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Competing Interests: None.

Competing Interests: Disclosures Dr Gaudino receives grant support from the National Institutes of Health and the Canadian Institutes of Health and Research. Dr Merz is supported by the National Institutes of Health (grant Nos. R01HL124649 and U54 AG065141), Edythe L. Broad and Constance Austin Women’s Heart Research Fellowships (Cedars-Sinai Medical Center, Los Angeles, CA), Barbra Streisand Women’s Cardiovascular Research and Education Program (Cedars-Sinai Medical Center, Los Angeles, CA), Society for Women’s Health Research (Washington, DC), Linda Joy Pollin Women’s Heart Health Program (Brigham and Women's Hospital, Boston, MA), Erika Glazer Women’s Heart Health Project (Cedars-Sinai Medical Center, Los Angeles, CA), and the Adelson Family Foundation (Los Angeles, CA). Dr Mehran reports personal fees from Abbott Vascular Laboratories, Boston Scientific, Medscape/Web MD, Siemens Medical Solutions, Phillips/Volcano/Spectranetics, Roivant Sciences, Sanofi (Italy), Bracco Group, Medintelligence (Janssen), and Bayer; grants from Astra Zeneca, Bayer, Beth Israel Deaconess, Commonwealth Serum Laboratories, Drug Services InPharmatics, Medtronic, Novartis Pharmaceuticals, OrbusNeich, Osprey Medical, Viveve Medical Incorporated/RenalGuard, and Abbott Vascular; grants and other support from Bristol Myers Squibb; and personal fees and other from American College of Cardiology and Watermark Research Funding, all of which are outside the submitted work. Dr Fremes receives grants as the PI of the ROMA and STICH3C trials from the Canadian Institutes of Health and Research; he is a co-PI of the ACURATE IDE trial that is supported by Boston Scientific; and he is a co-PI of the SURTAVI and Low-Risk trials supported by Medtronic.

Background: Graft patency is the postulated mechanism for the benefits of coronary artery bypass grafting (CABG). However, systematic graft imaging assessment after CABG is rare, and there is a lack of contemporary data on the factors associated with graft failure and on the association between graft failure and clinical events after CABG., Methods: We pooled individual patient data from randomized clinical trials with systematic CABG graft imaging to assess the incidence of graft failure and its association with clinical risk factors. The primary outcome was the composite of myocardial infarction or repeat revascularization occurring after CABG and before imaging. A 2-stage meta-analytic approach was used to evaluate the association between graft failure and the primary outcome. We also assessed the association between graft failure and myocardial infarction, repeat revascularization, or all-cause death occurring after imaging., Results: Seven trials were included comprising 4413 patients (mean age, 64.4±9.1 years; 777 [17.6%] women; 3636 [82.4%] men) and 13 163 grafts (8740 saphenous vein grafts and 4423 arterial grafts). The median time to imaging was 1.02 years (interquartile range [IQR], 1.00-1.03). Graft failure occurred in 1487 (33.7%) patients and in 2190 (16.6%) grafts. Age (adjusted odds ratio [aOR], 1.08 [per 10-year increment] [95% CI, 1.01-1.15]; P =0.03), female sex (aOR, 1.27 [95% CI, 1.08-1.50]; P =0.004), and smoking (aOR, 1.20 [95% CI, 1.04-1.38]; P =0.01) were independently associated with graft failure, whereas statins were associated with a protective effect (aOR, 0.74 [95% CI, 0.63-0.88]; P <0.001). Graft failure was associated with an increased risk of myocardial infarction or repeat revascularization occurring between CABG and imaging assessment (8.0% in patients with graft failure versus 1.7% in patients without graft failure; aOR, 3.98 [95% CI, 3.54-4.47]; P <0.001). Graft failure was also associated with an increased risk of myocardial infarction or repeat revascularization occurring after imaging (7.8% versus 2.0%; aOR, 2.59 [95% CI, 1.86-3.62]; P <0.001). All-cause death after imaging occurred more frequently in patients with graft failure compared with patients without graft failure (11.0% versus 2.1%; aOR, 2.79 [95% CI, 2.01-3.89]; P <0.001)., Conclusions: In contemporary practice, graft failure remains common among patients undergoing CABG and is strongly associated with adverse cardiac events., Competing Interests: Disclosures Dr Bhatt discloses the following relationships - Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: Angiowave (stock options), Boston Veterans Affairs (VA) Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Consultant: Broadview Ventures, Hims; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, Pulmonary EmbolIsm THrOmbolysis [PEITHO] trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, Protection Against Emboli During Carotid Artery Stenting Using the Neuroguard IEP System [PERFORMANCE 2]), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the Edoxaban Compared to Standard Care After Heart Valve Replacement Using a Catheter in Patients With Atrial Fibrillation [ENVISAGE] trial, funded by Daiichi Sankyo; for the Abluminus DES+ Sirolimus-Eluting Stents Versus Everolimus-Eluting Stents in Coronary Artery Disease Patients With Diabetes Mellitus Global [ABILITY-DM] trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the National Institutes of Health [NIH]-funded myocardial ischemia and transfusion [MINT] Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, American College of Cardiology [ACC] Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; Randomized Evaluation of Dual Antithrombotic Therapy with Dabigatran versus Triple Therapy with Warfarin in Patients with Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention [RE-DUAL PCI] clinical trial steering committee funded by Boehringer Ingelheim; ApoA-I Event Reducing in Ischemic Syndromes II [AEGIS-II] executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease [PRONOUNCE] trial, funded by Ferring Pharmaceuticals), Healthcare Made Practical (HMP) Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Knowledge to Practice (K2P) (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (continuing medical education [CME] steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the Cardiovascular Outcomes for People Using Anticoagulation Strategies [COMPASS] operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor), National Cardiovascular Data Registry [NCDR]-ACTION Registry Steering Committee (Chair), VA Cardiovascular Assessment, Reporting, and Tracking System (VA CART) Research and Publications Committee (Chair); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Takeda. Dr Di Franco has consulted for Novo Nordisk, Servier, and is an Advisory Board Member for Scharper. The other authors report no conflicts.

