Coronary artery bypass grafting: Part 2--optimizing outcomes and future prospects.

Since first introduced in the mid-1960s, coronary artery bypass grafting (CABG) has become the standard of care for patients with coronary artery disease. Surprisingly, the fundamental surgical technique itself did not change much over time. Nevertheless, outcomes after CABG have dramatically improved over the first 50 years. Randomized trials comparing percutaneous coronary intervention (PCI) to CABG have shown converging outcomes for select patient populations, providing more evidence for wider use of PCI. It is increasingly important to focus on the optimization of the short- and long-term outcomes of CABG and to reduce the level of invasiveness of this procedure. This review provides an overview on how new techniques and widespread consideration of evolving strategies have the potential to optimize outcomes after CABG. Such developments include off-pump CABG, clampless/anaortic CABG, minimally invasive CABG with or without extending to hybrid procedures, arterial revascularization, endoscopic vein harvesting, intraprocedural epiaortic scanning, graft flow assessment, and improved secondary prevention measures. In addition, this review represents a framework for future studies by summarizing the areas that need more rigorous clinical (randomized) evaluation.

The impact of prosthesis-patient mismatch on long-term survival after aortic valve replacement: a systematic review and meta-analysis of 34 observational studies comprising 27 186 patients with 133 141 patient-years.

AIMS: Numerous studies have linked prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) to adverse outcomes. Its correlation with long-term survival has been described but with contradicting results. This systematic review and meta-analysis of observational studies aims to determine the hazard of PPM after AVR. METHODS AND RESULTS: The Medline and EMBase databases were searched for English-language original publications. Two researchers independently screened studies and extracted data. Pooled estimates were obtained by random effects model. Subgroup analyses were performed to detect sources of heterogeneity. The search yielded 348 potentially relevant studies; 34 were included comprising 27 186 patients and 133 141 patient-years. Defined by the universally accredited indexed effective orifice area <0.85 cm(2)/m(2), 44.2% of patients were categorized as having PPM. In 34.2 and 9.8% of patients moderate (0.65-0.85 cm(2)/m(2)) and severe (<0.65 cm(2)/m(2)) PPM was present, respectively. Prosthesis-patient mismatch was associated with a statistically significant increase in all-cause mortality (HR = 1.34, 95% CI: 1.18-1.51), but only a trend to an increase in cardiac-related mortality (HR = 1.51, 95% CI: 0.88-2.60) was recognized. Analysis by severity of PPM demonstrated that both moderate and severe PPM increased all-cause mortality (HR = 1.19, 95% CI: 1.07-1.33 and HR = 1.84, 95% CI: 1.38-2.45) and cardiac-related mortality (HR = 1.32, 95% CI: 1.02-1.71 and HR = 6.46, 95% CI: 2.79-14.97). Further analyses showed a consistent effect over separate time intervals during follow-up. CONCLUSION: Prosthesis-patient mismatch is associated with an increase in all-cause and cardiac-related mortality over long-term follow-up. We recommend that current efforts to prevent PPM should receive more emphasis and a widespread acceptance to improve long-term survival after AVR.

Towards excellence in revascularization for left main coronary artery disease.

PURPOSE OF REVIEW: The aim of this article is to review the current revascularization strategies in patients presenting with unprotected left main coronary artery disease (LMCAD). RECENT FINDINGS: Coronary artery bypass grafting (CABG) is the current standard of treatment for patients with LMCAD. The development and refinement of techniques increased the number of percutaneous coronary interventions (PCI) in LMCAD patients. SUMMARY: Although several observational studies show comparable results of CABG and/or PCI in patients with LMCAD, there is currently no convincing randomized evidence that either one of the two is associated with better long-term survival. Recent meta-analyses of four small randomized trials revealed a similar rate of 1-year major adverse cardiovascular and cerebrovascular events, higher rates of target vessel revascularization and lower stroke rates for PCI. Pooling randomized patients studies stratified by lesion complexity strengthened the hypothesis that CABG is better in more complex LMCAD patients. However, the randomized comparisons are affected by methodological limitations and lack power to be conclusive. The ongoing Evaluation of XIENCE V Everolimus Eluting Stent System Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial is expected to provide a better answer on the optimal treatment strategy for LMCAD patients. In the meantime, risk models need to be improved and the most appropriate revascularization strategy for the individual LMCAD patient should be chosen using a multidisciplinary heart team that considers not only risk models but also other clinical and economic facets.

