Andrea Barbieri

Association between early surgical intervention vs watchful waiting and outcomes for mitral regurgitation due to flail mitral valve leaflets.

IMPORTANCE The optimal management of severe mitral valve regurgitation in patients without class I triggers (heart failure symptoms or left ventricular dysfunction) remains controversial in part due to the poorly defined long-term consequences of current management strategies. In the absence of clinical trial data, analysis of large multicenter registries is critical. OBJECTIVE To ascertain the comparative effectiveness of initial medical management (nonsurgical observation) vs early mitral valve surgery following the diagnosis of mitral regurgitation due to flail leaflets. DESIGN, SETTING, AND PARTICIPANTS The Mitral Regurgitation International Database (MIDA) registry includes 2097 consecutive patients with flail mitral valve regurgitation (1980-2004) receiving routine cardiac care from 6 tertiary centers (France, Italy, Belgium, and the United States). Mean follow-up was 10.3 years and was 98% complete. Of 1021 patients with mitral regurgitation without the American College of Cardiology (ACC) and the American Heart Association (AHA) guideline class I triggers, 575 patients were initially medically managed and 446 underwent mitral valve surgery within 3 months following detection. MAIN OUTCOMES AND MEASURES Association between treatment strategy and survival, heart failure, and new-onset atrial fibrillation. RESULTS There was no significant difference in early mortality (1.1% for early surgery vs 0.5% for medical management, P=.28) and new-onset heart failure rates (0.9% for early surgery vs 0.9% for medical management, P=.96) between treatment strategies at 3 months. In contrast, long-term survival rates were higher for patients with early surgery (86% vs 69% at 10 years, P < .001), which was confirmed in adjusted models (hazard ratio [HR], 0.55 [95% CI, 0.41-0.72], P < .001), a propensity-matched cohort (32 variables; HR, 0.52 [95% CI, 0.35-0.79], P = .002), and an inverse probability-weighted analysis (HR, 0.66 [95% CI, 0.52-0.83], P < .001), associated with a 5-year reduction in mortality of 52.6% (P < .001). Similar results were observed in relative reduction in mortality following early surgery in the subset with class II triggers (59.3 after 5 years, P = .002). Long-term heart failure risk was also lower with early surgery (7% vs 23% at 10 years, P < .001), which was confirmed in risk-adjusted models (HR, 0.29 [95% CI, 0.19-0.43], P < .001), a propensity-matched cohort (HR, 0.44 [95% CI, 0.26-0.76], P = .003), and in the inverse probability-weighted analysis (HR, 0.51 [95% CI, 0.36-0.72], P < .001). Reduction in late-onset atrial fibrillation was not observed (HR, 0.85 [95% CI, 0.64-1.13], P = .26). CONCLUSION AND RELEVANCE Among registry patients with mitral valve regurgitation due to flail mitral leaflets, performance of early mitral surgery compared with initial medical management was associated with greater long-term survival and a lower risk of heart failure, with no difference in new-onset atrial fibrillation.

Survival Implication of Left Ventricular End-Systolic Diameter in Mitral Regurgitation Due to Flail Leaflets : A Long-Term Follow-Up Multicenter Study

OBJECTIVES This study analyzed the association of left ventricular end-systolic diameter (LVESD) with survival after diagnosis in organic mitral regurgitation (MR) due to flail leaflets. BACKGROUND LVESD is a marker of left ventricular function in patients with organic MR but its association to survival after diagnosis is unknown. METHODS The MIDA (Mitral Regurgitation International Database) registry is a multicenter registry of echocardiographically diagnosed organic MR due to flail leaflets. We enrolled 739 patients with MR due to flail leaflets (age 65 +/- 12 years; ejection fraction: 65 +/- 10%) in whom LVESD was measured (36 +/- 7 mm). RESULTS Under conservative management, 10-year survival and survival free of cardiac death were higher with LVESD <40 mm versus > or =40 mm (64 +/- 5% vs. 48 +/- 10%; p < 0.001, and 73 +/- 5% vs. 63 +/- 10%; p = 0.001). LVESD > or =40 mm independently predicted overall mortality (hazard ratio [HR]: 1.95, 95% confidence interval [CI]: 1.01 to 3.83) and cardiac mortality (HR: 3.09, 95% CI: 1.35 to 7.09) under conservative management. Mortality risk increased linearly with LVESD >40 mm (HR: 1.15, 95% CI: 1.04 to 1.27 per 1-mm increment). During the entire follow-up (including post-surgical), LVESD > or =40 mm independently predicted overall mortality (HR: 1.86, 95% CI: 1.24 to 2.80) and cardiac mortality (HR: 2.14, 95% CI: 1.29 to 3.56), due to persistence of excess mortality in patients with LVESD > or =40 mm after surgery (HR: 1.86, 95% CI: 1.11 to 3.15 for overall death, and HR: 1.81, 95% CI: 1.05 to 3.54 for cardiac death). CONCLUSIONS In MR due to flail leaflets, LVESD > or =40 mm is independently associated with increased mortality under medical management but also after mitral surgery. These findings support prompt surgical rescue in patients with LVESD > or =40 mm but also suggest that best preservation of survival is achieved in patients operated before LVESD reaches 40 mm.

