Dan Rusinaru

Outcome After Aortic Valve Replacement for Low-Flow/Low-Gradient Aortic Stenosis Without Contractile Reserve on Dobutamine Stress Echocardiography

OBJECTIVES This study investigated whether aortic valve replacement (AVR) is associated with improved survival in patients with severe low-flow/low-gradient aortic stenosis (LF/LGAS) without contractile reserve (CR) on dobutamine stress echocardiography (DSE). BACKGROUND Patients with LF/LGAS without CR have a high mortality rate with conservative therapy. The benefit of AVR in this subset of patients remains controversial. METHODS Eighty-one consecutive patients with symptomatic calcified LF/LGAS (valve area <or=1 cm(2), left ventricular ejection fraction <or=40%, mean pressure gradient [MPG] <or=40 mm Hg) without CR on DSE were enrolled. Absence of CR was defined as the absence of increase in stroke volume of >or=20% compared with the baseline value. Multivariable analysis and propensity scores were used to compare survival according to whether or not AVR was performed (n = 55). RESULTS Five-year survival was higher in AVR patients compared with medically managed patients (54 +/- 7% vs. 13 +/- 7%, p = 0.001) despite a high operative mortality of 22% (n = 12). An AVR was independently associated with lower 5-year mortality (adjusted hazard ratio from 0.16 to 5.21 varying with time [95% confidence interval: 0.12-3.16 to 0.21-8.50], p = 0.00026). In 42 propensity-matched patients, 5-year survival was markedly improved by AVR (65 +/- 11% vs. 11 +/- 7%, p = 0.019). Associated bypass surgery (p = 0.007) and MPG <or=20 mm Hg (p = 0.035) were independently predictive of operative mortality. Late survival after AVR (excluding operative death) was 69 +/- 8% at 5 years. CONCLUSIONS In patients with LF/LGAS without CR on DSE, AVR is associated with better outcome compared with medical management. Surgery should not be withheld from this subset of patients solely on the basis of lack of CR on DSE.

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.

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.

Low-Gradient, Low-Flow Severe Aortic Stenosis With Preserved Left Ventricular Ejection Fraction: Characteristics, Outcome, and Implications for Surgery

BACKGROUND Severe low-gradient, low-flow (LG/LF) aortic stenosis with preserved left ventricular ejection fraction (EF) has been described as a more advanced form of aortic stenosis. However, the natural history and need for surgery in patients with LG/LF aortic stenosis remain subjects of intense debate. OBJECTIVES We sought to investigate the outcome of LG/LF aortic stenosis in comparison with moderate aortic stenosis and with high-gradient (HG) aortic stenosis in a real-world study, in the context of routine practice. METHODS This analysis included 809 patients (ages 75 ± 12 years) diagnosed with aortic stenosis and preserved EF (≥50%). Patients were divided into 4 groups: mild-to-moderate aortic stenosis; HG aortic stenosis; LG/LF aortic stenosis; and low-gradient, normal-flow (LG/NF) aortic stenosis. RESULTS Compared with mild-to-moderate aortic stenosis patients, LG/LF aortic stenosis patients had smaller valve areas and stroke volumes, higher mean gradients, and comparable degrees of ventricular hypertrophy. Under medical management (22.8 months; range 7 to 53 months), compared with mild-to-moderate aortic stenosis patients, HG aortic stenosis patients were at higher risk of death (adjusted hazard ratio [HR]: 1.47; 95% confidence interval [CI]: 1.03 to 2.07), whereas LG/LF aortic stenosis patients did not have an excess mortality risk (adjusted HR: 0.88; 95% CI: 0.53 to 1.48). During the entire (39.0 months; range 11 to 69 months) follow-up (with medical and surgical management), the mortality risk associated with LG/LF aortic stenosis was close to that of mild-to-moderate aortic stenosis (adjusted HR: 0.96; 95% CI: 0.58 to 1.53), whereas the excess risk of death associated with HG aortic stenosis was confirmed (adjusted HR: 1.74; 95% CI: 1.27 to 2.39). The benefit associated with aortic valve replacement was confined to the HG aortic stenosis group (adjusted HR: 0.29; 95% CI: 0.18 to 0.46) and was not observed for LG/LF aortic stenosis (adjusted HR: 0.75; 95% CI: 0.14 to 4.05). CONCLUSIONS In this study, the outcome of severe LG/LF aortic stenosis with preserved EF was similar to that of mild-to-moderate aortic stenosis and was not favorably influenced by aortic surgery. Further research is needed to better understand the natural history and the progression of LG/LF aortic stenosis.

Impact of chronic obstructive pulmonary disease on long-term outcome of patients hospitalized for heart failure.

