James L. Velianou

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.

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.

Transcatheter aortic valve implantation in patients with bicuspid aortic valve stenosis.

OBJECTIVES We evaluated transcatheter aortic valve implantation (TAVI) in high-risk patients with bicuspid aortic valve (BAV) stenosis. BACKGROUND TAVI shows promise in the treatment of severe stenosis of triscupid aortic valves, especially in high-risk patients. However, BAV stenosis has been considered a contraindication to TAVI. METHODS Eleven patients (age 52 to 90 years) with symptomatic severe BAV stenosis underwent TAVI at 3 Canadian tertiary hospitals between May 2006 and April 2010. All patients were considered high risk for surgical aortic valve replacement. Edwards-SAPIEN transcatheter heart valves (Edwards Lifesciences, Inc., Irvine, California) were used. Transfemoral or transapical access was selected, depending on the adequacy of femoral access. RESULTS Access was transfemoral in 7 patients and transapical in 4 patients. There were no intraprocedural complications. Significant symptomatic and hemodynamic improvement was observed in 10 of 11 patients. Baseline aortic valve area of 0.65 ± 0.17 cm(2) and mean transaortic pressure gradient of 41 ± 22.4 mm Hg were improved to 1.45 ± 0.3 cm(2) and 13.4 ± 5.7 mm Hg, respectively. Two patients had moderate perivalvular leaks. At the 30-day follow-up there were 2 deaths due to multisystem failure in 2 transapical patients. In 1 patient an undersized, suboptimally positioned, unstable valve required late conversion to open surgery. CONCLUSIONS TAVI in selected high-risk patients with severe BAV stenosis can be successfully performed with acceptable clinical outcomes but will require further evaluation.

Randomized, Blinded Trial Comparing Fondaparinux With Unfractionated Heparin in Patients Undergoing Contemporary Percutaneous Coronary Intervention Arixtra Study in Percutaneous Coronary Intervention: A Randomized Evaluation (ASPIRE) Pilot Trial

Background—Factor Xa plays a central role in the generation of thrombin, making it a novel target for treatment of arterial thrombosis. Fondaparinux is a synthetic factor Xa inhibitor that has been shown to be superior to standard therapies for the prevention of venous thrombosis. We performed a randomized trial to determine the safety and feasibility of fondaparinux in the percutaneous coronary intervention (PCI) setting. Methods and Results—A total of 350 patients undergoing elective or urgent PCI were randomized in a blinded manner to receive unfractionated heparin (UFH), 2.5 mg fondaparinux IV, or 5.0 mg fondaparinux IV. Randomization was stratified for planned or no planned use of glycoprotein (GP) IIb/IIIa antagonists. The primary safety outcome was total bleeding, which was a combination of major and minor bleeding events. The incidence of total bleeding was 7.7% in the UFH group and 6.4% in the combined fondaparinux groups (hazard ratio, 0.81; 95% confidence interval, 0.35 to 1.84; P=0.61). Bleeding was less common in the 2.5-mg fondaparinux group compared with the 5-mg fondaparinux group (3.4% versus 9.6%, P=0.06). The composite efficacy outcome of all-cause mortality, myocardial infarction, urgent revascularization, or need for a bailout GPIIb/IIIa antagonist was 6.0% in the UFH group and 6.0% in the fondaparinux group, with no significant difference in efficacy among the fondaparinux doses compared with UFH. Coagulation marker analysis at 6 and 12 hours after PCI demonstrated that fondaparinux was superior to UFH in inducing a sustained reduction in markers of thrombin generation, as measured by prothrombin fragment F1.2 (P=0.02). Conclusions—In this pilot study of patients undergoing contemporary PCI, factor Xa inhibition with the synthetic anticoagulant fondaparinux in doses of 2.5 and 5.0 mg was comparable to UFH for clinical safety and efficacy outcomes. These data form the basis for further evaluation of fondaparinux in arterial thrombosis.

