Effects of α-lipoic acid therapy on sympathetic heart innervation in patients with previous experience of transient takotsubo cardiomyopathy.

BACKGROUND: Takotsubo syndrome is a stress cardiomyopathy, characterized by reversible left ventricle (LV) apical ballooning in the absence of significant angiographic coronary artery stenosis. The frequent association with emotional stress suggests in this disease an autonomic nervous system involvement. We could think that a therapeutic treatment targeting heart sympathetic dysfunction could be of crucial importance. METHODS: From January 2010 to June 2012, 886 patients were consecutively evaluated at Cardarelli Hospital, Naples, Italy. Among these, 48 patients met takotsubo cardiomyopathy (TCM) criteria. Each patient was assessed with history and physical examination, 12-lead electrocardiogram, serum troponin, coronary arteriography, and left ventricular angiogram, perfusion myocardial scintigraphy with technetium 99m, with echocardiography and 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. At discharge, the surviving patients were randomly assigned to α-lipoic acid (ALA) treatment (600mg once daily) or placebo. Following discharge, after the initial TCM event, patients returned to our outpatient clinic at Internal Medicine of the Second University Naples for the follow-up evaluation quarterly until 12 months. Routine analysis, myocardial damage serum markers, oxidative stress serum markers, pro-inflammatory cytokines, and sympathetic tone activity were evaluated in all patients. RESULTS: ALA administration improved MIBG defect size at 12 months compared to placebo. CONCLUSIONS: Adrenergic cardiac innervation dysfunction in TCM patients persists after previous experience of transient stress-induced cardiac dysfunction. ALA treatment improves the adrenergic cardiac innervation. This study evaluates whether sympatho-vagal alterations are TCM event-related.

Peri-procedural tight glycemic control during early percutaneous coronary intervention is associated with a lower rate of in-stent restenosis in patients with acute ST-elevation myocardial infarction.

OBJECTIVE: We examined the effects of peri-procedural intensive glycemic control (IGC) during early percutaneous coronary intervention (PCI) on restenosis rate in hyperglycemic patients with ST-segment elevation myocardial infarction (STEMI). RESEARCH DESIGN AND METHODS: A total of 165 hyperglycemic patients (glucose ≥ 140 mg/dl) with first STEMI undergoing PCI were studied. Patients were randomized to IGC for almost 24 h after PCI (n = 82; glucose, 80-140 mg/dl) followed by multidose sc insulin during the hospital stay or conventional glycemic control (CGC; n = 83; glucose, 180-200 mg/dl) followed by conventional therapy. Coronary angiography was performed at study entry and at 6-month follow-up. Blood samples for glycemia, hemoglobin A1c, inflammatory markers (C-reactive protein and TNF-α), monocyte chemoattractant-protein-1, and oxidative stress (nitrotyrosine) were collected immediately before and 24 h, 30 and 180 d after PCI. RESULTS: After insulin infusion, mean plasma glucose during the peri-procedural period was greater in the CGC group than in the IGC group (CGC, 191 ± 15 mg/dl; IGC, 145 ± 35 mg/dl; P < 0.001). After the insulin infusion period, the levels of markers of oxidative stress (nitrotyrosine), inflammation (C-reactive protein, TNF-α), and monocyte chemoattractant-protein-1 were significantly higher in CGC patients compared with IGC patients. Moreover, ICG during PCI reduces restenosis by half (48 and 24%) at 6 months. During follow-up, there was no difference in mortality rates, glucose, inflammatory and oxidative stress markers among the groups. In-stent restenosis was positively associated with mean plasma glucose levels as well as oxidative stress and inflammatory markers during the insulin infusion period. CONCLUSIONS: In hyperglycemic patients with STEMI, optimal peri-procedural glycemic control by reducing oxidative stress and inflammation may improve the outcome after PCI.

Comparison of two diets of varying glycemic index on carotid subclinical atherosclerosis in obese children.

