The effect of rosiglitazone on integrated cardiovascular performance, cardiac structure, function and myocardial triglyceride: trial design and rationale

Abstract

T he thiazolidinedione (TZD) class of medications has been associated with increased risk for peripheral oedema, as well as incident and worsening heart failure (HF). The mechanism of these observed effects remains unclear. Here we present the rationale and study design for a randomised clinical trial designed to evaluate the cardiac effects of rosiglitazone on integrated cardiovascular performance, cardiac structure and function.The study is a randomised, single-centre, doubleblind, placebo-controlled, parallel-group clinical trial to evaluate the effect of rosiglitazone on integrated cardiovascular performance in a cohort of patients with type 2 diabetes mellitus (T2DM) at increased risk for developing heart failure (HF). Participants will be randomised to receive rosiglitazone or matching placebo for six months. All subjects will undergo maximal treadmill cardiopulmonary exercise testing at baseline and after six months on study drug, with the primary trial end point of peak oxygen uptake indexed to fat-free mass (VO 2peak -FFM). Approximately two-thirds of the study cohort will undergo cardiac magnetic resonance imaging (MRI) and spectroscopy (MRS) at baseline and after six months of study therapy to assess cardiac structure, function and myocardial triglyceride content.While concerns for peripheral oedema and HF continue to confound clinical use of TZD medications, the direct cardiac effects of these drugs remain poorly understood and the clinical relevance of these clinical observations remains unclear. The present study will combine a series of state-of-the-art assessments to evaluate the cardiac effects of rosiglitazone treatment. (ClinicalTrials.gov NCT00424762).

Adiponectin and cardiovascular risk profile in patients with type 2 diabetes mellitus: parameters associated with adiponectin complex distribution

“…6 For the present analyses, a subset of 53 subjects were selected from the overall cohort (150) based on completeness of their data set for all measured parameters. The protocol was approved by the University of Texas Southwestern Medical Center Institutional Review Board, and all subjects provided written informed consent.…”

“…6 We assessed correlations between the adiponectin complex distribution and physiological parameters associated with metabolic dysfunction and cardiovascular risk to gain insight into what pathophysiological states may affect the distribution of circulating adiponectin isoforms.…”

Is cardiorespiratory fitness a determinant of cardiomyopathy in the setting of type 2 diabetes?

“…4,16 Spectroscopy data were collected at end expiration and end systole, triggered by simultaneous respiratory and ECG gating. Spectra were collected using a whole body coil and a 17-cm surface coil for signal reception.…”

“…16 Participants were recruited from outpatient clinics, research study rosters and public advertisement. Inclusion criteria were age >18 years, medically treated T2DM (previous diagnosis of T2DM or current use of hypoglycaemic medical therapy) and the presence of ⩾1 other CV disease risk factors, including smoking, hypertension (⩾140/90 mmHg), dyslipidemia (treated, physician diagnosed or self-reported), albuminuria, family history of coronary artery disease or high-sensitivity C-reactive protein >3 mg/L.…”

“…16 Briefly dynamic images were used to quantify LV diastolic and systolic volume using short-axis slices. LV mass was computed as the product of LV enddiastolic volume (EDV) and myocardial density (1.05 g/ mL), divided by body surface area.…”