Asim N. Cheema

Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk: acute and late outcomes of the multicenter Canadian experience.

OBJECTIVES The aim of this study was: 1) to evaluate the acute and late outcomes of a transcatheter aortic valve implantation (TAVI) program including both the transfemoral (TF) and transapical (TA) approaches; and 2) to determine the results of TAVI in patients deemed inoperable because of either porcelain aorta or frailty. BACKGROUND Very few data exist on the results of a comprehensive TAVI program including both TA and TF approaches for the treatment of severe aortic stenosis in patients at very high or prohibitive surgical risk. METHODS Consecutive patients who underwent TAVI with the Edwards valve (Edwards Lifesciences, Inc., Irvine, California) between January 2005 and June 2009 in 6 Canadian centers were included. RESULTS A total of 345 procedures (TF: 168, TA: 177) were performed in 339 patients. The predicted surgical mortality (Society of Thoracic Surgeons risk score) was 9.8 +/- 6.4%. The procedural success rate was 93.3%, and 30-day mortality was 10.4% (TF: 9.5%, TA: 11.3%). After a median follow-up of 8 months (25th to 75th interquartile range: 3 to 14 months) the mortality rate was 22.1%. The predictors of cumulative late mortality were peri-procedural sepsis (hazard ratio [HR]: 3.49, 95% confidence interval [CI]: 1.48 to 8.28) or need for hemodynamic support (HR: 2.58, 95% CI: 1.11 to 6), pulmonary hypertension (PH) (HR: 1.88, 95% CI: 1.17 to 3), chronic kidney disease (CKD) (HR: 2.30, 95% CI: 1.38 to 3.84), and chronic obstructive pulmonary disease (COPD) (HR: 1.75, 95% CI: 1.09 to 2.83). Patients with either porcelain aorta (18%) or frailty (25%) exhibited acute outcomes similar to the rest of the study population, and porcelain aorta patients tended to have a better survival rate at 1-year follow-up. CONCLUSIONS A TAVI program including both TF and TA approaches was associated with comparable mortality as predicted by surgical risk calculators for the treatment of patients at very high or prohibitive surgical risk, including porcelain aorta and frail patients. Baseline (PH, COPD, CKD) and peri-procedural (hemodynamic support, sepsis) factors but not the approach determined worse outcomes.

Current Perspectives on Coronary Chronic Total Occlusions The Canadian Multicenter Chronic Total Occlusions Registry

OBJECTIVES The purpose of this study was to determine the prevalence, clinical characteristics, and management of coronary chronic total occlusions (CTOs) in current practice. BACKGROUND There is little evidence in contemporary literature concerning the prevalence, clinical characteristics, and treatment decisions regarding patients who have coronary CTOs identified during coronary angiography. METHODS Consecutive patients undergoing nonurgent coronary angiography with CTO were prospectively identified at 3 Canadian sites from April 2008 to July 2009. Patients with previous coronary artery bypass graft surgery or presenting with acute ST-segment elevation myocardial infarction were excluded. Detailed baseline clinical, angiographic, electrocardiographic, and revascularization data were collected. RESULTS Chronic total occlusions were identified in 1,697 (18.4%) patients with significant coronary artery disease (>50% stenosis in ≥1 coronary artery) who were undergoing nonemergent angiography. Previous history of myocardial infarction was documented in 40% of study patients, with electrocardiographic evidence of Q waves corresponding to the CTO artery territory in only 26% of cases. Left ventricular function was normal in >50% of patients with CTO. Half the CTOs were located in the right coronary artery. Almost half the patients with CTO were treated medically, and 25% underwent coronary artery bypass graft surgery (CTO bypassed in 88%). Percutaneous coronary intervention was done in 30% of patients, although CTO lesions were attempted in only 10% (with 70% success rate). CONCLUSIONS Chronic total occlusions are common in contemporary catheterization laboratory practice. Prospective studies are needed to ascertain the benefits of treatment strategies of these complex patients.

