Olcay Aksoy

Percutaneous coronary intervention in patients with severe aortic stenosis: implications for transcatheter aortic valve replacement.

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). In addition, AS patients with high Society of Thoracic Surgeons score (≥10) had a higher 30-day post-PCI mortality than those with a Society of Thoracic Surgeons score <10 (10.4% [10 of 96] versus 0%; P<0.001). Conclusions— PCI can be performed in patients with severe symptomatic AS and coronary artery disease without an increased risk of short-term mortality compared with propensity-matched patients without AS. Patients with ejection fraction ⩽30% and Society of Thoracic Surgeons score ≥10% are at a highest risk of 30-day mortality after PCI. This finding has significant implications in the management of severe coronary artery disease in high-risk severe symptomatic AS patients being considered for transcatheter aortic valve replacement.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). In addition, AS patients with high Society of Thoracic Surgeons score (≥10) had a higher 30-day post-PCI mortality than those with a Society of Thoracic Surgeons score <10 (10.4% [10 of 96] versus 0%; P <0.001). Conclusions— PCI can be performed in patients with severe symptomatic AS and coronary artery disease without an increased risk of short-term mortality compared with propensity-matched patients without AS. Patients with ejection fraction ≤30% and Society of Thoracic Surgeons score ≥10% are at a highest risk of 30-day mortality after PCI. This finding has significant implications in the management of severe coronary artery disease in high-risk severe symptomatic AS patients being considered for transcatheter aortic valve replacement. # Clinical Perspective {#article-title-29}

Do Bisphosphonates Slow the Progression of Aortic Stenosis

OBJECTIVES The aim of this study was to investigate the impact of bisphosphonates on the progression of aortic stenosis. BACKGROUND Valvular calcification is associated with the development and progression of aortic stenosis. Bisphosphonates have been suggested to slow this progression. METHODS Female patients older than the age of 60 years with an aortic valve area (AVA) between 1.0 and 2.0 cm(2) were identified and studied retrospectively. Only those who had follow-up echocardiograms at least a year apart were included. Primary outcomes were the change in AVA and valvular gradients over time. Mortality and freedom from aortic valve replacement were also studied. A propensity-matching method was applied for the probability of the use of bisphosphonates. RESULTS The study included 801 female patients (mean age, 76 ± 7.6 years) with a mean follow-up of 5.1 ± 2.4 years. The mean duration of bisphosphonate use was 3.1 ± 2.6 years. At the time of the initial echocardiogram, 323 patients (38%) were taking bisphosphonates. The mean ejection fraction at baseline was 56.7 ± 9.6% with a mean AVA of 1.32 ± 0.25 cm(2). Peak and mean gradients were 28.4 ± 11 mm Hg and 15.6 ± 6.8 mm Hg, respectively. Propensity matching was successfully performed for 438 patients. On follow-up, there were no differences in the rate of change in AVA or peak and mean gradients when patients were stratified based on the use of bisphosphonates. Bisphosphonates also had no impact on survival or freedom from aortic valve replacement. CONCLUSIONS In this retrospective analysis of older female patients, bisphosphonates do not have a significant impact on the hemodynamic or clinical progression of aortic stenosis.

Significance of Aortic Valve Calcification in Patients With Low‐Gradient Low‐Flow Aortic Stenosis

Assessment of patients with aortic stenosis (AS) and impaired left ventricular function remains challenging. Aortic valve calcium (AVC) scoring with computed tomography (CT) and fluoroscopy has been proposed as means of diagnosing and predicting outcomes in patients with severe AS.

Comparison of Ascending Aortic Size in Patients With Severe Bicuspid Aortic Valve Stenosis Treated With Versus Without a Statin Drug

