Constrictive pericarditis following heart transplantation: Reality or fiction?

Constrictive pericarditis (CP) is a curable cause of diastolic heart failure with prior cardiac surgery being a recognizable etiology. We report a patient who developed CP one year following heart transplantation. Several clinical and imaging related factors may lead to diagnostic delays in similar patients, including the mistaken belief that transplanted hearts are devoid of pericardium and thus do not develop constriction. Post-transplantation pericardial effusion, mediastinitis, and cardiac rejection predispose to future CP. Caretakers should consider this entity in allograft recipients who develop heart failure symptoms of unclear etiology.

Rate, Timing, Correlates, and Outcomes of Hemodynamic Valve Deterioration After Bioprosthetic Surgical Aortic Valve Replacement.

BACKGROUND: The incidence of structural valve deterioration after bioprosthesis (BP) aortic valve replacement (AVR) established on the basis of reoperation may substantially underestimate the true incidence. The objective is to determine the rate, timing, correlates, and association between hemodynamic valve deterioration (HVD) and outcomes assessed by Doppler echocardiography after surgical BP AVR. METHODS: A total of 1387 patients (62.2% male, 70.5±7.8 years of age) who underwent BP AVR were included in this retrospective study. Baseline echocardiography was performed at a median time of 4.1 (1.3-6.5) months after AVR. All patients had an echocardiographic follow-up ≥2 years after AVR (926 at least 5 years and 385 at least 10 years). HVD was defined by Doppler assessment as a ≥10 mm Hg increase in mean gradient or worsening of transprosthetic regurgitation ≥1/3 class. HVD was classified according to the timing after AVR: "very early," during the first 2-years; "early," between 2 and 5 years; "midterm," between 5 and 10 years; and "long-term," >10 years. RESULTS: A total of 428 patients (30.9%) developed HVD. Among these patients, 52 (12.0%) were classified as "very early," 129 (30.1%) as "early," 158 (36.9%) as "midterm," and 89 (20.8%) as "long-term" HVD. Factors independently associated with HVD occurring within the first 5 years after AVR were diabetes mellitus ( P=0.01), active smoking ( P=0.01), renal insufficiency ( P=0.01), baseline postoperative mean gradient ≥15 mm Hg ( P=0.04) or transprosthetic regurgitation ≥mild ( P=0.04), and type of BP (stented versus stentless, P=0.003). Factors associated with HVD occurring after the fifth year after AVR were female sex ( P=0.03), warfarin use ( P=0.007), and BP type ( P<0.001). HVD was independently associated with mortality (hazard ratio, 2.18; 95% CI, 1.86-2.57; P<0.001). CONCLUSIONS: HVD as identified by Doppler echocardiography occurred in one third of patients and was associated with a 2.2-fold higher adjusted mortality. Diabetes mellitus and renal insufficiency were associated with early HVD, whereas female sex, warfarin use, and stented BPs (versus stentless) were associated with late HVD.

Cardiac remodeling after six weeks of high-intensity interval training to exhaustion in endurance-trained men.

High-intensity interval training (HIIT) improves physical performance of endurance athletes, although studies examining its cardiovascular effects are sparse. We evaluated the impact of HIIT on blood pressure, heart rate, and cardiac cavities' size and function in endurance-trained adults. Seventeen endurance-trained men underwent 24-h ambulatory blood pressure monitoring and Doppler echocardiography at baseline and after 6 wk of HIIT. Participants were divided into 2 groups [85% maximal aerobic power (HIIT85), n = 8 and 115% maximal aerobic power (HIIT115), n = 9] to compare the impact of different HIIT intensities. Ambulatory blood pressure monitoring and cardiac chambers' size and function were similar between groups at baseline. HIIT reduced heart rate (55 ± 8 vs. 51 ± 7 beats/min; P = 0.003), systolic blood pressure (121 ± 11 vs. 118 ± 9 mmHg; P = 0.01), mean arterial pressure (90 ± 8 vs. 89 ± 6 mmHg; P = 0.03), and pulse pressure (52 ± 6 vs. 49 ± 5 mmHg; P = 0.01) irrespective of training intensity. Left atrium volumes increased after HIIT (maximal: 50 ± 14 vs. 54 ± 14 mL; P = 0.02; minimal: 15 ± 5 vs. 20 ± 8 mL; P = 0.01) in both groups. Right ventricle global longitudinal strain lowered after training in the HIIT85 group only (20 ± 4 vs. 17 ± 3%, P = 0.04). In endurance-trained men, 6 wk of HIIT reduced systolic blood pressure and mean arterial pressure and increased left atrium volumes irrespective of training intensity, whereas submaximal HIIT deteriorated right ventricle systolic function.NEW & NOTEWORTHY The novel findings of this study are that 6 wk of high-intensity interval training increases left atrial volumes irrespective of training intensity (85 or 115% maximal aerobic power), whereas the submaximal training decreases right ventricular systolic function in endurance-trained men. These results may help identify the exercise threshold for potential toxicity of intense exercise training for at-risk individuals and ideal exercise training regimens conferring optimal cardiovascular protection and adapted endurance training for athletes.

