Jean-Jacques Goy

Gene transfer of cytoprotective and immunomodulatory molecules for prevention of cardiac allograft rejection.

Current treatments of heart transplantation are limited by incomplete effectiveness, significant toxicity, and failure to prevent chronic rejection. Genetic manipulation of the donor heart at the time of removal offers the unique opportunity to produce a therapeutic molecule within the graft itself, while minimizing systemic effects. Cytoprotective approaches including gene transfer of heme oxygenase (HO)-1, endothelial nitric oxide synthase, and antisense oligodeoxynucleotides specific for nuclear factor (NF)-kappa B or intercellular adhesion molecule (ICAM)-1 reduced ischaemia-reperfusion injury and delayed cardiac allograft rejection in small animals. Exogenous overexpression of immunomodulatory cytokines such as interleukin (IL)-4, IL-10 and transforming growth factor-beta, as well as gene transfer of inhibitors of pro-inflammatory cytokines also delayed graft rejection. Gene transfer-based blockade of T-cell costimulatory activation with CTLA4-Ig or CD40-Ig resulted in long-lasting graft survival and donor-specific unresponsiveness, as manifested by acceptance of a second graft from the original donor strain but rejection of third-party grafts. Similar results were obtained with donor major histocompatibility complex class I gene transfer into bone marrow cells. Gene therapy approaches to chronic rejection included gene transfer of HO-1, soluble Fas, tissue plasminogen activator and antisense oligodeoxynucleotides specific for the anti-apoptotic mediator Bcl-x or the E2F transcription factor. Despite major experimental advances, however, gene therapy for heart transplantation has not entered the clinical arena yet. Fundamental questions regarding the most suitable vector, the best gene, and safety issues remain unanswered. Well-controlled studies that compare gene therapy with established treatments in non-human primates are needed before clinical trials can be started.

Heart rate never lies: interventional cardiologist and Braude's quote revised

Background Interventional cardiologists may be immune to stress, allowing them to perform complex percutaneous interventions under pressure. Objectives To assess heart rate (HR) variations as a surrogate marker of stress of interventional cardiologists during percutaneous cardiac procedures and in every-day life. Design This is a single-centre observational study including a total of six male interventional cardiologists performing coronary interventions and pacemaker implantations. Participants were asked to record their HR with the Apple Watch Device during procedures, every-day life and control activities such as outpatient consultations, sport, marital conflicts and sexual intercourse. Results Average daily HR was 88±17 bpm. During work days, HR increased significantly during procedures (90±17 bpm) compared with days outside the cathlab (87±17 bpm, p=0.02). The average HR was higher during a regular week working (88±16 bpm) compared with weekends off (84±18 bpm, p=0.002). Complex cardiac procedures were associated with higher HR up to 122 bpm. Peak HR were higher during physical exertion. Of note, participants complained of hypersexuality and mania after night shifts. Conclusions Work and especially percutaneous cardiac procedures increase HR independently of physical exertion suggesting that interventional cardiologists experience mental stress and emotions.

Multianalysis with optical coherence tomography and vasomotion in everolimus-eluting stents and everolimus-eluting biovascular scaffolds: the MOVES trial

Aims To compare endothelium-dependent vasomotor function and vascular healing 15 months after implantation of two new-generation drug-eluting stents and biovascular scaffolds (BVS). Methods and results A total of 28 patients previously treated with a SYNERGY stent (bioabsorbable polymer everolimus-eluting stents (BP-EES)), a PROMUS stent (persistent polymer everolimus-eluting stents (PP-EES)) or an ABSORB (BVS) underwent control coronary angiography, 15 months after implantation, coupled with optical coherence tomography imaging and supine bicycle exercise. Intracoronary nitroglycerin was administered after exercise testing. Coronary vasomotor response was assessed using quantitative coronary angiography at rest, during supine bicycle exercise and after nitroglycerin. The primary end point was the percent change in mean lumen diameter compared with baseline. Secondary end points were strut coverage and apposition. There were no significant differences in vasomotor response between the three treatment groups. Patients with PP-EES showed significant vasoconstriction of the proximal peristent segment at maximum exercise (P=0.02). BP-EES (2.7%, 95% CI 0 to 5.5) and BVS (3.2%, 95% CI 0 to 6.7) showed less uncovered struts than PP-EES (12.1%, 95% CI 2.9 to 21.3, P=0.02 and 0.09, respectively). Complete strut apposition was more frequently seen with BP-EES (99.6%, 95% CI 99.2 to 100) than with BVS (98.9%, 95% CI 98.2 to 99.6, P=0.04) or PP-EES (95.0%, 95% CI 91.6 to 98.5, P=0.001). Conclusion BVS and thin strut BP-EES have a reassuring vasomotion profile, suggesting minimal endothelial dysfunction 15 months after implantation.

PATIENT IRRADIATION DURING INTERVENTIONAL CARDIOLOGY PROCEDURES: A MULTI-CENTRIC SWISS REGISTRY

As the number and complexity of fluoroscopically-guided interventions increase, effort has to be made to optimize the X-ray dose delivered to the patient. In order to set up this optimization process, the clinical practice for cardiology centers has to be analyzed with great statistical power and

Clinical Classification of Coronary Artery Disease: Who Should Be Treated?

Coronary heart disease affects 2–6% of the general population; in the USA, it is responsible for more than 400,000 deaths each year. Epidemiological data show that, annually, approximately 785,000 Americans experience a heart attack [{cr1}], underlining the urgency of detection, quantification, and the prompt initiation of treatment of ischemic heart disease. Obstructive coronary disease causes an imbalance between oxygen supply and oxygen consumption, leading to the various clinical syndromes described below. Atherosclerotic plaque growth proceeds from the accumulation of fatty deposits, cholesterol, and cellular waste products in the inner layer of the coronary arteries. Other substances, such as calcium, can also be found in the fatty streaks. Over time, fibrous atherosclerotic plaques develop, narrowing the arteries and thereby limiting coronary blood flow. At this stage, coronary artery disease can be asymptomatic or associated with angina pectoris, and it is typically accompanied by calcification of the atherosclerotic plaque. Calcification is an active process, a part of the atherosclerotic burden, similar to metaphysis in bone formation. In addition, the plaque may rupture, due to the atherosclerotic burden, leading to vessel occlusion, blood flow interruption, and acute coronary syndrome.