Ascending aortic dilation commonly occurs in patients with bicuspid aortic valve (BAV). Statins have been shown to reduce the expression of matrix metalloproteinases and slow the progression of abdominal aortic aneurysms. The role of statins in slowing ascending aortic dilation in patients with BAV is unknown. We sought to compare the ascending aortic dimensions in patients with BAV stenosis treated with versus without a statin. From our catheterization laboratory database, all patients undergoing preoperative coronary angiography before aortic valve with or without ascending aorta replacement for bicuspid aortic stenosis (AS) from 2004 to 2007 were identified. The ascending aortic size was measured on their preoperative transesophageal echocardiogram. Data on statin use were obtained from chart review, and the ascending aortic size was compared between patients taking and not taking a statin. The study sample included 147 patients, of whom 76 were treated with statins (mean age 62 ± 9 years, 72% men) and 71 were not (mean age 59 ± 12 years, 68% men). The total and low-density lipoprotein cholesterol and triglyceride levels were significantly lower in the statin group. The ascending aorta size was significantly lower in the statin subgroup of the pure severe AS group (3.6 ± 0.7 cm vs 3.9 ± 0.6 cm, p < 0.01) but not in the mixed severe AS and severe aortic regurgitation group. In the pure severe AS group, significantly fewer patients taking a statin had an ascending aorta ≥ 4 cm (29% vs 52%, p < 0.02). On multivariate analysis, statin use was the only independent predictor of aortic size and was associated with a 0.33-cm reduction in aortic size (95% confidence interval 0.06 to 0.59, p < 0.01). In conclusion, patients with statin-treated BAV stenosis have a smaller ascending aortic size than patients with BAV untreated with statins.

Carotid stenting vs surgery: Parsing the risk of stroke and MI

The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) is the largest randomized prospective study to date to compare carotid artery stenting and carotid endarterectomy in a patient population similar to that seen in everyday practice. CREST showed stenting and surgery to be equivalent in terms of the composite end point of stroke, myocardial infarction (MI), or death within 30 days, as well as for the rate of stroke at up to 4 years (N Engl J Med 2010; 363:11–23). Importantly, the risk of major stroke was low with either intervention. However, the results need to be considered in the context of the impact of each procedure on stroke and MI. For patients with carotid artery stenosis, percutaneous intervention with stenting is as good as surgery—with some qualifications.The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) is the largest randomized prospective study to date to compare carotid artery stenting and carotid endarterectomy in a patient population similar to that seen in everyday practice. CREST showed stenting and surgery to be equivalent in terms of the composite end point of stroke, myocardial infarction (MI), or death within 30 days, as well as for the rate of stroke at up to 4 years (N Engl J Med 2010; 363:11-23). Importantly, the risk of major stroke was low with either intervention. However, the results need to be considered in the context of the impact of each procedure on stroke and MI.

Renin-angiotensin system blockade therapy after surgical aortic valve replacement for severe aortic stenosis: A cohort study