Outcomes in Mitral Regurgitation Due to Flail Leaflets: A Multicenter European Study

OBJECTIVES The purpose of this study was to assess incidence and predictors of events associated with nonsurgical and surgical management of severe mitral regurgitation (MR) in European institutions. BACKGROUND The management of patients with MR remains disputed, warranting multicenter studies to define clinical outcome in routine clinical practice. METHODS The MIDA (Mitral Regurgitation International DAtabase) is a registry created for multicenter study of MR with echocardiographically diagnosed flail leaflet as a model of pure, organic MR. Our cases were collected from 4 European centers. We enrolled 394 patients (age 64 +/- 11 years; 67% men; 64% in New York Heart Association functional class I to II; left ventricular ejection fraction 67 +/- 10%). RESULTS During a median follow-up of 3.9 years, linearized event rates/year under nonsurgical management were 5.4% for atrial fibrillation (AF), 8.0% for heart failure (HF), and 2.6% for death. Mitral valve (MV) surgery was performed in 315 (80%) patients (repair in 250 of 315, 80%). Perioperative mortality, defined as death within 30 days from the operation, was 0.7% (n = 2). Surgery during follow-up was independently associated with reduced risk of death (adjusted hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.21 to 0.84; p = 0.014). Benefit was largely driven by MV repair (adjusted HR vs. replacement 0.37, 95% CI 0.18 to 0.76; p = 0.007). In 102 patients strictly asymptomatic and with normal ventricular function, 5-year combined incidence of AF, HF, or cardiovascular death (CVD) was 42 +/- 8%. In these patients, surgery also reduced rates of CVD/HF (HR 0.26, 95% CI 0.08 to 0.89; p = 0.032). CONCLUSIONS In this multicenter study, nonsurgical management of severe MR was associated with notable rates of adverse events. Surgery especially MV repair performed during follow-up was beneficial in reducing rates of cardiac events. These findings support surgical consideration in patients with MR due to flail leaflets for whom MV repair is feasible.

Prognostic and therapeutic implications of pulmonary hypertension complicating degenerative mitral regurgitation due to flail leaflet: A Multicenter Long-term International Study

AIMS To determine the frequency, predictors, and outcome implications of pulmonary hypertension (PH) diagnosed by Doppler echocardiography in a large cohort of patients with the homogenous diagnosis of degenerative mitral regurgitation (MR) due to flail leaflets. METHODS AND RESULTS The Mitral Regurgitation International DAtabase (MIDA) is a registry including patients with MR due to flail leaflets consecutively referred at tertiary centres in Europe and the USA. Between 1987 and 2004, pulmonary artery systolic pressure (PASP) was measured at baseline by Doppler echocardiography in 437 patients (age 67 ± 11 years; 66% men). Pulmonary hypertension (PASP > 50 mmHg) was observed in 102 patients (23%). Independent predictors of PH were age and left atrial size (P < 0.0001). During a mean follow-up of 4.8 ± 2.8 years, PH was a strong independent predictor of death [adjusted HR 2.03 (1.30-3.18) P = 0.002], cardiovascular death [CVD; adjusted HR 2.21 (1.30-3.76) P = 0.003], and heart failure [adjusted HR 1.70 (1.10-2.62) P = 0.018]. Mitral valve surgery at any time during follow-up (performed in 325 patients, 75%) was beneficial [adjusted HR for death 0.22 (0.14-0.36) P < 0.001], but PH was associated with the increased risk of postoperative death and CVD (P = 0.01). CONCLUSION Pulmonary hypertension is a frequent complication of significant MR due to flail leaflet and is associated with major outcome implications, approximately doubling the risk of death and heart failure after diagnosis. Mitral valve surgery performed during follow-up is beneficial but does not completely abolish the adverse effects of PH once it is established and is particularly beneficial in patients without PH. These data support relieving PH secondary to MR due to flail leaflet, but also careful consideration for mitral surgery before PH is established.

