Multimodal functional and anatomic imaging identifies preclinical microvascular abnormalities in type 1 diabetes mellitus.

Structural and functional changes in the microcirculation in type 1 diabetes mellitus predict future end-organ damage and macrovascular events. We explored the utility of novel signal processing techniques to detect and track changes in ocular hemodynamics in patients with this disease. Twenty-four patients with uncomplicated type 1 diabetes mellitus and eighteen age- and sex-matched control subjects were studied. Doppler ultrasound was used to interrogate the carotid and ophthalmic arteries, and digital photography was used to image the retinal vasculature. Frequency analysis algorithms were applied to quantify velocity waveform structure and retinal photographic data at baseline and after inhalation of 100% O2. Frequency data were compared between groups. No significant differences were found in the resistive index between groups at baseline or after inhaled O2. Frequency analysis of Doppler flow velocity waveforms identified significant differences in bands 3-7 between patients and control subjects in data captured from the ophthalmic artery (P < 0.01 for each band). In response to inhaled O2, changes in frequency band amplitudes were significantly greater in control subjects compared with patients (P < 0.05). Only control subjects demonstrated a positive correlation (R = 0.61) between changes in retinal vessel diameter and frequency band amplitudes derived from ophthalmic artery waveform data. The use of multimodal signal processing techniques applied to Doppler flow velocity waveforms and retinal photographic data identified preclinical changes in the ocular microcirculation in patients with uncomplicated diabetes mellitus. An impaired autoregulatory response of the retinal microvasculature may contribute to the future development of retinopathy in such patients.

Experience using the new GORE Septal Occluder at the margins.

Complex atrial anatomy continues to challenge transcatheter device closure of septal defects. Devices and technology continue to evolve. We report three cases from our institution where the new Gore Septal Occluder was utilized for the closure of a lateral tunnel fenestration, a moderate-sized secundum atrial septal defect and a long tunnel patent foramen ovale. Each case highlights the successful use of this new generation device in challenging circumstances.

Closure of multiple fenestrations in an aneurismal atrial septum using overlapping GORE HELEX septal occluders.

Complex atrial septal anatomy can continue to present a challenge for transcatheter closure. We present the successful use of overlapping GORE HELEX atrial septal defect occluders in an adult patient with five distinct fenestrations in an aneurismal septum and how 3D echo can aid device positioning.

Flow-mediated dilatation of the brachial artery is a poorly reproducible indicator of microvascular function in Type I diabetes mellitus.

BACKGROUND: Flow-mediated dilatation (FMD) of the brachial artery is commonly measured as a surrogate marker of endothelial function. Its measurement is, however, technically demanding and reports regarding its reproducibility have not always been favourable. AIM: Two Type I diabetes and control group comparator studies were conducted to assess the reproducibility of FMD and to analyse blood flow data normally discarded during FMD measurement. DESIGN: The studies were sequential and differed only with regard to operator and ultrasound machine. Seventy-two subjects with diabetes and 71 controls were studied in total. METHODS: Subjects had FMD measured conventionally. Blood velocity waveforms were averaged over 10 pulses post forearm ischaemia and their component frequencies analysed using the wavelet transform, a mathematical tool for waveform analysis. The component frequencies were grouped into 11 bands to facilitate analysis. RESULTS: Subjects were well-matched between studies. In Study 1, FMD was significantly impaired in subjects with Type I diabetes vs. controls (median 4.35%, interquartile range 3.10-4.80 vs. 6.50, 4.79-9.42, P < 0.001). No differences were detected between groups in Study 2, however. However, analysis of blood velocity waveforms yielded significant differences between groups in two frequency bands in each study. CONCLUSION: This report highlights concerns over the reproducibility of FMD measures. Further work is required to fully elucidate the role of analysing velocity waveforms after forearm ischaemia.

Comparison of rootMUSIC and discrete wavelet transform analysis of Doppler ultrasound blood flow waveforms to detect microvascular abnormalities in type I diabetes.

The earliest signs of cardiovascular disease occur in microcirculations. Changes to mechanical and structural properties of these small resistive vessels alter the impedance to flow, subsequent reflected waves, and consequently, flow waveform morphology. In this paper, we compare two frequency analysis techniques: 1) rootMUSIC and 2) the discrete wavelet transform (DWT) to extract features of flow velocity waveform morphology captured using Doppler ultrasound from the ophthalmic artery (OA) in 30 controls and 38 age and sex matched Type I diabetics. Conventional techniques for characterizing Doppler velocity waveforms, such as mean velocity, resistive index, and pulsatility index, revealed no significant differences between the groups. However, rootMUSIC and the DWT provided highly correlated results with the spectral content in bands 2-7 (30-0.8 Hz) significantly elevated in the diabetic group (p < 0.05). The spectral distinction between the groups may be attributable to manifestations of underlying pathophysiological processes in vascular impedance and consequent wave reflections, with bands 5 and 7 related to age. Spectral descriptors of OA blood velocity waveforms are better indicators of preclinical microvascular abnormalities in Type I diabetes than conventional measures. Although highly correlated DWT proved slightly more discriminatory than rootMUSIC and has the advantage of extending to subheart rate frequencies, which may be of interest.

Effect of pioglitazone on endothelial function in impaired glucose tolerance.

