Michael J. Davidson

5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial

BACKGROUND The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that mortality at 1 year, 2 years, and 3 years is much the same with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) for high-risk patients with aortic stenosis. We report here the 5-year outcomes. METHODS We did this randomised controlled trial at 25 hospitals, in Canada (two), Germany (one), and the USA (23). We used a computer-generated randomisation sequence to randomly assign high-risk patients with severe aortic stenosis to either SAVR or TAVR with a balloon-expandable bovine pericardial tissue valve by either a transfemoral or transapical approach. Patients and their treating physicians were not masked to treatment allocation. The primary outcome of the trial was all-cause mortality in the intention-to-treat population at 1 year, we present here predefined outcomes at 5 years. The study is registered with ClinicalTrials.gov, number NCT00530894. FINDINGS We screened 3105 patients, of whom 699 were enrolled (348 assigned to TAVR, 351 assigned to SAVR). Overall mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 11·7%. At 5 years, risk of death was 67·8% in the TAVR group compared with 62·4% in the SAVR group (hazard ratio 1·04, 95% CI 0·86-1·24; p=0·76). We recorded no structural valve deterioration requiring surgical valve replacement in either group. Moderate or severe aortic regurgitation occurred in 40 (14%) of 280 patients in the TAVR group and two (1%) of 228 in the SAVR group (p<0·0001), and was associated with increased 5-year risk of mortality in the TAVR group (72·4% for moderate or severe aortic regurgitation vs 56·6% for those with mild aortic regurgitation or less; p=0·003). INTERPRETATION Our findings show that TAVR as an alternative to surgery for patients with high surgical risk results in similar clinical outcomes. FUNDING Edwards Lifesciences.

5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): a randomised controlled trial.

BACKGROUND Based on the early results of the Placement of Aortic Transcatheter Valves (PARTNER) trial, transcatheter aortic valve replacement (TAVR) is an accepted treatment for patients with severe aortic stenosis who are not suitable for surgery. However, little information is available about the late clinical outcomes in such patients. METHODS We did this randomised controlled trial at 21 experienced valve centres in Canada, Germany, and the USA. We enrolled patients with severe symptomatic inoperable aortic stenosis and randomly assigned (1:1) them to transfemoral TAVR or to standard treatment, which often included balloon aortic valvuloplasty. Patients and their treating physicians were not masked to treatment allocation. The randomisation was done centrally, and sites learned of the assignment only after a patient had been screened, consented, and entered into the database. The primary outcome of the trial was all-cause mortality at 1 year in the intention-to-treat population, here we present the prespecified findings after 5 years. This study is registered with ClinicalTrials.gov, number NCT00530894. FINDINGS We screened 3015 patients, of whom 358 were enrolled (mean age 83 years, Society of Thoracic Surgeons Predicted Risk of Mortality 11·7%, 54% female). 179 were assigned to TAVR treatment and 179 were assigned to standard treatment. 20 patients crossed over from the standard treatment group and ten withdrew from study, leaving only six patients at 5 years, of whom five had aortic valve replacement treatment outside of the study. The risk of all-cause mortality at 5 years was 71·8% in the TAVR group versus 93·6% in the standard treatment group (hazard ratio 0·50, 95% CI 0·39-0·65; p<0·0001). At 5 years, 42 (86%) of 49 survivors in the TAVR group had New York Heart Association class 1 or 2 symptoms compared with three (60%) of five in the standard treatment group. Echocardiography after TAVR showed durable haemodynamic benefit (aortic valve area 1·52 cm(2) at 5 years, mean gradient 10·6 mm Hg at 5 years), with no evidence of structural valve deterioration. INTERPRETATION TAVR is more beneficial than standard treatment for treatment of inoperable aortic stenosis. TAVR should be strongly considered for patients who are not surgical candidates for aortic valve replacement to improve their survival and functional status. Appropriate selection of patients will help to maximise the benefit of TAVR and reduce mortality from severe comorbidities. FUNDING Edwards Lifesciences.

Antithrombotic management of patients with prosthetic heart valves: current evidence and future trends

Over 4 million people worldwide have received a prosthetic heart valve, and an estimated 300,000 valves are being implanted every year. Prosthetic heart valves improve quality of life and survival of patients with severe valvular heart disease, but the need for antithrombotic therapy to prevent thrombotic complications in valve recipients poses challenges for clinicians and patients. Here, we review antithrombotic therapies for patients with prosthetic heart valves and management of thromboembolic complications. Advances in antithrombotic therapy and valve technologies are likely to improve the management of patients with prosthetic heart valves in developed countries, but the most important unmet need and potential for benefit from these new therapies is in developing countries where a massive and rapidly increasing burden of valvular heart disease exists.