Effects of Radial Versus Femoral Artery Access in Patients With Acute Coronary Syndromes With or Without ST-Segment Elevation

OBJECTIVES The purpose of this study was to determine the consistency of the effects of radial artery access in patients with ST-segment elevation myocardial infarction (STEMI) and in those with non-ST-segment elevation acute coronary syndrome (NSTEACS). BACKGROUND The safety associated with radial access may translate into mortality benefit in higher-risk patients, such as those with STEMI. METHODS We compared efficacy and bleeding outcomes in patients randomized to radial versus femoral access in RIVAL (RadIal Vs femorAL access for coronary intervention trial) (N = 7,021) separately in those with STEMI (n = 1,958) and NSTEACS (n = 5,063). Interaction tests between access site and acute coronary syndrome type were performed. RESULTS Baseline characteristics were well matched between radial and femoral groups. There were significant interactions for the primary outcome of death/myocardial infarction/stroke/non-coronary artery bypass graft-related major bleeding (p = 0.025), the secondary outcome of death/myocardial infarction/stroke (p = 0.011) and mortality (p = 0.001). In STEMI patients, radial access reduced the primary outcome compared with femoral access (3.1% vs. 5.2%; hazard ratio [HR]: 0.60; p = 0.026). For NSTEACS, the rates were 3.8% and 3.5%, respectively (p = 0.49). In STEMI patients, death/myocardial infarction/stroke were also reduced with radial access (2.7% vs. 4.6%; HR 0.59; p = 0.031), as was all-cause mortality (1.3% vs. 3.2%; HR: 0.39; p = 0.006), with no difference in NSTEACS patients. Operator radial experience was greater in STEMI versus NSTEACS patients (400 vs. 326 cases/year, p < 0.0001). In primary PCI, mortality was reduced with radial access (1.4% vs. 3.1%; HR: 0.46; p = 0.041). CONCLUSIONS In patients with STEMI, radial artery access reduced the primary outcome and mortality. No such benefit was observed in patients with NSTEACS. The radial approach may be preferred in STEMI patients when the operator has considerable radial experience. (A Trial of Trans-radial Versus Trans-femoral Percutaneous Coronary Intervention (PCI) Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy [RIVAL]; NCT01014273).

Long-Term Outcomes After Transcatheter Aortic Valve Implantation Insights on Prognostic Factors and Valve Durability From the Canadian Multicenter Experience

OBJECTIVES This study sought to evaluate the long-term outcomes after transcatheter aortic valve implantation (TAVI) in the Multicenter Canadian Experience study, with special focus on the causes and predictors of late mortality and valve durability. BACKGROUND Very few data exist on the long-term outcomes associated with TAVI. METHODS This was a multicenter study including 339 patients considered to be nonoperable or at very high surgical risk (mean age: 81 ± 8 years; Society of Thoracic Surgeons score: 9.8 ± 6.4%) who underwent TAVI with a balloon-expandable Edwards valve (transfemoral: 48%, transapical: 52%). Follow-up was available in 99% of the patients, and serial echocardiographic exams were evaluated in a central echocardiography core laboratory. RESULTS At a mean follow-up of 42 ± 15 months 188 patients (55.5%) had died. The causes of late death (152 patients) were noncardiac (59.2%), cardiac (23.0%), and unknown (17.8%). The predictors of late mortality were chronic obstructive pulmonary disease (hazard ratio [HR]: 2.18, 95% confidence interval [CI]: 1.53 to 3.11), chronic kidney disease (HR: 1.08 for each decrease of 10 ml/min in estimated glomerular filtration rate, 95% CI: 1.01 to 1.19), chronic atrial fibrillation (HR: 1.44, 95% CI: 1.02 to 2.03), and frailty (HR: 1.52, 95% CI: 1.07 to 2.17). A mild nonclinically significant decrease in valve area occurred at 2-year follow-up (p < 0.01), but no further reduction in valve area was observed up to 4-year follow-up. No changes in residual aortic regurgitation and no cases of structural valve failure were observed during the follow-up period. CONCLUSIONS Approximately one-half of the patients who underwent TAVI because of a high or prohibitive surgical risk profile had died at a mean follow-up of 3.5 years. Late mortality was due to noncardiac comorbidities in more than one-half of patients. No clinically significant deterioration in valve function was observed throughout the follow-up period.

