an-isolated-working-heart-system-for-large-animal-models

An Isolated Working Heart System for Large Animal Models

Since its introduction in the late 19th century, the Langendorff isolated heart perfusion apparatus, and the subsequent development of the working heart ...

Duke University Medical Center

Right ventricular (RV) failure after left ventricular assist device (LVAD) placement is a serious complication and is difficult to predict. In the era of destination therapy and the total artificial heart, predicting post-LVAD RV failure requiring mechanical support is extremely important.

Risk score derived from pre-operative data analysis predicts the need for biventricular mechanical circulatory support.

It is generally accepted that patients who require biventricular assist device support have poorer outcomes than those requiring isolated left ventricular assist device support. However, it is unknown how the timing of biventricular assist device insertion affects outcomes. We hypothesized that planned biventricular assist device insertion improves survival compared with delayed conversion of left ventricular assist device support to biventricular assist device support.

Early planned institution of biventricular mechanical circulatory support results in improved outcomes compared with delayed conversion of a left ventricular assist device to a biventricular assist device.

Ischemic cardiovascular disease remains the leading cause of death worldwide. Despite advances in the medical management of atherosclerosis over the past several decades, many patients require arterial revascularization to reduce mortality and alleviate ischemic symptoms. Technological advancements have led to dramatic increases in the use of percutaneous and endovascular approaches, yet surgical revascularization (bypass surgery) with autologous vein grafts remains a mainstay of therapy for both coronary and peripheral artery disease. Although bypass surgery is highly efficacious in the short term, long-term outcomes are limited by relatively high failure rates as a result of intimal hyperplasia, which is a common feature of vein graft disease. The supply of native veins is limited, and many individuals require multiple grafts and repeat procedures. The need to prevent vein graft failure has led to great interest in gene therapy approaches to this problem. Bypass grafting presents an ideal opportunity for gene therapy, as surgically harvested vein grafts can be treated with gene delivery vectors ex vivo, thereby maximizing gene delivery while minimizing the potential for systemic toxicity and targeting the pathogenesis of vein graft disease at its onset. Here we will review the pathogenesis of vein graft disease and discuss vector delivery strategies and potential molecular targets for its prevention. We will summarize the preclinical and clinical literature on gene therapy in vein grafting and discuss additional considerations for future therapies to prevent vein graft disease.

Gene therapy for the prevention of vein graft disease.

Cardiac transplantation is an effective therapy for patients with end-stage heart failure, but it is still hindered by the lack of donor organs. A history of donor cardiac arrest raises trepidation regarding the possibility of poor post-transplant outcomes. The impact of donor cardiac arrest following successful cardiopulmonary resuscitation on heart transplant outcomes is unknown. Therefore, we sought to evaluate the impact of donor cardiac arrest on orthotropic heart transplantation using the United Network for Organ Sharing database.

Impact of donor cardiac arrest on heart transplantation.

There are a myriad of surgical therapies for patients with end-stage congestive heart failure. Coronary revascularization and mitral valve repair have clear clinical benefits in appropriately selected patients. Further investigation is required before the widespread adoption of volume-reduction strategies. Cardiac stem cell therapies have yielded promising results in preclinical and phase I studies.

Article	Year
Risk score derived from pre-operative data analysis predicts the need for biventricular mechanical circulatory support. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation\| PubMed ID: 19059108	2008
Early planned institution of biventricular mechanical circulatory support results in improved outcomes compared with delayed conversion of a left ventricular assist device to a biventricular... The Journal of thoracic and cardiovascular surgery\| PubMed ID: 19327526	2009
Gene therapy for the prevention of vein graft disease. Translational research : the journal of laboratory and clinical medicine\| PubMed ID: 23274305	2013
Impact of donor cardiac arrest on heart transplantation. Surgery\| PubMed ID: 23889957	2013
Current readings: Surgical management of heart failure. Seminars in thoracic and cardiovascular surgery\| PubMed ID: 24216532	2013

Kevin W. Southerland

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