Renin-Angiotensin System Blockade Improves Cardiac Indices in Acromegaly Patients.

Blockade of the angiotensin-renin system, with angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), has been shown to improve cardiac outcomes following myocardial infarction and delay progression of heart failure. Acromegaly is associated with a disease-specific cardiomyopathy, the pathogenesis of which is poorly understood.The cardiac indices of patients with active acromegaly with no hypertension (Group A, n=4), established hypertension not taking ACEi/ARBs (Group B, n=4) and established hypertension taking ACEi/ARBs (Group C, n=4) were compared using cardiac magnetic imaging.Patients taking ACEi/ARBs had lower end diastolic volume index (EDVi) and end systolic volume index (ESVi) than the other 2 groups ([C] 73.24 vs. [A] 97.92 vs. [B] 101.03 ml/m2, ANOVA p=0.034, B vs. C p<0.01). Groups A and B had EDVi and ESVi values at the top of published reference range values; Group C had values in the middle of the range.Acromegaly patients on ACEi/ARBs for hypertension demonstrate improved cardiac indices compared to acromegaly patients with hypertension not taking these medications. Further studies are needed to determine if these drugs have a beneficial cardiac effect in acromegaly in the absence of demonstrable hypertension.

Characterisation of myocardial structure and function in adult-onset growth hormone deficiency using cardiac magnetic resonance.

Growth hormone (GH) can profoundly influence cardiac function. While GH excess causes well-defined cardiac pathology, fewer data are available regarding the more subtle cardiac changes seen in GH deficiency (GHD). This preliminary study uses cardiac magnetic resonance imaging (CMR) to assess myocardial structure and function in GHD. Ten adult-onset GHD patients underwent CMR, before and after 6 and 12 months of GH replacement. They were compared to 10 age-matched healthy controls and sex-matched healthy controls. Left ventricular (LV) mass index (LVMi) increased with 1 year of GH replacement (53.8 vs. 57.0 vs. 57.3 g/m2, analysis of variance p = 0.0229). Compared to controls, patients showed a trend towards reduced LVMi at baseline (51.4 vs. 60.0 g/m2, p = 0.0615); this difference was lost by 1 year of GH treatment (57.3 vs. 59.9 g/m2, p = 0.666). Significantly reduced aortic area was observed in GHD (13.2 vs. 19.0 cm2/m2, p = 0.001). This did not change with GH treatment. There were no differences in other LV parameters including end-diastolic volume index (EDVi), end-systolic volume index, stroke volume index (SVi), cardiac index and ejection fraction. There was a trend towards reduced baseline right ventricular (RV)SVi (44.1 vs. 49.1 ml/m2, p = 0.0793) and increased RVEDVi over 1 year (70.3 vs. 74.3 vs. 73.8 ml/m2, p = 0.062). Two patients demonstrated interstitial expansion, for example with fibrosis, and three myocardial ischaemia as assessed by late gadolinium enhancement and stress perfusion. The increased sensitivity of CMR to subtle cardiac changes demonstrates that adult-onset GHD patients have reduced aortic area and LVMi increases after 1 year of GH treatment. These early data should be studied in larger studies in the future.

Pheochromocytoma Is Characterized by Catecholamine-Mediated Myocarditis, Focal and Diffuse Myocardial Fibrosis, and Myocardial Dysfunction.

BACKGROUND: Pheochromocytoma is associated with catecholamine-induced cardiac toxicity, but the extent and nature of cardiac involvement in clinical cohorts is not well-characterized. OBJECTIVES: This study characterized the cardiac phenotype in patients with pheochromocytoma using cardiac magnetic resonance (CMR). METHODS: A total of 125 subjects were studied, including patients with newly diagnosed pheochromocytoma (n = 29), patients with previously surgically cured pheochromocytoma (n = 31), healthy control subjects (n = 51), and hypertensive control subjects (HTN) (n = 14), using CMR (1.5-T) cine, strain imaging by myocardial tagging, late gadolinium enhancement, and native T1 mapping (Shortened Modified Look-Locker Inversion recovery [ShMOLLI]). RESULTS: Patients who were newly diagnosed with pheochromocytoma, compared with healthy and HTN control subjects, had impaired left ventricular (LV) ejection fraction (<56% in 38% of patients), peak systolic circumferential strain (p < 0.05), and diastolic strain rate (p < 0.05). They had higher myocardial T1 (974 ± 25 ms, as compared with 954 ± 16 ms in healthy and 958 ± 23 ms in HTN subjects; p < 0.05), areas of myocarditis (median 22% LV with T1 >990 ms, as compared with 1% in healthy and 2% in HTN subjects; p < 0.05), and focal fibrosis (59% had nonischemic late gadolinium enhancement, as compared with 14% in HTN subjects). Post-operatively, impaired LV ejection fraction typically normalized, but systolic and diastolic strain impairment persisted. Focal fibrosis (median 5% LV) and T1 abnormalities (median 12% LV) remained, the latter of which may suggest some diffuse fibrosis. Previously cured patients demonstrated abnormal diastolic strain rate (p < 0.001), myocardial T1 (median 12% LV), and small areas of focal fibrosis (median 1% LV). LV mass index was increased in HTN compared with healthy control subjects (p < 0.05), but not in the 2 pheochromocytoma groups. CONCLUSIONS: This first systematic CMR study characterizing the cardiac phenotype in pheochromocytoma showed that cardiac involvement was frequent and, for some variables, persisted after curative surgery. These effects surpass those of hypertensive heart disease alone, supporting a direct role of catecholamine toxicity that may produce subtle but long-lasting myocardial alterations.

Adult GH deficiency throughout lifetime.

It is now accepted that adults with severe GH deficiency (GHD) demonstrate impaired physical and psychological well-being and may benefit from replacement with recombinant human GH. Post-marketing surveillance surveys, such as the Pfizer International Metabolic Database (KIMS), were initially set-up to provide safety data on long-term treatment but have the added benefit of providing ongoing observational data on the effect of GH replacement on body composition, lipid and glucose status, hypertension, bone density and quality of life. These data demonstrate that although GHD has clinical impact at all ages, the individual consequences of this condition may take on greater significance at different stages in life. At all ages, accurate, safe diagnosis and appropriate GH dosing are necessary to provide the individual with the best possible outcome.