Alberto Marra | Università degli Studi di Napoli "Federico II" (original) (raw)
Papers by Alberto Marra
The Journal of Clinical Endocrinology & Metabolism, 2009
A reduced activity of the GH/IGF-I axis in chronic heart failure (CHF) has been described by seve... more A reduced activity of the GH/IGF-I axis in chronic heart failure (CHF) has been described by several independent groups and is associated with poor clinical status and outcome.
European Heart Journal, 2013
European Journal of Internal Medicine, 2013
Cardiovascular Research, 2012
The suppressors of cytokine signalling (SOCS) are identified inhibitors of cytokine and growth fa... more The suppressors of cytokine signalling (SOCS) are identified inhibitors of cytokine and growth factor signalling that act via the Janus kinase (JAK) signal transducers and activators of transcription (STAT) pathways. Aberrant JAK/STAT signalling promotes progression from hypertrophy to heart failure. Little information is available concerning the role of SOCS in the transition from hypertrophy to heart failure. To this aim, we investigated the effects of SOCS1 overexpression obtained by in vivo adeno-associated gene transfer using an aortopulmonary cross-clamping technique in a chronic pressure-overload cardiac rat model.
The Journal of Clinical Endocrinology & Metabolism, 2009
A reduced activity of the GH/IGF-I axis in chronic heart failure (CHF) has been described by seve... more A reduced activity of the GH/IGF-I axis in chronic heart failure (CHF) has been described by several independent groups and is associated with poor clinical status and outcome.
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo, 2011
Despite recent and exponential improvements in diagnostic-therapeutic pathways, an existing "... more Despite recent and exponential improvements in diagnostic-therapeutic pathways, an existing "GAP" has been revealed between the "real world care" and the "optimal care" of patients with chronic heart failure (CHF). We present the T.O.S.CA. Project (Trattamento Ormonale dello Scompenso CArdiaco), an Italian multicenter initiative involving different health care professionals and services aiming to explore the CHF "metabolic pathophysiological model" and to improve the quality of care of HF patients through research and continuing medical education.
International journal of cardiology, Jan 19, 2015
Riociguat is a soluble guanylate cyclase stimulator approved for pulmonary arterial hypertension ... more Riociguat is a soluble guanylate cyclase stimulator approved for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The objective of this study was to evaluate the change of right heart size and function assessed by echocardiography during long-term treatment with riociguat. We assessed patients who started riociguat treatment (1.0-2.5mg tid) within the trials PATENT, PATENTplus, EAS and CHEST and continued for 3-12months. Echocardiography, 6-minute walking distance (6MWD) and further clinical parameters were analyzed at baseline, after 3, 6 and 12months. Right heart catheterization was performed at baseline and after 3months. For missing data we performed the last and baseline observation carried forward (LOCF, BOCF) method as sensitivity analyses. Thirty-nine patients (21 PAH, 18 CTEPH, mean pulmonary arterial pressure 43±2mmHg, PVR 600±43dyn∗s∗cm(-5), 56.4% treatment-naïve) were included. Mean right ventricular (RV) area significantly...
![Research paper thumbnail of [Anabolic/catabolic imbalance in chronic heart failure]](https://attachments.academia-assets.com/45656736/thumbnails/1.jpg)
](Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo
A metabolic imbalance between anabolic drive and catabolic forces is commonly observed in chronic... more A metabolic imbalance between anabolic drive and catabolic forces is commonly observed in chronic heart failure (CHF) patients, with the latter prevailing over anabolic hormones. Moreover, anabolic deficiencies are independent markers of poor prognosis. This finding represents a solid background for the implementation of therapeutic trials based on replacement therapy. The somatotropic axis (GH/IGF-1) is the most powerful anabolic axis of the body and its decline is related with a poor outcome and a worse clinical status. Growth hormone (GH) administration may enter the therapeutic arena as adjunctive treatment in patients affected by CHF and GH/IGF-1 deficiency. The T.O.S.CA. project aims at investigating the relationship between CHF and hormonal deficiency.
International journal of cardiology, Jan 20, 2014
European Journal of Internal Medicine, 2015
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo, 2011
Despite recent and exponential improvements in diagnostic-therapeutic pathways, an existing "... more Despite recent and exponential improvements in diagnostic-therapeutic pathways, an existing "GAP" has been revealed between the "real world care" and the "optimal care" of patients with chronic heart failure (CHF). We present the T.O.S.CA. Project (Trattamento Ormonale dello Scompenso CArdiaco), an Italian multicenter initiative involving different health care professionals and services aiming to explore the CHF "metabolic pathophysiological model" and to improve the quality of care of HF patients through research and continuing medical education.