Statistical primer: basics of survival analysis for the cardiothoracic surgeon.

Survival analysis incorporates various statistical methods specific to data on time until an event of interest. While the event is often death, giving rise to the phrase 'survival analysis', the event might also be, for example, a reoperation. As such, it is sometimes referred to as 'time-to-event analysis'. Censoring sets survival analysis apart from other analyses: at the end of the follow-up period, not all subjects have experienced the event of interest, and some subjects may drop out of the study prior to completion. Survival data for a group of subjects is usually visualized by the Kaplan-Meier estimator, representing the probability of a subject remaining free of the event during follow-up. There are several methods to compare survival between the study groups, for example, treatment arms, including the log-rank test and the Cox proportional hazards model. The log-rank test is an unadjusted non-parametric method, whereas the Cox proportional hazards model allows comparison while adjusting for multiple covariates. A principal assumption of the Cox proportional hazards model is that the relative hazard stays constant over time-the so-called proportionality. Specific methods exist for comparison of survival with the general population. This article describes the fundamental concepts every cardiothoracic surgeon should be aware of when analysing survival data and are illustrated with a clinical example.

Statistical primer: a cost-effectiveness analysis.

Cost-effectiveness analyses (CEAs) of new treatment strategies are increasingly reported. This can be a part of a clinical trial or as a separate study. Governments and healthcare payers frequently require a CEA to decide whether a new treatment strategy will be reimbursed. CEA is a framework to assess the effectiveness and costs of a new treatment strategy (e.g. a drug or intervention) when compared with a reference strategy. Effectiveness is often measured in life-years or quality-adjusted life-years, whereas costs consist of direct costs (the costs of the treatment), induced costs (downstream costs and cost offsets) and indirect costs. In this statistical primer, the rationale for assessing the economic consequences of new therapies is explained, followed by the fundamental concepts of CEAs, the different types of CEAs and an introduction to interpretation of CEAs. Finally, a real-world example of a CEA is discussed, comparing cost-effectiveness of transcatheter versus surgical aortic valve replacement in patients with severe aortic stenosis at intermediate surgical risk.

Patient selection for TAVI in 2014: is there a justification for treating low- or intermediate-risk patients? The surgeon's view.

The introduction of transcatheter aortic valve implantation (TAVI) has revolutionised the treatment of patients with symptomatic severe aortic valve stenosis (AS). In extreme and high-risk patients, randomised studies have shown the benefit of this new therapy. However, there are still a lot of unknowns, and the question has arisen whether it is justified to expand the indication of TAVI to other patient groups, especially intermediate-or even low-risk patients.

Role of percutaneous coronary intervention in the treatment of left main coronary artery disease.

Revascularization with coronary artery bypass graft surgery is the choice of therapy in patients with left main (LM) coronary artery stenosis. During the last decade, the introduction of drug-eluting stents, together with antiplatelet and antithrombotic treatments, has improved the outcome of percutaneous coronary interventions (PCIs) by reducing the number of repeat revascularizations and the risk of stent thrombosis. Many institutions inside and outside the United States have adopted stent treatment of unprotected LM coronary artery disease as a more routine strategy. However, coronary bypass surgery has improved as well by using more arterial grafts, better perioperative care, and optimizing medical treatment postoperatively. The advances in stent technique may reduce the gap between coronary surgery and PCIs further, but the results of the Evaluation of Xience Prime versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization study, randomizing patients with LM coronary artery disease between coronary bypass grafting and PCIs, will be needed to test whether PCIs is noninferior to coronary bypass surgery.

Influence of diabetes mellitus on long-term clinical and economic outcomes after coronary artery bypass grafting.

