H.J. Lamb

Ectopic fat and insulin resistance: pathophysiology and effect of diet and lifestyle interventions.

The storage of triglyceride (TG) droplets in nonadipose tissues is called ectopic fat storage. Ectopic fat is associated with insulin resistance and type 2 diabetes mellitus (T2DM). Not the triglycerides per se but the accumulation of intermediates of lipid metabolism in organs, such as the liver, skeletal muscle, and heart seem to disrupt metabolic processes and impair organ function. We describe the mechanisms of ectopic fat depositions in the liver, skeletal muscle, and in and around the heart and the consequences for each organs function. In addition, we systematically reviewed the literature for the effects of diet-induced weight loss and exercise on ectopic fat depositions.

Cardiac imaging in coronary artery disease: differing modalities

Coronary artery disease (CAD) remains one of the leading causes of morbidity and mortality worldwide. Moreover, the disease is reaching endemic proportions and will put an enormous strain on health care economics in the near future. Non-invasive testing is important to exclude CAD with a high certainty on the one hand, and to detect CAD with its functional consequences at an early stage, to guide optimal patient management, on the other hand. For these purposes, non-invasive imaging techniques have been developed and used extensively over the last years. Currently, the main focus of non-invasive imaging for diagnosis of CAD is twofold: (1) functional imaging , assessing the haemodynamic consequences of obstructive coronary artery disease; and (2) anatomical imaging , visualising non-invasively the coronary artery tree.nnFor functional imaging, nuclear cardiology, stress echocardiography, and magnetic resonance imaging (MRI) are used, whereas for anatomical imaging or non-invasive angiography, MRI, multislice CT (MSCT), and electron beam CT (EBCT) are used.nnThis manuscript will update the reader on the current status of non-invasive imaging, with a special focus on functional imaging versus anatomical imaging for the detection of CAD. The accuracies of the different imaging modalities are illustrated using pooled analyses of the available literature data when available.nn### What information does functional imaging provide?nnThe hallmark of functional imaging is the detection of CAD by assessing the haemodynamic consequences of CAD rather than by direct visualisation of the coronary arteries. For this purpose, regional perfusion or wall motion abnormalities are induced (or worsened) during stress, reflecting the presence of stress induced ischaemia. Ischaemia induction is based on the principle that although resting myocardial blood flow in regions supplied by stenotic coronary arteries is preserved, the increased flow demand during stress cannot be met, resulting in a sequence of events referred to as “the ischaemic cascade”.1 Initially perfusion abnormalities are …

Comprehensive cardiac assessment with multislice computed tomography: evaluation of left ventricular function and perfusion in addition to coronary anatomy in patients with previous myocardial infarction

Objective: To evaluate a comprehensive multislice computed tomography (MSCT) protocol in patients with previous infarction, including assessment of coronary artery stenoses, left ventricular (LV) function and perfusion. Patients and methods: 16-slice MSCT was performed in 21 patients with previous infarction; from the MSCT data, coronary artery stenoses, (regional and global) LV function and perfusion were assessed. Invasive coronary angiography and gated single-photon emission computed tomography (SPECT) served as the reference standards for coronary artery stenoses and LV function/perfusion, respectively. Results: 236 of 241 (98%) coronary artery segments were interpretable on MSCT. The sensitivity and specificity for detection of stenoses were 91% and 97%. Pearson’s correlation showed excellent agreement for assessment of LV ejection fraction between MSCT and SPECT (49 (13)% v 53 (12)%, respectively, r u200a=u200a 0.85). Agreement for assessment of regional wall motion was excellent (92%, κ u200a=u200a 0.77). In 68 of 73 (93%) segments, MSCT correctly identified a perfusion defect as compared with SPECT, whereas the absence of perfusion defects was correctly detected in 277 of 284 (98%) segments. Conclusions: MSCT permits accurate, non-invasive assessment of coronary artery stenoses, LV function and perfusion in patients with previous infarction. All parameters can be assessed from a single dataset.

Cardiovascular response to physical exercise in adult patients after atrial correction for transposition of the great arteries assessed with magnetic resonance imaging

Objective: To assess with magnetic resonance imaging (MRI) cardiovascular function in response to exercise in patients after atrial correction of transposition of the great arteries (TGA). Methods: Cardiac function at rest and during submaximal exercise was assessed with MRI in 27 patients with TGA (mean (SD) age 26 (5) years) late (23 (2) years) after atrial correction and in 14 control participants (25 (5) years old). Results: At rest, only right ventricular ejection fraction was significantly lower in patients than in controls (56 (7)% v 65 (7)%, p < 0.05). In response to exercise, increases in right ventricular end diastolic (155 (55) ml to 163 (57) ml, p < 0.05) and right ventricular end systolic volumes (70 (34) ml to 75 (36) ml, p < 0.05) were observed in patients. Furthermore, right and left ventricular stroke volumes and ejection fraction did not increase significantly in patients. Changes in right ventricular ejection fraction with exercise correlated with diminished exercise capacity (r u200a=u200a 0.43, p < 0.05). Conclusions: In patients with atrially corrected TGA, MRI showed an abnormal response to exercise of both systemic right and left ventricles. Exercise MRI provides a tool for close monitoring of cardiovascular function in these patients, who are at risk for late death.

