality persisted adjusting for sPAP/right ventricular function (P &lt; 0.0001), by matching [adjusted hazard ratios 2.08 (1.50–2.89), P &lt; 0.0001] and vs. expected survival [risk ratio 1.79 (1.48–2.16), P &lt; 0.0001]. Within 5-year of diagnosis valve surgery was performed in 73% (70–75%) and 15% (13–17%) of severe and moderate DMR and in only 26% (19–34%) and 6% (4–8%) of severe and moderate FTR. Valvular surgery improved outcome without alleviating completely higher mortality associated with FTR (P &lt; 0.0001). Conclusion In this large DMR cohort, FTR was frequent and causally, not only linked to PHTN but also to other factors, particularly AFib. Higher FTR severity is associated at diagnosis with more severe clinical presentation. Long term, FTR is independently of all confounders, associated with considerably worse mortality. Functional tricuspid regurgitation moderate and even severe is profoundly undertreated. Thus careful assessment, consideration for tricuspid surgery, and testing of new transcatheter therapy is warranted.

Abstract Background In patients with hemodynamically-significant chronic aortic valve regurgitation (AR), the prognostic significance of routinely-measured diastolic blood pressure (DBP), resting heart rate (RHR) and physical examination signs of heart failure (HF), is unknown. Purpose To investigate the association of DBP, RHR and HF signs, with all-cause mortality. Methods This retrospective cohort study included all consecutive patients with moderately-severe or severe AR within a tertiary-referral center from 2006–2017. Patients with ≥moderate aortic stenosis and those with ≥moderate mitral stenosis/regurgitation were excluded. Results Of 820 patients (age 59±17 years; 82% men) with DBP 64±13mmHg and RHR 64±12bpm, followed for 5.5±3.5 years, 104 died under medical management and 400 underwent aortic valve surgery (AVS). In multivariable analysis, DBP (adjusted-hazard ratio [HR] 0.82 [0.68–0.98] p=0.031, per 10mmHg increase), RHR (adjusted HR 1.2 [1.01–1.41] p=0.034 per 10bpm increase), and any HF signs (adjusted HR 1.66 [1.04–2.61] p=0.032) were associated with all-cause death independently of demographics, comorbidities, and guideline-derived surgical triggers. Mortality increased in a J-curve fashion for DBP starting at 70 mmHg and peaking at 55 mmHg (Fig A,C), and in a linear fashion for RHR starting at 60bpm (Fig B, D). The association persisted after additional adjustment for medications, presence of hypertension and time-dependent AVS. A clinical score combining DBP, RHR and any HF signs increased the mortality risk-discrimination of demographics and comorbidities from 74% to 79% (p=0.01), and from 79% to 82% after addition of surgical triggers (p=0.04). Figure. Risk of death by DBP and RHR Conclusions In patients with AR, routinely-measured vital signs and physical examination are strongly associated with all-cause mortality; lower DBP, higher RHR and any HF signs are independent predictors of mortality, and provide incremental mortality risk-discriminating value to baseline demographics, comorbidities and guideline-derived surgical triggers. These findings represent a clinical paradigm shift and have guideline implications.