Coronary occlusion: cause or consequence of acute myocardial infarction?

A 45-year-old man with unstable angina developed persistent ECG changes of myocardial ischemia during coronary angiography. Occlusion of the left anterior descending branch (LAD) was documented 20 minutes after these changes. Intracoronary nitrate, Ca antagonist, urokinase, removal by percutaneous transluminal coronary angioplasty (PTCA) of atherosclerotic obstructions, and emergency bypass surgery failed to restore myocardial perfusion. Only short periods of reflow were obtained by urokinase and PTCA. The repeated coronary injections demonstrated a progressive disappearance of the left anterior descending artery (LAD) starting from the distal portion and progressing retrogradely up to the origin of the vessel. The patient developed a transmural anterolateral myocardial infarction and 12 months later underwent cardiac transplantation for untractable failure. His heart was examined and the infarct confirmed. Analysis of this case suggests that coronary occlusion in acute myocardial infarction can be an event secondary to increased intramyocardial resistance rather than the cause of reduced coronary blood flow in subepicardial coronary arteries

Acute Effects Of Triiodothyronine T. (T3) Replacement Therapy in Patients with Chronic Heart Failure and Low-T3 Syndrome: A Randomized, Placebo-Controlled Study

Context: Low-T3 syndrome is a predictor of poor outcome in patients with cardiac dysfunction. The study aimed to assess the short-term effects of synthetic L-T3 replacement therapy in patients with low-T3 syndrome and ischemic or nonischemic dilated cardiomyopathy (DC). Design:Atotal of 20 clinically stable patients with ischemic (n12) or nonischemic (n8) DC were enrolled. There were 10 patients (average age 72 yr, range 66–77; median, 25–75th percentile) who underwent 3-d synthetic L-T3 infusion (study group); the other 10 patients (average age 68 yr, range 64–71) underwent placebo infusion (control group). Clinical examination, electrocardiography, cardiac magnetic resonance, and bio-humoral profile (free thyroid hormones, TSH, plasma renin activity, aldosterone, noradrenaline, N-terminal-pro-B-Type natriuretic peptide, and IL-6) were assessed at baseline and after 3-d synthetic L-T3 (initial dose: 20 g/m2 body surfaced) or placebo infusion. Results: After T3 administration, free T3 concentrations increased until reaching a plateau at 24–48 h (3.43, 3.20–3.84 vs. 1.74, 1.62–1.93 pg/ml; P 0.03) without side effects. Heart rate decreased significantly after T3 infusion (63, 60–66 vs. 69, 60–76 beats per minute; P 0.008). Plasma noradrenaline (347; 270–740 vs. 717, 413–808 pg/ml; P 0.009), N-terminal pro-B-Type natriuretic peptide (3000, 438-4005 vs. 3940, 528-5628 pg/ml; P0.02), and aldosterone (175, 152–229 vs. 231, 154–324 pg/ml; P 0.047) significantly decreased after T3 administration. Neurohormonal profile did not change after placebo infusion in the control group. After synthetic L-T3 administration, left-ventricular end-diastolic volume (142, 132–161 vs. 133, 114–158 ml/m2 body surface; P 0.02) and stroke volume (40, 34–44 vs. 35, 28–39 ml/m2 body surface; P 0.01) increased, whereas external and intracardiac workload did not change. Conclusions: In DC patients, short-term synthetic L-T3 replacement therapy significantly improved neuroendocrine profile and ventricular performance. These data encourage further controlled trials with more patients and longer periods of synthetic L-T3 administration

Association Between Increased Mortality and Mild Thyroid Dysfunction in Cardiac Patients