Risk of Elective Major Noncardiac Surgery After Coronary Stent Insertion A Population-Based Study

Background— Guidelines recommend that noncardiac surgery be delayed until 30 to 45 days after bare-metal stent implantation and 1 year after drug-eluting stent implantation. Methods and Results— We used linked registry data and population-based administrative health care databases to conduct a cohort study of 8116 patients (≥40 years of age) who underwent major elective noncardiac surgery in Ontario, Canada between 2003 and 2009, and received coronary stents within 10 years before surgery. Approximately 34% (n=2725) underwent stent insertion within 2 years before surgery, of whom 905 (33%) received drug-eluting stents. For comparison, we assembled a separate cohort of 341 350 surgical patients who had not undergone coronary revascularization. The primary outcome was 30-day major adverse cardiac events (mortality, readmission for acute coronary syndrome, or repeat coronary revascularization). The overall rate of 30-day events in patients with coronary stents was 2.1% (n=170). When the interval between stent insertion and surgery was <45 days, event rates were high for bare-metal (6.7%) and drug-eluting (20.0%) stents. When the interval was 45 to 180 days, the event rate for bare-metal stents was 2.6%, approaching that of intermediate-risk nonrevascularized individuals. Adjusted analyses suggested that event rates were increased if this interval exceeded 180 days. For drug-eluting stents, the event rate was 1.2% once the interval exceeded 180 days, approaching that of intermediate-risk nonrevascularized individuals. Conclusions— The earliest optimal time for elective surgery is 46 to 180 days after bare-metal stent implantation or >180 days after drug-eluting stent implantation.

Survival Following Coronary Angioplasty Versus Coronary Artery Bypass Surgery in Anatomic Subsets in Which Coronary Artery Bypass Surgery Improves Survival Compared With Medical Therapy Results From the Bypass Angioplasty Revascularization Investigation (BARI)

OBJECTIVES We sought to compare survival after coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA) in high-risk anatomic subsets. BACKGROUND Compared with medical therapy, CABG decreases mortality in patients with three-vessel disease and two-vessel disease involving the proximal left anterior descending artery (LAD), particularly if left ventricular (LV) dysfunction is present. How survival after PTCA and CABG compares in these high-risk anatomic subsets is unknown. METHODS In the Bypass Angioplasty Revascularization Investigation (BARI), 1,829 patients with multivessel disease were randomized to an initial strategy of PTCA or CABG between 1988 and 1991. Stents and IIb/IIIa inhibitors were not utilized. Since patients in BARI with diabetes mellitus had greater survival with CABG, separate analyses of patients without diabetes were performed. RESULTS Seven-year survival among patients with three-vessel disease undergoing PTCA and CABG (n = 754) was 79% versus 84% (p = 0.06), respectively, and 85% versus 87% (p = 0.36) when only non-diabetics (n = 592) were analyzed. In patients with three-vessel disease and reduced LV function (ejection fraction <50%), seven-year survival was 70% versus 74% (p = 0.6) in all PTCA and CABG patients (n = 176), and 82% versus 73% (p = 0.29) among non-diabetic patients (n = 124). Seven-year survival was 87% versus 84% (p = 0.9) in all PTCA and CABG patients (including diabetics) with two-vessel disease involving the proximal LAD (n = 352), and 78% versus 71% (p = 0.7) in patients with two-vessel disease involving the proximal LAD with reduced LV function (n = 72). CONCLUSION In high-risk anatomic subsets in which survival is prolonged by CABG versus medical therapy, revascularization by PTCA and CABG yielded equivalent survival over seven years.

Radial Artery Access as a Predictor of Increased Radiation Exposure During a Diagnostic Cardiac Catheterization Procedure

OBJECTIVES We sought to determine whether radial artery access is associated with increased radiation exposure during cardiac catheterization and whether this relationship differs between operators, after adjustment for clinical and patient characteristics associated with greater radiation exposure. BACKGROUND Although previous studies have demonstrated a relationship between radial access and increased radiation exposure to the patient during fluoroscopy-guided cardiac procedures, such studies did not account for differences in operator technique or clustering of patients, procedure complexity, or patient size. Those studies included data from few operators. METHODS Data were collected prospectively on 5,954 diagnostic cardiac catheterizations performed at a tertiary cardiac center. A multilevel regression analysis was used to determine the relationship between radial artery access and radiation exposure. RESULTS After adjustment for multiple factors, radial access was associated with increased exposure (beta = 0.22, p < 0.0001) when compared with the use of femoral access, as measured using the logarithmically transformed air kerma (LogAK). On average, radial access accounted for a 23% increase in measured AK. This was consistent between operators. There were observed differences in the mean LogAK between operators (p = 0.0158), as well as substantial variation in measured LogAK between patients within each operators practice (p < 0.001). CONCLUSIONS Radial artery access cardiac catheterization was associated with increased radiation exposure to the patient when compared with femoral access. The measured AK was still far below the threshold for deterministic effects in most patients studied. Observed variations in AK between and within operators may point to better opportunities to reduce exposure.