Predictive factors, management, and clinical outcomes of coronary obstruction following transcatheter aortic valve implantation: Insights from a large multicenter registry

OBJECTIVES This study sought to evaluate the main baseline and procedural characteristics, management, and clinical outcomes of patients from a large cohort of patients undergoing transcatheter aortic valve implantation (TAVI) who suffered coronary obstruction (CO). BACKGROUND Very little data exist on CO following TAVI. METHODS This multicenter registry included 44 patients who suffered symptomatic CO following TAVI of 6,688 patients (0.66%). Pre-TAVI computed tomography data was available in 28 CO patients and in a control group of 345 patients (comparisons were performed including all patients and a cohort matched 1:1 by age, sex, previous coronary artery bypass graft, transcatheter valve type, and size). RESULTS Baseline and procedural variables associated with CO were older age (p < 0.001), female sex (p < 0.001), no previous coronary artery bypass graft (p = 0.043), the use of a balloon-expandable valve (p = 0.023), and previous surgical aortic bioprosthesis (p = 0.045). The left coronary artery was the most commonly involved (88.6%). The mean left coronary artery ostia height and sinus of Valsalva diameters were lower in patients with obstruction than in control subjects (10.6 ± 2.1 mm vs. 13.4 ± 2.1 mm, p < 0.001; 28.1 ± 3.8 mm vs. 31.9 ± 4.1 mm, p < 0.001). Differences between groups remained significant after the case-matched analysis (p < 0.001 for coronary height; p = 0.01 for sinus of Valsalva diameter). Most patients presented with persistent severe hypotension (68.2%) and electrocardiographic changes (56.8%). Percutaneous coronary intervention was attempted in 75% of the cases and was successful in 81.8%. Thirty-day mortality was 40.9%. After a median follow-up of 12 (2 to 18) months, the cumulative mortality rate was 45.5%, and there were no cases of stent thrombosis or reintervention. CONCLUSIONS Symptomatic CO following TAVI was a rare but life-threatening complication that occurred more frequently in women, in patients receiving a balloon-expandable valve, and in those with a previous surgical bioprosthesis. Lower-lying coronary ostium and shallow sinus of Valsalva were associated anatomic factors, and despite successful treatment, acute and late mortality remained very high, highlighting the importance of anticipating and preventing the occurrence of this complication.

Comparison of coronary artery bypass surgery and percutaneous coronary intervention in patients with diabetes: a meta-analysis of randomised controlled trials

BACKGROUND The choice between coronary artery bypass surgery (CABG) and percutaneous coronary intervention (PCI) for revascularisation in patients with diabetes and multivessel coronary artery disease, who account for 25% of revascularisation procedures, is much debated. We aimed to assess whether all-cause mortality differed between patients with diabetes who had CABG or PCI by doing a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing CABG with PCI in the modern stent era. METHODS We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from Jan 1, 1980, to March 12, 2013, for studies reported in English. Eligible studies were those in which investigators enrolled adult patients with diabetes and multivessel coronary artery disease, randomised them to CABG (with arterial conduits in at least 80% of participants) or PCI (with stents in at least 80% of participants), and reported outcomes separately in patients with diabetes, with a minimum of 12 months of follow-up. We used random-effects models to calculate risk ratios (RR) and 95% CIs for pooled data. We assessed heterogeneity using I(2). The primary outcome was all-cause mortality in patients with diabetes who had CABG compared with those who had PCI at 5-year (or longest) follow-up. FINDINGS The initial search strategy identified 3414 citations, of which eight trials were eligible. These eight trials included 7468 participants, of whom 3612 had diabetes. Four of the RCTs used bare metal stents (BMS; ERACI II, ARTS, SoS, MASS II) and four used drug-eluting stents (DES; FREEDOM, SYNTAX, VA CARDS, CARDia). At mean or median 5-year (or longest) follow-up, individuals with diabetes allocated to CABG had lower all-cause mortality than did those allocated to PCI (RR 0.67, 95% CI 0.52-0.86; p=0.002; I(2)=25%; 3131 patients, eight trials). Treatment effects in individuals without diabetes showed no mortality benefit (1.03, 0.77-1.37; p=0.78; I(2)=46%; 3790 patients, five trials; p interaction=0.03). We identified no differences in outcome whether PCI was done with BMS or DES. When present, we identified no clear causes of heterogeneity. INTERPRETATION In the modern era of stenting and optimum medical therapy, revascularisation of patients with diabetes and multivessel disease by CABG decreases long-term mortality by about a third compared with PCI using either BMS or DES. CABG should be strongly considered for these patients.