BACKGROUND: The effects of subclinical thyroid dysfunction on cardiac outcome are not well defined. METHODS: To assess the relationship between mild thyroid dysfunction and the incidence of death in cardiac patients, we evaluated 3121 cardiac patients. Cardiac and overall deaths were considered. Four groups were defined: euthyroidism, subclinical hypothyroidism (SCH), subclinical hyperthyroidism (SCT), and low triiodothyronine syndrome (low T3). RESULTS: After mean follow-up of 32 months, there were 65 and 140 cardiac and overall deaths (3.4% and 7.3%), respectively, in euthyroidism, 15 and 27 (7.2% and 13.0%) in SCH, 8 and 9 (8.2% and 9.2%) in SCT, and 59 and 119 (6.5% and 13.1%) in low T3. Survival rates for cardiac death were lower in SCH, SCT, and low T3 than in euthyroidism (log-rank test; chi2 = 19.46; P < .001). Survival rates for overall death were lower in SCH and low T3 than in euthyroidism (log-rank test; chi2 = 26.67; P < .001). After adjustment for several risk factors, hazard ratios (HRs) for cardiac death were higher in SCH (HR, 2.40; 95% confidence interval [CI], 1.36-4.21; P = .02), SCT (HR, 2.32; 95% CI, 1.11-4.85; P = .02), and low T(3) (HR, 1.63; 95% CI, 1.14-2.33; P = .007) than in euthyroidism; HRs for overall death were higher in SCH (HR, 2.01; 95% CI, 1.33-3.04; P < .001) and low T3 (HR, 1.57; 95% CI, 1.22-2.01; P < .001) but not in SCT. CONCLUSION: A mildly altered thyroid status is associated with an increased risk of mortality in patients with cardiac disease

Mind-body relationships in elite apnea divers during breath holding: a study of autonomic responses to acute hypoxemia

The mental control of ventilation with all associated phenomena, from relaxation to modulation of emotions, from cardiovascular to metabolic adaptations, constitutes a psychophysiological condition characterizing voluntary breath-holding (BH). BH induces several autonomic responses, involving both autonomic cardiovascular and cutaneous pathways, whose characterization is the main aim of this study. Electrocardiogram and skin conductance (SC) recordings were collected from 14 elite divers during three conditions: free breathing (FB), normoxic phase of BH (NPBH) and hypoxic phase of BH (HPBH). Thus, we compared a set of features describing signal dynamics between the three experimental conditions: from heart rate variability (HRV) features (in time and frequency-domains and by using nonlinear methods) to rate and shape of spontaneous SC responses (SCRs). The main result of the study rises by applying a Factor Analysis to the subset of features significantly changed in the two BH phases. Indeed, the Factor Analysis allowed to uncover the structure of latent factors which modeled the autonomic response: a factor describing the autonomic balance (AB), one the information increase rate (IIR), and a latter the central nervous system driver (CNSD). The BH did not disrupt the FB factorial structure, and only few features moved among factors. Factor Analysis indicates that during BH (1) only the SC described the emotional output, (2) the sympathetic tone on heart did not change, (3) the dynamics of interbeats intervals showed an increase of long-range correlation that anticipates the HPBH, followed by a drop to a random behavior. In conclusion, data show that the autonomic control on heart rate and SC are differentially modulated during BH, which could be related to a more pronounced effect on emotional control induced by the mental training to BH

T-786→C polymorphism of the endothelial nitric oxide synthase gene is associated with insulin resistance in patients with ischemic or non ischemic cardiomyopathy

Background: Insulin resistance (IR) and endothelial dysfunction are frequently associated in cardiac disease. The T-786→C variant in the promoter region of the endothelial nitric oxide synthase (eNOS) gene has been associated with IR in both non-diabetic and diabetic subjects. Aim of the study was to assess the reciprocal relationships between T-786→C eNOS polymorphism and IR in ischemic and non-ischemic cardiomyopathy.Method: A group of 132 patients (108 males, median age 65 years) with global left ventricular (LV) dysfunction secondary to ischemic or non-ischemic heart disease was enrolled. Genotyping of T-786→C eNOS gene promoter, fasting glucose, insulin, and insulin resistance (defined as HOMA-IR index &gt; 2.5) were determined in all patients.Results: Genotyping analysis yielded 37 patients homozygous for the T allele (TT), 70 heterozygotes (TC) and 25 homozygous for C (CC). Patients with CC genotype had significantly higher systemic arterial pressure, blood glucose, plasma insulin and HOMA index levels than TT. At multivariate logistic analysis, the history of hypertension and the genotype were the only predictors of IR. In particular, CC genotype increased the risk of IR (CI% 1.4-15.0, p &lt; 0.01) 4.5-fold. The only parameter independently associated with the extent of LV dysfunction and the presence of heart failure (HF) was the HOMA index (2.4 CI% 1.1-5.6, p &lt; 0.04).Conclusions: T-786→C eNOS polymorphism was the major independent determinant of IR in a population of patients with ischemic and non-ischemic cardiomyopathy. The results suggest that a condition of primitive eNOS lower expression can predispose to an impairment of glucose homeostasis, which in turn is able to affect the severity of heart disease. © 2012 Vecoli et al.; licensee BioMed Central Ltd