Echocardiographic evaluation of prosthetic heart valves.

The specific flow pattern and imaging features of prosthetic heart valves poses major challenges for the Doppler echocardiographic assessment of prosthetic valve structure and function. A comprehensive approach that integrates several semi-quantitative and quantitative parameters obtained from multiple views is key to appropriately detect and quantitate prosthetic valve dysfunction and complications. In patients with prosthetic valves, and particularly in those with mitral prostheses, transesophageal echocardiography is often required to confirm and/or complement information obtained by transthoracic echocardiography. Three-dimensional echocardiography may provide incremental information for the identification of the underlying etiology of prosthetic valve stenosis or regurgitation. Transcatheter aortic valve implantation has rapidly expanded in the past 10 years and paravalvular regurgitation is frequent following this procedure. Given that paravalvular regurgitant jets are often multiple, irregular, and eccentric, the grading of this type of regurgitation is particularly challenging and requires an integrative multiwindow, multiplane, multiparametric approach.

Left ventricular contractile reserve in asymptomatic primary mitral regurgitation.

AIMS: There are very few data regarding the assessment and prognostic value of left ventricular contractile reserve (LVCR) in asymptomatic patients with primary mitral regurgitation (MR). We aimed to quantify LVCR and to evaluate its usefulness for risk stratification in asymptomatic patients with primary MR. METHODS AND RESULTS: Comprehensive resting and exercise (EX) transthoracic echocardiography, including two-dimensional speckle tracking quantification, were performed in 115 consecutive asymptomatic patients with ≥ moderate degenerative MR and no LV dysfunction/dilatation. Left ventricular contractile reserve was defined as an EX-induced increase in LV ejection fraction (LVCR(LVEF)) ≥ 4% or in LV global longitudinal strain (LVCR(GLS)) ≥ 2%. LVCR(LVEF) was present in 54 patients (47%) and LVCR(GLS) in 58 (50%). The brain natriuretic peptide (BNP) level was significantly correlated with EX-induced changes in GLS (r = 0.45, P < 0.0001), but not in LVEF (r = 0.09, P = 0.31). Patients with no LVCR(GLS) had significant lower 3-year cardiac event-free survival (42 ± 8 vs. 69 ± 7%, P = 0.0008). In contrast, there was no significant difference in outcome regarding to the presence or absence of LVCR(LVEF) (60 ± 7 vs. 51 ± 8%, P = 0.40). The multivariable Cox proportional hazard model showed that the absence of LVCR(GLS) was a strong independent predictor of cardiac events (HR = 2.27, 95% CI: 1.05-4.76, P = 0.037), even after adjustment for Ex-echo variables and BNP level. The association between LVCR(GLS) and outcome remained significant (HR = 1.6, 95% CI: 1.1-2.3, P = 0.01) after further adjustment for the resting echocardiographic parameters included in the ESC Guidelines. CONCLUSION: In asymptomatic primary MR, LVCR seems to be better assessed using EX-induced changes in LV myocardial longitudinal function rather than in LVEF. In patients with preserved LV function, the absence of LVCR is independently associated with two-fold increase in risk of cardiac events. Left ventricular contractile reserve may be useful to improve risk stratification and clinical decision-making in these patients.

Lp-PLA2 is associated with structural valve degeneration of bioprostheses.