Acute postoperative myocardial ischemia (PMI) after cardiac surgery is an infrequent event that can evolve rapidly and become a potentially life-threatening complication. Multiple factors are associated with acute PMI after cardiac surgery and may vary by the type of surgical procedure performed. Although the criteria defining nonprocedural myocardial ischemia are well established, there are no universally accepted criteria for the diagnosis of acute PMI. In addition, current evidence on the management of acute PMI after cardiac surgery is sparse and generally of low methodological quality. Once acute PMI is suspected, prompt diagnosis and treatment are imperative, and options range from conservative strategies to percutaneous coronary intervention and redo coronary artery bypass grafting. In this document, a multidisciplinary group including experts in cardiac surgery, cardiology, anesthesiology, and postoperative care summarizes the existing evidence on diagnosis and treatment of acute PMI and provides clinical guidance.

Cardiac surgery presents specific methodological challenges in the design, implementation, and analysis of randomized controlled trials. The purposes of this scientific statement are to review key standards in cardiac surgery randomized trial design and implementation, and to provide recommendations for conducting and interpreting cardiac surgery trials. Recommendations include a careful evaluation of the suitability of the research question for a clinical trial, assessment of clinical equipoise, feasibility of enrolling a representative patient cohort, impact of practice variations on the safety and efficacy of the study intervention, likelihood and impact of crossover, and duration of follow-up. Trial interventions and study end points should be predefined, and appropriate strategies must be used to ensure adequate deliverability of the trial interventions. Every effort must be made to ensure a high completeness of follow-up; trial design and analytic techniques must be tailored to the specific research question and trial setting.

