Severe aortic stenosis and coronary artery disease--implications for management in the transcatheter aortic valve replacement era: a comprehensive review.

With increased life expectancy and aging of the population, aortic stenosis is now one of the most common valvular heart diseases. Early recognition and management of aortic stenosis are of paramount importance because untreated symptomatic severe disease is universally fatal. The advent of transcather aortic valve replacement technologies provides exciting avenues of care to patients with this disease in whom traditional surgical procedures could not be performed or were associated with high risk. This review for clinicians offers an overview of aortic stenosis and updated information on the current status of various treatment strategies. An electronic literature search of PubMed, MEDLINE, EMBASE, and Scopus was performed from conception July 1, 2016, through November 30, 2017, using the terms aortic stenosis, aortic valve replacement, transcatheter aortic valve replacement (TAVR), transcatheter aortic valve insertion (TAVI), surgical aortic valve replacement, aortic stenosis flow-gradient patterns, low-flow aortic valve stenosis, natural history, stress testing, pathophysiology, bicuspid aortic valve, and congenital aortic valve disease.

Management of Patients With Aortic Valve Stenosis

The human cardiovascular system is a complex arrangement of specialized structures with distinct functions. The molecular landscape, including the genome, transcriptome and proteome, is pivotal to the biological complexity of both normal and abnormal mammalian processes. Despite our advancing knowledge and understanding of cardiovascular disease (CVD) through the principal use of rodent models, this continues to be an increasing issue in today's world. For instance, as the ageing population increases, so does the incidence of heart valve dysfunction. This may be because of changes in molecular composition and structure of the extracellular matrix, or from the pathological process of vascular calcification in which bone-formation related factors cause ectopic mineralization. However, significant differences between mice and men exist in terms of cardiovascular anatomy, physiology and pathology. In contrast, large animal models can show considerably greater similarity to humans. Furthermore, precise and efficient genome editing techniques enable the generation of tailored models for translational research. These novel systems provide a huge potential for large animal models to investigate the regulatory factors and molecular pathways that contribute to CVD in vivo. In turn, this will help bridge the gap between basic science and clinical applications by facilitating the refinement of therapies for cardiovascular disease.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cbf.3173

Large animal models of cardiovascular disease

Background The impact of coronary artery disease (CAD) on outcomes after transcatheter aortic valve replacement (TAVR) is understudied. Literature on the prognostic role of CAD in the survival of patients undergoing TAVR shows conflicting results. This meta‐analysis aims to investigate how CAD impacts patient survival following TAVR. Methods and Results We completed a comprehensive literature search of Embase, MEDLINE, and the Cochrane Library, and included studies reporting outcome of TAVR based on CAD status of patients for the analysis. From the initial 1631 citations, 15 studies reporting on 8013 patients were analyzed using a random‐effects model. Of the 8013 patients undergoing TAVR, with a median age of 81.3 years (79–85.1 years), 46.6% (40–55.7) were men and 3899 (48.7%) had CAD (ranging from 30.8% to 78.2% in various studies). Overall, 3121 SAPIEN/SAPIEN XT/SAPIEN 3 (39.6%) and 4763 CoreValve (60.4%) prostheses were implanted, with transfemoral access being the most frequently used approach for the implantation (76.1%). Our analysis showed no significant difference between patients with and without CAD for all‐cause mortality at 30 days post TAVR, with a cumulative odds ratio of 1.07 (95% confidence interval, 0.82–1.40; P= 0.62). However, there was a significant increase in all‐cause mortality at 1 year in the CAD group compared with patients without CAD, with a cumulative odds ratio of 1.21 (95% confidence interval, 1.07–1.36; P =0.002). Conclusions Even though coexisting CAD does not impact 30‐day mortality, it does have an impact on 1‐year mortality in patients undergoing TAVR. Our results highlight a need to revisit the revascularization strategies for concomitant CAD in patients with TAVR.

Impact of coronary artery disease on 30-day and 1-year mortality in patients undergoing transcatheter Aortic valve replacement: A meta-analysis

Background—With the availability of transcatheter aortic valve replacement, management of coronary artery disease in patients with severe aortic stenosis (AS) is posing challenges. Outcomes of percutaneous coronary intervention (PCI) in patients with severe AS and coronary artery disease remain unknown. We sought to compare the short-term outcomes of PCI in patients with and without AS. Methods and Results—From our PCI database, we identified 254 patients with severe AS who underwent PCI between 1998 and 2008. Using propensity matching, we found 508 patients without AS who underwent PCI in the same period. The primary end point of 30-day mortality after PCI was similar in patients with and without severe AS (4.3% [11 of 254] versus 4.7% [24 of 508]; hazard ratio, 0.93; 95% confidence interval, 0.51–1.69; P=0.2). Patients with low ejection fraction (≤30%) and severe AS had a higher 30-day post-PCI mortality compared with those with an ejection fraction >30% (5.4% [7 of 45] versus 1.2% [4 of 209]; P<0.001)....

Percutaneous Coronary Intervention in Patients With Severe Aortic Stenosis Implications for Transcatheter Aortic Valve Replacement

Background: Traditional cardiovascular risk factors have been associated with aortic stenosis and coronary artery disease. As these two conditions often co-exist, the association of cardiovascular risk factors with aortic stenosis may reflect confounding. Objective: To compare the cardiovascular risk profile in patients with severe aortic stenosis undergoing elective coronary angiography with that of patients without aortic stenosis or calcification undergoing coronary angiography for suspected coronary artery disease. Methods: 523 patients referred for elective diagnostic left heart catheterisation because of severe aortic stenosis formed the case population; 3925 patients without valve disease referred for elective diagnostic left heart catheterisation formed the base control population. Of the latter, 523 were pair matched to the case population for sex, age, and prevalence of relevant coronary artery disease, forming a pair matched control population. Cardiovascular risk factors (male sex, hypertension, hypercholesterolaemia, smoking, diabetes mellitus, family history of coronary artery disease) were assessed in all the patients. Results: None of the cardiovascular risk factors was more prevalent in patients with aortic stenosis than in the base control population or in the pair matched control population. However, male sex, hypercholesterolaemia, smoking, diabetes mellitus, and a family history of coronary artery disease were significantly associated with the presence of additional coronary artery disease in patients with aortic stenosis. Conclusions: Cardiovascular risk factors are commonly present in patients with aortic stenosis. However, when compared with controls matched for age, sex, and angiographically defined coronary artery disease, no risk factor was significantly associated with the prevalence of aortic stenosis. Thus other factors are likely to be more important in the pathogenesis of aortic stenosis.

https://heart.bmj.com/content/heartjnl/89/9/1019.full.pdf

Cardiovascular risk factors in patients with aortic stenosis predict prevalence of coronary artery disease but not of aortic stenosis: an angiographic pair matched case–control study

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Cardiovascular risk factors in patients with aortic stenosis predict prevalence of coronary artery disease but not of aortic stenosis: an angiographic pair matched case–control study