The Emerging Role of Cardiovascular Magnetic Resonance Imaging in the Evaluation of Metabolic Cardiomyopathies.

The aim of this review is to discuss the role of Cardiovascular Magnetic Resonance (CMR) in the diagnosis, risk stratification, and follow-up of metabolic cardiomyopathies. The classification of myocardial diseases, proposed by WHO/ISFC task force, distinguished specific cardiomyopathies, caused by metabolic disorders, into 4 types: 1) endocrine disorders, 2) storage or infiltration disorders (amyloidosis, hemochromatosis and familial storage disorders), 3) nutritional disorders (Kwashiorkor, beri-beri, obesity, and alcohol), and 4) diabetic heart. Thyroid disease, pheochromocytoma, and growth hormone excess or deficiency may contribute to usually reversible dilated cardiomyopathy. Glucogen storage diseases can be presented with myopathy, liver, and heart failure. Lysosomal storage diseases can provoke cardiac hypertrophy, mimicking hypertrophic cardiomyopathy and arrhythmias. Hereditary hemochromatosis, an inherited disorder of iron metabolism, leads to tissue iron overload in different organs, including the heart. Cardiac amyloidosis is the result of amyloid deposition in the heart, formed from breakdown of normal or abnormal proteins that leads to increased heart stiffness, restrictive cardiomyopathy, and heart failure. Finally, nutritional disturbances and metabolic diseases, such as Kwashiorkor, beri-beri, obesity, alcohol consumption, and diabetes mellitus may also lead to severe cardiac dysfunction. CMR, through its capability to reliably assess anatomy, function, inflammation, rest-stress myocardial perfusion, myocardial fibrosis, aortic distensibility, iron and/or fat deposition can serve as an excellent tool for early diagnosis of heart involvement, risk stratification, treatment evaluation, and long term follow-up of patients with metabolic cardiomyopathies.

The diagnostic role of cardiac magnetic resonance imaging in detecting myocardial inflammation in systemic lupus erythematosus. Differentiation from viral myocarditis.

OBJECTIVE: The objective of this paper is to evaluate the diagnostic role of cardiac magnetic resonance imaging (CMR) in detecting myocardial inflammation in systemic lupus erythematosus (SLE) and its differentiation from viral myocarditis. PATIENTS AND METHODS: Fifty patients with suspected infective myocarditis (IM), with chest pain, dyspnoea or altered ECG, increase in troponin I and/or NT-pro BNP, with or without a history of flu-like syndrome or gastroenteritis and elevated C-reactive protein (CRP) within three to five (median four) weeks before admission, 25 active SLE patients, aged 38 ± 3 years, and 20 age-matched controls were prospectively evaluated by clinical assessment, ECG, echocardiogram and CMR. All patients underwent coronary angiography, and those with significant coronary artery disease (CAD) were excluded. CMR was performed using STIR T2-W (T2W), early T1-W (EGE) and late T1-W (LGE). Endomyocardial biopsies were performed when clinically indicated by current guidelines. Specimens were examined by immunohistological and polymerase chain reaction (PCR) analysis. RESULTS: Positive coronary angiography for CAD excluded 10/50 suspected IM and 5/25 active SLE. Positive clinical criteria for acute myocarditis were fulfilled by 28/40 suspected IM and only 5/20 active SLE. CMR was positive for myocarditis in 35/40 suspected IM and in 16/20 active SLE. Endomyocardial biopsy (EMB), performed in 25/35 suspected IM and 7/16 active SLE with positive CMR, showed positive immunohistology in 18/25 suspected IM and 3/7 active SLE. Infectious genomes were identified in 24/25 suspected IM and 1/7 active SLE. CONCLUSIONS: CMR-positive IM patients were more symptomatic than active SLE. More than half of CMR-positive patients also had positive EMB. PCR was positive in almost all IM, but unusual in SLE. Due to the subclinical presentation of SLE myocarditis and the limitations of EMB, CMR presents the best alternative for the diagnosis of SLE myocarditis.

Doppler-ultrasound as a predictor of uterine fibroid response to GnRH therapy.