BACKGROUND: China has the most patients with diabetes mellitus (DM) in the world and, annually, approximately 1 million Chinese become diabetic. We investigated both clinical and economic outcomes in a large Chinese cohort of diabetic patients undergoing coronary artery bypass graft surgery (CABG). METHODS: All 9,240 consecutive patients who underwent isolated, primary, elective CABG between January 1999 and December 2008 were included and analyzed for long-term major adverse cardiovascular and cerebrovascular events and economic outcomes up to 2 years after the procedure. The DM patients were divided into DM subgroups controlled by diet (n = 375), medication (n = 1,826) or insulin (n = 481). RESULTS: During the study period, the proportion of patients undergoing CABG who have DM increased from 20.1% to 31.8% in China. None of the DM subgroups was independently associated with in-hospital death, but DM was an independent predictor for long-term major adverse cardiovascular and cerebrovascular events (hazard ratio 1.29, 95% confidence interval: 1.14 to 1.46). Medically controlled DM and insulin-dependent DM, but not diet-controlled DM were independent predictors of long-term outcomes after CABG. Cost for initial hospitalization was higher for DM patients (76,782 Ren Min Bi [RMB] versus 65,521 RMB, respectively; p < 0.001). At 2 years after CABG, costs for DM patients were 11,261 RMB (approximately US $1,623) higher than for non-DM patients (p < 0.001). CONCLUSIONS: CABG for patients with DM was significantly more expensive and was associated with worse long-term outcomes compared with non-DM patients. The rising incidence of DM, combined with the significant incremental costs represents significant clinical, economic, and social challenges for the Chinese healthcare system.

Cost-effectiveness of transcatheter valvular interventions: economic challenges.

The unsustainable trend of rising healthcare costs necessitates difficult allocation decisions by governments, policymakers, and physicians. Consequently, recent advances in transcatheter valve therapies require not only clinical evaluation, but also careful economic evaluation. Under current indications, each year there are nearly 18,000 new candidates for transcatheter aortic valve implantation (TAVI) in European countries and an additional 9,200 in North America, with an estimated cost of more than $2 billion per year. Nonetheless, when compared with standard medical therapy for severe aortic stenosis (AS), TAVI leads to gains in life expectancy at an incremental cost that is acceptable by most Western standards. On the other hand, for high-risk (but operable) patients with severe AS, TAVI provides no proven survival advantage and only a transient quality of life benefit compared with surgical aortic valve replacement (SAVR). Thus, for these patients, the cost-effectiveness of TAVI compared with SAVR hinges on the magnitude and duration of the quality of life benefit as well as the relative cost of both procedures. Current data suggest that, for patients who are eligible for transfemoral access, TAVI is economically attractive (or even economically dominant) compared with high-risk SAVR. However, the cost-effectiveness of TAVI for patients who are not suitable for a transfemoral approach appears to be less favourable. Transcatheter mitral valve repair is in an earlier stage of clinical implementation than TAVI. As the evidence for this procedure accumulates, more formal economic analysis should be feasible.

Failing surgical bioprosthesis in aortic and mitral position.

Bioprosthetic heart valves are preferentially selected over mechanical prostheses in the majority of patients undergoing valve replacement surgery. These bioprostheses are prone to structural degeneration, and hence an increasing number of patients are presenting with bioprosthetic failure requiring redo surgery. In selected high-risk cases, successful implantation of a transcatheter aortic valve (TAV) within the failing bioprosthetic surgical aortic valve (SAV) or mitral valve (SMV) has been performed. Herein, we summarise the available evidence, describe the technical challenges, and highlight important procedural considerations for these innovative interventions.

Multivessel coronary artery disease: quantifying how recent trials should influence clinical practice.

The majority (70%) of coronary revascularizations concern patients with multivessel disease (MVD). Treatment options include medical therapy, percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). CABG surgery has been shown to improve survival compared with medical therapy. PCI relieves angina compared with medical therapy and is equivalent to CABG in low complex MVD. Other benefits are currently being evaluated in ongoing trials. In complex MVD, CABG results in lower rates of long-term mortality, myocardial infarction and repeat revascularization compared with PCI. These results are more pronounced in diabetics and in patients with lesions that are anatomically more complex. The application of the results of clinical trials may be limited due to restrictive eligibility criteria. Comparative effectiveness studies are, therefore, needed to complement the results of trials, but also have inherent limitations. Inappropriateness criteria provide an important tool to measure how evidence from trials, large registries and guidelines is integrated in clinical practice. Checklists and decision aids may also lead to better application of the latest evidence and lower rates of inappropriate use. Decision-making is centered around heart team discussions and risk scores. Economic considerations will increasingly be included in decision-making, since the economic impact of ischemic heart disease is high and the growth of healthcare expenditure is unsustainable. In this context, CABG is associated with higher upfront costs, but is economically attractive at long-term follow-up.