Context Although angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers improve survival rates in heart failure, whether reninangiotensin system (RAS) blockade therapy is associated with improved survival rates after surgical aortic valve replacement (SAVR) for severe aortic stenosis is unknown. Contribution This retrospective cohort study found that prescribing RAS blockade therapy after SAVR for severe aortic stenosis was associated with improved survival rates. Caution Patient treatments were not randomly assigned, so whether RAS blockade therapy caused the observed improved survival rates cannot be determined. Implication A randomized trial is needed to evaluate the use of RAS blockade after SAVR for severe aortic stenosis. The Editors Aortic stenosis (AS) is a common valve disease in the aging population (1). Surgical aortic valve replacement (SAVR) is the gold standard therapy for operable patients with severe symptomatic AS (2). Severe AS is associated with progressive left ventricular hypertrophy (LVH) and diastolic dysfunction. Persistence of LVH and diastolic dysfunction after SAVR are associated with reduced long-term survival (35). Inhibition of the reninangiotensin system (RAS) with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) is associated with modulation of adverse left ventricular (LV) remodeling and reduction in myocardial hypertrophy and fibrosis, resulting in clinical improvement in patients with heart failure; however, this has not been studied in patients with severe AS. In addition, the role of RAS blockade therapy after SAVR for severe AS is unknown. We hypothesize that RAS inhibition may improve outcomes in patients after SAVR and that the mechanism may be related to LV remodeling secondary to regression of LVH and LV mass. Therefore, we sought to investigate the association between RAS blockade therapy and outcomes after SAVR for severe symptomatic AS. Methods Patients The study population consisted of adult patients who had primary SAVR for severe AS at the Cleveland Clinic Foundation (Cleveland, Ohio) from 1 January 1991 through 31 December 2010. Severe AS was defined as an aortic valve area of less than 1 cm2. Patients with predominant aortic regurgitation, infective endocarditis, rheumatic valve disease, or indications for SAVR other than AS were excluded. This cohort was then stratified on the basis of postoperative usage of RAS blockade therapy with ACE inhibitors or ARBs. Patients who were discharged with prescriptions for ACE inhibitors or ARBs after SAVR and had at least 2 confirmed refills (that is, the prescription was dispensed to the patient twice, 90 days apart) constituted the RAS blockade group, and those not prescribed any ACE inhibitor or ARB were in the control group. A patient had to be alive long enough to have had a prescription refilled 90 days after discharge after SAVR to be qualified to be in the ACE inhibitor or ARB group. Therefore, a patient had to survive 90 days after discharge to be eligible for this study. Patients who did not have at least 90 days of follow-up were excluded. It is assumed that the patient filled the prescription and consumed the medication as advised when the prescription was dispensed. The duration of treatment with ACE inhibitors or ARBs was ascertained by reviewing the electronic medical chart for refills ordered by the managing health provider. We excluded patients who did not have at least a 6-month follow-up in our health system after SAVR and patients who were not treated with ACE inhibitors or ARBs after SAVR but were prescribed them at some point during follow-up (crossover patients) (Figure 1). Preoperative, operative, and postoperative variables were retrieved from the computerized, prospective Cleveland Clinic Cardiovascular Information Registry and echocardiographic variables from the Echocardiography Database. Both databases were approved for research by the Institutional Review Board at the Cleveland Clinic Foundation, with patient consent waived. Figure 1. Study flow diagram. ACE = angiotensin-converting enzyme; ARB = angiotensin-receptor blocker; AS = aortic stenosis; RAS = reninangiotensin system; SAVR = surgical aortic valve replacement. Echocardiography Preoperative measurements were retrieved from the transthoracic echocardiography performed nearest to, but preceding, the date of SAVR. Left ventricular mass was calculated using the formula validated by Devereux and colleagues (6). Peak instantaneous aortic valve gradients were calculated from Doppler velocity, and aortic valve area was calculated using the continuity equation. Echocardiography was done routinely before discharge and at the discretion of referring physicians during follow-up. Identical measurements were made on all available postoperative transthoracic echocardiographies. Postoperative echocardiography reports were used to assess the intermediate and long-term changes in LV mass, left ventricular ejection fraction (LVEF), and left atrial (LA) size. Follow-up echocardiography was evaluated at as many time points as possible for each patient. Follow-up Follow-up was obtained through the Cleveland Clinic Cardiovascular Information Registry at the Cleveland Clinic Foundation and supplemented with Social Security Death Index data. The Social Security Death Index was last run on 27 October 2011 with a lag time of 6 months and the closing date set for 27 April 2011. Outcomes All-cause mortality was the primary outcome we assessed. Secondary outcomes were regression of LV mass and changes in LVEF and LA size after SAVR. Statistical Analysis Group Differences and Propensity Score Matching To reduce or eliminate bias between the RAS blockade and nonRAS blockade groups, differences between these groups were determined and a propensity score was formed to adjust for group differences in subsequent analyses. Multivariable logistic regression was first performed to identify preoperative factors associated with RAS blockade therapy after SAVR. Variables that were considered in this analysis are listed in the Supplement. We used bootstrap bagging with automated analysis of 500 resampled data sets, followed by tabulating the frequency of occurrence at a P value of 0.05 or less of both single factors and closely related clusters of factors (7, 8). A parsimonious model was then constructed, retaining factors that occurred in 50% or more of the bootstrap models. Thereafter, this model was augmented with all other available preoperative variables (or a single representative factor from every cluster of highly correlated variables) in an attempt to account for any unrecorded selection factors and to form a saturated model (9). By solving this equation, we estimated a propensity score, which represents the probability of the patient receiving RAS blockade therapy with ACE inhibitors or ARBs, for each patient. Propensity scores were used for matching to evaluate the outcomes between more comparable groups. Using the propensity score on the probability scale, we matched patients receiving RAS blockade therapy to those who were not receiving it by using a greedy matching strategy (10). Greedy matching obtains matches patient by patient, finding the nearest neighbor; once a match is formed, that patient is not reused. Patients receiving RAS blockade therapy whose propensity scores deviated more than 0.10 from those of patients who were not receiving RAS blockade therapy were considered unmatched. This caliper was chosen because it provided a sufficient set of matches (80%) and matches across the range of propensity scores. In this retrospective observational study, many variables had small amounts of missing values. Therefore, we used 5-fold multiple imputation (11) applying Markov chain Monte Carlo technique to impute the missing values (SAS PROC MI, SAS Software, SAS Institute). On the basis of each imputed complete data set, we estimated propensity scores for each patient. We then used the average of the propensity scores over the 5 imputed complete data sets as the final estimate of the propensity score for each patient (12). Supplement. Additional Data for Propensity Analyses, Echocardiography Data, and Separate Analyses Without Exclusion of Patients Who Were Not Followed at the Cleveland Clinic Foundation Survival Overall and stratified nonparametric survival estimates were obtained by the KaplanMeier method. A parametric method was used to resolve the number of phases of instantaneous risk for death (hazard function) and to estimate the shaping variables (13, 14). The effects of RAS therapy and concomitant coronary artery bypass grafting (CABG) were analyzed in the overall and matched cohorts. Adjusted survival rates comparing the RAS blockade and nonRAS blockade groups were evaluated by using the propensity score as a continuous variable and forcing it into each phase of the hazard model and by using the matched groups and forcing the group variable only into each hazard phase. In addition, subgroup analyses were done using simple Cox proportional hazard models (SAS PROC PHREG) containing RAS group, the subgroup factor, and the corresponding interaction term. Hazard ratios and 95% CIs are provided for several subgroups that were defined a priori and investigated. Time zero for all analyses was the date of SAVR. Left Heart Reverse Remodeling Time Course To assess the temporal trend of the LV mass index, LVEF, and LA size, we analyzed follow-up transthoracic echocardiograms longitudinally for patterns of change across time, from time of SAVR. Nonlinear mixed model regression analysis (1517) was used to resolve many time phases to form a temporal decomposition model and to estimate the shaping variables at each phase (18). Mixed model regression for continuous repeated measurements (SAS PROC NLMIXED) was used to implement the temporal decomposition model. A normal distribution was assumed for the patient-spec