OBJECTIVES: In this study, we sought to determine the metabolic markers associated with structural valve degeneration (SVD). BACKGROUND: Structural valve degeneration (SVD) is the major cause of bioprosthetic valve failure leading to bioprostheses (BPs) stenosis or regurgitation. We hypothesized that lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the SVD of BPs. METHODS: We included 197 patients who underwent aortic valve replacement with a bioprosthetic valve and had echocardiographic follow-up to evaluate valve function. Moreover, explanted BPs (n = 39) were analysed by immunohistochemistry for the expression of Lp-PLA2. RESULTS: After a mean follow-up of 7·9 ±0·2 years, forty-one patients (21%) were identified as developing SVD. Patients with SVD had significantly higher plasma level of Lp-PLA2 mass (151·8 ± 9·2 ng/mL vs. 133·2 ± 3·4 ng/mL, P = 0·03) and activity (27·6 ± 0·9 nmol/min/mL vs. 25·0 ± 0·4 nmol/min/mL, P = 0·005). Multivariate analysis revealed that Lp-PLA2 activity (OR: 1·09, 95% CI: 1·01-1·18; P = 0·03) was the strongest independent predictor of SVD. Immunohistochemistry studies of explanted BP showed that 77% of explanted BPs had the expression of Lp-PLA2, which correlated with the density of macrophages (CD68), and ox-LDL levels in bioprosthetic tissues. CONCLUSIONS: Increased blood plasma activity of Lp-PLA2 is associated with higher prevalence of SVD. These findings open new avenues for the identification of patients at risk for SVD and for the development of pharmacotherapy aiming at the prevention of SVD.

Clinical significance of myocardial contraction fraction in significant primary mitral regurgitation.

BACKGROUND: The optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains a matter of debate. Myocardial contraction fraction (MCF) - the ratio of the left ventricular (LV) stroke volume to that of the myocardial volume - is a volumetric measure of LV myocardial shortening independent of size or geometry. AIM: To assess the relationship between MCF and outcome in patients with significant chronic primary MR due to prolapse managed in contemporary practice. METHODS: Clinical, Doppler-echocardiographic and outcome data prospectively collected in 174 patients (mean age 62 years, 27% women) with significant primary MR and no or mild symptoms were analysed. The impact of MCF< or ≥30% on cardiac events (cardiovascular death, acute heart failure or MV surgery) was studied. RESULTS: During an estimated median follow-up of 49 (22-77) months, cardiac events occurred in 115 (66%) patients. The 4-year estimates of survival free from cardiac events were 21±5% for patients with MCF <30% and 40±6% for those with ≥30% (P<0.001). MCF <30% was associated with a considerable increased risk of cardiac events after adjustment for established clinical risk factors, MR severity and current recommended class I triggers for MV surgery (adjusted hazard ratio: 2.33, 95% confidence interval: 1.51-3.58; P<0.001). Moreover, MCF<30% improved the predictive performance of models, with better global fit, reclassification and discrimination. CONCLUSIONS: MCF<30% is strongly associated with occurrence of cardiac events in patients with significant primary MR due to prolapse. Further studies are needed to assess the direct impact of MCF on patient management and outcomes.

Association between remnant cholesterol and progression of bioprosthetic valve degeneration.

AIMS: Remnant cholesterol (RC) seems associated with native aortic stenosis. Bioprosthetic valve degeneration may share similar lipid-mediated pathways with aortic stenosis. We aimed to investigate the association of RC with the progression of bioprosthetic aortic valve degeneration and ensuing clinical outcomes. METHODS AND RESULTS: We enrolled 203 patients with a median of 7.0 years (interquartile range: 5.1-9.2) after surgical aortic valve replacement. RC concentration was dichotomized by the top RC tertile (23.7 mg/dL). At 3-year follow-up, 121 patients underwent follow-up visit for the assessment of annualized change in aortic valve calcium density (AVCd). RC levels showed a curvilinear relationship with an annualized progression rate of AVCd, with increased progression rates when RC >23.7 mg/dL (P = 0.008). There were 99 deaths and 46 aortic valve re-interventions in 133 patients during a median clinical follow-up of 8.8 (8.7-9.6) years. RC >23.7 mg/dL was independently associated with mortality or re-intervention (hazard ratio: 1.98; 95% confidence interval: 1.31-2.99; P = 0.001). CONCLUSION: Elevated RC is independently associated with faster progression of bioprosthetic valve degeneration and increased risk of all-cause mortality or aortic valve re-intervention.