Chronic obstructive pulmonary disease (COPD) is a frequently neglected co-morbidity in patients with heart failure (HF). The aim of this study was to evaluate the prognostic impact of COPD in patients hospitalized for HF. Consecutive patients (n=799) admitted for a first episode of HF in all healthcare establishments of the Somme department (France) during 2000 were prospectively enrolled. Baseline characteristics and long-term prognosis were compared according to COPD status. COPD was diagnosed in 156 patients (19.5%). Compared with the no-COPD group, patients with COPD were predominantly men, more often smokers, and had lower discharge prescription rates of beta blockers (6% vs 27%, p<0.001). Five-year survival rate in patients with COPD was significantly lower than that of the no-COPD group (31% vs 42%, p=0.03). Compared with the expected survival of the age- and gender-matched general population, the 5-year survival rate in patients with COPD was dramatically lower (31% vs 71%). On multivariable analysis, COPD was a strong predictor of poorer outcome (hazard ratio 1.53, 95% confidence interval 1.21 to 1.94, p<0.001). COPD was an independent predictor of mortality in patients with preserved left ventricular ejection fraction and in patients with reduced ejection fraction. In conclusion, patients with HF and associated COPD have a poor prognosis with an impressive excess mortality compared to HF patients without COPD and the general population. Beta-blocker prescription rates remain deceptively low in this category of patients with HF.

Outcomes of pseudo-severe aortic stenosis under conservative treatment

AIMS In the setting of low-flow/low-gradient aortic stenosis (LF/LGAS), outcomes of pseudo-severe aortic stenosis (AS) remain poorly described. This study was aimed to assess the outcome of patients with pseudo-severe AS under conservative treatment. METHODS AND RESULTS Among 305 patients from the European Registry of LF/LGAS, the outcomes of the 107 patients followed under conservative treatment were analysed. Based on the results of dobutamine echocardiography, patients were divided into group IA [left ventricular (LV) contractile reserve present with true-severe AS, n = 43], group IB [pseudo-severe AS (n = 29) defined as LV contractile reserve with a final aortic valve area ≥1.2 cm(2) and a mean transaortic pressure gradient <40 mmHg at peak dobutamine infusion], or group II (exhausted LV contractile reserve, n = 35). The rate of death within 5 years was significantly lower in the group IB (43 ± 11%, n = 10), when compared with the group IA (91 ± 6%, n = 33; P = 0.001) and the group II (100%, n = 23; P < 0.001). The Cox proportional hazard model analysis demonstrated that the hazard ratio for death in the group IB remained significantly lower than in the other groups, even after adjustment for currently established risk factors. Furthermore, the 5-year survival of pseudo-severe AS patients was comparable with that of propensity-matched patients with systolic heart failure and no evidence of valve disease. CONCLUSION In patients with pseudo-severe AS, the 5-year survival under conservative treatment is better than in true-severe AS and comparable with that of propensity-matched patients with LV systolic dysfunction and no evidence of valve disease. Further studies are needed to define optimal therapeutic management in these patients.

Long‐term survival in patients older than 80 years hospitalised for heart failure. A 5‐year prospective study

Although heart failure (HF) is frequent in elderly patients, few studies have focused on patients older than 80 years.

Relationship of serum sodium concentration to mortality in a wide spectrum of heart failure patients with preserved and with reduced ejection fraction: an individual patient data meta-analysis

Hyponatraemia has been associated with reduced survival in patients with heart failure and reduced ejection fraction (HF‐REF). The relationship between serum sodium and outcome is unclear in heart failure with preserved (≥50%) ejection fraction (HF‐PEF). Therefore, we used a large individual patient data meta‐analysis to study the risk of death associated with hyponatraemia in HF‐REF and in HF‐PEF.

Effects of age on pulmonary artery systolic pressure at rest and during exercise in normal adults.

AIMS The aim of this study was to explore the range of pulmonary artery systolic pressure (PASP) at rest and with exercise in healthy individuals of various ages, as most studies assumed PASP > 35 mmHg with exercise as the upper limits of normal. METHODS AND RESULTS Seventy healthy volunteers, with a good continuous wave Doppler tricuspid regurgitation signal at rest, underwent quantitative Doppler echocardiographic measurements at rest and during semi-supine exercise test. Pulmonary artery systolic pressure was estimated at rest, at low level (25 W), and at peak exercise using four times tricuspid valve regurgitation velocity squared adding a right atrial pressure of 5 mmHg. During exercise, PASP increased from rest (27 +/- 4 mmHg) to peak (51 +/- 9 mmHg). None of the individuals reached a PASP > or = 60 mmHg at 25 W. Pulmonary artery systolic pressure at peak was higher in individuals > or =60 years old compared with those from 20 to 59 years old (56 +/- 9 vs. 49 +/- 7 mmHg, P = 0.02). Pulmonary artery systolic pressure at peak exercise > or =60 mmHg was found in 36% of the individuals aged from 60 to 70 and in 50% after 70. Age, LV mass, and PASP at rest were independent predictors of PASP at peak exercise. CONCLUSION Pulmonary artery systolic pressure at peak exercise can reach values > or =60 mmHg in many healthy individuals older than 60 with good exercise capacity. However, high levels of PASP > 60 mmHg for low level of exercise should be considered abnormal.