Effects of Acute Triiodothyronine Treatment in Patients with Anterior Myocardial Infarction Undergoing Primary Angioplasty: Evidence from a Pilot Randomized Clinical Trial (ThyRepair Study).

Background: Thyroid hormone has a differential action on healthy and ischemic heart. Triiodothyronine (T3) administration improved postischemic cardiac function while it limited apoptosis in experimentally induced ischemia. Thus, the present study investigated the potential effects of acute liothyronine (LT3) treatment in patients with anterior myocardial infarction. Methods: This study is a pilot, randomized, double-blind, placebo-controlled trial (ThyRepair study). We randomized 52 patients and analyzed data from 37 patients (n = 16 placebo and n = 21 LT3), per prespecified per protocol analysis. We excluded three patients who had died of cardiovascular causes (one in placebo and two in LT3 arm), four with small infarct size below a pre-specified threshold (in the placebo arm), and the rest, who lacked follow-up data. LT3 treatment started after stenting as an intravenous (i.v.) bolus injection of 0.8 µg/kg of LT3 followed by a constant infusion of 0.113 µg/kg/h i.v. for 48 hours. All patients had cardiac magnetic resonance (CMR) at hospital discharge and 6 months follow-up. The primary end point was CMR left ventricular (LV) ejection fraction (LVEF) and secondary endpoints were LV volumes, infarct volume (IV), and safety. Results: The CMR LVEF% at 6 months was 53.6 ± 9.5 for the LT3-treated group and 48.6 ± 11 for placebo, p = 0.15. Acute LT3 treatment resulted in a significantly lower LV end-diastolic volume index (92.2 ± 16.8 mL/m2 vs. 107.5 ± 22.2, p = 0.022) and LV systolic volume index (47.5 ± 13.9 mL/m2 vs. 61.3 ± 21.7, p = 0.024) at hospital discharge, but not at 6 months. There was no statistically significant difference in CMR IV at hospital discharge between the groups (p = 0.24). CMR IV tended to be lower in the LT3-treated group at 6 months (18.7 ± 9.5 vs. 25.9 ± 11.7, in placebo, p = 0.05). Serious, life-threatening events related to LT3 treatment were not observed. A tendency for an increased incidence of atrial fibrillation (AF) was found in the LT3 group during the first 48 hours (19% for T3 group vs. 5% for placebo, p = 0.13). Conclusion: This pilot randomized, placebo-controlled trial study suggests potential favorable effects (acute cardiac dilatation and 6-month IV) as well as potential concerns regarding a higher risk of AF after LT3 administration early after myocardial infarction, which should be tested in a larger scale study.

The Tree of Sirtuins and the Garden of Cardiovascular Youth.

Sirtuins (SIRTs) are a class of nicotine adenine dinucleotide (NAD+)-dependent proteins which participate in numerous molecular pathways involved in various age-related human diseases, such as type II diabetes, cardiovascular (CV) diseases and cancer. They have a major role in apoptosis, inflammation, oxidative stress and metabolism regulation, traits that have a great impact on CV physiology and pathology. Their unique profile of NAD+ energy dependency makes them an appealing target for human intervention in cellular and metabolic processes. This review focuses on the recent advances of SIRTs research aiming to shed light on the emerging roles of SIRTs in the pathophysiology of CV and metabolic diseases.

The effect of heart rate on wave reflections may be determined by the level of aortic stiffness: clinical and technical implications.

BACKGROUND: Augmentation Index (AIx) is related to cardiovascular diseases, risk, and mortality. AIx is associated with heart rate but the effect of aortic stiffness on this relationship has not been studied. The purpose of our study was to investigate the relationship between AIx and heart rate at different aortic stiffness levels. METHODS: The study consisted of 425 normotensive and untreated hypertensive subjects. Wave reflections and pulse-wave velocity (PWV) were determined by the Sphygmocor and the Complior systems, respectively. RESULTS: AIx was independently associated with heart rate, age, gender, height, mean blood pressure (BP) and the effective reflection site distance (ERD). The population was divided into three groups of those with different PWV levels (tertiles). The regression lines for AIx with heart rate differed significantly between the 3rd and the other two tertiles of PWV (P = 0.039 for slopes and P = 0.002 for intercepts). This difference remained significant even after adjustment for age, gender, height, mean BP, and distance of wave reflections. CONCLUSIONS: A significantly stronger correlation of AIx with heart rate was observed in subjects with higher levels of aortic stiffness as compared to those with lower levels; namely, the same increase in the heart rate between subjects, induced a greater decrease in the AIx at higher compared to lower PWV levels. The correction of AIx for heart rate should be reconsidered based on the aortic stiffness level. This finding has implications for interventional studies that aim to improve central hemodynamics but simultaneously affect heart rate. Further studies that show acute modifications of heart rate at different arterial stiffness levels are required to support these findings.

Dobutamine stress echocardiography for the evaluation of cardiac reserve late after Fontan operation.

INTRODUCTION: This study aimed to assess the potential role and safety of dobutamine stress echocardiography (DSE) in the evaluation of cardiac reserve in asymptomatic patients several years after a Fontan operation. METHODS: We studied 10 asymptomatic patients, 28 +/- 5 years old, 14 +/- 6 years after their Fontan operation. All patients and 10 healthy, matched controls underwent two-dimensional and Doppler echocardiography at baseline and throughout dobutamine infusion (given in 3-minute increments of 5, 10, 20, 30, and 40 microg/kg/min). Multivariate analysis for repeated measurements was used to detect differences between patients and controls. RESULTS: There were no adverse events during dobutamine infusion. Heart rate increased appropriately in both patients and controls. Patients reached peak stroke volume at infusion rates of 20 microg/kg/min, whereas controls peaked at 10 microg/kg/min. Mean stroke volume, cardiac output and cardiac index were significantly different between the two groups only up to infusion rates of 10 microg/kg/min. The velocity time integral of the left ventricular outflow tract flow was significantly lower in patients than controls throughout the study. CONCLUSION: DSE is a safe method of stress testing for the assessment of adult Fontan patients and provides insights into the pathophysiology of their cardiac performance. Cardiac reserve in these patients is impaired compared to healthy controls.

Relation of habitual cocoa consumption to aortic stiffness and wave reflections, and to central hemodynamics in healthy individuals.

The effect of habitual cocoa consumption on arterial stiffness and wave reflection indexes, as well as on peripheral and central blood pressure, was assessed in 198 healthy subjects. In conclusion, higher cocoa intake was an independent determinant of low arterial stiffness and wave reflection indexes and was also independently associated with significantly lower central (aortic) pulse pressure.