A systematic review of risk prediction in adult cardiac surgery: considerations for future model development.

OBJECTIVES: Risk prediction in adult patients undergoing cardiac surgery remains inaccurate and should be further improved. Therefore, we aimed to identify risk factors that are predictive of mortality, stroke, renal failure and/or length of stay after adult cardiac surgery in contemporary practice. METHODS: We searched the Medline database for English-language original contributions from January 2000 to December 2011 to identify preoperative independent risk factors of one of the following outcomes after adult cardiac surgery: death, stroke, renal failure and/or length of stay. Two investigators independently screened the studies. Inclusion criteria were (i) the study described an adult cardiac patient population; (ii) the study was an original contribution; (iii) multivariable analyses were performed to identify independent predictors; (iv) ≥ 1 of the predefined outcomes was analysed; (v) at least one variable was an independent predictor, or a variable was included in a risk model that was developed. RESULTS: The search yielded 5768 studies. After the initial title screening, a second screening of the full texts of 1234 studies was performed. Ultimately, 844 studies were included in the systematic review. In these studies, we identified a large number of independent predictors of mortality, stroke, renal failure and length of stay, which could be categorized into variables related to: disease pathology, planned surgical procedure, patient demographics, patient history, patient comorbidities, patient status, blood values, urine values, medication use and gene mutations. Many of these variables are frequently not considered as predictive of outcomes. CONCLUSIONS: Risk estimates of mortality, stroke, renal failure and length of stay may be improved by the inclusion of additional (non-traditional) innovative risk factors. Current and future databases should consider collecting these variables.

Costs for surgical aortic valve replacement according to preoperative risk categories.

BACKGROUND: The introduction of transcatheter aortic valve replacement (TAVR) led to more rigorous evaluation of surgical aortic valve replacement (SAVR) as a benchmark for TAVR. However, limited real-life cost data of SAVR are available. Therefore, the purpose of our study was to assess actual costs and resource utilization of SAVR in patients at different operating risk. METHODS: Study data were drawn from a multi-institutional statewide database comprised of all cardiac surgical procedures in the Commonwealth of Virginia. The study included 2,530 elective, primary, isolated SAVRs performed from 2003 to 2012. Clinical data were matched with universal billing data. Patients were stratified into low-, intermediate- and high-risk categories according to the Society of Thoracic Surgeons- Predicted Risk of Mortality (STS-PROM) score: 0% to 4%, 4% to 8% , and greater than 8%, respectively. Clinical outcomes, resource use, and costs were compared between categories. RESULTS: With increasing risk, there were higher rates of postoperative mortality (low 1.2% versus intermediate 2.7% versus high 6.2%, p < 0.001) and renal failure (2.7% vs 7.2% vs 10.6%; p < 0.001). The proportion of patients with any postoperative complication was higher with increasing risk (34% vs 48% vs 53%; p < 0.001). Length-of-stay increased from 6.8 days in the low-risk category to 10.2 and 11.3 days in the intermediate- and high-risk category, respectively (p < 0.001). There was an increase in mean total costs from the low- (n = 2,002) to intermediate- (n = 415) to high-risk (n = 113) category ($35,021 ± $22,642 vs $46,101 ± $42,460 vs $51,145 ± $31,655; p < 0.001). CONCLUSIONS: Higher STS-PROM was significantly associated with higher postoperative mortality, complications, length-of-stay, and costs. The SAVR cost data provide a basis for the analysis of TAVR cost-effectiveness and its impact on payment systems.

The European Association for Cardio-Thoracic Surgery (EACTS) database: an introduction.