Integrating Echocardiography Parameters With Explainable Artificial Intelligence for Data-Driven Clustering of Primary Mitral Regurgitation Phenotypes.

BACKGROUND: Primary mitral regurgitation (MR) is a heterogeneous clinical disease requiring integration of echocardiographic parameters using guideline-driven recommendations to identify severe disease. OBJECTIVES: The purpose of this preliminary study was to explore novel data-driven approaches to delineate phenotypes of MR severity that benefit from surgery. METHODS: The authors used unsupervised and supervised machine learning and explainable artificial intelligence (AI) to integrate 24 echocardiographic parameters in 400 primary MR subjects from France (n = 243; development cohort) and Canada (n = 157; validation cohort) followed up during a median time of 3.2 years (IQR: 1.3-5.3 years) and 6.8 (IQR: 4.0-8.5 years), respectively. The authors compared the phenogroups' incremental prognostic value over conventional MR profiles and for the primary endpoint of all-cause mortality incorporating time-to-mitral valve repair/replacement surgery as a covariate for survival analysis (time-dependent exposure). RESULTS: High-severity (HS) phenogroups from the French cohort (HS: n = 117; low-severity [LS]: n = 126) and the Canadian cohort (HS: n = 87; LS: n = 70) showed improved event-free survival in surgical HS subjects over nonsurgical subjects (P = 0.047 and P = 0.020, respectively). A similar benefit of surgery was not seen in the LS phenogroup in both cohorts (P = 0.70 and P = 0.50, respectively). Phenogrouping showed incremental prognostic value in conventionally severe or moderate-severe MR subjects (Harrell C statistic improvement; P = 0.480; and categorical net reclassification improvement; P = 0.002). Explainable AI specified how each echocardiographic parameter contributed to phenogroup distribution. CONCLUSIONS: Novel data-driven phenogrouping and explainable AI aided in improved integration of echocardiographic data to identify patients with primary MR and improved event-free survival after mitral valve repair/replacement surgery.

Significance of Left Ventricular Ejection Time in Primary Mitral Regurgitation.

The optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains controversial. We aimed at evaluating the relation between left ventricular ejection time (LVET) and outcome in patients with moderate or severe chronic primary MR because of prolapse. Clinical, Doppler echocardiographic, and outcome data prospectively collected from 302 patients (median age 61 [54 to 74] years, 34% women) with moderate or severe primary MR were analyzed. Patients were retrospectively stratified by quartiles of LVET. The primary end point of the study was the composite of need for MV surgery or all-cause mortality. During a median follow-up time of 66 (25th to 75th percentile, 33 to 95) months, 178 patients reached the primary end point. Patients in the lowest quartile of LVET (<260 ms) were at high risk for adverse events compared with those in the other quartiles of LVET (global p = 0.005), whereas the rate of events was similar for the other quartiles (p = NS for all). After adjustment for clinical predictors of outcome, including age, gender, history of atrial fibrillation, MR severity, and current recommended triggers for MV surgery in asymptomatic primary MR, LVET <260 ms was associated with an increased risk of events (adjusted hazard ratio 1.49, 95% confidence interval 1.03 to 2.16, p = 0.033). In conclusion, we observed that shorter LVET is associated with increased risk of adverse events in patients with moderate or severe primary MR because of prolapse. Further studies are required to investigate whether shorter LVET has a direct effect on outcomes or is solely a risk marker in primary MR.

Cardiac Damage Staging Classification in Asymptomatic Moderate or Severe Primary Mitral Regurgitation.