Outcomes of Patients With Ischemic Mitral Regurgitation Undergoing Percutaneous Coronary Intervention

Ischemic mitral regurgitation (IMR) is associated with poor outcomes in patients with coronary artery disease. The impact of percutaneous coronary intervention (PCI) on patients with IMR is not well elucidated. We sought to determine the outcomes of patients with severe IMR who underwent PCI. Patients with severe (≥3+) IMR who underwent PCI from 1998 to 2010 were identified. Improvement in IMR was defined as reduction in severity from ≥3+ to ≤2+ without any other invasive intervention beyond PCI. Outcomes were compared between patients with and without improvement in IMR after PCI. One hundred thirty-seven patients with severe IMR were included in our study. After PCI, 50 patients (36.5%) had improvement in IMR with PCI alone and 24 patients (18.5%) required another intervention. Left atrial size was a significant predictor of improvement in IMR (odds ratio 0.39, 95% confidence interval 0.2 to 0.8). Left ventricular size decreased (systolic diameter 3.9±0.3 vs 4.6±0.2 cm, p=0.0008 and diastolic diameter 5.2±0.2 vs 5.7±0.2 cm, p=0.002) and ejection fraction increased (39.1±4.0% vs 33.1±1.9%, p=0.002) significantly after PCI in the patients with improvement in IMR compared with patients without improvement. Patients with improvement in IMR had numerically better survival; however, it was not statistically significant (p log-rank=0.2). In conclusion, 1/3 of the patients with IMR had improvement in severity of IMR with PCI alone. Improvement in IMR was associated with left ventricular reverse remodeling. Left atrial size was an important predictor of improvement in IMR after PCI.

Comparison of acute elastic recoil between the SAPIEN‐XT and SAPIEN valves in transfemoral–transcatheter aortic valve replacement

The SAPIEN‐XT is a newer generation balloon‐expandable valve created of cobalt chromium frame, as opposed to the stainless steel frame used in the older generation SAPIEN valve. We sought to determine if there was difference in acute recoil between the two valves.

Percutaneous coronary revascularization in coronary artery disease: lessons from a single center experience.

To determine the role of percutaneous coronary intervention (PCI) and its impact on mortality in coronary artery disease (CAD).

Evaluation of Cardiac Allograft Vasculopathy: From Angiography to Intravascular Ultrasound and Beyond

Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality after heart transplantation and results from complex mechanisms ultimately leading to diffuse intimal hyperplasia throughout the coronary vasculature. Available treatment options, at best slow the progression of disease and if diagnosed late, outcomes remain poor. Early diagnosis of CAV is of critical importance as timely and aggressive treatments can be associated with improved long-term outcomes.