Distinct effects of pioglitazone and metformin on circulating sclerostin and biochemical markers of bone turnover in men with type 2 diabetes mellitus

OBJECTIVEnPatients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures and thiazolidinediones (TZDs) increase this risk. TZDs stimulate the expression of sclerostin, a negative regulator of bone formation, in vitro. Abnormal sclerostin production may, therefore, be involved in the pathogenesis of increased bone fragility in patients with T2DM treated with TZDs.nnnMETHODSnWe measured serum sclerostin, procollagen type 1 amino-terminal propeptide (P1NP), and carboxy-terminal cross-linking telopeptide of type I collagen (CTX) in 71 men with T2DM treated with either pioglitazone (PIO) (30 mg once daily) or metformin (MET) (1000 mg twice daily). Baseline values of sclerostin and P1NP were compared with those of 30 healthy male controls.nnnRESULTSnCompared with healthy controls, patients with T2DM had significantly higher serum sclerostin levels (59.9 vs 45.2 pg/ml, P<0.001) but similar serum P1NP levels (33.6 vs 36.0 ng /ml, P=0.39). After 24 weeks of treatment, serum sclerostin levels increased by 11% in PIO-treated patients and decreased by 1.8% in MET-treated patients (P=0.018). Changes in serum sclerostin were significantly correlated with changes in serum CTX in all patients (r=0.36, P=0.002) and in PIO-treated patients (r=0.39, P=0.020), but not in MET-treated patients (r=0.17, P=0.31).nnnCONCLUSIONSnMen with T2DM have higher serum sclerostin levels than healthy controls, and these levels further increase after treatment with PIO, which is also associated with increased serum CTX. These findings suggest that increased sclerostin production may be involved in the pathogenesis of increased skeletal fragility in patients with T2DM in general and may specifically contribute to the detrimental effect of TZDs on bone.

MR Imaging Evaluation of Cardiovascular Risk in Metabolic Syndrome

Metabolic syndrome has become an important public health problem and has reached epidemic proportions globally. Metabolic syndrome is characterized by a cluster of metabolic abnormalities in an individual, with insulin resistance as the main characteristic. The major adverse consequence of metabolic syndrome is cardiovascular disease, which is often already present without clinical signs or symptoms. In this early stage of disease, interventions (eg, lifestyle intervention, medication) can be used to prevent further cardiovascular deterioration or even to reverse cardiovascular disease. Therefore, risk stratification on an individual basis and early detection of cardiovascular disease are essential. Magnetic resonance (MR) imaging is a powerful tool for demonstrating cardiovascular risk factors in metabolic syndrome, such as increased fat depots and arterial stiffening. Furthermore, MR imaging is an established modality for the assessment of myocardial function. This review provides a summary of the current MR applications in metabolic syndrome and discusses how these MR techniques can be used to identify subclinical cardiovascular damage.

Circulating long-non coding RNAs as biomarkers of left ventricular diastolic function and remodelling in patients with well-controlled type 2 diabetes

Contractile dysfunction is underdiagnosed in early stages of diabetic cardiomyopathy. We evaluated the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers of subclinical cardiac abnormalities in type 2 diabetes. Forty-eight men with well-controlled type 2 diabetes and 12 healthy age-matched volunteers were enrolled in the study. Left ventricular (LV) parameters were measured by magnetic resonance imaging. A panel of lncRNAs was quantified in serum by RT-qPCR. No differences in expression levels of lncRNAs were observed between type 2 diabetes patients and healthy volunteers. In patients with type 2 diabetes, long intergenic non-coding RNA predicting cardiac remodeling (LIPCAR) was inversely associated with diastolic function, measured as E/A peak flow (Pu2009<u20090.050 for all linear models). LIPCAR was positively associated with grade I diastolic dysfunction (Pu2009<u20090.050 for all logistic models). Myocardial infarction-associated transcript (MIAT) and smooth muscle and endothelial cell-enriched migration/differentiation-associated long noncoding RNA (SENCR) were directly associated with LV mass to LV end-diastolic volume ratio, a marker of cardiac remodelling (Pu2009<u20090.050 for all linear models). These findings were validated in a sample of 30 patients with well-controlled type 2 diabetes. LncRNAs are independent predictors of diastolic function and remodelling in patients with type 2 diabetes.