Good Prognosis for Pericarditis With and Without Myocardial Involvement Results From a Multicenter, Prospective Cohort Study

Background— The natural history of myopericarditis/perimyocarditis is poorly known, and recently published studies have presented contrasting data on their outcomes. The aim of the present article is to assess the prognosis of myopericarditis/perimyocarditis in a multicenter, prospective cohort study. Methods and Results— A total of 486 patients (median age, 39 years; range, 18–83 years; 300 men) with acute pericarditis or a myopericardial inflammatory syndrome (myopericarditis/perimyocarditis; 85% idiopathic, 11% connective tissue disease or inflammatory bowel disease, 5% infective) were prospectively evaluated from January 2007 to December 2011. The diagnosis of acute pericarditis was based on the presence of 2 of 4 clinical criteria (chest pain, pericardial rubs, widespread ST-segment elevation or PR depression, and new or worsening pericardial effusion). Myopericardial inflammatory involvement was suspected with atypical ECG changes for pericarditis, arrhythmias, and cardiac troponin elevation or new or worsening ventricular dysfunction on echocardiography and confirmed by cardiac magnetic resonance. After a median follow-up of 36 months, normalization of left ventricular function was achieved in >90% of patients with myopericarditis/perimyocarditis. No deaths were recorded, as well as evolution to heart failure or symptomatic left ventricular dysfunction. Recurrences (mainly as recurrent pericarditis) were the most common complication during follow-up and were recorded more frequently in patients with acute pericarditis (32%) than in those with myopericarditis (11%) or perimyocarditis (12%; P<0.001). Troponin elevation was not associated with an increase in complications. Conclusions— The outcome of myopericardial inflammatory syndromes is good. Unlike acute coronary syndromes, troponin elevation is not a negative prognostic marker in this setting.Background— The natural history of myopericarditis/perimyocarditis is poorly known, and recently published studies have presented contrasting data on their outcomes. The aim of the present article is to assess the prognosis of myopericarditis/perimyocarditis in a multicenter, prospective cohort study. Methods and Results— A total of 486 patients (median age, 39 years; range, 18–83 years; 300 men) with acute pericarditis or a myopericardial inflammatory syndrome (myopericarditis/perimyocarditis; 85% idiopathic, 11% connective tissue disease or inflammatory bowel disease, 5% infective) were prospectively evaluated from January 2007 to December 2011. The diagnosis of acute pericarditis was based on the presence of 2 of 4 clinical criteria (chest pain, pericardial rubs, widespread ST-segment elevation or PR depression, and new or worsening pericardial effusion). Myopericardial inflammatory involvement was suspected with atypical ECG changes for pericarditis, arrhythmias, and cardiac troponin elevation or new or worsening ventricular dysfunction on echocardiography and confirmed by cardiac magnetic resonance. After a median follow-up of 36 months, normalization of left ventricular function was achieved in >90% of patients with myopericarditis/perimyocarditis. No deaths were recorded, as well as evolution to heart failure or symptomatic left ventricular dysfunction. Recurrences (mainly as recurrent pericarditis) were the most common complication during follow-up and were recorded more frequently in patients with acute pericarditis (32%) than in those with myopericarditis (11%) or perimyocarditis (12%; P <0.001). Troponin elevation was not associated with an increase in complications. Conclusions— The outcome of myopericardial inflammatory syndromes is good. Unlike acute coronary syndromes, troponin elevation is not a negative prognostic marker in this setting. # Clinical Perspective {#article-title-31}

Prognostic implications of functional mitral regurgitation according to the severity of the underlying chronic heart failure: a long-term outcome study

To examine the independent prognostic role of functional mitral regurgitation (FMR) and its impact across the severity of chronic heart failure (CHF) in a large population of outpatients with systolic CHF followed at two multidisciplinary clinics.

