Fraser W.H. Sutherland

Pharmacologic Approaches Against Advanced Glycation End Products (AGEs) in Diabetic Cardiovascular Disease.

Context: Advanced Glycation End-Products (AGEs) are signaling proteins associated to several vascular and neurological complications in diabetic and non-diabetic patients. AGEs proved to be a marker of negative outcome in both diabetes management and surgical procedures in these patients. The reported role of AGEs prompted the development of pharmacological inhibitors of their effects, giving rise to a number of both preclinical and clinical studies. Clinical trials with anti-AGEs drugs have been gradually developed and this review aimed to summarize most relevant reports. Evidence Acquisition: Evidence acquisition process was performed using PubMed and ClinicalTrials.gov with manually checked articles. Results: Pharmacological approaches in humans include aminoguanidine, pyridoxamine, benfotiamine, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statin, ALT-711 (alagebrium) and thiazolidinediones. The most recent promising anti-AGEs agents are statins, alagebrium and thiazolidinediones. The role of AGEs in disease and new compounds interfering with their effects are currently under investigation in preclinical settings and these newer anti-AGEs drugs would undergo clinical evaluation in the next years. Compounds with anti-AGEs activity but still not available for clinical scenarios are ALT-946, OPB-9195, tenilsetam, LR-90, TM2002, sRAGE and PEDF. Conclusions: Despite most studies confirm the efficacy of these pharmacological approaches, other reports produced conflicting evidences; in almost any case, these drugs were well tolerated. At present, AGEs measurement has still not taken a precise role in clinical practice, but its relevance as a marker of disease has been widely shown; therefore, it is important for clinicians to understand the value of new cardiovascular risk factors. Findings from the current and future clinical trials may help in determining the role of AGEs and the benefits of anti-AGEs treatment in cardiovascular disease.

Old Myths, New Concerns: the Long-Term Effects of Ascending Aorta Replacement with Dacron Grafts. Not All That Glitters Is Gold

Synthetic grafts are widely used in cardiac and vascular surgery since the mid-1970s. Despite their general good performance, inability of mimicking the elastomechanical characteristics of the native arterial tissue, and the consequent lack of adequate compliance, leads to a cascade of hemodynamic and biological alterations deeply affecting cardiovascular homeostasis. Those concerns have been reconsidered in more contemporaneous surgical and experimental reports which also triggered some research efforts in the tissue engineering field towards the realization of biomimetic arterial surrogates. The present review focuses on the significance of the “compliance mismatch” phenomenon occurring after aortic root or ascending aorta replacement with prosthetic grafts and discusses the clinical reflexes of this state of tissue incompatibility, as the loss of the native elastomechanical properties of the aorta can translate into detrimental effects on the normal efficiency of the aortic root complex with impact in the long-term results of patients undergoing aortic replacement.

Cells and extracellular matrix interplay in cardiac valve disease: because age matters

Cardiovascular aging is a physiological process affecting all components of the heart. Despite the interest and experimental effort lavished on aging of cardiac cells, increasing evidence is pointing at the pivotal role of extracellular matrix (ECM) in cardiac aging. Structural and molecular changes in ECM composition during aging are at the root of significant functional modifications at the level of cardiac valve apparatus. Indeed, calcification or myxomatous degeneration of cardiac valves and their functional impairment can all be explained in light of age-related ECM alterations and the reciprocal interplay between altered ECM and cellular elements populating the leaflet, namely valvular interstitial cells and valvular endothelial cells, is additionally affecting valve function with striking reflexes on the clinical scenario. The initial experimental findings on this argument are underlining the need for a more comprehensive understanding on the biological mechanisms underlying ECM aging and remodeling as potentially constituting a pharmacological therapeutic target or a basis to improve existing prosthetic devices and treatment options. Given the lack of systematic knowledge on this topic, this review will focus on the ECM changes that occur during aging and on their clinical translational relevance and implications in the bedside scenario.

