Background-Depressed myocardial blood flow (MBF) has been reported in dilated cardiomyopathy. The aim of this study was to investigate whether MBF impairment is an independent predictor of prognosis in patients with idiopathic left ventricular (LV) dysfunction. Methods and Results-Sixty-seven patients (52 male, mean age 52Ϯ12 years) with different degrees of idiopathic LV systolic dysfunction (average LV ejection fraction, 0.34Ϯ0.10; range, 0.07 to 0.49) were prospectively enrolled. Thirty-four subjects (51%) had no history of heart failure symptoms at enrollment (NYHA class I). All patients underwent clinical and functional evaluation and a PET study to measure absolute MBF at rest and after intravenous dipyridamole. During a mean follow-up of 45Ϯ37 months, 24 patients had major cardiac events, including cardiac death in 8 and development or progression of heart failure in 16 patients. Multivariate regression analysis (Cox proportional hazards model) revealed heart rate ( 2 11.06, PϽ0.001), LV end-diastolic dimension ( 2 11.73, PϽ0.001), and dipyridamole MBF ( 2 11.04, PϽ0.001) as independent predictors of subsequent cardiac events. Dipyridamole MBF Յ1.36 mL ⅐ min Ϫ1 ⅐ g Ϫ1 was associated with an increase in the relative risk of death, development, or progression of heart failure of 3.5 times over other more common clinical and functional variables. Conclusions-The present study demonstrates that severely depressed MBF is a predictor of poor prognosis in patients with idiopathic LV dysfunction independently of the degree of LV functional impairment and of the presence of overt heart failure.

The aim of this study was to evaluate how the diagnostic accuracy of a stress echocardiographic procedure, such as a dipyridamole echocardiography test, depends on the specific experience of the physician interpreting the test. Recordings of 50 consecutive dipyridamole echocardiographic tests were selected for the first part of the study. They were analyzed by 20 experienced echocardiographers with different backgrounds in stress echocardiography: 10 beginners (less than 20 stress studies interpreted with trained staff) and 10 experienced observers (greater than or equal to 100 stress studies performed). Diagnostic accuracy (true positive + true negative/total number of tests) versus the angiographic reference standard (greater than 70% coronary stenosis of at least one major coronary artery) was 62 +/- 6% for beginners and 85 +/- 3% for experienced observers (p less than 0.0001). In the second part of the study, 10 observers (5 beginners and 5 experienced observers) evaluated 2 different sets of 50 dipyridamole echocardiographic test studies before and after the training of the beginners. Before training, the accuracy of beginners was lower than that of experienced observers (61 +/- 7% versus 85 +/- 3%; p less than 0.001). After training, the accuracy gap was closed (83 +/- 3% versus 86 +/- 2%; p = NS). Therefore, interpretation of stress echocardiographic tests by an echocardiographer without specific training severely underestimates the diagnostic potential of this technique. One hundred stress echocardiographic studies are more than adequate to build the individual learning curve and reach the plateau of diagnostic accuracy that the test can yield.

Vitamin D and all its metabolites are bound to a specific vitamin D binding protein, DBP. This protein was originally first discovered by its worldwide polymorphism and called Group-specific Component (GC). We now know that DBP and GC are the same protein and appeared early in the evolution of vertebrates. DBP is genetically the oldest member of the albuminoid family (including albumin, α-fetoprotein and afamin, all involved in transport of fatty acids or hormones). DBP has a single binding site for all vitamin D metabolites and has a high affinity for 25OHD and 1,25(OH)2D, thereby creating a large pool of circulating 25OHD, which prevents rapid vitamin D deficiency. DBP of higher vertebrates (not amphibians or reptiles) binds with very high affinity actin, thereby preventing the formation of polymeric actin fibrils in the circulation after tissue damage. Megalin is a cargo receptor and is together with cubilin needed to reabsorb DBP or the DBP-25OHD complex, thereby preventing the urinary loss of these proteins and 25OHD. The total concentrations of 25OHD and 1,25(OH)2D in DBP null mice or humans are extremely low but calcium and bone homeostasis remain normal. This is the strongest argument for claiming that the "free hormone hypothesis" also applies to the vitamin D hormone, 1,25(OH)2D. DBP also transports fatty acids, and can play a role in the immune system. DBP is genetically very polymorphic with three frequent alleles (DBP/GC 1f, 1s, and 2) but in total more than 120 different variants but its health consequences, if any, are not understood. A standardization of DBP assays is essential to further explore the role of DBP in physiology and diseases.