OBJECTIVES: GnRH agonists (GnRHa) are able to reduce the bleeding and size of fibroids. We monitored the response of fibroids to GnRHa with power-Doppler ultrasound. METHODS: Thirty-five women with fibroids, aged 32-48, received a 6-month course with the GnRHa triptorelin (Decapeptyl, Ipsen, France). The resistance index (RI) of the uterine artery was measured with power-Doppler ultrasound. RESULTS: The uterine volume reduced from 470+/-347 to 297+/-295 cm3 (P<0.01) at the 6th month of treatment. The fibroid volume reduced after 3 months of treatment from 62+/-81 to 44+/-78 cm3 (P<0.05) and after 6 months of treatment to 30+/-70 cm3 (P<0.001 from baseline). Uterine artery RI increased from 0.73+/-0.16 to 1.05+/-0.27 at the 3rd month of treatment (P<0.001). The percent reduction of fibroid volume at the 6th month correlated with the percent increase of uterine RI at the 3rd month of treatment (r=0.45, P=0.01). CONCLUSIONS: The administration of triptorelin reduced fibroid dimensions. The increase of the uterine artery resistance index (RI) at the 3rd month correlated with fibroid shrinkage at the 6th month of treatment and may be used to predict the response to this therapeutic maneuver.

T2 relaxation time study of iron overload in b-thalassemia.

Myocardial iron deposition occurs as a result of blood transfusion therapy in b-thalassemia major patients. Since this deposition causes various cardiac complications, it is of interest to assess the iron content of the myocardium in relation to the clinical picture of the patients. Two different MRI indices were used to achieve this purpose: the T2 relaxation time and the heart/skeletal muscle signal intensity ratio. ECG gated spin echo images were obtained from 54 adult thalassemic patients, with a mean age of 26 (18-44) years, at TE = 22 ms and 60 ms, using a 1.5 T system. Patients were divided into 2 groups (A and B), according to their serum ferritin levels (> or < 2000 ng ml(-1)). Results were compared with nine controls, with a mean age of 25 (18-43) years. Heart T2 relaxation time in controls (44.3 +/- 3.5 ms) was higher than in group A (29.9 +/- 5.7 ms, P < 0.001) and group B (33.4 +/- 6.8 ms, P < 0.01). T2 was measurable in 66% of group A and 83% of group B patients. The heart/muscle signal intensity ratio in group A (0.45 +/- 0.27) was lower than in group B (0.82 +/- 0.33, P < 0.001) and the controls (1.15 +/- 0.20, P < 0.001). The heart/muscle signal intensity ratio was measurable in 94% of the patients and demonstrated an inverse relationship with the serum ferritin levels (r = -0.52, P < 0.01). This study indicates that the heart/muscle ratio is a sensitive index of iron overload and it can be measured in the majority of patients, irrespective of tissue iron concentration, thereby offering an advantage over the use of T2 relaxation time.

Abnormal carotid arterial wall dynamics in symptom-free hypopituitary adults.

OBJECTIVE: Although vascular mortality is increased in hypopituitary adults on routine replacement, there are limited data on the atherosclerotic process during life in these patients. Measurement of arterial stiffness may provide an index of early vascular changes that predispose to the development of major vascular accidents. DESIGN: Thirty-four hypopituitary adults on conventional replacement therapy and 39 age- and sex-matched controls were studied. They had no history or clinical evidence of macrovascular disease. The common carotid artery distensibility coefficient (DC), compliance coefficient (CC) and arterial stiffness index (beta index) were calculated from high-resolution ultrasonic imaging of the two common carotid arteries and from the brachial blood pressure. RESULTS: There was no difference between patients and controls in carotid diastolic diameter (mean +/- S.E.M) (5.55 +/- 0.16 vs 5.45 +/- 0.08 mm) and pulse pressure (6.66 +/- 0.30 vs 6.58 +/- 0.24 kPa). The increase in diameter during systole was significantly lower in the hypopituitary patients (0.39 +/- 0.02 vs 0.50 +/- 0.03 mm, P < 0.001). The DC was significantly lower in patients than in controls (24.2 +/- 2.29 vs 30.1 +/- 2.01 10(-3) kPa-1, P < 0.05). The carotid CC was also significantly lower in patients than in controls (5.7 +/- 0.49 vs 7.0 +/- 0.45 10(-7) m2 kPa-1, P < 0.05). The beta index was higher in the patient group (8.4 +/- 1.3 vs 5.9 +/- 0.37, P < 0.05). When men and women were considered separately, the differences between patients and controls were statistically significant in women but not in men and were more marked in the older women subgroup. CONCLUSIONS: Asymptomatic hypopituitary adults (especially women) on conventional replacement therapy have increased stiffness of the common carotid arteries. These findings provide additional evidence for a process leading to premature atherosclerosis in this group of patients.

The role of insulin in ovarian size in patients with the polycystic ovary syndrome.