Effect of Preoperative Aspirin Replacement With Enoxaparin in Patients Undergoing Primary Isolated On-Pump Coronary Artery Bypass Grafting

Management of preoperative antiplatelet therapy in coronary artery bypass grafting (CABG) is variable among surgeons: guidelines collide with prejudices because replacement of aspirin with low-molecular-weight heparin is still performed because of a presumed minor bleeding risk. This study aims to analyze postoperative bleedings and complications in patients scheduled for elective primary isolated on-pump CABG, depending on preoperative aspirin treatment or its replacement with enoxaparin. In this cohort study, we propensity score matched 200 patients in whom aspirin was stopped at least 5 days before CABG and replaced with enoxaparin and 200 patients who continued aspirin therapy until the day before surgery. Postoperative bleedings and complications were monitored during hospitalization. Among patients who continued aspirin treatment, mean overall bleeding was 701.0 ± 334.6 ml, whereas in the matched enoxaparin group, it was significantly greater (882.6 ± 64.6 ml, p value <0.001); this was associated with reduced postoperative complications, lower values of postoperative C-reactive protein in aspirin takers, and a presumed protective effect for statins. After propensity score adjustment, aspirin treatment carried a protective effect against major postoperative bleeding (odds ratio 0.312, p = 0.001). In conclusion, postoperative bleeding is reduced in patients who continued aspirin, likely due to a reduction in postoperative inflammation. The practice of empirically discontinuing aspirin and replacing it with enoxaparin before CABG should be abandoned. Patients with coronary artery disease referred to CABG should continue antiplatelet medications until the surgical procedure. Those results might be extended to patients under oral anticoagulant therapy requiring CABG.

Preliminary in vivo evaluation of a hybrid armored vascular graft combining electrospinning and additive manufacturing techniques

In this study, we tested in vivo effectiveness of a previously developed poly-L-lactide/poly-8-caprolactone armored vascular graft releasing heparin. This bioprosthesis was designed in order to overcome the main drawbacks of tissue-engineered vascular grafts, mainly concerning poor mechanical properties, thrombogenicity, and endothelialization. The bioprosthesis was successfully implanted in an aortic vascular reconstruction model in rabbits. All grafts implanted were patent at four weeks postoperatively and have been adequately populated by endogenous cells without signs of thrombosis or structural failure and with no need of antiplatelet therapy. The results of this preliminary study might warrant for further larger controlled in vivo studies to further confirm these findings.

Off-pump coronary artery bypass grafting versus optimal medical therapy alone: effectiveness of incomplete revascularization in high risk patients

Background Geriatric patients with multivessel coronary artery disease (CAD) are a challenging group to treat; these cases elicit discussion within heart teams regarding the actual benefit of undertaking major surgery on these patients and often lead to abandon the surgical option. Percutaneous procedures represent an important option, but coronary anatomy may be unfavorable. Off-pump coronary artery bypass (OPCAB) provides good quality graft on left anterior descending (LAD) without exposing the patient to cardiopulmonary bypass, and might be the ideal choice in patients with multiple comorbidities, not eligible to percutaneous or on-pump procedures. The objective of this study was to compare survival during a mid-term follow-up in high-risk patients with no percutaneous alternative, either treated with OPCAB or discharged in medical therapy. Methods We retrospectively evaluated from June 2008 to June 2013, 83 high-risk patients with multivessel CAD were included: 42 were treated with incomplete off-pump revascularization using left internal mammary artery (LIMA) on LAD; 41 were discharged in optimal medical therapy (OMT), having refused surgery. Follow-up ended in March 2015, with a telephonic interview. Primary endpoint was survival from all-cause mortality; secondary endpoints were survival from cardiac-related mortality and freedom from non-fatal major adverse cardiac events (MACEs). Results During follow up, 11 deaths in OPCAB group and 27 deaths in OMT group occurred. Death was due to cardiac factors in 6 and 15 patients, respectively. MACEs were observed in 6 patients in OPCAB group and in 4 patients in OMT group. With regards to survival from all-cause mortality, patients who underwent OPCAB survived more than those discharged in OMT (Log Rank < 0.001), and OMT group carries a propensity score-adjusted hazard ratio of 3.862 (P < 0.001). With regards to survival from cardiac-related events, patients who underwent OPCAB survived more than those discharged in OMT (Log Rank = 0.002), and OMT group carries a propensity score-adjusted hazard ratio of 3.663 (P = 0.010). There is no statistically significant difference concerning freedom from MACEs (Log Rank = 0.273). Conclusions For high-risk patients with multivessel CAD, not eligible to on-pump complete revascularization surgery or percutaneous procedures, incomplete revascularization with OPCAB LIMA-on-LAD offers benefits in survival when compared to OMT alone.

