Mark Osten

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.

Percutaneous Left Atrial Appendage Closure With the AMPLATZER Cardiac Plug Device in Patients With Nonvalvular Atrial Fibrillation and Contraindications to Anticoagulation Therapy

OBJECTIVES The aim of this study was to evaluate the results associated with left atrial appendage closure (LAAC) with the AMPLATZER Cardiac Plug (ACP) (St. Jude Medical, Minneapolis, Minnesota) in patients with nonvalvular atrial fibrillation and absolute contraindications to anticoagulation therapy. BACKGROUND Few data exist on the late outcomes after LAAC in patients with absolute contraindications to warfarin. METHODS A total of 52 patients with nonvalvular atrial fibrillation underwent LAAC with the ACP device in 7 Canadian centers. Most patients received short-term (1 to 3 months) dual-antiplatelet therapy after the procedure and single-antiplatelet therapy thereafter. A transesophageal echocardiography was performed in 74% of patients at the 6-month follow-up. No patient was lost to follow-up (≥ 12 months in all patients). RESULTS The mean age and median (interquartile range) CHADS2 score were 74 ± 8 years and 3 (2 to 4), respectively. The procedure was successful in 98.1% of the patients, and the main complications were device embolization (1.9%) and pericardial effusion (1.9%), with no cases of periprocedural stroke. At a mean follow-up of 20 ± 5 months, the rates of death, stroke, systemic embolism, pericardial effusion, and major bleeding were 5.8%, 1.9%, 0%, 1.9%, and 1.9%, respectively. The presence of mild peridevice leak was observed in 16.2% of patients at the 6-month follow-up as evaluated by transesophageal echocardiography. There were no cases of device thrombosis. CONCLUSIONS In patients with nonvalvular atrial fibrillation at high risk of cardioembolic events and absolute contraindications to anticoagulation, LAAC using the ACP device followed by dual-/single-antiplatelet therapy was associated with a low rate of embolic and bleeding events after a mean follow-up of 20 months. No cases of severe residual leak or device thrombosis were observed at the 6-month follow-up.

Transcatheter aortic valve implantation for high risk patients With severe aortic stenosis using the Edwards Sapien balloon‐expandable bioprosthesis: A single centre study with immediate and medium‐term outcomes

Background: Transcatheter aortic valve implantation (TCAVI) is an emerging alternative therapy to open‐heart surgery in high‐risk patients with symptomatic aortic stenosis. Methods: Between January 2007 and May 2009, 46 patients underwent TCAVI with the 23 mm or 26 mm Edwards Sapien bioprosthesis via either the transapical (TA‐AVI) or transfemoral (TF‐AVI) approach. All patients had an estimated operative mortality risk of >15%. Results: A total of 46 patients (30 TA‐AVI, 16 TF‐AVI) with a mean aortic valve area (AVA) of 0.63 ± 0.2 cm2 and mean gradient of 54 ± 16 mm Hg were treated. Predicted operative mortality was 25.3% by logistic Euroscore and 8.7% by Society of Thoracic Surgeons risk score. Procedural success was 93% in the TA‐AVI group and 88% in the TF‐AVI group. There was one intraprocedural death in the TA‐AVI group. Overall 30‐day mortality was 6.5% (2‐TA‐AVI, 1‐TF‐AVI). Four patients (9.5%) died from noncardiac causes after 30 days. Successful TCAVI was associated with a significant increase in AVA from 0.6 ± 0.1 cm2 to 1.6 ± 0.6 cm2 in the TA‐AVI group and 0.6 ± 0.1 cm2 to 1.4 ± 0.2 cm2 in the TF‐AVI group at a mean follow up of 7.4 ± 4.4 and 8.3 ± 5.0 months, respectively. At discharge, there was significant improvement in AVA (P < 0.0001), transaortic mean gradient (P < 0.0001), and mitral regurgitation (P = 0.01). At medium term follow up, the valve area was maintained and there was significant improvement in NYHA class in both groups (P < 0.0001). Conclusion: At medium term follow‐up, both transcatheter approaches demonstrated good valve durability with no cardiac‐related mortality post hospital discharge.

Impact of renal insufficiency on angiographic, procedural, and in-hospital outcomes following percutaneous coronary intervention.