The objective of this study was to evaluate whether the degree of suppression of ovarian volume effected by a gonadotropin releasing hormone (GnRH) agonist in patients with polycystic ovary syndrome (PCOS) correlated with basal insulin secretion and insulin secretion provoked by a glucose challenge. Eighteen PCOS patients received the GnRH agonist D-tryptophan-6-LHRH (Decapeptyl, 3.75 mg monthly i.m.) for 6 months and had blood glucose and insulin measured during a 75 g oral glucose tolerance test (OGTT) prior to and at the end of therapy. According to ovarian volume suppression after GnRH agonist therapy, two groups were defined: in group A (n = 10; mean body mass index (BMI) +/- SEM, 25.6 +/- 1.6 kg/m2) ovarian volume regressed from 17.9 +/- 1.6 to 6.7 +/- 0.3 ml (full responders) and in group B (n = 8; mean BMI +/- SEM, 28.1 +/- 2.3 kg/m2) from 21.5 +/- 1.1 to 15.1 +/- 1.0 ml (partial responders). Results showed that GnRH agonist therapy did not affect significantly BMI or fasting levels and area under the curve (AUC) for glucose and insulin in the respective groups. Fasting insulin levels correlated positively with ovarian volume prior to (r = 0.56, p < 0.05) and after 6 months of GnRH agonist therapy (r = 0.80, p < 0.005). The suppressibility of ovarian volume with GnRH agonist therapy correlated negatively with the difference between maximal and basal levels (r = -0.68), the area under the curve (r = -0.62) and maximal levels (r = -0.72) for insulin during the OGTT.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of chronic therapy with the gonadotrophin releasing hormone agonist decapeptyl in patients with polycystic ovary syndrome.

Our objective was to assess the endocrine and morphological response of polycystic ovary syndrome (PCOS) in patients receiving 6 months of therapy with the long-acting gonadotrophin releasing hormone agonist (GnRH agonist) decapeptyl (3.75 mg monthly injections). Eighteen documented PCOS patients were basally evaluated for hirsutism, gonadotrophin and androgen concentrations and ovarian morphology using trans-vaginal ultrasonography. Measurements were repeated at 3 and 6 months. The results (values as mean +/- SD) showed a significant improvement in hirsutism (Ferriman score 11.0 +/- 5.9 versus 6.6 +/- 2.7, P < 0.01), acne and seborrhoea. A significant post-treatment decrease in gonadotrophins [follicle-stimulating hormone (FSH): 5.8 +/- 1.8 versus 3.8 +/- 1.1 IU/l, P < 0.01; luteinizing hormone (LH): 10.8 +/- 8.3 versus 3.4 +/- 3.3 IU/l, P < 0.01], LH/FSH ratio (1.8 +/- 1.1 versus 0.8 +/- 0.6, P < 0.01) and androgen concentrations (free testosterone: 4.0 +/- 1.9 versus 1.9 +/- 0.7 pg/ml, P < 0.01, delta 4-androstenedione: 3.9 +/- 1.2 versus 1.9 +/- 0.6 ng/ml, P < 0.001) was also found, while oestradiol approximated castration concentrations (68.4 +/- 29.5 versus 29.1 +/- 6.7 pg/ml, P < 0.001). Finally, mean ovarian volume (19.7 +/- 6.2 versus 10.9 +/- 4.6 cm3, P < 0.001), capsule thickness (2.5 +/- 0.8 versus 1.9 +/- 0.7 mm, P < 0.05) and stromal density dropped significantly, as did uterine volume (34.2 +/- 10.5 versus 19.9 +/- 8.9 cm3, P < 0.01). In conclusion, treatment of our PCOS patients for 6 months with the GnRH agonist decapeptyl proved efficient in inducing significant clinical, biochemical and ovarian morphological improvement.

Octreotide effect on ovarian morphology in insulin-resistant PCOS patients following six-month decapeptyl treatment.

