The Current Role of Viability Imaging to Guide Revascularization and Therapy Decisions in Patients With Heart Failure and Reduced Left Ventricular Function

This review describes the current evidence and controversies for viability imaging to direct revascularization decisions and the impact on patient outcomes. Balancing procedural risks and possible benefit from revascularization is a key question in patients with heart failure of ischemic origin (IHF). Different stages of ischemia induce adaptive changes in myocardial metabolism and function. Viable but dysfunctional myocardium has the potential to recover after restoring blood flow. Modern imaging techniques demonstrate different aspects of viable myocardium; perfusion (single-photon emission computed tomography [SPECT], positron emission tomography [PET], cardiovascular magnetic resonance [CMR]), cell metabolism (PET), cell membrane integrity and mitochondrial function (201Tl and 99mTc-based SPECT), contractile reserve (stress echocardiography, CMR) and scar (CMR). Observational studies suggest that patients with IHF and significant viable myocardium may benefit from revascularization compared with medical treatment alone but that in patients without significant viability, revascularization appears to offer no survival benefit or could even worsen the outcome. This was not supported by 2 randomized trials (Surgical Treatment for Ischemic Heart Failure [STICH] and PET and Recovery Following Revascularization [PARR] -2) although post-hoc analyses suggest that benefit can be achieved if decisions had been strictly based on viability imaging recommendations. Based on current evidence, viability testing should not be the routine for all patients with IHF considered for revascularization but rather integrated with clinical data to guide decisions on revascularization of high-risk patients with comorbidities.Peer reviewe

Randomized trial of bilateral versus single internal-thoracic-artery grafts

Background: The use of bilateral internal thoracic (mammary) arteries for coronary-artery bypass grafting (CABG) may improve long-term outcomes as compared with the use of a single internal-thoracic-artery plus vein grafts. Methods: We randomly assigned patients scheduled for CABG to undergo single or bilateral internal-thoracic-artery grafting in 28 cardiac surgical centers in seven countries. The primary outcome was death from any cause at 10 years. The composite of death from any cause, myocardial infarction, or stroke was a secondary outcome. Interim analyses were prespecified at 5 years of follow-up. Results: A total of 3102 patients were enrolled; 1554 were randomly assigned to undergo single internal-thoracic-artery grafting (the single-graft group) and 1548 to undergo bilateral internal-thoracic-artery grafting (the bilateral-graft group). At 5 years of follow-up, the rate of death was 8.7% in the bilateral-graft group and 8.4% in the single-graft group (hazard ratio, 1.04; 95% confidence interval [CI], 0.81 to 1.32; P=0.77), and the rate of the composite of death from any cause, myocardial infarction, or stroke was 12.2% and 12.7%, respectively (hazard ratio, 0.96; 95% CI, 0.79 to 1.17; P=0.69). The rate of sternal wound complication was 3.5% in the bilateral-graft group versus 1.9% in the single-graft group (P=0.005), and the rate of sternal reconstruction was 1.9% versus 0.6% (P=0.002). Conclusions: Among patients undergoing CABG, there was no significant difference between those receiving single internal-thoracic-artery grafts and those receiving bilateral internal-thoracic-artery grafts with regard to mortality or the rates of cardiovascular events at 5 years of follow-up. There were more sternal wound complications with bilateral internal-thoracic-artery grafting than with single internal-thoracic-artery grafting. Ten-year follow-up is ongoing. (Funded by the British Heart Foundation and others; ART Current Controlled Trials number, ISRCTN46552265.

A New Simple and Objective Method for Graft Sizing in Valve-Sparing Root Replacement Using the Reimplantation Technique

The methods of graft sizing in valve-sparing surgery are criticized for their complexity and subjectivity in application. We propose a simple method for graft sizing in valve-sparing root replacement using the reimplantation technique. Practically, the height of the commissure between the noncoronary cusp and the left coronary cusp give the size of the graft. This new method of graft sizing was successfully applied in the last 27 consecutive patients with good immediate results. Graft sizing with this objective and reproducible simple method results in restoration of normal aortic valve geometry and function

Three Arterial Grafts Improve Late Survival:A Meta-Analysis of Propensity-Matched Studies

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

ChemR23 Dampens Lung Inflammation and Enhances Anti-viral Immunity in a Mouse Model of Acute Viral Pneumonia

