Despite the progress made in the prevention and treatment of rejection of the transplanted heart, cardiac allograft vasculopathy(CAV) remains the main cause of death in late survival transplanted patients. CAV consist...Despite the progress made in the prevention and treatment of rejection of the transplanted heart, cardiac allograft vasculopathy(CAV) remains the main cause of death in late survival transplanted patients. CAV consists of a progressive diffuse intimal hyperplasia and the proliferation of vascular smooth muscle cells, ending in wall thickening of epicardial vessels, intramyocardial arteries(50-20 μm), arterioles(20-10 μm), and capillaries(< 10 μm). The etiology of CAV remains unclear; both immunologic and non-immunologic mechanisms contribute to endothelial damage with a sustained inflammatory response. The immunological factors involved are Human Leukocyte Antigen compatibility between donor and recipient, alloreactive T cells and the humoral immune system. The non-immunological factors are older donor age, ischemia-reperfusion time, hyperlipidemia and CMV infections. Diagnostic techniques that are able to assess microvascular function are lacking. Intravascular ultrasound and fractional flow reserve, when performed during coronary angiography, are able to detect epicardial coronary artery disease but are not sensitive enough to assess microvascular changes. Some authors have proposed an index of microcircula-tory resistance during maximal hyperemia, which is calculated by dividing pressure by flow(distal pressure multiplied by the hyperemic mean transit time). Non-invasive methods to assess coronary physiology are stress echocardiography, coronary flow reserve by transthoracic Doppler echocardiography, single photon emission computed tomography, and perfusion cardiac magnetic resonance. In this review, we intend to analyze the mechanisms, consequences and therapeutic implications of microvascular dysfunction, including an extended citation of relevant literature data.展开更多
Heart transplantation (HT) is an accepted treatment for end-stage heart failure (HF). Heart transplantation significantly increases survival, exercise capacity, quality of life and return to work in selected patients ...Heart transplantation (HT) is an accepted treatment for end-stage heart failure (HF). Heart transplantation significantly increases survival, exercise capacity, quality of life and return to work in selected patients with advanced heart failure compared with conventional treatment. The survival rates have improved with the use of new immunosuppressive drugs, with a median survival after transplantation of approximately 11 years. The shortage of donor hearts represents a major limitation in this field. In addition many are the consequences of the limited effectiveness and complications of immunosuppressive therapy (i.e. antibody-mediated rejection, infection, hypertension, renal failure, malignancy and coronary artery vasculopathy). In particular, chronic rejection may occur months to years after the transplantation and is referred to as cardiac allograft vasculopathy (CAV). CAV occurs in 32% of the patients after 5 years and ensuing allograft failure from CAV eventually accounts for 30% of recipient deaths after transplantation. Cardiac allograft vasculopathy, involving coronary macro- and microcirculation, is caused by complicated interplay between immunologic and non-immunologic factors resulting in repetitive endothelial injury and localized sustained inflammatory response. Early diagnosis of microvascular dysfunction is substantial. In this review we analyze signs and symptoms of CAV presentation and the different methodologies to achieve an early and precise diagnosis. We will discuss invasive and non-invasive diagnostic tools and their specific role in evaluating graft’s function, morphology, the presence of coronary artery disease and possible microcirculation involvement.展开更多
In this view point paper,we briefly summarize some of the clinical,biochemical and biophysical results obtained in our research on Relaxation Response.We also qualitatively describe the theoretical biophysical model t...In this view point paper,we briefly summarize some of the clinical,biochemical and biophysical results obtained in our research on Relaxation Response.We also qualitatively describe the theoretical biophysical model that could link them.Our work points to a unified view of the human biological system activity,joining the dynamics ruling the interactions and correlations of the microscopic components to the knowledge of their specific individual properties in the effort of going beyond a purely atomistic approach.展开更多
文摘Despite the progress made in the prevention and treatment of rejection of the transplanted heart, cardiac allograft vasculopathy(CAV) remains the main cause of death in late survival transplanted patients. CAV consists of a progressive diffuse intimal hyperplasia and the proliferation of vascular smooth muscle cells, ending in wall thickening of epicardial vessels, intramyocardial arteries(50-20 μm), arterioles(20-10 μm), and capillaries(< 10 μm). The etiology of CAV remains unclear; both immunologic and non-immunologic mechanisms contribute to endothelial damage with a sustained inflammatory response. The immunological factors involved are Human Leukocyte Antigen compatibility between donor and recipient, alloreactive T cells and the humoral immune system. The non-immunological factors are older donor age, ischemia-reperfusion time, hyperlipidemia and CMV infections. Diagnostic techniques that are able to assess microvascular function are lacking. Intravascular ultrasound and fractional flow reserve, when performed during coronary angiography, are able to detect epicardial coronary artery disease but are not sensitive enough to assess microvascular changes. Some authors have proposed an index of microcircula-tory resistance during maximal hyperemia, which is calculated by dividing pressure by flow(distal pressure multiplied by the hyperemic mean transit time). Non-invasive methods to assess coronary physiology are stress echocardiography, coronary flow reserve by transthoracic Doppler echocardiography, single photon emission computed tomography, and perfusion cardiac magnetic resonance. In this review, we intend to analyze the mechanisms, consequences and therapeutic implications of microvascular dysfunction, including an extended citation of relevant literature data.
文摘Heart transplantation (HT) is an accepted treatment for end-stage heart failure (HF). Heart transplantation significantly increases survival, exercise capacity, quality of life and return to work in selected patients with advanced heart failure compared with conventional treatment. The survival rates have improved with the use of new immunosuppressive drugs, with a median survival after transplantation of approximately 11 years. The shortage of donor hearts represents a major limitation in this field. In addition many are the consequences of the limited effectiveness and complications of immunosuppressive therapy (i.e. antibody-mediated rejection, infection, hypertension, renal failure, malignancy and coronary artery vasculopathy). In particular, chronic rejection may occur months to years after the transplantation and is referred to as cardiac allograft vasculopathy (CAV). CAV occurs in 32% of the patients after 5 years and ensuing allograft failure from CAV eventually accounts for 30% of recipient deaths after transplantation. Cardiac allograft vasculopathy, involving coronary macro- and microcirculation, is caused by complicated interplay between immunologic and non-immunologic factors resulting in repetitive endothelial injury and localized sustained inflammatory response. Early diagnosis of microvascular dysfunction is substantial. In this review we analyze signs and symptoms of CAV presentation and the different methodologies to achieve an early and precise diagnosis. We will discuss invasive and non-invasive diagnostic tools and their specific role in evaluating graft’s function, morphology, the presence of coronary artery disease and possible microcirculation involvement.
文摘In this view point paper,we briefly summarize some of the clinical,biochemical and biophysical results obtained in our research on Relaxation Response.We also qualitatively describe the theoretical biophysical model that could link them.Our work points to a unified view of the human biological system activity,joining the dynamics ruling the interactions and correlations of the microscopic components to the knowledge of their specific individual properties in the effort of going beyond a purely atomistic approach.