Improved myocardial perfusion in chronic diabetic mice by the up-regulation of pLKB1 and AMPK signaling

Previous studies related impaired myocardial microcirculation in diabetes to oxidative stress and endothelial dysfunction. Thus, this study was aimed to determine the effect of up-regulating pAMPK-pAKT signaling on coronary microvascular reactivity in the isolated heart of diabetic mice. We measured coronary resistance in wild-type and streptozotocin (STZ)-treated mice, during perfusion pressure changes. Glucose, insulin, and adiponectin levels in plasma and superoxide formation, NOx levels and heme oxygenase (HO) activity in myocardial tissue were determined. In addition, the expression of HO-1, 3-nitrotyrosine, pLKB1, pAMPK, pAKT, and peNOS proteins in control and diabetic hearts were measured. Coronary response to changes in perfusion pressure diverged from control in a time-dependent manner following STZ administration. The responses observed at 28 weeks of diabetes (the maximum time examined) were mimicked by L-NAME administration to control animals and were associated with a decrease in serum adiponectin and myocardial pLKB1, pAMPK, pAKT, and pGSK-3 expression. Cobalt protoporphyrin treatment to induce HO-1 expression reversed the microvascular reactivity seen in diabetes towards that of controls. Up-regulation of HO-1 was associated with an increase in adiponectin, pLKB1, pAKT, pAMPK, pGSK-3, and peNOS levels and a decrease in myocardial superoxide and 3-nitrotyrosine levels. In the present study we describe the time course of microvascular functional changes during the development of diabetes and the existence of a unique relationship between the levels of serum adiponectin, pLKB1, pAKT, and pAMPK activation in diabetic hearts. The restoration of microvascular function suggests a new therapeutic approach to even advanced cardiac microvascular derangement in diabetes

t(15;21) translocations leading to the concurrent downregulation of RUNX1 and its transcription factor partner genes SIN3A and TCF12 in myeloid disorders.

Through a combined approach integrating RNA-Seq, SNP-array, FISH and PCR techniques, we identified two novel t(15;21) translocations leading to the inactivation of RUNX1 and its partners SIN3A and TCF12. One is a complex t(15;21)(q24;q22), with both breakpoints mapped at the nucleotide level, joining RUNX1 to SIN3A and UBL7-AS1 in a patient with myelodysplasia. The other is a recurrent t(15;21)(q21;q22), juxtaposing RUNX1 and TCF12, with an opposite transcriptional orientation, in three myeloid leukemia cases. Since our transcriptome analysis indicated a significant number of differentially expressed genes associated with both translocations, we speculate an important pathogenetic role for these alterations involving RUNX1

Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy.

Under resting conditions, the failing heart shifts fuel use toward greater glucose and lower free fatty acid (FFA) oxidation. We hypothesized that chronic metabolic abnormalities in patients with dilated cardiomyopathy (DCM) are associated with the absence of the normal increase in myocardial glucose uptake and maintenance of cardiac mechanical efficiency in response to pacing stress. In 10 DCM patients and 6 control subjects, we measured coronary flow by intravascular ultrasonometry and sampled arterial and coronary sinus blood. Myocardial metabolism was determined at baseline, during atrial pacing at 130 beats/min, and at 15 min of recovery by infusion of [(3)H]oleate and [(13)C]lactate and measurement of transmyocardial arteriovenous differences of oxygen and metabolites. At baseline, DCM patients showed depressed coronary flow, reduced uptake and oxidation of FFA, and preferential utilization of carbohydrates. During pacing, glucose uptake increased by 106% in control subjects but did not change from baseline in DCM patients. Lactate release increased by 122% in DCM patients but not in control subjects. Cardiac mechanical efficiency in DCM patients was not different compared with control subjects at baseline but was 34% lower during stress. Fatty acid uptake and oxidation did not change with pacing in either group. Our results show that in DCM there is preferential utilization of carbohydrates, which is associated with reduced flow and oxygen consumption at rest and an impaired ability to increase glucose uptake during stress. These metabolic abnormalities might contribute to progressive cardiac deterioration and represent a target for therapeutic strategies aimed at modulating cardiac substrate utilization