Patients with chronic renal insufficiency (RI) have higher in-hospital mortality and major adverse cardiac event (MACE) rates after percutaneous coronary intervention (PCI). The mechanisms of this adverse course are not well understood. It was hypothesized that this worse outcome may be caused by inadequate PCI results secondary to more complex coronary anatomy in patients with RI. Baseline, procedural, and outcome variables of all PCI cases at the University Health Network are entered prospectively in the PCI Registry. All PCI cases between April 1, 2000, and October 31, 2005, excluding patients in shock, who had preprocedural creatinine clearance (CrCl) measured were included in this study (n = 10,821 of 11,023 patients). Moderate RI (CrCl <60 ml/min) was evaluated as an independent predictor of procedural outcomes, death, and MACE (defined as death, myocardial infarction, abrupt closure, or coronary artery bypass grafting). Moderate RI (CrCl <60 ml/min) independently predicted the procedural outcomes of worse residual stenosis >20% (p = 0.03), number of undeliverable stents (p = 0.003), and smallest stent diameter (p <0.001). Worst residual stenosis >20% and any undeliverable stent were significantly associated with in-hospital MACEs (odds ratio [OR] 3.97, 95% confidence interval [CI] 3.0 to 5.3, p <0.001 and OR 1.89, 95% CI 1.2 to 2.9, p = 0.002) and mortality (OR 3.82, 95% CI 2.2 to 6.7, p <0.001 and OR 3.0, 95% CI 1.6 to 5.9, p = 0.002). These risks were independent of all other measured variables. In conclusion, moderate to severe RI was a strong predictor of worse procedural results during PCI, which, in turn, were independent predictors of in-hospital MACE and mortality and independent contributors to the higher risk of in-hospital adverse events observed after PCI in patients with RI.

Transcatheter Pulmonary Valve Replacement With the Edwards Sapien System: The Toronto Experience

OBJECTIVES This study sought to review the outcomes for the Sapien and Sapien XT valves (Edwards Lifesciences, Irvine, California) for percutaneous pulmonary valve implantation (PPVI). BACKGROUND PPVI has emerged as a viable alternative to surgery in patients with right ventricular (RV) outflow tract dysfunction. Limited data are available for the Sapien and Sapien XT valves in this setting. METHODS Retrospective analysis was performed for all patients to have undergone PPVI using the Edwards Sapien system at a large quaternary center. RESULTS Twenty-five patients (70% male, mean age 34 ± 8.9 years) were identified. Primary underlying diagnosis was tetralogy of Fallot (n = 15), Ross procedure (n = 5), and other (n = 5). RV outflow tract characteristics included: biological valve (n = 16) and homograft (n = 9). Technical success was 96%. One patient required elective surgical pulmonary valve replacement for a high residual gradient. Pre-stenting was performed in all cases (52% covered stents). Valve sizes were 23 mm (n = 8), 26 mm (n = 15), and 29 mm (n = 2). Procedural hemodynamics revealed a decrease in the mean RV-to-systemic pressure ratio from 0.64 to 0.36 (p < 0.001) and RV-to-pulmonary artery (PA) gradient from 39 to 9 mm Hg (p < 0.001). No patient had clinically significant pulmonary regurgitation (PR). At a mean follow-up of 3.5 ± 2.1 years (range 0.3 to 7.2 years), there were no deaths. One patient required reintervention (no PR evident immediately post-procedure but severe valvular PR at 1 year requiring a valve-in-valve procedure). There were no episodes of endocarditis and no stent fractures. There was preserved valve function during follow-up with no change in RV-to-PA gradient nor PR severity. CONCLUSIONS The Edwards Sapien system is a viable and durable option for PPVI in this single-center study.

Clinical characteristics of coronary artery disease in adults with congenital heart defects

BACKGROUND There are now more adults with congenital heart disease than children. This aging cohort is at risk for acquired heart diseases such as coronary artery disease (CAD). The purpose of the study was to examine the clinical features of the CAD in adults with congenital heart disease. METHODS A retrospective chart review was performed. The clinical characteristics of adults with congenital heart disease and angiographically confirmed atherosclerotic CAD were examined. RESULTS One hundred and forty-one adults with CAD (69% male) were identified from a total of 12,124 patients (1%) seen in our congenital cardiac clinic. The most common cardiac diagnoses were atrial septal defect, bicuspid aortic valve disease, tetralogy of Fallot and coarctation of the aorta. We identified 7 adults with Eisenmenger physiology and CAD. The mean age of diagnosis of CAD was 56 ±13years. Twenty patients had premature CAD (14%) presenting before age 40years. Traditional risk factors of patients with CAD were common and were present in the majority (82%) of patients. While many adults had symptoms of angina or myocardial infarction, a significant proportion (38%) were asymptomatic. The age at diagnosis in patients with coarctation of the aorta was younger than other subgroups (48±13years). Seventy-seven percent (109/141) underwent percutaneous or surgical coronary interventions. CONCLUSION Atherosclerotic coronary artery disease may coexist with congenital heart disease. Coronary artery disease in adults with congenital heart disease typically occurs later in adulthood and in patients with traditional cardiovascular risk factors. This study highlights the need for cardiovascular risk factor screening and therapy when indicated.