Childhood obesity is associated with an increased carotid intima-media thickness (IMT) and stiffness. Increased carotid wall thickening and rigidity are considered markers of subclinical atherosclerosis. The aim of the present study was to test the effect of two hypocaloric diets of varying glycemic index on weight loss and markers of subclinical atherosclerosis in obese children. Seventy consecutive obese children attending the Outpatient Weight Clinic of the Department of Pediatrics were invited to participate in an intensive dietary protocol. Twenty-six accepted and were randomly assigned to two different groups: the first group followed a hypocaloric low-glycemic index diet and the second a hypocaloric high-glycemic index diet. Anthropometric measures and biochemical tests were performed in all children. Quantitative B-mode ultrasound scans were used to measure intima-media thickness (IMT) and diameters of the common carotid artery. Considering both groups together, at 6 months, body mass index decreased from 28.3 +/- 3.1 to 25.8 +/- 3.3 kg/m(2), systolic blood pressure from 119 +/- 12 to 110 +/- 11 mmHg (P< 0.001), diastolic blood pressure from 78 +/- 8 to 74 +/- 7 mmHg (P< 0.001), IMT from 0.48 +/- 0.05 to 0.43 +/- 0.07 mm (P< 0.001), stiffness from 3.57 +/- 1.04 to 2.98 +/- 0.94 mm (P = 0.002), and high-sensitivity C-reactive protein from 1.5 +/- 0.9 (values log transformed) to 0.4 +/- 1.1 (P < 0.001). No differences were detectable in fasting serum triglycerides, total cholesterol, and high-density lipoprotein cholesterol. Insulin resistance (calculated by the HOmeostatic Model Assessment index [HOMA] score) significantly reduced only in the low-glycemic-index diet group (P < 0.04). In conclusion, this study confirms a benefit of hypocaloric diets on carotid IMT and stiffness in obese children and demonstrates, for the first time, an amelioration of insulin sensitivity in obese children after a low-glycemic index diet. These results justify the advice to obese children to follow a low-glycemic index diet in order to improve their cardiometabolic profile.

Effects of different degrees of sympathetic antagonism on cytokine network in patients with ischemic dilated cardiomyopathy.

BACKGROUND: The proinflammatory cytokines have been implicated in the pathogenesis of heart failure. Recent studies have shown that beta-adrenergic blockade can modulate cytokine production. This study investigates the different impact of different degrees of sympathetic antagonism on circulating levels of cytokines in patients with heart failure resulting from ischemic dilated cardiomyopathy (IDC). METHODS AND RESULTS: Thirty-five patients with IDC were randomly assigned to receive metoprolol or carvedilol in an open-label study. Echocardiographic measurements and circulating levels of tumor necrosis (TNF)-alpha and interleukin (IL)-1beta and IL-6 were obtained at baseline and after 3 months of treatment. The 2 beta-blockers significantly improved the left ventricular ejection fraction and reduced end-diastolic and end-systolic volume. The magnitude of these changes was greater with carvedilol than with metoprolol (respectively P < .001, P < .05, and P < .05). Both treatments induced a significant decrease in the levels of cytokines (for all P < .01), but the decrease in TNF-alpha and IL-1beta was more consistent in the carvedilol group ( P < .01). CONCLUSION: Our results support the hypothesis that a more complete block of sympathetic activity by carvedilol induces a greater decrease in the circulating levels of proinflammatory cytokines that could explain, at least in part, the better improvement in the left ventricular remodelling and systolic function in patients with IDC.

Exercise training improves diastolic perfusion time in patients with coronary artery disease.

Exercise training elicits an improvement in work capacity and in left-ventricular function in patients with coronary artery disease. An improvement in myocardial oxygen supply accounts for these effects. The aim of this study was to test the hypothesis that exercise training could favorably influence diastolic perfusion time, a major determinant of subendocardial perfusion. Twenty-two male patients with coronary artery disease were randomized to a training or control group. At the study entry and after one year, all patients underwent an exercise stress test. After one year, rest heart rate was lower and diastolic perfusion time was higher in the training group but not in the control group. At peak of exercise, diastolic perfusion time increased and ST-segment depression decreased significantly in the training group but not in the control group. A significant relation was found between the R-R interval and the diastolic perfusion time either before or after training, with a difference in the intercepts of two regressions. Training shifted updown-line regression, effecting a higher value of diastolic perfusion time for a given value of heart rate. Thus, training increases diastolic perfusion time, independently from the effect on heart rate. This mechanism may contribute to the improvement of myocardial perfusion.