Background: Optimal timing for intervention remains uncertain in asymptomatic patients with primary mitral regurgitation (MR). We aimed to assess the prognostic value of a new cardiac damage staging classification in patients with asymptomatic moderate or severe primary MR. Methods: Clinical, Doppler-echocardiographic, and outcome data prospectively collected in 338 asymptomatic patients (64 ± 15 years, 68% men) with at least moderate primary MR were retrospectively analyzed. Patients were hierarchically classified as per the following staging classification: no cardiac damage (stage 0), mild left ventricular or left atrial damage (stage 1), moderate or severe left ventricular or left atrial damage (stage 2), pulmonary vasculature or tricuspid valve damage (stage 3), or right ventricular damage (stage 4). Results: There was a stepwise increase in 10-year mortality rates as per cardiac damage stage: 20.0% in stage 0, 25.6% in stage 1, 31.5% in stage 2, and 61.3% in stage 3-4 (p < 0.001). The staging classification was significantly associated with increased risk of mortality (hazard ratio = 1.41 per one-stage increase, 95% confidence interval: 1.07-1.85, p = 0.015) and the composite of cardiovascular mortality or hospitalization (hazard ratio = 1.51 per one-stage increase, 95% confidence interval: 1.07-2.15, p = 0.020) in multivariable analysis adjusted for EuroSCORE II, mitral valve intervention as a time-dependent variable, and other risk factors. The proposed scheme showed incremental value over several clinical variables (net reclassification index = 0.40, p = 0.03). Conclusions: The new staging classification provides independent and incremental prognostic value in patients with asymptomatic moderate or severe MR.

Spectral Doppler Interrogation of the Pulmonary Veins for the Diagnosis of Cardiac Disorders: A Comprehensive Review.

Data obtained from echocardiographic studies are used on a daily basis to guide clinical decision-making regarding patient management and the need for additional diagnostic investigations. Interrogation of blood flow in the pulmonary veins by spectral, most often pulsed-wave, Doppler is an important component of any comprehensive echocardiographic study. Whereas it is most often used to help assess left-sided filling pressure and quantify the severity of mitral regurgitation, the pulmonary vein Doppler profile provides added diagnostic insights into several disorders that affect heart function and allows assessment of their hemodynamic consequences on the heart. The aim of this review is to summarize current knowledge in the field of PV Doppler interrogation, highlight the physiological and pathological parameters that influence it, and delineate the manifestations of various cardiovascular disorders on the flow profile.

Association of Bioprosthetic Aortic Valve Leaflet Calcification on Hemodynamic and Clinical Outcomes.

BACKGROUND: The prognostic value of aortic valve calcification (AVC) measured by using multidetector computed tomography imaging has been well validated in native aortic stenosis, and sex-specific thresholds have been proposed. However, few data are available regarding the impact of leaflet calcification on outcomes after biological aortic valve replacement (AVR). OBJECTIVES: The goal of this study was to analyze the association of quantitative bioprosthetic leaflet AVC with hemodynamic and clinical outcomes, as well as its possible interaction with sex. METHODS: From 2008 to 2010, a total of 204 patients were prospectively enrolled with a median of 7.0 years (interquartile range: 5.1 to 9.2 years) after biological surgical AVR. AVC measured by using the Agatston method was indexed to the cross-sectional area of aortic annulus measured by echocardiography to calculate the AVC density (AVCd). Presence of hemodynamic valve deterioration (HVD; increase in mean gradient [MG] ≥10 mm Hg and/or increase in transprosthetic regurgitation ≥1) was assessed by echocardiography in 137 patients at the 3-year follow-up. The primary clinical endpoint was mortality or aortic valve re-intervention. RESULTS: There was no significant sex-related difference in the relationship between bioprosthetic AVCd and the progression of MG. Baseline AVCd showed an independent association with HVD at 3 years. During follow-up, there were 134 (65.7%) deaths (n = 100) or valve re-interventions (n = 47). AVCd ≥58 AU/cm2 was independently associated with an increased risk of mortality or aortic valve re-intervention (adjusted hazard ratio: 2.23; 95% confidence interval: 1.44 to 3.35; p < 0.001). The AVCd threshold combined with an MG progression threshold of 10 mm Hg amplified the stratification of patients at risk (log-rank, p < 0.001). The addition of AVCd threshold into the prediction model including traditional risk factors improved outcome prediction (net classification improvement: 0.25, p = 0.04; likelihood ratio test, p < 0.001). CONCLUSIONS: Aortic bioprosthetic leaflet calcification is strongly and independently associated with HVD and the risk of death or aortic valve re-intervention. As opposed to native aortic stenosis, there is no sex-related differences in the relationship between AVCd and hemodynamic or clinical outcomes.