PROBLEM: Regulation of ovarian folliculogenesis involves bidirectional communication between the immune and endocrine systems. Somatostatin analogues have been reported to acutely suppress elevated androgens in polycystic ovary syndrome (PCOS). The aim of our study was to analyze the morphologic and hormonal-metabolic response to octreotide therapy for one month in insulin-resistant PCOS patients in whom luteinizing hormone (LH) effect had formerly been separated by a six-month GnRH-agonist (GnRH-a) course. METHOD: Fifteen PCOS patients were studied two months after completing a six-month GnRH-a (decapeptyl 3.75 mg monthly injection) course. Seven of the patients (group A), who were insulin-resistant and gave hyperinsulinemic response to a glucose challenge, received a 50-micrograms subcutaneous injection of octreotide twice a day for one month. The nonhyperinsulinemic patients (group B) received placebo injections. Hormonal measurements, oral glucose tolerance test (OGTT), and transvaginal ovarian ultrasound were performed before and toward the end of the treatment period. RESULTS: After octreotide ovarian volume dropped significantly in group A (x +/- SD) (19.2 +/- 5.1 versus 14.7 +/- 5.5 cc, P = .02). LH levels increased (3.25 +/- 1.22 versus 5.95 +/- 4.34 mu/ml, P = .05) as did E2 levels (38.0 +/- 11.4 versus 55.1 +/- 12.7 pg/ml, P = .005). There was no change in follicle-stimulating hormone, 17-hydroxy-progesterone, free testosterone, or androstenedione levels. Insulin secretion during OGTT dropped significantly (555 +/- 294 versus 68 +/- 29 mu u/ml/hr, P = .002). Glucose tolerance was not affected. In contrast, the placebo-treated group B patients showed an increase in ovarian volume (10.9 +/- 3.5 versus 14.8 +/- 3.3 cc, P = .001) while their gonadotropin and steroid profile relapsed, similarly to our patients receiving octreotide. CONCLUSIONS: Octreotide has an adjunctive beneficial effect to GnRH-a on ovarian morphology although, at the dose used, there was no suppression of gonadotropin or ovarian steroid levels. The changes in ovarian morphology are probably mediated through suppression of insulin levels and/or other ovarian growth factors.

Therapeutic use of gonadotropin-releasing hormone agonists in polycystic ovarian syndrome.

Polycystic ovarian syndrome is a heterogeneous disorder characterized by abnormal function of the hypothalamic-pituitary-gonadal axis, excessive production of androgens, aberrant intermediary metabolism, and structural changes in ovarian morphology. Long-term administration of the GnRH agonistic analogues brings about pituitary gonadotroph down-regulation after an initial period of stimulation of FSH/LH release. The resulting decrease in LH output and ovarian androgen production exerts beneficial effects on the clinical and biochemical parameters of the PCO syndrome. Ovarian volume and stroma usually decrease, but the results of treatment are not permanent, since relapse of the syndrome is usually observed a few months after cessation of the agonist. There are no serious side effects, and a small decrease in bone mineral content is recovered after discontinuation of the treatment. Possible indications for this regime include patients with very large ovaries and resistant hyperandrogenemia. On the other hand, the use of GnRH agonists in the preparation of PCOS patients for ovulation induction is already established.

Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults.

Retrospective analysis suggests that there is increased mortality from vascular disease in hypopituitary adults, but vascular status before death is unknown. High resolution B-mode ultrasonic imaging of both carotid and femoral arteries was therefore done in 34 adult hypopituitary patients on routine replacement therapy and was compared with that in 39 matched controls. Changes were related to risk factors for vascular disease. Carotid intima-media thickness was greater in patients than in controls (mean [SD] 0.74 [0.16] vs 0.65 [0.13] mm, p < 0.02). This difference was seen in middle-aged and elderly patients. More patients than controls had one or more atheromatous plaques (65% vs 41%, p < 0.05). The percentage of individual arteries with a plaque was also higher in patients (32% vs 18%, p < 0.005). In multiple regression analysis, patients' age was the dominant factor determining carotid intima-media thickness. Symptom-free adults with hypopituitarism show an increased prevalence of atherosclerosis.

Metabolic changes and vascular risk factors in hypopituitarism.

Adults with hypopituitarism die prematurely, and the excess mortality is from vascular disease. On echocardiography we have demonstrated abnormalities of myocardial diastolic function in hypopituitary adults, indicating possible early ischaemic change. Peripheral arterial disease is evident on ultrasonography. Vascular risk factors have also been examined. Impaired glucose tolerance and unrecognized diabetes are common in hypopituitary adults. Total cholesterol levels are elevated, particularly in hypopituitary women. The role of growth hormone (GH) deficiency in the vascular disease and in the vascular-risk-factor abnormalities is unknown at present. Prolonged GH therapy causes a decrease in the levels of fasting total cholesterol, without any adverse effects on glucose homeostasis. GH therapy trials in adults will clarify the role of GH in the excess vascular risk of hypopituitarism. Prolonged GH therapy will be necessary for the vascular effects to be defined.