Transit time flow measurement (TTFM) allows quality control in coronary artery bypass grafting but remains largely underused, probably because of limited information and the lack of standardization. We performed a systematic review of the evidence on TTFM and other methods for quality control in coronary artery bypass grafting following PRISMA standards and elaborated expert recommendations by using a structured process. A panel of 19 experts took part in the consensus process using a 3-step modified Delphi method that consisted of 2 rounds of electronic voting and a final face-to-face virtual meeting. Eighty percent agreement was required for acceptance of the statements. A 2-level scale (strong, moderate) was used to grade the statements based on the perceived likelihood of a clinical benefit. The existing evidence supports an association between TTFM readings and graft patency and postoperative clinical outcomes, although there is high methodological heterogeneity among the published series. The evidence is more robust for arterial, rather than venous, grafts and for grafts to the left anterior descending artery. Although TTFM use increases the duration and the cost of surgery, there are no data to quantify this effect. Based on the systematic review, 10 expert statements for TTFM use in clinical practice were formulated. Six were approved at the first round of voting, 3 at the second round, and 1 at the virtual meeting. In conclusion, although TTFM use may increase the costs and duration of the procedure and requires a learning curve, its cost/benefit ratio seems largely favorable, in view of the potential clinical consequences of graft dysfunction. These consensus statements will help to standardize the use of TTFM in clinical practice and provide guidance in clinical decision-making.

Background: An internal thoracic artery graft to the left anterior descending artery is standard in coronary bypass surgery, but controversy exists on the best second conduit. The RAPCO trials (Radial Artery Patency and Clinical Outcomes) were designed to compare the long-term patency of the radial artery (RA) with that of the right internal thoracic artery (RITA) and the saphenous vein (SV)., Methods: In RAPCO-RITA (the RITA versus RA arm of the RAPCO trial), 394 patients <70 years of age (or <60 years of age if they had diabetes mellitus) were randomized to receive RA or free RITA graft on the second most important coronary target. In RAPCO-SV (the SV versus RA arm of the RAPCO trial), 225 patients ≥70 years of age (or ≥60 years of age if they had diabetes mellitus) were randomized to receive RA or SV graft. The primary outcome was 10-year graft failure. Long-term mortality was a nonpowered coprimary end point. The main analysis was by intention to treat., Results: In the RA versus RITA comparison, the estimated 10-year patency was 89% for RA versus 80% for free RITA (hazard ratio for graft failure, 0.45 [95% CI, 0.23-0.88]). Ten-year patient survival estimate was 90.9% in the RA arm versus 83.7% in the RITA arm (hazard ratio for mortality, 0.53 [95% CI, 0.30-0.95]). In the RA versus SV comparison, the estimated 10-year patency was 85% for the RA versus 71% for the SV (hazard ratio for graft failure, 0.40 [95% CI, 0.15-1.00]), and 10-year patient survival estimate was 72.6% for the RA group versus 65.2% for the SV group (hazard ratio for mortality, 0.76 [95% CI, 0.47-1.22])., Conclusions: The 10-year patency rate of the RA is significantly higher than that of the free RITA and better than that of the SV. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00475488.

Perioperative stroke is one of the most severe and feared complications of cardiac surgery. Based on the timing of onset and detection, perioperative stroke can be classified as intraoperative or postoperative. The pathogenesis of perioperative stroke is multifactorial, which makes prediction and prevention challenging. However, information on its incidence, mechanisms, diagnosis, and treatment can be helpful in minimizing the perioperative neurological risk for individual patients. We herein provide suggestions on preoperative, intraoperative, and postoperative strategies aimed at reducing the risk of perioperative stroke and at improving the outcomes of patients who experience a perioperative stroke.

Background: Recent clinical trial results showed that transcatheter aortic valve replacement (TAVR) is noninferior and may be superior to surgical aortic valve replacement (SAVR) for mortality, stroke, and rehospitalization. However, the impact of transcatheter valve durability remains uncertain., Methods: Discrete event simulation was used to model hypothetical scenarios of TAVR versus SAVR durability in which TAVR failure times were varied to determine the impact of TAVR valve durability on life expectancy in a cohort of low-risk patients similar to those in recent trials. Discrete event simulation modeling was used to estimate the tradeoff between a less invasive procedure with unknown valve durability (TAVR) and that of a more invasive procedure with known durability (SAVR). Standardized differences were calculated, and a difference >0.10 was considered clinically significant. In the base-case analysis, patients with structural valve deterioration requiring reoperation were assumed to undergo a valve-in-valve TAVR procedure. A sensitivity analysis was conducted to determine the impact of TAVR valve durability on life expectancy in younger age groups (40, 50, and 60 years)., Results: Our cohort consisted of patients with aortic stenosis at low surgical risk with a mean age of 73.4±5.9 years. In the base-case scenario, the standardized difference in life expectancy was <0.10 between TAVR and SAVR until transcatheter valve prosthesis failure time was 70% shorter than that of surgical prostheses. At a transcatheter valve failure time <30% compared with surgical valves, SAVR was the preferred option. In younger patients, life expectancy was reduced when TAVR durability was 30%, 40%, and 50% shorter than that of surgical valves in 40-, 50-, and 60-year-old patients, respectively., Conclusions: According to our simulation models, the durability of TAVR valves must be 70% shorter than that of surgical valves to result in reduced life expectancy in patients with demographics similar to those of recent trials. However, in younger patients, this threshold for TAVR valve durability was substantially higher. These findings suggest that durability concerns should not influence the initial treatment decision concerning TAVR versus SAVR in older low-risk patients on the basis of current evidence supporting TAVR valve durability. However, in younger low-risk patients, valve durability must be weighed against other patient factors such as life expectancy.

