Coronary microvasculopathy in heart transplantation: Consequences and therapeutic implications.

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 mum), arterioles (20-10 mum), and capillaries (< 10 mum). 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 microcirculatory 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

Systemic inflammation is related to coronary microvascular dysfunction in obese patients without obstructive coronary disease.

Background and Aims: Obesity, systemic inflammation and changes in the heart functions are associated with increased cardiovascular risk. This study aimed to investigate coronary microvascular dysfunction as an early marker of atherosclerosis in obese patients without any evidence of cardiovascular disease. Methods and results: 86 obese subjects (aged 44±12 years, body mass index (BMI) 41±8kgm-2), without evidence of heart disease, and 48 lean controls were studied using transthoracic Doppler echocardiography for detecting coronary flow reserve (CFR). A value of CFR≤2.5 was considered abnormal. We measured interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and adiponectin in all patients. Patients with abnormal CFR underwent coronary multislice computed tomography (MSCT) in order to exclude an epicardial stenosis. CFR in obese subjects was lower than in lean subjects (3.2±0.8 vs. 3.7±0.7, p=0.02) and was abnormal in 27 (31%) obese patients and in one (2%) control (p<0.0001). All subjects with abnormal CFR showed no coronary stenosis at MSCT. At multivariable analysis, IL-6 and TNF-α were the only determinants of CFR (p<0.02 and p<0.02, respectively). At multivariable logistic regression analysis, IL-6 and TNF-α were the only determinants of CFR≤2.5 (p<0.03 and p<0.03, respectively). Conclusions: CFR is often reduced in obese subjects without clinical evidence of heart disease, suggesting a coronary microvascular impairment. This microvascular dysfunction seems to be related to a chronic inflammation mediated by adipocytokines. Our findings may explain the increased cardiovascular risk in obesity, independently of BM

Coronary microvascular dysfunction may be related to IGF-1 in acromegalic patients and can be restored by therapy.

Background and aims: Acromegaly increases the risk of cardiovascular mortality. Data on the cardiovascular risk in asymptomatic acromegaly are limited. In particular, data on coronary microvascular abnormalities are lacking. We assessed coronary flow reserve (CFR) as a marker of coronary microvascular function in asymptomatic acromegaly. Methods: We studied 40 acromegalic patients (23 male, age 52 ± 11 years) without clinical evidence of cardiovascular disease, and 40 control subjects matched for age and sex. Coronary flow velocity in the left anterior descending coronary artery was detected by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. CFR was the ratio of hyperaemic to resting diastolic flow velocity. Results: CFR was lower in patients than in controls (2.9 ± 0.8 vs. 3.7 ± 0.6, p < 0.0001) and was abnormal (2.5) in 13 patients (32.5%) compared with any control subjects (0%) (p < 0.0001). CFR was inversely related to insulin-like growth factor 1 (IGF-1) levels (r¼0.5, p < 0.004). In patients with CFR2.5, IGF-1 was higher (756 [381e898] mg/l versus 246 [186e484] mg/l, p < 0.007) whereas growth hormone (GH) levels were similar (6.3 [2.8e13.7] mg/l versus 5 [2.8e8.9] mg/l, p ¼ 0.8). In multivariable linear regression analysis, IGF-1 was independently associated with CFR (p < 0.0001). In multiple logistic regression analysis, IGF-1 independently increased the probability of CFR2.5 (p ¼ 0.009). In four patients with active disease (all with CFR<2.5), treatment with somatostatin analogues normalized CFR. However the other four patients with active disease were not responder. Conclusions: Acromegalic patients have coronary microvascular dysfunction that may be restored by therapy with somatostatin analogues. IGF-1 independently correlates with the coronary microvascular impairment, suggesting the pivotal role of this hormone in explaining the increased cardiovascular risk in acromegaly

A single biosynthetic gene cluster is responsible for the production of Bagremycin antibiotics and Ferroverdin iron chelators

Microbial Biotechnolog

Systemic inflammation is related to coronary microvascular dysfunction in obese patients without obstructive coronary disease.

Background and Aims: Obesity, systemic inflammation and changes in the heart functions are associated with increased cardiovascular risk. This study aimed to investigate coronary microvascular dysfunction as an early marker of atherosclerosis in obese patients without any evidence of cardiovascular disease.Methods and results: 86 obese subjects (aged 44 +/- 12 years, body mass index (BMI) 41 +/- 8 kg m(-2)), without evidence of heart disease, and 48 lean controls were studied using transthoracic Doppler echocardiography for detecting coronary flow reserve (CFR). A value of CFR <= 2.5 was considered abnormal. We measured interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and adiponectin in all patients. Patients with abnormal CFR underwent coronary multislice computed tomography (MSCT) in order to exclude an epicardial stenosis. CFR in obese subjects was lower than in lean subjects (3.2 +/- 0.8 vs. 3.7 +/- 0.7, p = 0.02) and was abnormal in 27 (31%) obese patients and in one (2%) control (p < 0.0001). All subjects with abnormal CFR showed no coronary stenosis at MSCT. At multivariable analysis, IL-6 and TNF-alpha were the only determinants of CFR (p < 0.02 and p < 0.02, respectively). At multivariable logistic regression analysis, IL-6 and TNF-alpha were the only determinants of CFR <= 2.5 (p < 0.03 and p < 0.03, respectively).Conclusions: CFR is often reduced in obese subjects without clinical evidence of heart disease, suggesting a coronary microvascular impairment. This microvascular dysfunction seems to be related to a chronic inflammation mediated by adipocytokines. Our findings may explain the increased cardiovascular risk in obesity, independently of BMI. (C) 2013 Elsevier B. V. All rights reserved