Early and late outcomes in minimally invasive mitral valve repair: An eleven-year experience in 707 patients

OBJECTIVE This study analyzes a single institution experience with minimally invasive mitral valve repair and evaluates long-term surgical outcomes of morbidity, mortality, and rates of reoperation. Late follow-up of mitral regurgitation and left ventricular function were also assessed. METHODS Between August 1996 and October 2007, minimally invasive mitral valve repair was performed in 713 patients (mean follow-up 5.7 years). Excluding 6 repairs with robotic assistance, an perspective analysis of the remaining 707 patients was carried forth. Mean age was 57 +/- 13 years. Mean preoperative ejection fraction was 60% +/- 10%. Surgical access was through a lower ministernotomy (74%), right parasternal incision (24%), right thoracotomy (1.4%), or upper ministernotomy (0.7%). Exposure of the mitral valve was through the left atrium in 58% of the cases and transeptal in 42%. A ring annuloplasty was incorporated into 680 (96%) of 707 repairs. The Kaplan-Meier and Student t test for paired samples were used for statistical analysis. RESULTS There were 3 (0.4%) operative deaths. Perioperative morbidity included new-onset atrial fibrillation (20%), reoperation for bleeding (2%), stroke (1.9%), permanent pacemaker implantation (1.7%), deep sternal wound infection (0.7%), and aortic dissection (0.4%). Median hospital stay was 5 days. Only 31% of patients required blood transfusion during the hospital course. There were 49 (6.9%) late deaths and 34 (4.8%) failed repairs necessitating reoperation. At 11.2 years, survival was 83% (95% confidence intervals, 76.5-88.1); freedom from reoperation was 92% (95% confidence intervals, 86.2-94.9). Nine (1.3%) patients were lost to follow-up. A total of 2369 patient-years of echocardiography time were obtained in 544 patients (mean 4.36 years, range 0.47-11.09). Mean grade of mitral regurgitation decreased from 3.80 to 1.42 (P < .0001) Mean left ventricular ejection fraction decreased from 60.7% to 56.3% (P < .0001). Combined risk of death, reoperation, and recurrence of moderately severe to severe mitral regurgitation was 7.7% (43/555). CONCLUSION Minimally invasive mitral valve repair is safe, with low perioperative morbidity, low rates of recurrent mitral regurgitation, and low rates of reoperation and death at late follow-up.

Cardiac Gene Delivery With Cardiopulmonary Bypass

Background—Cardiac gene therapy offers the possibility of enhancing myocardial performance in the compromised heart. However, current gene delivery techniques have limited myocardial transgene expression and pose the risk of extracardiac expression. Isolation of the coronary circulation during cardiac surgery may allow for more efficient and cardiac-selective gene delivery in a clinically relevant model. Methods and Results—Neonatal piglets (3 kg) underwent a median sternotomy and cardiopulmonary bypass, followed by aortic cross-clamping with 30 minutes of cardioplegic arrest. Adenoviral vectors containing transgenes for either &bgr;-galactosidase (adeno-&bgr;-gal, n=11) or the human &bgr;2-adrenergic receptor (adeno-&bgr;2-AR, n=15) were administered through the cardioplegia cannula immediately after arrest and were allowed to dwell in the coronary circulation during the cross-clamp period. After 1 week, the animals were killed, and their heart, lungs, and liver were excised and examined for gene expression. Analysis of &bgr;-galactosidase staining revealed transmural myocardial gene expression among animals receiving adeno-&bgr;-gal. No marker gene expression was detected in liver or lung tissue. &bgr;-AR density in the left ventricle after adeno-&bgr;2-AR delivery was 396±85% of levels in control animals (P <0.01). Animals receiving adeno-&bgr;2-AR and control animals demonstrated similar &bgr;-AR density in both the liver (114±8% versus 100±9%, P =NS) and lung (114±7% versus 100±9%, P =NS). There was no evidence of cardiac inflammation. Conclusions—By using cardiopulmonary bypass and cardioplegic arrest, intracoronary delivery of adenoviral vectors resulted in efficient myocardial uptake and expression. Undetectable transgene expression in liver or lung tissue suggests cardiac-selective expression.