Antithrombotic Therapy After Coronary Stenting in Patients With Nonvalvular Atrial Fibrillation

BACKGROUND The safety and efficacy of triple therapy (TT; warfarin with dual antiplatelet therapy [DAPT]) in post-percutaneous coronary intervention (PCI) patients with atrial fibrillation (AF) are unclear. We aimed to determine whether TT is associated with a decreased stroke rate and an acceptable bleeding rate in this population. METHODS This was a single-centre, retrospective study. Primary composite outcome was death, ischemic stroke, or transient ischemic attack. Secondary outcomes included components of primary outcome, bleeding, and blood transfusion rates. RESULTS Of 602 post-PCI patients with AF between 2000 and 2009, 382 received TT, 220 DAPT. Mean follow-up post PCI was 5.9 ± 5.0 months. The TT group had a higher CHADS(2) score (2.6 vs 2.1, P < 0.001), older age (72.9 vs 70.5 years, P = 0.039), more heart failure (72.3% vs 36.9%, P = 0.010), and more strokes (14.4% vs 6.4%, P = 0.010). Neither primary outcome, major bleeding, nor blood transfusion rates differed between treatment groups, but more gastrointestinal bleeding occurred with TT use (2.6% vs 0.5%, P = 0.045). Net clinical benefit was -5.2 (CHADS(2) ≤ 2), 0.9 (CHADS(2) > 2), and -3.2 (overall) per 100 patient-years. CONCLUSIONS Although we found no association with TT usage and a reduction in cerebrovascular ischemic or major bleeding events in post-PCI patients with AF regardless of CHADS(2) score vs DAPT, the study was likely underpowered to demonstrate a clinically relevant reduction. TT was associated with a 5-fold increase in gastrointestinal bleeding vs DAPT. Net clinical benefit calculations suggest benefits of TT in patients with CHADS(2) > 2. Stratification with CHADS(2) might be useful to determine the optimal antithrombotic therapy post PCI.

The sPLA2 Inhibition to Decrease Enzyme Release After Percutaneous Coronary Intervention (SPIDER-PCI) Trial

Background— Secretory phospholipase A2 (sPLA2) may play a role in myonecrosis after elective percutaneous coronary intervention (PCI). Inhibition of this enzyme may have a beneficial effect. The central hypothesis of this study was that treatment with varespladib, a small-molecule inhibitor of sPLA2 would reduce postprocedural release of cardiac biomarkers after elective percutaneous coronary intervention. Methods and Results— Between October 2007 and June 2009, 144 stable patients were randomized in a phase II trial to receive varespladib 500 mg PO BID or placebo 3 to 5 days before and for 5 days after elective percutaneous coronary intervention. The primary end point was elevation of troponin I or creatine kinase-MB above the upper limit of normal at 6 to 8 or 18 to 24 hours after percutaneous coronary intervention. Mean age was 63±10 and 64±10 years, with 38% and 42% with diabetes mellitus and 29% and 28% with prior myocardial infarction for the varespladib and placebo groups, respectively. The primary end point occurred in 75% of varespladib and 63% of placebo patients (P=0.14). Troponin I 3 times the upper limit of normal was observed in 57% and 50% (P=0.39) and creatine kinase-MB 2 times the upper limit of normal in 14% and 3% (P=0.018). Median (first and third quartiles) change in high-sensitivity C-reactive protein in these 2 groups was 0.65 mg/L (−0.18 and 1.48) and 0.70 mg/L (0.00 and 1.50) at 18 to 24 hours (P=0.81) and 0.20 mg/L (−0.70 and 1.40) and 0.60 mg/L (−0.12 and 1.72) at 3 to 5 days (P=0.23), whereas change in sPLA2 activity at 3 to 5 days in a subset was −2.85 ng/ml (−3.40 and −1.85) and 0.25 ng/ml (−0.20 and 0.85) (P<0.001). Conclusions— Inhibition of sPLA2 by varespladib administered for 3 to 5 days before the procedure does not reduce periprocedural myonecrosis associated with elective percutaneous coronary intervention. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00533039.

Postcardiac Transplant Transcatheter Core Valve Implantation for Aortic Insufficiency Secondary to Impella Device Placement

Conventional cardiac surgical procedures or transcatheter interventions after orthotopic heart transplantation are generally uncommon. We report the case of a 45-year-old woman who developed severe aortic insufficiency after insertion of a 5-L Impella device 16 weeks after heart transplantation. After joint evaluation by the transcatheter valve team, transcatheter aortic valve implantation was planned because of associated comorbid conditions. A 29-mm CoreValve prosthesis (Medtronic, Minneapolis, MN) was inserted percutaneously. At 6 months after prosthesis implantation, the patient was asymptomatic in New York Heart Association functional class II, and the echocardiogram showed a mean transvalvular gradient of 1 mm Hg, an aortic valve area of 1.5 cm2, and no paravalvular aortic insufficiency.