AIM: Flow-mediated dilation (FMD) is a surrogate marker of endothelial function, which has been proposed as a barometer of vascular health. Impaired microvascular response to reactive hyperaemia is thought to be the mechanism behind reduced shear stress and subsequently impaired FMD, which has been associated with cardiovascular events. This study aims to assess the effect of pioglitazone on the vasculature of patients with impaired glucose tolerance (IGT). MATERIALS AND METHODS: Forty IGT patients with no cardiovascular disease were compared with 24 healthy age- and sex-matched controls. Endothelial function was assessed using FMD of the brachial artery. Adiponectin (ADN) levels were measured and insulin sensitivity was calculated using homeostasis model assessment of insulin resistance (HOMA-IR). A randomised double-blind placebo-controlled trial of the IGT subjects was then performed, with subjects receiving either pioglitazone 30 mg od or matched placebo for 12 weeks before the measurements were repeated. RESULTS: The IGT subjects had a significantly impaired FMD compared with the controls (p < 0.001). Diastolic shear stress (DSS) was also significantly reduced in IGT (p = 0.04). High molecular weight (HMW) ADN was significantly lower in the IGT group than in controls (p = 0.03). On analysis of the IGT group after 12 weeks treatment, FMD was significantly increased in the pioglitazone group compared with placebo (p = 0.03) as was endothelium-independent dilation (EID) (p = 0.03). A significant increase in total ADN (p < 0.001), HMW ADN (p < 0.001) and HMW/total ratio (p = 0.001) occurred in the pioglitazone group compared with placebo. CONCLUSIONS: Pioglitazone improved endothelial function in IGT. Treatment with pioglitazone may reduce the risk of cardiovascular disease in this patient group.

Colour Doppler ultrasound of the ocular circulation in patients with systemic lupus erythematosus identifies altered microcirculatory haemodynamics.

We assessed whether quantitative analysis of Doppler flow velocity waveforms is able to identify subclinical microvascular abnormalities in SLE and whether eigenvector analysis can detect changes not detectable using the resistive index (RI). Fifty-four SLE patients with no conventional cardiovascular risk factors, major organ involvement or retinopathy were compared to 32 controls. Flow velocity waveforms were obtained from the ophthalmic artery (OA), central retinal artery (CRA) and common carotid artery (CA). The waveforms were analysed using eigenvector decomposition and compared between groups at each arterial site. The RI was also determined. The RI was comparable between groups. In the OA and CRA, there were significant differences in the lower frequency sinusoidal components (P < 0.05 for each component). No differences were apparent in the CA between groups. Eigenvector analysis of Doppler flow waveforms, recorded in proximity of the terminal vascular bed, identified altered ocular microvascular haemodynamics in SLE. Altered waveform structure could not be identified by changes in RI, the traditional measure of downstream vascular resistance. This analytical approach to waveform analysis is more sensitive in detecting preclinical microvascular abnormalities in SLE. It may hold potential as a useful tool for assessing disease activity, response to treatment, and predicting future vascular complications.

Root-MUSIC analysis of nitric oxide-mediated changes in ophthalmic artery blood flow velocity waveforms.

Clinical and experimental studies indicate that structural and functional changes in the microvasculature can predate or accompany risk factors for cardiovascular disease at the earliest stages in the disease process. In the current work, both simulated and actual Doppler ultrasound maximum blood velocity waveform envelopes recorded from the ophthalmic artery were analysed using a root-MUSIC and least squares fitting approach to determine amplitude frequency spectra. Both amplitude and frequency components of noise contaminated simulated waveforms were reliably determined indicating the robustness of the technique. The technique was then used to compare the spectral content of the ophthalmic artery blood velocity waveforms of normal controls in three test states: at baseline, following administration of GTN, a nitric oxide donor, and following administration of L-Name, a nitric oxide inhibitor. Principal components derived from root-MUSIC analysis discriminated between waveforms in baseline and non-baseline test states (p<0.00001) and between GTN and non-GTN test states (p=0.0002).

Thiazolidinediones: effects on insulin resistance and the cardiovascular system.

Thiazolidinediones (TZDs) have been used for the treatment of hyperglycaemia in type 2 diabetes for the past 10 years. They may delay the development of type 2 diabetes in individuals at high risk of developing the condition, and have been shown to have potentially beneficial effects on cardiovascular risk factors. TZDs act as agonists of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) primarily in adipose tissue. PPAR-gamma receptor activation by TZDs improves insulin sensitivity by promoting fatty acid uptake into adipose tissue, increasing production of adiponectin and reducing levels of inflammatory mediators such as tumour necrosis factor-alpha (TNF-alpha), plasminogen activator inhibitor-1(PAI-1) and interleukin-6 (IL-6). Clinically, TZDs have been shown to reduce measures of atherosclerosis such as carotid intima-media thickness (CIMT). However, in spite of beneficial effects on markers of cardiovascular risk, TZDs have not been definitively shown to reduce cardiovascular events in patients, and the safety of rosiglitazone in this respect has recently been called into question. Dual PPAR-alpha/gamma agonists may offer superior treatment of insulin resistance and cardioprotection, but their safety has not yet been assured.

Elevated CA 125 and ascites: not always malignancy.

BACKGROUND: We present two clinical cases from a single institution where a final diagnosis of cardiac failure was made following the initial finding of ascites and an elevated CA 125 level. In both cases gynaecological malignancy was initially suspected. METHODS: Following negative confirmatory tests for gynaecological malignancy, echocardiography was undertaken. RESULTS: Patient 1 had severe right ventricular dilatation and dysfunction. Patient 2 had biventricular dysfunction with pulmonary hypertension. Both patients responded to standard therapy for heart failure, including loop diuretics.