Context: Low-T 3 syndrome is a predictor of poor outcome in patients with cardiac dysfunction. The study aimed to assess the short-term effects of synthetic L-T 3 replacement therapy in patients with low-T 3 syndrome and ischemic or nonischemic dilated cardiomyopathy (DC).Design: A total of 20 clinically stable patients with ischemic (n ϭ 12) or nonischemic (n ϭ 8) DC were enrolled. There were 10 patients (average age 72 yr, range 66 -77; median, 25-75th percentile) who underwent 3-d synthetic L-T 3 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-T 3 (initial dose: 20 g/m 2 body surface⅐d) or placebo infusion.Results: After T 3 administration, free T 3 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 ϭ 0.03) without side effects. Heart rate decreased significantly after T 3 infusion (63, 60 -66 vs. 69, 60 -76 beats per minute; P ϭ 0.008). Plasma noradrenaline (347; 270 -740 vs. 717, 413-808 pg/ml; P ϭ 0.009), N-terminal pro-B-Type natriuretic peptide (3000, 438-4005 vs. 3940, 528-5628 pg/ml; P ϭ 0.02), and aldosterone (175, 152-229 vs. 231, 154 -324 pg/ml; P ϭ 0.047) significantly decreased after T 3 administration. Neurohormonal profile did not change after placebo infusion in the control group. After synthetic L-T 3 administration, left-ventricular end-diastolic volume (142, 132-161 vs. 133, 114 -158 ml/m 2 body surface; P ϭ 0.02) and stroke volume (40, 34 -44 vs. 35, 28 -39 ml/m 2 body surface; P ϭ 0.01) increased, whereas external and intracardiac workload did not change. Conclusions:In DC patients, short-term synthetic L-T 3 replacement therapy significantly improved neuroendocrine profile and ventricular performance. These data encourage further controlled trials with more patients and longer periods of synthetic L-T 3 administration. (J Clin Endocrinol

Obesity-associated inflammation causes insulin resistance. Obese adipose tissue displays hypertrophied adipocytes and increased expression of the cannabinoid-1 receptor. Cobalt protoporphyrin (CoPP) increases heme oxygenase-1 (HO-1) activity, increasing adiponectin and reducing inflammatory cytokines. We hypothesize that CoPP administration to Zucker diabetic fat (ZDF) rats would improve insulin sensitivity and remodel adipose tissue. Twelve-week-old Zucker lean and ZDF rats were divided into 4 groups: Zucker lean, Zucker lean–CoPP, ZDF, and ZDF–CoPP. Control groups received vehicle and treatment groups received CoPP (2 mg/kg body weight) once weekly for 6 weeks. Serum insulin levels and glucose response to insulin injection were measured. At 18 weeks of age, rats were euthanized, and aorta, kidney, and subcutaneous and visceral adipose tissues were harvested. HO-1 expression was measured by Western blot analysis and HO-1 activity by serum carbon monoxide content. Adipocyte size and cannabinoid-1 expression were measured. Adipose tissue volumes were determined using MRI. CoPP significantly increased HO-1 activity, phosphorylated AKT and phosphorylated AMP kinase, and serum adiponectin in ZDF rats. HO-1 induction improved hyperinsulinemia and insulin sensitivity in ZDF rats. Subcutaneous and visceral adipose tissue volumes were significantly decreased in ZDF rats. Adipocyte size and cannabinoid-1 expression were both significantly reduced in ZDF–CoPP rats in subcutaneous and visceral adipose tissues. This study demonstrates that HO-1 induction improves insulin sensitivity, downregulates the peripheral endocannabinoid system, reduces adipose tissue volume, and causes adipose tissue remodeling in a model of obesity-induced insulin resistance. These findings suggest HO-1 as a potential therapeutic target for obesity and its associated health risks.