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.

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.

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

BACKGROUND: Although heart failure (HF) is frequent in elderly patients, few studies have focused on patients older than 80 years. AIMS: To evaluate the clinical features, treatment and long-term prognosis of HF in patients older than 80 years. METHODS AND RESULTS: Consecutive patients hospitalised for a first HF episode in the Somme Department (France) during 2000 were prospectively included. Of the 799 included patients, 305 (38%) were aged over 80 years. The elderly patients were mostly women with a high prevalence of atrial fibrillation, ischaemic and hypertensive heart disease. Ejection fraction (EF) was assessed in 68.5% of elderly patients and 61% had EF >or=50%. Angiotensin-converting enzyme inhibitors, beta-blockers, oral anticoagulants and statins were prescribed less frequently in elderly patients. The 5-year survival in elderly patients was 19%, dramatically lower than the survival of age- and sex-matched general population (48%). Cardiovascular causes were recorded in over 60% of deaths. On multivariable analysis, cancer, renal insufficiency, old myocardial infarction, diabetes, hyponatraemia and age were predictors of mortality in elderly patients. Reduced EF was a potent predictor of death (HR 1.72, 95%CI 1.24-2.37, p=0.001) in elderly patients. CONCLUSION: Long-term prognosis in HF patients older than 80 years is poor, with a dramatic excess mortality compared to the elderly general population. Life-saving drugs are largely underused in elderly HF patients.

Clinical and genetic investigation of atrial septal defect with atrioventricular conduction defect in a large consanguineous Tunisian family.

BACKGROUND: Atrial septal defect (ASD) is an autosomal dominant disease characterized by left-to-right shunting and increased right ventricular output. Approximately 5-10% of congenital heart diseases (CHD) are due to ASD, which is one of the most frequent CHD found in adults. The gene responsible for ASD was mapped to chromosome 5q35 encoding the transcription factor NKX2-5 that plays an important role for the regulation of septation during cardiac morphogenesis. METHODS: A Tunisian family including four affected members was investigated. Individuals were genotyped using the polymorphic microsatellite markers D5S394 and D5S2069 overlapping the NKX2-5 gene. RESULTS: We report here clinical and molecular investigation of a Tunisian consanguineous family with four affected members. Two presented with ASD associated with prolonged PR interval, whereas the other two presented only a prolonged PR interval. We also identified five asymptomatic individuals in the same family with ventricular preexcitation. Although the patients were products of a consanguineous marriage, no other abnormalities were observed in this family. Genotyping and linkage analysis showed exclusion of linkage between the gene responsible for ASD in this family and NKX2.5 gene. CONCLUSIONS: Our results further confirm the genetic heterogeneity of ASD.

Hemodynamic Deterioration of Surgically Implanted Bioprosthetic Aortic Valves.