Respiration, 2015
Most recently, a specialized and carefully monitored exercise training and rehabilitation program... more Most recently, a specialized and carefully monitored exercise training and rehabilitation program has been recommended as add-on to medical treatment in patients with pulmonary arterial hypertension (class I, level of evidence A). Three prospective randomized, controlled trials, 10 prospective uncontrolled trials, 2 retrospective studies and 2 case series in more than 470 patients with severe pulmonary hypertension (PH) and right heart failure reported beneficial effects of a specialized exercise training and rehabilitation program, i.e. significant improvement in symptoms, exercise capacity, cardiorespiratory function and quality of life, compared with untrained controls. All training studies reported an acceptable safety profile, and some uncontrolled studies showed excellent 1- and 2-year survival rates. However, most studies had a quite small sample size (ranging from 2 to 183 patients) and an uncontrolled design, and they were not designed to assess hemodynamic changes, time to clinical worsening and survival. Nevertheless, there is large evidence that exercise training programs should be performed by centers experienced in both PH patient care and rehabilitation. The best method and duration of the training, characteristics of supervision, and the mechanisms resulting in symptom improvement and increased functional capacity are unclear. In this review, we summarize data of molecular and clinical effects of exercise training in PH patients. Furthermore, we discuss safety data and the role of a self-care management of exercise training in these patients. © 2015 S. Karger AG, Basel.
Nutrition, Metabolism and Cardiovascular Diseases, 2015
Background and aim: Exercise intolerance is one of the key features of pulmonary arterial hyperte... more Background and aim: Exercise intolerance is one of the key features of pulmonary arterial hypertension (PAH). The main determinants of exercise impairment include hypoxemia, reduced right ventricular output, perfusion/ventilation mismatch, and weakness of skeletal and breathing muscles. The aim of the current review is to describe the findings in the existing literature about respiratory and muscle dysfunction in PAH. Animal and clinical studies regarding both respiratory and peripheral skeletal muscles and the effect of exercise training on muscle function in PAH patients are analyzed. Data synthesis: PAH myopathy is characterized by reduced skeletal muscle mass, reduced volitional and non-volitional contractility, reduced generated force, a fiber switch from type I to type II, increased protein degradation through ubiquitineproteasome system (UPS) activation, reduced mitochondrial functioning, and impaired activationecontractility coupling. Increased inflammatory response, impaired anabolic signaling, hypoxemia, and abnormalities of mitochondrial function are involved in the pathophysiology of this process. Exercise training has been shown to improve exercise capacity, peak oxygen uptake, quality of life, and possibly clinical outcomes of PAH patients. Conclusions: The skeletal muscles of PAH patients show a wide spectrum of cellular abnormalities that finally culminate in muscle atrophy and reduced contractility. Exercise training improves muscle function and bears a positive impact on the clinical outcomes of PAH patients. ª jo urnal homep age: www.el sevie r.co m/locate/nm cd
The Journal of Clinical Endocrinology & Metabolism, 2015
Patients with classic Congenital Adrenal Hyperplasia (CAH) are treated with lifelong glucocortico... more Patients with classic Congenital Adrenal Hyperplasia (CAH) are treated with lifelong glucocorticoids (GCS). Cardiovascular (CV) and metabolic effects of such therapy in adolescents have never been quantified.
Internal and Emergency Medicine, 2011
International Journal of Cardiology, 2013
Background: Several epidemiological studies have demonstrated an increased mortality from cardiov... more Background: Several epidemiological studies have demonstrated an increased mortality from cardiovascular causes in patients with Klinefelter Syndrome (KS). Little information is available about the nature of the underlying cardiovascular abnormalities. Aim of the study was to investigate exercise performance, left ventricular architecture and function, vascular reactivity, and carotid intima-media thickness in a group of patients with KS. Materials and methods: Sixty-nine patients with KS and 48 age-matched controls participated in our population-controlled study. Forty-eight Klinefelter subjects were on testosterone treatment at the time of the investigation while 21 were naive and underwent a complete Doppler echocardiographic examination, a cardiopulmonary exercise test as well as a vascular study including measures of carotid intima-media thickness and endothelial function with flow-mediated dilation of the brachial artery. Patients with KS on testosterone therapy (n=48) were also matched against a population of men with treated secondary hypogonadism (n=21). Results: Patients with KS exhibited a wide array of cardiovascular abnormalities including left ventricular diastolic dysfunction, reduced maximal oxygen consumption (pb 0.01), increased intima-media thickness (p b 0.05) (−34% and +42% vs. controls, respectively) and a high prevalence of chronotropic incompetence (55% of patients, pb 0.01). No significant difference was found between treated and untreated KS in variance with men treated for secondary hypogonadism. Conclusion: Left ventricular diastolic dysfunction, impaired cardiopulmonary performance, chronotropic incompetence, and increased intima-media thickness suggest that cardiovascular abnormalities are a common finding in KS that is not reversed by testosterone replacement therapy and may represent the pathophysiological underpinnings of the increased risk of dying from heart disease.