Observational and randomized evidence shows that arterial grafts have better patency rates than saphenous vein grafts (SVGs) in coronary artery bypass grafting. Observational studies suggest that the use of multiple arterial grafts is associated with longer postoperative survival, but this must be interpreted in the context of treatment allocation bias and hidden confounders intrinsic to the study designs. Recently, a pooled analysis of 6 randomized trials comparing the radial artery with the SVG as the second conduit and the largest randomized trial comparing the use of single and bilateral internal thoracic arteries have provided apparently divergent results about a clinical benefit with the use of >1 arterial conduit. However, both analyses have methodological limitations that may have influenced their results. At present, it is unclear whether the well-documented increased patency rate of arterial grafts translates into clinical benefits in the majority of patients undergoing coronary artery bypass grafting. A large randomized trial testing the arterial grafts hypothesis (ROMA [Randomized Comparison of the Clinical Outcome of Single Versus Multiple Arterial Grafts]) is underway and will report the results in a few years.

Background: Observational studies have shown better survival in patients undergoing coronary artery bypass grafting (CABG) with 2 arterial grafts compared with 1. However, whether a third arterial graft is associated with incremental benefit remains uncertain. We sought to analyze the outcomes of 3 versus 2 arterial grafts during CABG. As a secondary objective, we compared CABG with 2 or 3 arterial grafts (multiple arterial grafts [MAG]) with CABG using a single arterial graft (SAG)., Methods: Retrospective cohort analyses of all patients undergoing primary isolated CABG in Ontario, Canada, from October 2008 to March 2016. Propensity score matching was performed between patients with 3 arterial grafts (3Art group) versus 2 (2Art group). The primary outcome was time to first event of a composite of death, myocardial infarction, stroke, and repeat revascularization (major adverse cardiac and cerebrovascular events). Additional analyses were performed to evaluate the association between MAG versus SAG and long-term outcomes using propensity score matching., Results: Fifty thousand, two hundred thirty patients underwent isolated CABG during our study period; 3044 (6.1%) and 8253 (16.4%) patients had 3 and 2 arterial grafts, respectively, resulting in 2789 propensity score matching pairs for the primary analyses. Mean and maximum follow-up was 4.2 and 8.5 years, respectively. Radial artery grafting was more common in the 3Art versus 2Art group (79.3% versus 65.6%, P<0.01). In-hospital outcomes were not significantly different, including death (3Art 0.8% versus 2Art 0.5%, P=0.26). Up to 8 years, there were no differences in major adverse cardiac and cerebrovascular events (3Art 27%, 95% confidence interval [CI], 24% to 30% versus 2Art 25%, 95% CI, 22% to 28%; hazard ratio [HR], 1.08, 95% CI, 0.94-1.25), death (HR, 1.08; 95% CI, 0.90-1.29), myocardial infarction (HR, 1.15; 95% CI, 0.87-1.51), stroke (HR, 1.39; 95% CI, 0.95-2.06), or repeat revascularization (HR, 1.04; 95% CI, 0.82-1.32). When evaluating MAG versus SAG, 8629 patient pairs were formed using propensity score matching. At 8 years, cumulative incidences of major adverse cardiac and cerebrovascular events (HR, 0.82, 95% CI, 0.77-0.88), survival (HR, 0.80; 95% CI, 0.73-0.88), repeat revascularization (HR, 0.79; 95% CI, 0.69-0.90), and myocardial infarction (HR, 0.83; 95% CI, 0.72-0.97) were superior in the MAG group., Conclusions: CABG with 3 arterial grafts was not associated with increased in-hospital death nor with better clinical outcomes at 8-year follow-up, compared with CABG with 2 arterial grafts. MAG was associated with superior outcomes compared with SAG.