Risperidone in Elderly Schizophrenic Patients: An Open-Label Trial

The authors assessed the safety and efficacy of risperidone in a group of elderly patients with chronic schizophrenia and behavioral disturbances (N = 10). There were no clinically significant changes on physical examination. Also, schizophrenic symptoms and cognitive performance improved during risperidone administration. Patients showed a sufficient improvement in both areas to warrant a larger, double-blind study assessing the effects of risperidone on cognitive and psychiatric symptoms in elderly psychotic patients.

Incidence and implications of idiopathic thrombocytopenia following transcatheter aortic valve replacement with the Edwards Sapien© valves: A single center experience

To determine the incidence and etiology of thrombocytopenia following transcatheter Aortic valve replacement (TAVR).

Use of the Hybrid Operating Room in Cardiovascular Medicine

Hybrid cardiovascular interventions, which integrate techniques of interventional cardiology with those of cardiac/vascular surgery, aim to maximize procedural benefits while minimizing invasiveness. Such hybrid procedures include transcatheter aortic valve replacement (TAVR), endovascular thoracic (TEVAR) or abdominal (EVAR) aortic repair, and combined percutaneous coronary intervention (PCI) with structural heart intervention. Some, such as TAVR, TEVAR, and EVAR, have now become the standard of care for selected patient populations. With documented improvements in outcomes, the indications for such hybrid procedures are expanding. Though some of these novel procedures can be done in either a traditional operating suite or interventional suite, neither location is ideally suited to perform many of these hybrid procedures. Proper application of hybrid techniques requires either an operating room (OR) with a high-resolution angiographic capability or an interventional suite with appropriate operating room features—the “hybrid OR.” We aim to review the concept of an integrated heart team as well as the design and implementation of the hybrid OR. Until recently, patients have been managed with a “silo” approach, with each specialty separately evaluating and treating the underlying condition. This has led in some cases to inefficient competing treatment algorithms. The growth of hybrid procedures that cross traditional specialty lines has in turn spawned the development of interdisciplinary teams. Most frequently this has manifested as a heart team to manage complex valvular heart disease as it pertains to TAVR, but the concept has also been applied to other cardiovascular conditions such as acute aortic syndromes or arrhythmias. Although an integrated team approach has long been used in oncology or transplant patients, it is now integral to the care of patients with complex cardiovascular disease. We raise the concept of the team before reviewing the hybrid OR itself because we feel the team approach is more critical to programmatic success. The …

Transjugular Approach in Valve-in-Valve Transcatheter Mitral Valve Replacement: Direct Route to the Valve

With the recent emergence of transcatheter valve replacement, high-risk cases of structural valve deterioration after mitral bioprosthesis can be treated with valve-in-valve transcatheter mitral valve replacement (TMVR). The transapical approach has become the principal access for TMVR, but we report an alternative direct access for TMVR--transjugular transseptal route--in an 81-year-old woman with a degenerated mitral bioprosthesis.

Can the Off-Pump Coronary Artery Bypass Debate Shed Light on Postoperative Right Heart Dysfunction?

The debate over the relative merits of off-pump coronary artery bypass grafting (OPCAB) and conventional on-pump coronary artery bypass grafting (CABG) continues unabated and remains an area of great controversy. Given the known effects of cardiopulmonary bypass (CPB) on the inflammatory and coagulation cascades, as well as a suggestion of adverse neurological sequelae, there has been a logical argument to perform surgical revascularizations without its use. Proponents of OPCAB have cited advantages in terms of neurological outcomes, renal function, blood use, cost, length of stay, arrhythmias, infections, and ventricular function.1–3 Critics assert that OPCAB is more technically demanding than conventional CABG, and, moreover, that consistent data showing sustained benefits have been lacking and that some existing data suggest inferior revascularization.4,5 At present, analyses of randomized controlled trials have generally shown that OPCAB results in outcomes equivalent to those of conventional CABG in terms of mortality, long-term neurological function, and revascularization while reducing rates of blood use, renal impairment, and cost.3,6–8 Given the steep learning curve of OPCAB and lack of clear long-term cardiovascular or neurological benefit, however, many surgeons have reverted to or continued to favor conventional CABG as their strategy of choice. One criticism leveled at OPCAB is that the results reported usually come from surgeons and centers that are exceptionally experienced in the technique. Given the significantly higher technical demands of OPCAB, results equivalent to conventional CABG may not be applicable to most practicing surgeons. The implication, though unproven, is that the average cardiac surgeon might experience worse outcomes when using OPCAB than with conventional CABG. Indeed, this may explain the relatively low penetration of this technique, despite some demonstrable advantages. Thus, despite high expectations and initial enthusiasm for OPCAB, only about 20% to 25% of surgical coronary revascularizations in the United States are currently …