Characterization of Operator Learning Curve for Transradial Coronary Interventions

Background—Transradial percutaneous coronary intervention (TR-PCI) improves clinical outcomes compared to the transfemoral (TF) approach. However, inadequate training and experience has limited widespread adoption by interventional cardiologists. Methods and Results—Clinical and procedural characteristics for TR-PCI were prospectively collected from 1999 to 2008. To identify minimum case volume for optimum clinical benefit, single-vessel TR-PCI cases were chronologically ranked and stratified into 1 to 50, 51 to 100, 101 to 150 and 151 to 300 case volume groups for operators starting the TR approach at the study institution. Cases by operators with a >300 TR-PCI case volume comprised the control group. TR-PCI failure rates, contrast use, guide usage, and fluoroscopy time were compared among groups. A total of 1672 patients underwent TR-PCI by 28 operators. TR-PCI failure occurred in 4% and was higher in the 1 to 50 case volume group compared to the 51 to 100 (P=0.007) and control (P=0.01) groups. Contrast use was greater in the 1 to 50 group (180±79 mL) compared to the 151 to 300 (157±75 mL, P=0.02) and control (168±79 mL, P=0.05) groups. Fluoroscopy time was higher in the 1 to 50 group (15±10 minutes) compared to the 101 to 150 (13±10 minutes, P=0.04) and control (12±9 minutes, P=0.02) groups. Reasons for TR-PCI failure included spasm (38%), subclavian tortuousity (16%), poor guide support (16%), failed access (10%), and radial loop (7%). Case volume was significantly correlated with TR-PCI failure (&bgr;=−0.0076, P=0.0028), and odds of failure was reduced by 32% for each 50 increments in case volume. Conclusions—TR-PCI success depends on operator experience, and a case volume of ≥50 cases is required to achieve outcomes comparable to experienced operators. These findings have implications both for PCI operators looking to expand their skills and for defining standards for training.

Mechanism and Predictors of Failed Transradial Approach for Percutaneous Coronary Interventions

OBJECTIVES The study aimed to determine the mechanism and predictors of procedural failure in patients undergoing percutaneous coronary intervention (PCI) from the transradial approach (TR). BACKGROUND Transradial approach PCI reduces vascular complications compared with a transfemoral approach (TF). However, the mechanism and predictors of TR-PCI failure have not been well-characterized. METHODS The study population consisted of patients undergoing TR-PCI by low-to-intermediate volume operators with traditional TF guide catheters. Baseline characteristics, procedure details, and clinical outcomes were prospectively collected. Univariate and multivariate analyses were performed to determine independent predictors of TR-PCI failure. RESULTS A total of 2,100 patients underwent TR-PCI and represented 38% of PCI volume. Mean age was 64 +/- 12 years, and 17% were female. Vascular complications occurred in 22 (1%), and TR-PCI failure was observed in 98 (4.7%) patients. The mechanism of TR-PCI failure included inability to advance guide catheter to ascending aorta in 50 (51%), inadequate guide catheter support in 35 (36%), and unsuccessful radial artery puncture in 13 (13%) patients. The PCI was successful in 94 (96%) patients with TR-PCI failure by switching to TF. On multivariate analysis, age >75 years (odds ratio [OR]: 3.86; 95% confidence interval [CI]: 2.33 to 6.40, p = 0.0006), prior coronary artery bypass graft surgery (OR: 7.47; 95% CI: 3.45 to 16.19, p = 0.0002), and height (OR: 0.97; 95% CI: 0.95 to 0.99, p = 0.02) were independent predictors of TR-PCI failure. CONCLUSIONS Transradial approach PCI can be performed by low-to-intermediate volume operators with standard equipment with a low failure rate. Age >75 years, prior coronary artery bypass graft surgery, and short stature are independent predictors of TR-PCI failure. Appropriate patient selection and careful risk assessment are needed to maximize benefits offered by TR-PCI.

