Clinical, pathological and genetic basis of bicuspid aortic valve disease

Bicuspid aortic valve (BAV), the most common congenital heart defect, is a clinically heterogeneous disorder with valve dysfunction and related aortopathy being the major complications. While familial clustering and heritability of BAV have been increasingly recognised, the underlying genetic basis of BAV disease in humans remains mostly undetermined. The genes and molecular pathways that drive specific phenotypic expression and determine clinical outcome are poorly understood. Further, identification of individuals with BAV who are at the highest risk for complications presents a challenging task for most clinicians today. The works described in this thesis aimed to address these gaps on our present knowledge of BAV disease. These included the investigation of genetics underlying BAV development using candidate gene approach and exome sequencing, elucidation of genes and molecular pathway that determine valve degeneration in adults with BAV using RNA-sequencing, and efforts to identify novel imaging biomarkers that can be used to predict those with the highest risk for aortic complications using state-of-the-art real-time exercise CMR imaging. Overall, these works have provided an important step forward in our efforts to gain greater understanding on the pathogenetic basis of BAV disease, as well as forming an important foundation for future research within the field

Transcatheter aortic valve implantation for high-risk patients with severe aortic stenosis: A systematic review

ObjectivesThe present systematic review objectively assessed the safety and clinical effectiveness of transcatheter aortic valve implantation for patients at high surgical risk with severe aortic stenosis.MethodsElectronic searches were performed in 6 databases from January 2000 to March 2009. The end points included feasibility, safety, efficacy, and durability. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies.ResultsThe current evidence on transcatheter aortic valve implantation for aortic stenosis is limited to short-term observational studies. The overall procedural success rates ranged from 74% to 100%. The incidence of major adverse events included 30-day mortality (0%–25%), major ventricular tachyarrhythmia (0%–4%), myocardial infarction (0%–15%), cardiac tamponade (2%–10%), stroke (0%–10%), conversion to surgery (0%–8%), moderate to major paravalvular leak (4%–35%), vascular complication (8%–17%), valve-in-valve procedure (2%–12%), and aortic dissection/perforation (0%–4%). The overall 30-day major adverse cardiovascular and cerebral events ranged from 3% to 35%. The mean aortic valve area ranged from 0.5 to 0.8 cm2 before and 1.3 to 2.0 cm2 after transcatheter aortic valve implantation. The mean pressure gradient ranged from 34 to 58 mm Hg before and 3 to 12 mm Hg after transcatheter aortic valve implantation. There was no significant deterioration in echocardiography measurements during the assessment period. Death rate at 6 months postprocedure ranged from 18% to 48%. No studies had adequate follow-up to reliably evaluate long-term outcomes.ConclusionsThe procedure has a potential for serious complications. Although short-term efficacy based on echocardiography measurements is good, there is little evidence on long-term outcomes. The use of transcatheter aortic valve implantation should be considered only within the boundaries of clinical trials

Outcomes in moderate mixed aortic valve disease: is it time for a paradigm shift?

Background A direct comparison of outcomes between moderate mixed aortic valve disease (MAVD) and isolated aortic stenosis (AS) or aortic regurgitation (AR) has not been performed, making evidence-based recommendations difficult in patients with MAVD. Objectives This study sought to determine adverse event (AE) occurrence (the primary endpoint), defined as New York Heart Association functional class III/IV symptoms, aortic valve replacement, or cardiac death, and to compare AE rates between MAVD and isolated AS or AR. Methods Asymptomatic patients were identified with moderate MAVD and an ejection fraction ≥50% and were followed at Mayo Clinic from 1994 to 2013. Moderate MAVD was defined as a combination of moderate AS and moderate AR. Age- and sex-matched control groups were selected with isolated moderate AR (n = 117), moderate AS (n = 117), or severe AS (n = 117). Results At 9.1 ± 4.2 years of follow-up, patients with moderate MAVD (n = 251) had a mean age of 63 ± 11 years, 73% were male, and 38% had bicuspid valve. AE occurred in 193 (77%) patients in this group, including symptom development (69%), aortic valve replacement (67%), and cardiac death (4%). Predictors of AE were older age (hazard ratio [HR]: 1.71 per decade; 95% confidence interval [CI]: 1.38 to 1.97 per decade; p = 0.001), and relative wall thickness >0.42 (HR: 2.01; 95% CI: 1.86 to 2.33; p = 0.002). AE rates were similar in the MAVD and severe AS group (71% vs. 68% at 5 years; p = 0.49), but were significantly higher compared with the moderate AS and AR groups. Conclusions MAVD patients had outcomes comparable to those with severe AS, and preserved ejection fraction and should be monitored closely for symptoms

Off-pump coronary artery bypass surgery versus percutaneous coronary intervention : a meta-analysis of randomized and nonrandomized studies

We performed a meta-analysis of all studies comparing off-pump coronary artery bypass graft surgery (OPCABG) and percutaneous coronary intervention (PCI) for patients with coronary artery disease. Ten studies were included in the meta-analysis and 4,821 patients were compared, of whom 3,450 patients underwent PCI and 1,371 patients underwent OPCABG. The rates of stroke, myocardial infarction, cardiac mortality, and all-cause mortality were similar. The 12-month rate of major adverse cardiac or cerebrovascular events and need for repeat revascularization was significantly lower in the OPCABG group when compared with the PCI group.7 page(s

Drug-eluting stents versus coronary artery bypass grafting for the treatment of coronary artery disease : a meta-analysis of randomized and nonrandomized studies

Background: We performed the present systematic review and meta-analysis of randomized and nonrandomized comparative studies in an attempt to compare the safety and efficacy of drug-eluting stents with coronary artery bypass grafting for patients with coronary artery disease. Methods: Twenty-five eligible comparative studies (1 randomized and 24 nonrandomized) were assessed. Two reviewers independently appraised each study. Meta-analysis was performed by combining the results of reported incidence of morbidity, mortality, and repeat revascularization. The relative risk was used as a summary statistic. Results: In these 25 studies 34,278 patients were compared, of whom 18,538 received drug-eluting stents and 15,740 underwent coronary artery bypass grafting. It must be acknowledged that this comparison represented a selected group of patients who received drug-eluting stents or underwent coronary artery bypass grafting. The accumulative incidences of all-cause mortality at 12 months (4.5% vs 4.0%, P = .92) and 24 months (6.2% vs 8.4%, P = .27) and 30-day myocardial infarction (1.4% vs 2.0%, P = .60) were similar, respectively, between the drug-eluting stent and coronary artery bypass grafting groups. Drug-eluting stents were associated with lower rates of all-cause mortality at 30 days (0.9% vs 2.3%, P < .001), stroke (0.4% vs 1.7%, P < .001), and 30-day major adverse cardiac and cerebrovascular events (3.6% vs 5.5%, P < .04). However, the coronary artery bypass grafting group had a lower incidence of postprocedural myocardial infarction (5.5% vs 4.7%, P = .03), repeat revascularization (22.2% vs 4.1%, P < .001), and 12-month major adverse cardiac and cerebrovascular events (16.7% vs 10.5%, P < .001). Subgroup analysis of patients with multivessel coronary artery disease showed similar results. Conclusions: Drug-eluting stents are associated with less periprocedural risks but a higher incidence of postprocedural myocardial infarction, repeat revascularization, and 12-month major adverse cardiac and cerebrovascular events compared with coronary artery bypass grafting.11 page(s

The Genetic and molecular basis of bicuspid aortic valve associated thoracic aortopathy : a link to phenotype heterogeneity

9 page(s