Left Atrial Size is a Potent Predictor of Mortality in Mitral Regurgitation Due to Flail Leaflets: Results from a Large International Multicenter Study

Background— Left atrium (LA) enlargement is common in organic mitral regurgitation (MR) and is an emerging prognostic indicator. However, outcome implications of LA enlargement have not been analyzed in the context of routine clinical practice and in a multicenter study. Methods and Results— The Mitral Regurgitation International DAtabase (MIDA) registry enrolls patients with organic MR due to flail leaflets, diagnosed in routine clinical practice, in 5 US and European centers. We investigated the relation between LA diameter and mortality under medical treatment and after mitral surgery in 788 patients in sinus rhythm (64±12 years; median LA, 48 [43 to 52] mm). LA diameter was independently associated with survival after diagnosis (hazard ratio, 1.08 [1.04 to 1.12] per 1 mm increment). Compared with patients with LA <55 mm, those with LA ≥55 mm had lower 8-year overall survival (P<0.001). LA ≥55 mm independently predicted overall mortality (hazard ratio, 3.67 [1.95 to 6.88]) and cardiac mortality (hazard ratio, 3.74 [1.72 to 8.13]) under medical treatment. The association of LA ≥55 mm and mortality was consistent in subgroups. Similar excess mortality associated with LA ≥55 mm was observed in asymptomatic and symptomatic patients (P for interaction, 0.77). In patients who underwent mitral surgery, LA ≥55 mm had no impact on postoperative outcome (P>0.20). Mitral surgery was associated with greater survival benefit in patients with LA ≥55 mm compared with LA <55 mm (P for interaction, 0.008). Conclusions— In MR caused by flail leaflets, LA diameter ≥55 mm is associated with increased mortality under medical treatment, independent of the presence of symptoms or left ventricular dysfunction.

Twenty-Year Outcome after Mitral Repair Versus Replacement for Severe Degenerative Mitral Regurgitation. Analysis of a Large, Prospective, Multicenter International Registry.

Background: Mitral valve (MV) repair is preferred over replacement in clinical guidelines and is an important determinant of the indication for surgery in degenerative mitral regurgitation. However, the level of evidence supporting current recommendations is low, and recent data cast doubts on its validity in the current era. Accordingly, the aim of the present study was to analyze very long-term outcome after MV repair and replacement for degenerative mitral regurgitation with a flail leaflet. Methods: MIDA (Mitral Regurgitation International Database) is a multicenter registry enrolling patients with degenerative mitral regurgitation with a flail leaflet in 6 tertiary European and US centers. We analyzed the outcome after MV repair (n=1709) and replacement (n=213) overall, by propensity score matching, and by inverse probability-of-treatment weighting. Results: At baseline, patients undergoing MV repair were younger, had more comorbidities, and were more likely to present with a posterior leaflet prolapse than those undergoing MV replacement. After propensity score matching and inverse probability-of-treatment weighting, the 2 treatments groups were balanced, and absolute standardized differences were usually <10%, indicating adequate match. Operative mortality (defined as a death occurring within 30 days from surgery or during the same hospitalization) was lower after MV repair than after replacement in both the entire population (1.3% versus 4.7%; P<0.001) and the propensity-matched population (0.2% versus 4.4%; P<0.001). During a mean follow-up of 9.2 years, 552 deaths were observed, of which 207 were of cardiovascular origin. Twenty-year survival was better after MV repair than after MV replacement in both the entire population (46% versus 23%; P<0.001) and the matched population (41% versus 24%; P<0.001). Similar superiority of MV repair was obtained in patient subsets on the basis of age, sex, or any stratification criteria (all P<0.001). MV repair was also associated with reduced incidence of reoperations and valve-related complications. Conclusions: Among patients with degenerative mitral regurgitation with a flail leaflet referred to mitral surgery, MV repair was associated with lower operative mortality, better long-term survival, and fewer valve-related complications compared with MV replacement.

Long-term mortality associated with left ventricular dysfunction in mitral regurgitation due to flail leaflets: a multicenter analysis.

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.

Relevance of cardioverter defibrillators for the prevention of sudden cardiac death on the timing of heart transplantation

Abstract:  Information on the incidence of decompensation of chronic heart failure (CHF) in heart transplantation (HT) candidates eligible for prophylactic implantable cardioverter defibrillators (ICD) could provide insights into the influence of ICD on the timing for HT.