Permanent Pacemaker Implantation After Transcatheter Aortic Valve Implantation

Background— Very few data exist on the clinical impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation. The objective of this study was to assess the impact of PPI after transcatheter aortic valve implantation on late outcomes in a large cohort of patients. Methods and Results— A total of 1556 consecutive patients without prior PPI undergoing transcatheter aortic valve implantation were included. Of them, 239 patients (15.4%) required a PPI within the first 30 days after transcatheter aortic valve implantation. At a mean follow-up of 22±17 months, no association was observed between the need for 30-day PPI and all-cause mortality (hazard ratio, 0.98; 95% confidence interval, 0.74–1.30; P=0.871), cardiovascular mortality (hazard ratio, 0.81; 95% confidence interval, 0.56–1.17; P=0.270), and all-cause mortality or rehospitalization for heart failure (hazard ratio, 1.00; 95% confidence interval, 0.77–1.30; P=0.980). A lower rate of unexpected (sudden or unknown) death was observed in patients with PPI (hazard ratio, 0.31; 95% confidence interval, 0.11–0.85; P=0.023). Patients with new PPI showed a poorer evolution of left ventricular ejection fraction over time (P=0.017), and new PPI was an independent predictor of left ventricular ejection fraction decrease at the 6- to 12-month follow-up (estimated coefficient, −2.26; 95% confidence interval, −4.07 to −0.44; P=0.013; R2=0.121). Conclusions— The need for PPI was a frequent complication of transcatheter aortic valve implantation, but it was not associated with any increase in overall or cardiovascular death or rehospitalization for heart failure after a mean follow-up of ≈2 years. Indeed, 30-day PPI was a protective factor for the occurrence of unexpected (sudden or unknown) death. However, new PPI did have a negative effect on left ventricular function over time.Background— Very few data exist on the clinical impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation. The objective of this study was to assess the impact of PPI after transcatheter aortic valve implantation on late outcomes in a large cohort of patients. Methods and Results— A total of 1556 consecutive patients without prior PPI undergoing transcatheter aortic valve implantation were included. Of them, 239 patients (15.4%) required a PPI within the first 30 days after transcatheter aortic valve implantation. At a mean follow-up of 22±17 months, no association was observed between the need for 30-day PPI and all-cause mortality (hazard ratio, 0.98; 95% confidence interval, 0.74–1.30; P =0.871), cardiovascular mortality (hazard ratio, 0.81; 95% confidence interval, 0.56–1.17; P =0.270), and all-cause mortality or rehospitalization for heart failure (hazard ratio, 1.00; 95% confidence interval, 0.77–1.30; P =0.980). A lower rate of unexpected (sudden or unknown) death was observed in patients with PPI (hazard ratio, 0.31; 95% confidence interval, 0.11–0.85; P =0.023). Patients with new PPI showed a poorer evolution of left ventricular ejection fraction over time ( P =0.017), and new PPI was an independent predictor of left ventricular ejection fraction decrease at the 6- to 12-month follow-up (estimated coefficient, −2.26; 95% confidence interval, −4.07 to −0.44; P =0.013; R 2=0.121). Conclusions— The need for PPI was a frequent complication of transcatheter aortic valve implantation, but it was not associated with any increase in overall or cardiovascular death or rehospitalization for heart failure after a mean follow-up of ≈2 years. Indeed, 30-day PPI was a protective factor for the occurrence of unexpected (sudden or unknown) death. However, new PPI did have a negative effect on left ventricular function over time. # CLINICAL PERSPECTIVE {#article-title-43}

Decorin inhibition of PDGF-stimulated vascular smooth muscle cell function: potential mechanism for inhibition of intimal hyperplasia after balloon angioplasty.

Decorin is a small proteoglycan that binds to transforming growth factor-beta (TGF-beta) and inhibits its activity. However, its interaction with platelet-derived growth factor (PDGF), involved in arterial repair after injury, is not well characterized. The objectives of this study were to assess decorin-PDGF and decorin-PDGF receptor (PDGFR) interactions, the in vitro effects of decorin on PDGF-stimulated smooth muscle cell (SMC) functions and the in vivo effects of decorin overexpression on arterial repair in a rabbit carotid balloon-injury model. Decorin binding to PDGF was demonstrated by solid-phase binding and affinity cross-linking assays. Decorin potently inhibited PDGF-stimulated PDGFR phosphorylation. Pretreatment of rabbit aortic SMC with decorin significantly inhibited PDGF-stimulated cell migration, proliferation, and collagen synthesis. Decorin overexpression by adenoviral-mediated gene transfection in balloon-injured carotid arteries significantly decreased intimal cross-sectional area and collagen content by approximately 50% at 10 weeks compared to beta-galactosidase-transfected or balloon-injured, non-transfected controls. This study shows that decorin binds to PDGF and inhibits its stimulatory activity on SMCs by preventing PDGFR phosphorylation. Decorin overexpression reduces intimal hyperplasia and collagen content after arterial injury. Decorin may be an effective therapy for the prevention of intimal hyperplasia after balloon angioplasty.