Genetic Variants in FBN-1 and Risk for Thoracic Aortic Aneurysm and Dissection.

OBJECTIVES: A recent genome wide association study (GWAS) by LeMaire et al. found that two single nucleotide polymorphisms (SNPs), rs2118181 and rs10519177 in the FBN-1 gene (encoding Fibrillin-1), were associated with thoracic aortic dissection (TAD), non-dissecting thoracic aortic aneurysm (TAA), and thoracic aortic aneurysm or dissection (TAAD); the largest effect was observed for the association of rs2118181 with TAD. We investigated whether rs2118181 and rs10519177 were associated with TAD, TAA, and TAAD in the Yale study. METHODS: The genotypes of rs2118181 and rs10519177 were determined for participants in the Yale study: 637 TAAD cases (140 TAD, 497 TAA) and 275 controls from the United States, Hungary, and Greece. The association of the genotypes with TAD, TAA and TAAD were assessed using logistic regression models adjusted for sex, age, study center and hypertension. RESULTS AND CONCLUSIONS: In the Yale study, rs2118181 was associated with TAD: compared with non-carriers, carriers of the risk allele had an unadjusted odds ratio for TAD of 1.80 (95% CI 1.15-2.80) and they had odds ratio for TAD of 1.87 (95% CI 1.09-3.20) after adjusting for sex, age, study center and hypertension. We did not find significant differences in aortic size, a potential confounder for TAD, between rs2118181 risk variant carriers and non-carriers: mean aortic size was 5.56 (95% CI: 5.37-5.73) for risk variant carriers (CC+CT) and was 5.48 (95% CI: 5.36-5.61) for noncarriers (TT) (p = 0.56). rs2118181 was not associated with TAA or TAAD. rs10519177 was not associated with TAD, TAA, or TAAD in the Yale study. Thus, the Yale study provided further support for the association of the FBN-1 rs2118181SNP with TAD

Degenerative mitral valve regurgitation: best practice revolution

Degenerative mitral valve disease often leads to leaflet prolapse due to chordal elongation or rupture, and resulting in mitral valve regurgitation. Guideline referral for surgical intervention centres primarily on symptoms and ventricular dysfunction. The recommended treatment for degenerative mitral valve disease is mitral valve reconstruction, as opposed to valve replacement with a bioprosthetic or mechanical valve, because valve repair is associated with improved event free survival. Recent studies have documented a significant number of patients are not referred in a timely fashion according to established guidelines, and when they are subjected to surgery, an alarming number of patients continue to undergo mitral valve replacement. The debate around appropriate timing of intervention for asymptomatic severe mitral valve regurgitation has put additional emphasis on targeted surgeon referral and the need to ensure a very high rate of mitral valve repair, particularly in the non-elderly population. Current clinical practice remains suboptimal for many patients, and this review explores the need for a ‘best practice revolution’ in the field of degenerative mitral valve regurgitation

Role of computed tomography imaging for transcatheter valvular repair/insertion

During the last decade, the development of transcatheter based therapies has provided feasible therapeutic options for patients with symptomatic severe valvular heart disease who are deemed inoperable. The promising results of many nonrandomized series and recent landmark trials have increased the number of percutaneous transcatheter valve procedures in high operative risk patients. Pre-procedural imaging of the anatomy of the aortic or mitral valve and their spatial relationships is crucial to select the most appropriate device or prosthesis and to plan the percutaneous procedure. Multidetector row computed tomography provides 3-dimensional volumetric data sets allowing unlimited plane reconstructions and plays an important role in pre-procedural screening and procedural planning. This review will describe the evolving role of multidetector row computed tomography in patient selection and strategy planning of transcatheter aortic and mitral valve procedures

Clinical outcomes of conventional surgery versus MitraClip® therapy for moderate to severe symptomatic mitral valve regurgitation in the elderly population: an institutional experience