European Journal of Nuclear Medicine, 1991
We tested the feasibility of endobronchial administration of radiolabelled monoclonal antibodies ... more We tested the feasibility of endobronchial administration of radiolabelled monoclonal antibodies (MoAbs) and the biodistribution of the radiotracer. Ten patients with histological confirmed adenocarcinoma or squamous cell carcinoma were studied. Nine received 470 gCi (103 gg) of Iodine-131-B72.3, a monoclonal antibody reacting against TAG 72 antigen, while one patient received 502 gCi (291 gg) of 131I-4C4, an indifferent antibody used for comparison in a negative control study. The radiolabelled antibody was administered through a flexible fiberoptic bronchoscope and placed on the tumour mass under visual monitoring. Scans with a large field-of-view gamma-camera showed retention of 131I-B72.3 at the tumour site up to 6-9 days in six of eight patients. No other organs were visualized with the exception of faint activity in the gastrointestinal tract, bladder and thyroid. On the contrary, the indifferent antibody 13~I-4C4 was not retained at the tumour site 6 days after MoAb administration, and more prominent activity was found in the gastrointestinal tract. In one patient the study was not technically adequate because of failure of the delivery system. The vascular compartment contained less than 3% of the administered dose. We conclude that endobronchial administration is a feasible technique and allows stable and specific targetting of bronchial tumours. Furthermore, the low activity found in the plasma and other organs suggests that this approach may be used to deliver therapeutic doses of MoAbs to lung cancers.
The Journal of Clinical Endocrinology & Metabolism, 2009
A reduced activity of the GH/IGF-I axis in chronic heart failure (CHF) has been described by seve... more A reduced activity of the GH/IGF-I axis in chronic heart failure (CHF) has been described by several independent groups and is associated with poor clinical status and outcome.
European Heart Journal, 2013
European Journal of Internal Medicine, 2013
Cardiovascular Research, 2012
The suppressors of cytokine signalling (SOCS) are identified inhibitors of cytokine and growth fa... more The suppressors of cytokine signalling (SOCS) are identified inhibitors of cytokine and growth factor signalling that act via the Janus kinase (JAK) signal transducers and activators of transcription (STAT) pathways. Aberrant JAK/STAT signalling promotes progression from hypertrophy to heart failure. Little information is available concerning the role of SOCS in the transition from hypertrophy to heart failure. To this aim, we investigated the effects of SOCS1 overexpression obtained by in vivo adeno-associated gene transfer using an aortopulmonary cross-clamping technique in a chronic pressure-overload cardiac rat model.
The Journal of Clinical Endocrinology & Metabolism, 2009
A reduced activity of the GH/IGF-I axis in chronic heart failure (CHF) has been described by seve... more A reduced activity of the GH/IGF-I axis in chronic heart failure (CHF) has been described by several independent groups and is associated with poor clinical status and outcome.
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo, 2011
Despite recent and exponential improvements in diagnostic-therapeutic pathways, an existing "... more Despite recent and exponential improvements in diagnostic-therapeutic pathways, an existing "GAP" has been revealed between the "real world care" and the "optimal care" of patients with chronic heart failure (CHF). We present the T.O.S.CA. Project (Trattamento Ormonale dello Scompenso CArdiaco), an Italian multicenter initiative involving different health care professionals and services aiming to explore the CHF "metabolic pathophysiological model" and to improve the quality of care of HF patients through research and continuing medical education.
International journal of cardiology, Jan 19, 2015
Riociguat is a soluble guanylate cyclase stimulator approved for pulmonary arterial hypertension ... more Riociguat is a soluble guanylate cyclase stimulator approved for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The objective of this study was to evaluate the change of right heart size and function assessed by echocardiography during long-term treatment with riociguat. We assessed patients who started riociguat treatment (1.0-2.5mg tid) within the trials PATENT, PATENTplus, EAS and CHEST and continued for 3-12months. Echocardiography, 6-minute walking distance (6MWD) and further clinical parameters were analyzed at baseline, after 3, 6 and 12months. Right heart catheterization was performed at baseline and after 3months. For missing data we performed the last and baseline observation carried forward (LOCF, BOCF) method as sensitivity analyses. Thirty-nine patients (21 PAH, 18 CTEPH, mean pulmonary arterial pressure 43±2mmHg, PVR 600±43dyn∗s∗cm(-5), 56.4% treatment-naïve) were included. Mean right ventricular (RV) area significantly...