To assess regional coronary reserve in hypertrophic cardiomyopathy, regional myocardial blood flow was measured in 23 patients with hypertrophic cardiomyopathy and 12 control subjects by means of nitrogen-13 ammonia and dynamic positron emission tomography. In patients with hypertrophic cardiomyopathy at baseline study, regional myocardial blood flow was 1.14 +/- 0.43 ml/min per g in the hypertrophied (20 +/- 3 mm) interventricular septum and 0.90 +/- 0.35 ml/min per g (p less than 0.05 versus septal flow) in the nonhypertrophied (10 +/- 2 mm) left ventricular free wall. These were not statistically different from the corresponding values in control subjects (1.04 +/- 0.25 and 0.91 +/- 0.21 ml/min per g, respectively, p = NS). After pharmacologically induced coronary vasodilation (dipyridamole, 0.56 mg/kg intravenously over 4 min), regional myocardial blood flow in patients with hypertrophic cardiomyopathy increased significantly less than in control subjects both in the septum (1.63 +/- 0.58 versus 2.99 +/- 1.06 ml/min per g, p less than 0.001) and in the free wall (1.47 +/- 0.58 versus 2.44 +/- 0.82 ml/min per g, p less than 0.001). In addition, patients with hypertrophic cardiomyopathy who had a history of chest pain had more pronounced impairment of coronary vasodilator reserve than did those without a history of chest pain. After dipyridamole, coronary resistance in the septum decreased by 38% in patients without a history of chest pain, but decreased by only 14% in those with such a history (p less than 0.05). Coronary resistance in the free wall decreased by 45% in patients without and by 27% in those with a history of chest pain (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Background— Clinical and experimental data have suggested a potential negative impact of low-T3 state on the prognosis of cardiac diseases. The aim of the present prospective study was to assess the role of thyroid hormones in the prognosis of patient population with heart disease. Methods and Results— A total of 573 consecutive cardiac patients underwent thyroid function profile evaluation. They were divided in two subgroups: group I, 173 patients with low T3, ie, with free T3 (fT3) <3.1 pmol/L, and group II, 400 patients with normal fT3 (≥3.1 pmol/L). We considered cumulative and cardiac death events. During the 1-year follow-up, there were 25 cumulative deaths in group I and 12 in group II (14.4% versus 3%, P <0.0001); cardiac deaths were 13 in group I and 6 in group II (7.5% versus 1.5%, P =0.0006). According to the Cox model, fT3 was the most important predictor of cumulative death (hazard ratio [HR] 3.582, P <0.0001), followed by dyslipidemia (HR 2.955, P =0.023), age (HR 1.051, P <0.005), and left ventricular ejection fraction (HR 1.037, P =0.006). At the logistic multivariate analysis, fT3 was the highest independent predictor of death (HR 0.395, P =0.003). A prevalence of low fT3 levels was found in patients with NYHA class III-IV illness compared with patients with NYHA class I-II (χ 2 5.65, P =0.019). Conclusions— Low-T3 syndrome is a strong predictor of death in cardiac patients and might be directly implicated in the poor prognosis of cardiac patients.

The aim of this study was This approach, based on the time domain analysis of the radiofrequency signals, appears promising as a means to establish certain aspects of ultrasonic diagnosis on a more quantitative basis.3,4 The assessment of regional myocardial fibrosis would be of particular interest since excessive myocardial fibrosis is both an important sign and is associated with a variety of myocardial diseases.Even though there were substantial problems in comparing exactly the anatomic region interrogated by the ultrasound technique versus the same area sampled by the endomyocardial biopsy, the aim of this study was to assess in vivo whether the regional ultrasonic reflectivity, evaluated by a real-time integrated backscatter