BACKGROUND: The aim of this study was to compare treatment of moderate to severe symptomatic mitral regurgitation (MR) with either conventional surgery or the mitral valve edge-to-edge device (MitraClip®) in very elderly patients. The newly introduced MitraClip device has demonstrated promising acute results in treating this patient cohort. Also noteworthy is the fact that patients who otherwise would have been denied surgery are increasingly referred for treatment with the MitraClip device. We sought to review our institutional experience, comparing outcomes in both surgical and MitraClip arms of treatment in the elderly population with symptomatic MR. METHODS: From October 2008 through October 2014, 136 consecutive patients aged ≥ 80 with moderate to severe symptomatic MR were scheduled for either conventional surgery or MitraClip intervention. 56 patients ≥ 80 were operated for symptomatic MR and 80 patients ≥ 80 were treated with the mitraClip device. Patients suitable for this study were identified from our hospital database. Patients ≥80 with moderate/severe symptomatic MR treated with either conventional surgery or the MitraClip device were eligible for our analysis. We compared the surgical patient cohort with the mitraClip patient cohort after eliminating patients that did not meet our inclusion criteria. Forty-two patients were identified from the conventional cohort who were then compared with 42 patients from the mitraClip cohort. Forty-two patients (50%) underwent mitral valve repair or replacement (40.5% functional MR, 59.5% organic/mixed MR) and 42 patients (50%) underwent MitraClip intervention (50% functional MR, 50% organic/mixed MR). Associated procedures in the conventional surgical group were myocardial revascularization 38%, pulmonary vein ablation 23.8%, left atrial appendage resection 52.4% and PFO occlusion 11.9%. RESULTS: Patients who underwent MitraClip treatment were though slightly older but the differences did not attain statistical significance (mean, 82.2 ± 1.65 vs 81.7 ± 1.35 years, p = 0,100), had lower LVEF (mean, 47.6 ± 14.2 vs 53.4 ± 14.3, p = 0.072), lower logistic EuroScore II (mean, 11.3 ± 5.63 vs 12.1 ± 10.6, p = 0.655) but higher STS risk score (mean, 11.8 ± 6.7 vs 8.1 ± 5.6, p = 0.008) respectively compared to surgical patients. Procedural success was 100% vs 96% in surgery and MitraClip groups respectively. Thirty -day mortality was 7.1% vs 4.8% (p = 1.000) in surgery and MitraClip group respectively. Residual postoperative MR ≥2 at discharge was present in none of the patients treated surgically, whereas this was the case in 10 (23.8%) patients treated with the MitraClip device. At 1 year a cumulative number of four (9.52%) patients died in the surgical group vs 9 (21.4%) patients who died in the MitraClip group. CONCLUSIONS: Elderly patients presenting with moderate to severe symptomatic MR may either be treated by conventional surgery or with the MitraClip device with acceptable acute outcomes. The decision for treatment with the MitraClip device should not depend on age alone rather on cumulative risk of conventional surgery. Concomitant cardiac pathologies, often times treated simultaneously during surgery for symptomatic MR may be omitted, if patients are scheduled outright to MitraClip treatment. The effect of concomitant cardiac pathologies left untreated at the time of interventional mitral valve repair on outcome after MitraClip therapy remain widely unknown

Dynamic left ventricular dyssynchrony contributes to B-type natriuretic peptide release during exercise in patients with systolic heart failure.

AIMS: Plasma B-type natriuretic peptide (BNP) is an emerging biomarker in heart failure. In this setting, the extent of left ventricular (LV) dyssynchrony contributes to exercise symptoms. Whether exercise-induced changes in LV dyssynchrony might be a trigger of BNP release has never been investigated. METHODS AND RESULTS: Fifty-seven patients with systolic LV dysfunction underwent quantitative analysis of BNP, mitral regurgitation (MR), and dyssynchrony at rest and during exercise. None had inducible ischaemia on perfusion imaging. By multiple regression analysis, end-systolic volume index (P < 0.0001), effective regurgitant orifice (ERO) (P < 0.001), and E/Ea (P = 0.002) emerged as independent determinants of BNP at baseline (R(2) = 0.67). Exercise induced a significant rise in BNP levels (P < 0.0001). In multivariate analysis, a smaller change in systolic blood pressure (P = 0.04), a larger increase in ERO (P = 0.017), and in systolic dyssynchrony index (P = 0.006) during exercise emerged as independent determinants of exercise-induced increases in BNP (R(2) = 0.45). CONCLUSION: MR severity, volume overload, and LV filling pressure are surrogates of BNP at rest. During exercise, changes in BNP reflect the presence of dynamic changes in both LV dyssynchrony and MR severity in the absence of inducible ischaemia