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| 2. |
- Arcopinto, M., et al.
(författare)
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Growth Hormone Deficiency Is Associated with Worse Cardiac Function, Physical Performance, and Outcome in Chronic Heart Failure: Insights from the TOSCA. GHD Study
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Although mounting evidence supports the concept that growth hormone (GH) deficiency (GHD) affects cardiovascular function, no study has systematically investigated its prevalence and role in a large cohort of chronic heart failure (CHF) patients. Aim of this study is to assess the prevalence of GHD in mild-to-moderate CHF and to explore clinical and functional correlates of GHD. One-hundred thirty CHF patients underwent GH provocative test with GHRH+arginine and accordingly categorized into GH-deficiency (GHD, n = 88, age = 61.6 +/- 1.1 years, 68% men) and GH-sufficiency (GHS, n = 42, age = 63.6 +/- 1.5 years, 81% men) cohorts. Both groups received comprehensive cardiovascular examination and underwent Doppler echocardiography, cardiopulmonary exercise testing, and biochemical and hormonal assay. GHD was detected in roughly 30% of CHF patients. Compared to GHD, GHS patients showed smaller end-diastolic and end-systolic LV volumes (-28%, p=.008 and -24%, p=.015, respectively), lower LV end-systolic wall stress (-21%, p=.03), higher RV performance (+18% in RV area change, p=.03), lower estimated systolic pulmonary artery pressure (-11%, p=.04), higher peak VO2 (+20%, p=.001) and increased ventilatory efficiency (-12% in VE/VCO2 slope, p=.002). After adjusting for clinical covariates (age, gender, and tertiles of LV ejection fraction, IGF-1, peak VO2, VE/VCO2 slope, and NT-proBNP), logistic multivariate analysis showed that peak VO2 (beta = -1.92, SE = 1.67, p=.03), VE/VCO2 slope (beta = 2.23, SE = 1.20, p=.02) and NT-proBNP (beta = 2.48, SE = 1.02, p=.016), were significantly associated with GHD status. Finally, compared to GHS, GHD cohort showed higher all-cause mortality at median follow-up of 3.5 years (40% vs. 25%, p<.001, respectively), independent of age, sex, NT-proBNP, peak VO2 and LVEF. GH deficiency identifies a subgroup of CHF patients characterized by impaired functional capacity, LV remodeling and elevated NT-proBNP levels. GHD is also associated with increased all-cause mortality.
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- D'Assante, R., et al.
(författare)
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Myocardial expression of somatotropic axis, adrenergic signalling, and calcium handling genes in heart failure with preserved ejection fraction and heart failure with reduced ejection fraction
- 2021
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:2, s. 1681-1686
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Tidskriftsartikel (refereegranskat)abstract
- Aims Limited data are available regarding cardiac expression of molecules involved in heart failure (HF) pathophysiology. The majority of the studies have focused on end-stage HF with reduced ejection fraction (HFrEF) without comparison with healthy subjects, while no data are available with regard to HF with preserved ejection fraction (HFpEF). HFpEF is a condition whose multiple pathophysiological mechanisms are still not fully defined, with many proposed hypotheses remaining speculative due to limited access to human heart tissue. This study aimed at evaluating cardiac expression levels of key genes of interest in human biopsy samples from patients affected with HFrEF and HFpEF in order to possibly point out distinct phenotypes. Methods and results Total RNA was extracted from left ventricular cardiac biopsies collected from stable patients with HFrEF (n = 6) and HFpEF (n = 7) and healthy subjects (n = 9) undergoing elective cardiac surgery for valvular replacement, mitral valvuloplasty, aortic surgery, or coronary artery bypass. Real-time PCR was performed to evaluate the mRNA expression levels of genes involved in somatotropic axis regulation [IGF-1, IGF-1 receptor (IGF-1R), and GH receptor (GHR)], in adrenergic signalling (GRK2, GRK5, ADRB1, and ADRB2), in myocardial calcium handling (SERCA2), and in TNF-alpha. Patients with HFrEF and HFpEF showed reduced serum IGF-1 circulating levels when compared with controls (102 +/- 35.6, 138 +/- 11.5, and 160 +/- 13.2 ng/mL, P < 0.001, respectively). At myocardial level, HFrEF showed significant decreased GHR and increased IGF-1R expressions when compared with HFpEF and controls (0.54 +/- 0.27, 0.94 +/- 0.25, and 0.84 +/- 0.2, P < 0.05 and 1.52 +/- 0.9, 1.06 +/- 0.21, and 0.72 +/- 0.12, P < 0.05, respectively), while no differences in the local expression of IGF-1 mRNA were detected among the groups (0.80 +/- 0.45, 0.97 +/- 0.18, and 0.63 +/- 0.23, P = 0.09, respectively). With regard to calcium handling and adrenergic signalling, HFrEF displayed significant decreased levels of SERCA2 (0.19 +/- 0.39, 0.82 +/- 0.15, and 0.87 +/- 0.32, P < 0.01) and increased levels of GRK2 (3.45 +/- 2.94, 0.93 +/- 0.12, and 0.80 +/- 0.14, P < 0.01) and GRK5 (1.32 +/- 0.70, 0.71 +/- 0.14, and 0.77 +/- 0.15, P < 0.05), while no significant difference was found in ADRB1 (0.66 +/- 0.4, 0.83 +/- 0.3, and 0.86 +/- 0.4) and ADRB2 mRNA expression (0.65 +/- 0.3, 0.66 +/- 0.2, and 0.68 +/- 0.1) when compared with HFpEF and controls. Finally, no changes in the local expression of TNF-alpha were detected among groups. Conclusions Heart failure with reduced ejection fraction and HFpEF patients with stable clinical condition display a distinct molecular milieu of genes involved in somatotropic axis regulation, calcium handling, and adrenergic derangement at a myocardial level. The unique opportunity to compare these results with a control group, as reference population, may contribute to better understand HF pathophysiology and to identify novel potential therapeutic targets that could be modulated to improve ventricular function in patients with HF.