We summarize the evidence on the new strategies for coronary artery bypass grafting (CABG). Hybrid CABG implies surgical grafting of the left anterior descending artery and percutaneous treatment of the other target vessels, with the promise of combining the durable benefits of surgery with the less invasive approach of percutaneous coronary interventions. Robotic CABG and minimally invasive CABG are performed through minimal incision or port access with dedicated equipment and instruments. Anaortic coronary artery bypass refers to off-pump CABG using only in-situ grafts. The use of multiple arterial grafts has been shown to improve patency and is potentially associated with better clinical outcomes. All these techniques require dedicated training and are more complex than conventional CABG but can significantly improve the results of surgery. Validation of the results of these new approaches in large randomized trials is a priority for the surgical community.

Graft failure occurs in a sizeable proportion of coronary artery bypass conduits. We herein review relevant current evidence to give an overview of the incidence, pathophysiology, and clinical consequences of this multifactorial phenomenon. Thrombosis, endothelial dysfunction, vasospasm, and oxidative stress are different mechanisms associated with graft failure. Intrinsic morphological and functional features of the bypass conduits play a role in determining failure. Similarly, characteristics of the target coronary vessel, such as the severity of stenosis, the diameter, the extent of atherosclerotic burden, and previous endovascular interventions, are important determinants of graft outcome and must be taken into consideration at the time of surgery. Technical factors, such as the method used to harvest the conduits, the vasodilatory protocol, the storage solution, and the anastomotic technique, also play a major role in determining graft success. Furthermore, systemic atherosclerotic risk factors, such as age, sex, diabetes mellitus, hypertension, and dyslipidemia, have been variably associated with graft failure. The failure of a coronary graft is not always correlated with adverse clinical events, which vary according to the type, location, and reason for failed graft. Intraoperative flow verification and secondary prevention using antiplatelet and lipid-lowering agents can help reducing the incidence of graft failure., (© 2017 American Heart Association, Inc.)

Background: Little evidence shows whether a third arterial graft provides superior outcomes compared with the use of 2 arterial grafts in patients undergoing coronary artery bypass grafting. A meta-analysis of all the propensity score-matched observational studies comparing the long-term outcomes of coronary artery bypass grafting with the use of 2-arterial versus 3-arterial grafts was performed., Methods: A literature search was conducted using MEDLINE, EMBASE, and Web of Science to identify relevant articles. Long-term mortality in the propensity score-matched populations was the primary end point. Secondary end points were in-hospital/30-day mortality for the propensity score-matched populations and long-term mortality for the unmatched populations. In the matched population, time-to-event outcome for long-term mortality was extracted as hazard ratios, along with their variance. Statistical pooling of survival (time-to-event) was performed according to a random effect model, computing risk estimates with 95% confidence intervals., Results: Eight propensity score-matched studies reporting on 10 287 matched patients (2-arterial graft: 5346; 3-arterial graft: 4941) were selected for final comparison. The mean follow-up time ranged from 37.2 to 196.8 months. The use of 3 arterial grafts was not statistically associated with early mortality (hazard ratio, 0.93; 95% confidence interval, 0.71-1.22; P =0.62). The use of 3 arterial grafts was associated with statistically significantly lower hazard for late death (hazard ratio, 0.8; 95% confidence interval, 0.75-0.87; P <0.001), irrespective of sex and diabetic mellitus status. This result was qualitatively similar in the unmatched population (hazard ratio, 0.57; 95% confidence interval, 0.33-0.98; P =0.04)., Conclusions: The use of a third arterial conduit in patients with coronary artery bypass grafting is not associated with higher operative risk and is associated with superior long-term survival, irrespective of sex and diabetic mellitus status., (© 2017 American Heart Association, Inc.)