Assessment of regional myocardial wall motion and thickening by gated 99Tcm-tetrofosmin SPECT: a comparison with magnetic resonance imaging.

Gated single photon emission computed tomography (SPECT) imaging allows the simultaneous assessment of both perfusion and function by using one single study. The assessment of regional wall motion and thickening pattern with gated SPECT allows viability studies to be performed. Magnetic resonance imaging (MRI) is well validated for the assessment of myocardial wall motion and thickening in patients with normal and impaired ventricular function. The aim of the study was to analyse the concordance between wall motion and thickening scores derived by gated SPECT and MRI imaging. Furthermore, the agreement for myocardial wall motion and thickening according to myocardial perfusion was analysed with both techniques. We studied a group of 21 patients, including 13 with a previous myocardial infarction (all more than 4 months before the study), using both gated SPECT 99Tcm-tetrofosmin myocardial perfusion imaging and MRI. A 13-segment model was used for both gated SPECT and MRI and each segment was visually scored using a scale of 1-3 for wall motion and thickening. There was a high agreement between gated SPECT and MRI for both wall motion (229/273, 84%; k = 0.72, P<0.001) and wall thickening (236/273, 86%; k = 0.77, P<0.001). The agreement for wall motion and thickening was 80% (k = 0.66) and 83% (k = 0.70), respectively, for patients with myocardial infarction; and 90% (k = 0.81) and 92% (k = 0.86), respectively (P = NS), for patients without myocardial infarction. Agreement in segmental wall motion and thickening scores between gated SPECT and MRI was 90% (k = 0.80) and 91% (k = 0.84), respectively, for segments with normal or mild to moderate hypoperfusion; and 71% (k = 0.45) and 77% (k = 0.57), respectively, for segments with severe hypoperfusion or no perfusion. Of the 70 (41%) segments that had severely diminished or no perfusion in post-myocardial infarction patients, 22 (31%) showed preserved wall motion and 17 (24%) showed preserved wall thickening both by gated SPECT and MRI, suggesting residual myocardial viability in malperfused segments. Our results suggest that gated SPECT imaging is a reliable tool for the assessment of regional wall motion and thickening in patients with known or suspected coronary artery disease. In patients with a previous myocardial infarction gated SPECT imaging has the potential to detect preserved wall motion and thickening in regions with fixed perfusion defects indicating the potential presence of residual myocardial viability.

Chemotherapy for testicular cancer induces acute alterations in diastolic heart function

Background:After treatment with cisplatin-based chemotherapy for testicular cancer (TC), patients have higher prevalence of cardiovascular complications after long-term follow up. Little is known about acute cardiovascular effects of cisplatin-based chemotherapy. The aim of this study was to explore acute effects of chemotherapy on cardiac function in patients treated for TC.Methods:Fourteen TC patients (age 34.6±12.3 years) were studied before and 3 months after start with cisplatin-based chemotherapy. Cardiac function was assessed with magnetic resonance imaging. Fasting glucose and insulin levels were measured and insulin sensitivity, reflected by the quantitative insulin sensitivity index (Quicki index), was calculated.Results:Left ventricular (LV) end-diastolic volume and LV stroke volume (SV) significantly decreased from 192±27 to 175±26u2009ml (P<0.05) and 109±18 to 95±16u2009ml (P<0.05), respectively. The ratio of early and atrial filling velocities across the mitral valve, a parameter of diastolic heart function, decreased after chemotherapy from 1.87±0.43 to 1.64±0.45 (P<0.01). Metabolic parameters were unfavourably changed, reflected by a decreased Quicki index, which reduced from 0.39±0.05 to 0.36±0.05 (P<0.05).Conclusion:Chemotherapy for TC induces acute alterations in diastolic heart function, paralleled by unfavourable metabolic changes. Therefore, early after chemotherapy, metabolic treatment may be indicated to possibly reduce long-term cardiovascular complications.

Magnetic resonance imaging of ischemic heart disease : Why cardiac magnetic resonance imaging will play a significant role in the management of patients with coronary artery disease

The role of magnetic resonance imaging in the diagnosis of ischemic heart disease has great potential impact on patient management, because a number of aspects of ischemic heart disease can be evaluated in one imaging session. High resolution coronary magnetic resonance angiography is currently available, although several technical improvements are awaited to make the technique routinely applicable. A major advance will probably include the availability of magnetic resonance blood pool contrast agents to improve vessel visualization. Contrast media, in combination with either first pass or delayed myocardial scanning, will also play an important role in myocardial perfusion imaging. Functional magnetic resonance assessment of regional and global ventricular function is currently a well-established technique and is considered a new gold standard, which may impact on routine cardiology practice. This review summarizes some of the recent magnetic resonance developments for evaluating various aspects of ischemic heart disease, including magnetic resonance coronary angiography, flow imaging, and imaging of myocardial perfusion and function.