New minimally invasive surgical approach for excision of left atrial myxoma

A novel minimally invasive technique for left atrial myxoma surgery involving a combination of mini-sternotomy and restricted left atrial dome incision is described. Surgery is performed through a mini-J sternotomy at third intercostal space and a standard aorto-right atrial cannulation. Exposure of cardiac mass is obtained by a restricted incision of the left atrial dome which provides excellent view of the entire interatrial septum. Base of the tumor base is clearly visualized making the en-bloc excision extremely easy. Three cases were successfully treated with this technique and discharged with mild analgesic requirements. The limited invasiveness and the avoidance of wide incisions in the heart chambers are points of strength of this approach and allow to overcome the limitations of the currently used interatrial groove or transeptal approaches, as scarce visualization of the septum and site of tumor attachment and risk of conduction disturbances or traumatic injury to the mass.

TAVR vs SAVR: Rising Expectations and Changing Indications for Surgery in Response to PARTNER II

Despite the criticisms and concerns raised on the data published in the PARTNER II trial and related analyses, we are undeniably witnessing a revolution in the management of aortic valve disease, in which conventional full sternotomy surgical aortic valve replacement (SAVR), with all related complications and clinical burden, will soon become a nonviable option. Several of the findings described in the PARTNER II trial, although considerable as points of incongruence and study biases in comparison with SAVR, could be taken as lessons to found a new course in SAVR and redesign the respective roles of surgery and interventional procedures in aortic disease. In particular, the results of these trials can actually be considered as a stimulus to invest more effort to improve the current surgical practice that should embrace alternative solutions and least invasive approaches to provide a competitive advantage over percutaneous procedures. An analysis of these points in light of the more recent findings on transcatheter valve durability, thrombosis, and postprocedural complications is provided. Considerations on the parallel progress of SAVR and on the need for a behavioral change in the surgical community are discussed.

Is it time to change how we think about incomplete coronary revascularization

The optimal degree of revascularization for patients with chronic multivessel coronary artery disease remains an unsolved issue. Intuitively, complete revascularization decreases cardiovascular events and improves outcomes compared to incomplete procedures, but in recent years the concept of incomplete revascularization moved from a sub-optimal or a defective treatment towards the most appropriate revascularization technique in some categories of patients. A reasonable level of incomplete anatomic revascularization has been shown to be safe and achievable with both percutaneous (PCI) and surgical procedures (CABG), despite with different long-term outcomes. What are the mechanisms underlying the clinical benefits of an incomplete revascularization and what are the factors explaining the discrepancy in the long-term clinical outcomes between the two modes of revascularization PCI and CABG? The biological consequences of coronary reperfusion might provide valuable hints in this context and at the same time cast new light on the way we think about incomplete revascularization.

Single Centre Experience with Minimally Invasive Aortic Valve Replacement versus Conventional Full Sternotomy Approach - A Propensity Match Analysis

Minimally invasive approach to aortic valve replacement (AVR) is increasingly accepted as a valid alternative to conventional full sternotomy (FS-AVR), as reduces operative trauma with the final aim to improve the postoperative outcomes.