BACKGROUND: Dysmetabolic profile has been associated with native aortic valve stenosis. However, there are limited data on the effects of an atherogenic milieu and its potential implications on the structural and hemodynamic deterioration of aortic bioprosthetic valves. OBJECTIVES: This prospective longitudinal study sought to determine the predictors and impact on outcomes of hemodynamic valve deterioration (HVD) of surgically implanted aortic bioprostheses. METHODS: A total of 137 patients with an aortic bioprosthesis implanted for a median time of 6.7 (interquartile range: 5.1 to 9.1) years prospectively underwent a first (baseline) assessment with complete Doppler echocardiography, quantitation of bioprosthesis leaflet calcification by multidetector computed tomography (CT), and a fasting blood sample to assess cardiometabolic risk profile. All patients underwent a second (follow-up) Doppler echocardiography examination at 3 (interquartile range: 2.9 to 3.3) years post-baseline visit. HVD was defined by an annualized change in mean transprosthetic gradient ≥3 mm Hg/year and/or worsening or transprosthetic regurgitation by ≥1/3 class. The primary endpoint was a nonhierarchical composite of death from any cause or aortic reintervention procedure (redo surgical valve replacement or transcatheter valve-in-valve implantation) for bioprosthesis failure. RESULTS: Thirty-four patients (25.6%) had leaflet calcification on baseline CT, and 18 patients (13.1%) developed an HVD between baseline and follow-up echocardiography. Fifty-two patients (38.0%) met the primary endpoint during subsequent follow-up after the second echocardiographic examination. Leaflet calcification (hazard ratio [HR]: 2.58; 95% confidence interval [CI]: 1.35 to 4.82; p = 0.005) and HVD (HR: 5.12; 95% CI: 2.57 to 9.71; p < 0.001) were independent predictors of the primary endpoint. Leaflet calcification, insulin resistance (homeostatic model assessment index ≥2.7), lipoprotein-associated phospholipase A2 activity (Lp-PLA2 per 0.1 nmol/min/ml increase), and high level of proprotein convertase subtilisin/kexin 9 (PCSK9) (≥305 ng/ml) were associated with the development of HVD after adjusting for age, sex, and time interval since aortic valve replacement. CONCLUSIONS: HVD identified by Doppler echocardiography is independently associated with a marked increase in the risk of valve reintervention or mortality in patients with a surgical aortic bioprosthesis. A dysmetabolic profile characterized by elevated plasma Lp-PLA2, PCSK9, and homeostatic model assessment index was associated with increased risk of HVD. The presence of leaflet calcification as detected by CT was a strong predictor of HVD, providing incremental risk-predictive capacity.

Forward Left Ventricular Ejection Fraction: A Simple Risk Marker in Patients With Primary Mitral Regurgitation.

BACKGROUND: The timing of mitral valve surgery in asymptomatic patients with primary mitral regurgitation (MR) is controversial. We hypothesized that the forward left ventricular (LV) ejection fraction (LVEF; ie, LV outflow tract stroke volume divided by LV end-diastolic volume) is superior to the total LVEF to predict outcomes in MR. The objective of this study was to examine the association between echocardiographic parameters of MR severity and LV function and outcomes in patients with MR. METHODS AND RESULTS: The clinical and Doppler-echocardiographic data of 278 patients with ≥mild MR and no class I indication of mitral valve surgery at baseline were retrospectively analyzed. The primary study end point was the composite of mitral valve surgery or death. During a mean follow-up of 5.4±3.2 years, there were 147 (53%) events: 96 (35%) MV surgeries and 66 (24%) deaths. Total LVEF and global longitudinal strain were not associated with the occurrence of events, whereas forward LVEF (P<0.0001) and LV end-systolic diameter (P=0.0003) were. After adjustment for age, sex, MR severity, Charlson probability, coronary artery disease, and atrial fibrillation, forward LVEF remained independently associated with the occurrence of events (adjusted hazard ratio: 1.09, [95% confidence interval]: 1.02-1.17 per 5% decrease; P=0.01), whereas LV end-systolic diameter was not (P=0.48). CONCLUSIONS: The results of this study suggest that the forward LVEF may be superior to the total LVEF and LV end-systolic diameter to predict outcomes in patients with primary MR. This simple and easily measurable parameter may be useful to improve risk stratification and select the best timing for intervention in patients with primary MR.

Prosthesis-Patient Mismatch After Aortic Valve Replacement.

OPINION STATEMENT: Prosthesis-patient mismatch (PPM) occurs when the effective orifice area (EOA) of a normally functioning prosthesis is too small in relation to the patient's body size, resulting in abnormally high postoperative gradients. PPM is frequent following aortic valve replacement (AVR), and it is associated with increased risk of morbidity and mortality proportionally to its severity. Differential diagnosis between PPM and prosthetic valve stenosis is made by comparing the measured valve effective orifice area, by assessing the changes in valve area and gradient during follow-up and by evaluating leaflet morphology and mobility. Preventive strategies to avoid or minimize PPM should be implemented especially in the patients who are at high risk for severe PPM and in those who have vulnerability factors to PPM. Transcatheter AVR may be superior to surgical AVR for the prevention of PPM and associated adverse cardiac events, particularly in the subset of patients with a small (<21 mm) aortic annulus. In this article, we discuss the most updated data regarding the diagnosis, clinical impact, and prevention of PPM after AVR.