Need for permanent pacemaker as a complication of transcatheter aortic valve implantation and surgical aortic valve replacement in elderly patients with severe aortic stenosis and similar baseline electrocardiographic findings.

OBJECTIVES The aim of this study was to compare the incidence and predictive factors of complete atrioventricular block (AVB) and permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR). BACKGROUND No data exist on the need for PPI after TAVI versus SAVR in patients with similar baseline electrocardiographic (ECG) findings. METHODS A total of 411 patients with severe aortic stenosis (AS) and no prior pacemaker who underwent TAVI with the balloon-expandable Edwards valve (Edwards Lifesciences, Irvine, California) were matched (1:1) with 411 elderly patients with severe AS who underwent isolated SAVR on the basis of baseline ECG findings. The incidence, reasons, and predictive factors for PPI within 30 days after the procedure were compared between groups. RESULTS Mean age was similar in both groups (p = 0.11), and the TAVI group had a higher Society of Thoracic Surgeons score (p < 0.001). The rate of new PPI was higher after TAVI (7.3%) compared with SAVR (3.4%), p = 0.014. Complete AVB and severe symptomatic bradycardia, respectively, were the reasons for PPI in the TAVI (5.6% and 1.7%, respectively) and SAVR (2.7% and 0.7%, respectively) groups (p = 0.039 for complete AVB, p = NS for symptomatic bradycardia). The presence of baseline right bundle branch block was the only variable associated with PPI in the TAVI group (odds ratio: 8.61, 95% confidence interval: 3.14 to 23.67, p < 0.0001), whereas no variable was found in the SAVR group. CONCLUSIONS Transcatheter aortic valve implantation was associated with a higher rate of complete AVB and PPI compared with SAVR in elderly patients with severe AS and similar baseline ECG findings. The presence of baseline right bundle branch block correlated with the need for PPI in the TAVI group.

Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial

BACKGROUND Two large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice. METHODS The trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10,732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear. In this longer-term follow-up of the TOTAL study, we report the results on the primary outcome (cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure) and secondary outcomes at 1 year. Analyses of the primary outcome were by modified intention to treat and only included patients who underwent index PCI. This trial is registered with ClinicalTrials.gov, number NCT01149044. FINDINGS Between Aug 5, 2010, and July 25, 2014, 10,732 eligible patients were enrolled and randomly assigned to thrombectomy followed by PCI (n=5372) or to PCI alone (n=5360). After exclusions of patients who did not undergo PCI in each group (337 in the PCI and thrombectomy group and 331 in the PCI alone group), the final study population comprised 10,064 patients (5035 thrombectomy and 5029 PCI alone). The primary outcome at 1 year occurred in 395 (8%) of 5035 patients in the thrombectomy group compared with 394 (8%) of 5029 in the PCI alone group (hazard ratio [HR] 1·00 [95% CI 0·87-1·15], p=0·99). Cardiovascular death within 1 year occurred in 179 (4%) of the thrombectomy group and in 192 (4%) of 5029 in the PCI alone group (HR 0·93 [95% CI 0·76-1·14], p=0·48). The key safety outcome, stroke within 1 year, occurred in 60 patients (1·2%) in the thrombectomy group compared with 36 (0·7%) in the PCI alone group (HR 1·66 [95% CI 1·10-2·51], p=0·015). INTERPRETATION Routine thrombus aspiration during PCI for STEMI did not reduce longer-term clinical outcomes and might be associated with an increase in stroke. As a result, thrombus aspiration can no longer be recommended as a routine strategy in STEMI. FUNDING Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic Inc.