Background: The efficacy of bypass surgery in patients with ischemic cardiomyopathy is not easily predictable; preoperative clinical conditions may be similar, but the outcome may differ significantly. We hypothesized that the growth reserve of cardiac stem cells (CSCs) and circulating cytokines promoting CSC activation are critical determinants of ventricular remodeling in this patient population., Methods and Results: To document the growth kinetics of CSCs, population-doubling time, telomere length, telomerase activity, and insulin-like growth factor-1 receptor expression were measured in CSCs isolated from 38 patients undergoing bypass surgery. Additionally, the blood levels of insulin-like growth factor-1, hepatocyte growth factor, and vascular endothelial growth factor were evaluated. The variables of CSC growth were expressed as a function of the changes in wall thickness, chamber diameter and volume, ventricular mass-to-chamber volume ratio, and ejection fraction, before and 12 months after surgery. A high correlation was found between indices of CSC function and cardiac anatomy. Negative ventricular remodeling was not observed if CSCs retained a significant growth reserve. The high concentration of insulin-like growth factor-1 systemically pointed to the insulin-like growth factor-1-insulin-like growth factor-1 receptor system as a major player in the adaptive response of the myocardium. hepatocyte growth factor, a mediator of CSC migration, was also high in these patients preoperatively, as was vascular endothelial growth factor, possibly reflecting the vascular growth needed before bypass surgery. Conversely, a decline in CSC growth was coupled with wall thinning, chamber dilation, and depressed ejection fraction., Conclusions: The telomere-telomerase axis, population-doubling time, and insulin-like growth factor-1 receptor expression in CSCs, together with a high circulating level of insulin-like growth factor-1, represent a novel biomarker able to predict the evolution of ischemic cardiomyopathy following revascularization.

Background: It has been suggested that inflammation can have a role in the development of atrial arrhythmias after cardiac surgery and that a genetic predisposition to develop postoperative complications exists. This study was conceived to verify if a potential genetic modulator of the systemic inflammatory reaction to cardiopulmonary bypass (the -174 G/C polymorphism of the promoter of the Interleukin-6 gene) has a role in the pathogenesis of postoperative atrial fibrillation (AF). Patients and Results- In 110 primary isolated coronary artery bypass patients the -174G/C Interleukin-6 promoter gene variant was determined. Interleukin-6, fibrinogen and C-reactive protein plasma levels were determined preoperatively, 24, 48, and 72 hours after surgery and at discharge. Heart rate and rhythm were continuously monitored for the first 36 to 48 hours; daily 12-lead electrocardiograms were performed thereafter until discharge. GG, CT, and CC genotypes were found in 62, 38, and 10 patients, respectively. Multivariate analysis (which included genotype, age, sex, and classical risk factors for AF) identified the GG genotype as the only independent predictor of postoperative AF. The latter occurred in 33.9% of GG versus 10.4% of non-GG patients (hazard ratio 3.25, 95%CI 1.23 to 8.62). AF patients had higher blood levels of Interleukin-6 and fibrinogen after surgery (P<0.001 for difference between the area under the curve)., Conclusions: The -174G/C Interleukin-6 promoter gene variant appears to modulate the inflammatory response to surgery and to influence the development of postoperative AF. These data suggest an inflammatory component of postoperative atrial arrhythmias and a genetic predisposition to this complication.

Background: This study was conceived to elucidate the clinical and angiographic effects of chronic calcium channel blocker therapy (CCCBT) continued after the first postoperative year in patients in whom the radial artery (RA) was used for myocardial revascularization., Methods and Results: Patients who received RA grafts at our institution and who at 1 year had no scintigraphic evidence of ischemia in the RA territory or angiographic evidence of RA malfunction (n=120) were randomly assigned to continue (n=63) or suspend (n=57) the CCCBT with diltiazem (120 mg/d). After 5 years, all patients were reassessed clinically and by stress myocardial scintigraphy, and 87 of them (45 from the continued group that continued CCCBT and 42 from the group that suspended CCCBT) were restudied angiographically. No differences regarding either the clinical and scintigraphic results or the RA angiographic status were demonstrated between the 2 groups., Conclusions: After the first postoperative year, the continuation of CCCBT does not affect RA graft patency or clinical and scintigraphic results.