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| 5. |
- Accardo, G., et al.
(författare)
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Management of cardiovascular complications in Klinefelter syndrome patients
- 2019
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Ingår i: Expert Review of Endocrinology and Metabolism. - : Informa UK Limited. - 1744-6651 .- 1744-8417. ; 14:2, s. 145-152
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Klinefelter syndrome (KS), also known as 47, XXY, shows increased mortality when compared with mortality rates among the general population. Cardiovascular, hemostatic, metabolic diseases are implicated. Moreover, cardiac congenital anomalies in KS can contribute to the increase in mortality. Areas covered: In this study, we have systematically reviewed the relationships between KS and the cardiovascular system and the management of cardiovascular complication. In summary, patients with KS display increased cardiovascular risk profile, characterized by increased prevalence of metabolic alterations including dyslipidemia, diabetes mellitus (DM), and abnormalities in biomarkers of cardiovascular disease. KS subjects are characterized by subclinical abnormalities in endothelial function and in left ventricular (LV) systolic and diastolic function, which–when associated with chronotropic incompetence–may negatively influence cardiopulmonary performance. Moreover, KS patients appear to be at a higher risk for cardiovascular disease, due to thromboembolic events with high prevalence of recurrent venous ulcers, venous insufficiency, recurrent venous and arterial thromboembolism leading to deep venous thrombosis or pulmonary embolism. Expert opinion: Considering the unequivocal finding of increased mortality of KS patients, we suggest a periodic cardiovascular follow up in specialized centers with multidisciplinary care teams that comprise endocrinologists and cardiologists dedicated to KS syndrome. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
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| 6. |
- Arcopinto, M., et al.
(författare)
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Hormone replacement therapy in heart failure
- 2015
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Ingår i: Current Opinion in Cardiology. - : Ovid Technologies (Wolters Kluwer Health). - 0268-4705. ; 30:3, s. 277-284
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Forskningsöversikt (refereegranskat)abstract
- Purpose of review Despite major advances in medical treatments, survival rates of chronic heart failure (CHF) have not significantly changed in the past 50 years, making it imperative to search for novel pathophysiological mechanisms and therapeutic targets. In this article, we summarize the current knowledge regarding the possibility to treat such anabolic deficiencies with hormone replacement therapy (HRT). Mounting evidence supports the concept that CHF is a disease characterized not only by excessive neurohormonal activation but also by a reduced anabolic drive that carries functional and prognostic significance. The recent demonstration of overall beneficial effects of HRT in CHF may pave the way to slow the disease progression in patients with coexisting CHF and hormone deficiencies. The hypothesis is to identify a considerable subset of CHF patients also affected with hormone deficiency and to treat them with HRT. Single or multiple HRT may in theory be performed in CHF. Such a novel approach may improve left ventricular architecture, function, and physical capacity as well as quality of life. Larger randomized, controlled trials are needed to confirm this working hypothesis.
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| 7. |
- Bossone, Eduardo, et al.
(författare)
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Takotsubo cardiomyopathy: an integrated multi-imaging approach.