Viral diseases of the respiratory tract, which include influenza pandemic, children acute bronchiolitis, and viral pneumonia of the elderly, represent major health problems. Plasmacytoid dendritic cells play an important role in anti-viral immunity, and these cells were recently shown to express ChemR23, the receptor for the chemoattractant protein chemerin, which is expressed by epithelial cells in the lung. Our aim was to determine the role played by the chemerin/ChemR23 system in the physiopathology of viral pneumonia, using the pneumonia virus of mice (PVM) as a model. Wild-type and ChemR23 knock-out mice were infected by PVM and followed for functional and inflammatory parameters. ChemR23−/− mice displayed higher mortality/morbidity, alteration of lung function, delayed viral clearance and increased neutrophilic infiltration. We demonstrated in these mice a lower recruitment of plasmacytoid dendritic cells and a reduction in type I interferon production. The role of plasmacytoid dendritic cells was further addressed by performing depletion and adoptive transfer experiments as well as by the generation of chimeric mice, demonstrating two opposite effects of the chemerin/ChemR23 system. First, the ChemR23-dependent recruitment of plasmacytoid dendritic cells contributes to adaptive immune responses and viral clearance, but also enhances the inflammatory response. Second, increased morbidity/mortality in ChemR23−/− mice is not due to defective plasmacytoid dendritic cells recruitment, but rather to the loss of an anti-inflammatory pathway involving ChemR23 expressed by non-leukocytic cells. The chemerin/ChemR23 system plays important roles in the physiopathology of viral pneumonia, and might therefore be considered as a therapeutic target for anti-viral and anti-inflammatory therapies

The choice of the second graft

Coronary artery bypass surgery was first described 50 years ago (see Chapter 1). During this pioneering era, there were few discussions on which graft to use, with SVGs used exclusively for the first 20 years. Today, all cardiac surgeons are daily face the difficult choice of which graft to use for a selected patient. The choice of conduits depends on several factors, such as the patient’s intrinsic characteristics (age, body mass index, diabetes, pulmonary function, peripheral vascular disease, saphenous vein quality) and extrinsic characteristics (elective or urgent). Additionally, the characteristics of the coronary lesion, including the degree of stenosis, the minimum lumen diameter (MLD), and the fractional flow reserve (FFR) impact the choice of conduits. Even after the graft choice has been made, the manner of using it is still controversial. Some researchers propose in situ graft use, while others prefer free grafts use. When used free, the choice must be made to reimplant the graft in the aorta or in another graft in a composite fashion. The composite assembly is also debated: is it preferable to use a T or a Y shape, and where do we perform this crucial anastomosis? When used in situ, there is no evidence that it is better to use the right internal thoracic artery (ITA) on the left anterior descending (LAD) artery crossing the midline or through the transverse sinus to a first marginal. Moreover, some researchers suggest using one graft per distal anastomosis, while others prefer sequential anastomosis. After patient characteristics, the most important consideration is the coronary lesion itself. Most of the surgical literature on graft patency is based on visual inspection for coronary lesion evaluation. Cardiologists have tried to find a more accurate method to evaluate the severity of the coronary lesion (quantitative coronary angiography (QCA), FFR); unfortunately, these solutions have not been applied to the evaluation of graft performance. Historically, graft patency evaluation has been performed to evaluate the SVG. Since arterial conduits display a totally different endothelial response to shear stress and competitive flow, these historical definitions have become obsolete, leading to new concepts such as “graft functioning.” Moreover, in contradiction to the evidence-based medical literature, there are few evidence-based cardiac surgery reports. Indeed, most of the graft patency literature is retrospective, with few systematic angiographic controls. Most control studies were symptom-driven, leading to a false evaluation of the conduit performance. Recent studies have promoted the use of less-invasive graft evaluations but without evidence of a good correlation with gold-standard angiography. In addition to all discussions regarding graft choice, there is one last powerful factor: “The Surgeon.” Each cardiac surgeon with a given mentorship background is more prone to use a certain graft type even if there is evidence for better performance of another graft. The best example of this phenomenon is the rate of bilateral ITA (BITA) grafting in the USA: 5%, whereas some American surgeons have dedicated their careers to convincing their colleagues that two ITAs are better then one. On the other hand, some European surgeons use BITA in all ages (> 80 years) and without careful evaluation of the coronary lesion. Due to the lack of a clear answer to the question of which graft to use in a specific patient, we decided to investigate the different grafts we used daily: right and left ITA (RITA and LITA, respectively), SVG, and also the right gastroepiploic artery (RGEA). For this purpose, we started 2 prospective randomized trials in 2003 with systematic 6 months functional evaluation. We also performed systematic 6 months and 3 years angiographic evaluation. In the first trial, we studied the various BITA configurations possible to revascularize the left coronary system (Annex 1). In the second, we compared the RGEA versus SVG to revascularize the right coronary artery (RCA) (Annex 2). In addition to these 2 majors trials we analyzed a subgroup of patients with composite Y arterial or venous graft configuration. We used for the first time in literature the FFR in bypass graft to assess the efficiency of this type of assembling (Annex 3-4). We also compared the vasomotion of the free RITA reimplanted in the in-situ LITA with a specific endothelial vasodilatator (Substance P) (Annex 5). Afterwards we analyzed the causes of non-functioning of the free RITA (Annex 6). During the same period, we realized the same analysis with the in-situ LITA and RITA graft (Annex 7). Finally, we analyzed more carefully the coronary lesion with the QCA in order to identify if there was a correlation between the lesion and the graft patency and evaluated a new method to redefine graft patency in relation to the arterial grafting (Annex 2-8-9).(MED 3) -- UCL, 201