OBJECTIVES: Continuous monitoring of surgical outcomes through benchmarking and the identification of best practices has become increasingly important. A structured approach to data collection, coupled with validation, analysis and reporting, is a powerful tool in these endeavours. However, inconsistencies in standards and practices have made comparisons within and between European countries cumbersome. The European Association for Cardio-Thoracic Surgery (EACTS) has established a large international database with the goals of (i) working with other organizations towards universal data collection and creating a European-wide repository of information on the practice of cardio-thoracic surgery, and (ii) disseminating that information in scientific, peer-reviewed articles. We report on the process of data collection, as well as on an overview of the data in the database. METHODS: The EACTS Database Committee met for the first time in Monaco, September 2002, to establish the ground rules for the process of setting up the database. Subsequently, data have been collected and merged by Dendrite Clinical Systems Ltd. RESULTS: As of December 2008, the database included 1,074,168 patient records from 366 hospitals located in 29 countries. The latest submission from the years 2006-08 included 404,721 records. The largest contributors were the UK (32.0%), Germany (20.9%) and Belgium (7.3%). Isolated coronary bypass surgery was the most frequently performed operation; the proportion of surgical workload that comprised isolated coronary artery bypass grafting varied from country to country: 30% in Spain and almost 70% in Denmark. Isolated valve procedures constituted 12% of all procedures in Norway and 32% in Spain. Baseline demographics showed an increase in the mean age and the percentage of patients that were female over time. Remarkably, the mortality rates for all procedures declined over the period analysed, to 2.2% (95% confidence interval [CI] 2.2-2.3%) for isolated coronary bypass, 3.4% (95% CI 3.3-3.5%) for isolated valve and 6.2% (95% CI 6.0-6.5%) for bypass + valve procedures. CONCLUSION: The EACTS database has proven to be an important step forward in providing opportunities for monitoring cardiac surgical care across Europe. As the database continues to expand, it will facilitate research projects, establish benchmarking standards and identify potential areas for quality improvements.

Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study.

OBJECTIVES: The purpose of this study was to evaluate the prevalence of aortic stenosis (AS) in the elderly and to estimate the current and future number of candidates for transcatheter aortic valve replacement (TAVR). BACKGROUND: Severe AS is a major cause of morbidity and mortality in the elderly. A proportion of these patients is at high or prohibitive risk for surgical aortic valve replacement, and is now considered for TAVR. METHODS: A systematic search was conducted in multiple databases, and prevalence rates of patients (>75 years) were pooled. A model was based on a second systematic literature search of studies on decision making in AS. Monte Carlo simulations were performed to estimate the number of TAVR candidates in 19 European countries and North America. RESULTS: Data from 7 studies (n = 9,723 subjects) were used. The pooled prevalence of all AS in the elderly was 12.4% (95% confidence interval [CI]: 6.6% to 18.2%), and the prevalence of severe AS was 3.4% (95% CI: 1.1% to 5.7%). Among elderly patients with severe AS, 75.6% (95% CI: 65.8% to 85.4%) were symptomatic, and 40.5% (95% CI: 35.8% to 45.1%) of these patients were not treated surgically. Of those, 40.3% (95% CI: 33.8% to 46.7%) received TAVR. Of the high-risk patients, 5.2% were TAVR candidates. Projections showed that there are approximately 189,836 (95% CI: 80,281 to 347,372) TAVR candidates in the European countries and 102,558 (95% CI: 43,612 to 187,002) in North America. Annually, there are 17,712 (95% CI: 7,590 to 32,691) new TAVR candidates in the European countries and 9,189 (95% CI: 3,898 to 16,682) in North America. CONCLUSIONS: With a pooled prevalence of 3.4%, the burden of disease among the elderly due to severe AS is substantial. Under the current indications, approximately 290,000 elderly patients with severe AS are TAVR candidates. Nearly 27,000 patients become eligible for TAVR annually.

Transcatheter aortic valve replacement in Europe: adoption trends and factors influencing device utilization.