- 2014
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Ingår i: European heart journal cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2412 .- 2047-2404. ; 15:4, s. 366-377
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Tidskriftsartikel (refereegranskat)abstract
- Takotsubo cardiomyopathy (TTC) is a distinct clinical entity characterized by the presence of transient left ventricular wall dysfunction without significant culprit obstructive coronary artery disease. Invasive coronary angiography and ventriculography are the 'gold standard' for definitive diagnosis, with an integrated multi-modality imaging approach offering advantages in various clinical scenarios. Echocardiography is a widely available, first-line, non-invasive imaging technique appropriate both in emergency setting to confirm diagnosis, assess for various potential acute complications, and in serial follow-up to track myocardial recovery. Cardiac magnetic resonance (CMR) may be helpful to discriminate TTC from other acute cardiac syndromes with troponin elevation and ventricular dysfunction. Echocardiography, CMR, and nuclear imaging may also provide new insights into possible underlying pathophysiological mechanisms, and myocardial (123)I-metaiodobenzyl-guanidine imaging may have a role for retrospective diagnosis in the subacute phase of late-presenting cases. The potential diagnostic role of coronary computed tomography angiography in the emergency room requires a further study.
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| 8. |
- Ferrara, Francesco, et al.
(författare)
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Imaging the right heart pulmonary circulation unit : Insights from advanced ultrasound techniques
- 2017
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Ingår i: Echocardiography. - : Wiley. - 0742-2822. ; 34:8, s. 1216-1231
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Forskningsöversikt (refereegranskat)abstract
- The right heart pulmonary circulation unit (RH-PCU) is a key determinant of prognosis in several cardiorespiratory diseases. Although right heart catheterization is considered the gold standard for pulmonary hemodynamic assessment, a comprehensive cardiovascular ultrasound approach is an essential step in the diagnostic-prognostic clinical pathway of patients with suspect or overt pulmonary hypertension. The exponential development of advanced ultrasound techniques (strain, 3-dimensional echocardiography and lung ultrasound) has led to new insights into the evaluation of RH-PCU structure and function, overcoming some limitations of standard Doppler echocardiography. In the near future, exercise Doppler echocardiography may become a useful technique for detecting a latent stage of pulmonary hypertension and for evaluating right ventricular contractile reserve.
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| 10. |
- Strömer, Hinrik, et al.
(författare)
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Growth hormone- and pressure overload-induced cardiac hypertrophy evoke different responses to ischemia-reperfusion and mechanical stretch.
- 2006
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1096-6374. ; 16:1, s. 29-40
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare the molecular, histological, and functional characteristics of growth hormone (GH)- and pressure overload-induced cardiac hypertrophy, and their responses to ischemia-reperfusion and mechanical stretch. DESIGN: Four groups of male Wistar rats were studied: aortic banding (n=24, AB) or sham (n=24, controls) for 10 weeks, and GH treatment (n=24; 3.5mg/kg/day, GH) or placebo (n=24, controls) for 4 weeks. At 13 weeks, the rats were randomly subjected to: (i) assessment of basal left ventricular mRNA expression of sarcoplasmic reticulum calcium-ATPase (SERCA-2), phospholamban (PLB), and Na(+)-Ca(2+) exchanger (NCX) and collagen volume fraction (CVF) (Protocol A, 8 rats in each group); (ii) left ventricular no-flow ischemia with simultaneous evaluation of intracellular Ca(2+) handling and ATP, phosphocreatine (PCr) and inorganic phosphate (Pi) content (Protocol B, 12 rats in each group); or (iii) left ventricular mechanical stretch for 40 min with assessment of tumor necrosis-alpha (TNF-alpha) mRNA (Protocol C, 4 rats in each group). Protocol B and C were carried out in a Langendorff apparatus. RESULTS: In Protocol A, no difference was found as to myocardial mRNA content of Ca(2+) regulating proteins and CVF in GH animals vs controls. In contrast, in the AB group, myocardial mRNA expression of SERCA-2 and PLB was downregulated while that of NCX and CVF were increased vs. controls (p<0.05). In Protocol B, recovery of left ventricular function was significantly decreased in AB vs GH groups and controls and this was associated with 1.6-fold increase in intracellular Ca(2+) overload during reperfusion (p<0.05). Baseline ATP content was similar in the four study groups, whereas PCr and Pi was lower in AB vs GH rats and controls. However, the time courses of high-energy phosphate metabolic changes did not differ during ischemia and reperfusion in the four study groups. In Protocol C, no detectable TNF-alpha mRNA level was found in the left ventricular myocardium of GH treated rats and controls at baseline, while a modest expression was noted in AB animals. Mechanical stretch resulted in de novo myocardial TNF-alpha mRNA expression in GH group and controls, which was dramatically increased in AB animals ( approximately 5-fold above baseline, p<0.001). CONCLUSIONS: The data show that cardiac hypertrophy activated by short-term GH treatment confers cardioprotection compared with pressure overload with regard to molecular and histological characteristics, and responses to ischemia-reperfusion and mechanical stretch.
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