OBJECTIVES: The authors sought to examine the adoption of transcatheter aortic valve replacement (TAVR) in Western Europe and investigate factors that may influence the heterogeneous use of this therapy. BACKGROUND: Since its commercialization in 2007, the number of TAVR procedures has grown exponentially. METHODS: The adoption of TAVR was investigated in 11 European countries: Germany, France, Italy, United Kingdom, Spain, the Netherlands, Switzerland, Belgium, Portugal, Denmark, and Ireland. Data were collected from 2 sources: 1) lead physicians submitted nation-specific registry data; and 2) an implantation-based TAVR market tracker. Economic indexes such as healthcare expenditure per capita, sources of healthcare funding, and reimbursement strategies were correlated to TAVR use. Furthermore, we assessed the extent to which TAVR has penetrated its potential patient population. RESULTS: Between 2007 and 2011, 34,317 patients underwent TAVR. Considerable variation in TAVR use existed across nations. In 2011, the number of TAVR implants per million individuals ranged from 6.1 in Portugal to 88.7 in Germany (33 ± 25). The annual number of TAVR implants performed per center across nations also varied widely (range 10 to 89). The weighted average TAVR penetration rate was low: 17.9%. Significant correlation was found between TAVR use and healthcare spending per capita (r = 0.80; p = 0.005). TAVR-specific reimbursement systems were associated with higher TAVR use than restricted systems (698 ± 232 vs. 213 ± 112 implants/million individuals ≥ 75 years; p = 0.002). CONCLUSIONS: The authors' findings indicate that TAVR is underutilized in high and prohibitive surgical risk patients with severe aortic stenosis. National economic indexes and reimbursement strategies are closely linked with TAVR use and help explain the inequitable adoption of this therapy.

Appropriate coronary artery bypass grafting use in the percutaneous coronary intervention era: are we finally making progress?

Appropriate use criteria integrate guidelines, clinical trial evidence, and expert opinion in order to determine the most appropriate care for a range of distinct clinical scenarios. Inappropriate use estimates cannot be neglected. Approximately 12%-14% of all percutaneous coronary interventions and 1%-2% of all coronary artery bypass grafting procedures in patients with stable angina are deemed inappropriate. Several reasons for this difference are identified. Continuous improvement of the criteria, multidisciplinary discussions, and the correct financial incentives will be essential in reducing the number of inappropriate procedures, improve patient outcomes, and contain costs.

Costs of transcatheter versus surgical aortic valve replacement in intermediate-risk patients.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) offers a new treatment option for patients with aortic stenosis, but costs may play a decisive role in decision making. Current studies are evaluating TAVR in an intermediate-risk population. We assessed the in-hospital and 1-year follow-up costs of patients undergoing TAVR and surgical aortic valve replacement (SAVR) at intermediate operative risk and identified important cost components. METHODS: We prospectively collected clinical data on 141 patients undergoing TAVR and 405 undergoing SAVR. Propensity score matching yielded 42 matched pairs at intermediate risk. Costs were assessed using a detailed resource-use approach and compared using bootstrap methods. RESULTS: In-hospital costs were higher in TAVR patients than in SAVR patients (€40802 vs €33354, respectively; p=0.010). The total costs at 1 year were €46217 vs €35511, respectively (p=0.009). The TAVR was less costly with regard to blood products, operating room use, and length-of-stay. CONCLUSIONS: For intermediate-risk patients with severe aortic stenosis the costs at 1 year are higher for TAVR than for SAVR. The difference was mainly caused by the higher costs of the transcatheter valve and was not compensated by the lower costs for blood products and hospital stay in TAVR patients. Therefore, SAVR remains a clinically and economically attractive treatment option.

Surgery in current therapy for infective endocarditis.

The introduction of the Duke criteria and transesophageal echocardiography has improved early recognition of infective endocarditis but patients are still at high risk for severe morbidity or death. Whether an exclusively antibiotic regimen is superior to surgical intervention is subject to ongoing debate. Current guidelines indicate when surgery is the preferred treatment, but decisions are often based on physician preferences. Surgery has shown to decrease the risk of short-term mortality in patients who present with specific symptoms or microorganisms; nevertheless even then it often remains unclear when surgery should be performed. In this review we i) systematically reviewed the current literature comparing medical to surgical therapy to evaluate if surgery is the preferred option, ii) performed a meta-analysis of studies reporting propensity matched analyses, and iii), briefly summarized the current indications for surgery.