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo
A metabolic imbalance between anabolic drive and catabolic forces is commonly observed in chronic... more A metabolic imbalance between anabolic drive and catabolic forces is commonly observed in chronic heart failure (CHF) patients, with the latter prevailing over anabolic hormones. Moreover, anabolic deficiencies are independent markers of poor prognosis. This finding represents a solid background for the implementation of therapeutic trials based on replacement therapy. The somatotropic axis (GH/IGF-1) is the most powerful anabolic axis of the body and its decline is related with a poor outcome and a worse clinical status. Growth hormone (GH) administration may enter the therapeutic arena as adjunctive treatment in patients affected by CHF and GH/IGF-1 deficiency. The T.O.S.CA. project aims at investigating the relationship between CHF and hormonal deficiency.
International journal of cardiology, Jan 20, 2014
European Journal of Internal Medicine, 2015
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo, 2011
Despite recent and exponential improvements in diagnostic-therapeutic pathways, an existing "... more Despite recent and exponential improvements in diagnostic-therapeutic pathways, an existing "GAP" has been revealed between the "real world care" and the "optimal care" of patients with chronic heart failure (CHF). We present the T.O.S.CA. Project (Trattamento Ormonale dello Scompenso CArdiaco), an Italian multicenter initiative involving different health care professionals and services aiming to explore the CHF "metabolic pathophysiological model" and to improve the quality of care of HF patients through research and continuing medical education.
Respiration, 2015
Most recently, a specialized and carefully monitored exercise training and rehabilitation program... more Most recently, a specialized and carefully monitored exercise training and rehabilitation program has been recommended as add-on to medical treatment in patients with pulmonary arterial hypertension (class I, level of evidence A). Three prospective randomized, controlled trials, 10 prospective uncontrolled trials, 2 retrospective studies and 2 case series in more than 470 patients with severe pulmonary hypertension (PH) and right heart failure reported beneficial effects of a specialized exercise training and rehabilitation program, i.e. significant improvement in symptoms, exercise capacity, cardiorespiratory function and quality of life, compared with untrained controls. All training studies reported an acceptable safety profile, and some uncontrolled studies showed excellent 1- and 2-year survival rates. However, most studies had a quite small sample size (ranging from 2 to 183 patients) and an uncontrolled design, and they were not designed to assess hemodynamic changes, time to clinical worsening and survival. Nevertheless, there is large evidence that exercise training programs should be performed by centers experienced in both PH patient care and rehabilitation. The best method and duration of the training, characteristics of supervision, and the mechanisms resulting in symptom improvement and increased functional capacity are unclear. In this review, we summarize data of molecular and clinical effects of exercise training in PH patients. Furthermore, we discuss safety data and the role of a self-care management of exercise training in these patients. © 2015 S. Karger AG, Basel.
Nutrition, Metabolism and Cardiovascular Diseases, 2015
Background and aim: Exercise intolerance is one of the key features of pulmonary arterial hyperte... more Background and aim: Exercise intolerance is one of the key features of pulmonary arterial hypertension (PAH). The main determinants of exercise impairment include hypoxemia, reduced right ventricular output, perfusion/ventilation mismatch, and weakness of skeletal and breathing muscles. The aim of the current review is to describe the findings in the existing literature about respiratory and muscle dysfunction in PAH. Animal and clinical studies regarding both respiratory and peripheral skeletal muscles and the effect of exercise training on muscle function in PAH patients are analyzed. Data synthesis: PAH myopathy is characterized by reduced skeletal muscle mass, reduced volitional and non-volitional contractility, reduced generated force, a fiber switch from type I to type II, increased protein degradation through ubiquitineproteasome system (UPS) activation, reduced mitochondrial functioning, and impaired activationecontractility coupling. Increased inflammatory response, impaired anabolic signaling, hypoxemia, and abnormalities of mitochondrial function are involved in the pathophysiology of this process. Exercise training has been shown to improve exercise capacity, peak oxygen uptake, quality of life, and possibly clinical outcomes of PAH patients. Conclusions: The skeletal muscles of PAH patients show a wide spectrum of cellular abnormalities that finally culminate in muscle atrophy and reduced contractility. Exercise training improves muscle function and bears a positive impact on the clinical outcomes of PAH patients. ª jo urnal homep age: www.el sevie r.co m/locate/nm cd
The Journal of Clinical Endocrinology & Metabolism, 2015
Patients with classic Congenital Adrenal Hyperplasia (CAH) are treated with lifelong glucocortico... more Patients with classic Congenital Adrenal Hyperplasia (CAH) are treated with lifelong glucocorticoids (GCS). Cardiovascular (CV) and metabolic effects of such therapy in adolescents have never been quantified.
Internal and Emergency Medicine, 2011
International Journal of Cardiology, 2013
Background: Several epidemiological studies have demonstrated an increased mortality from cardiov... more Background: Several epidemiological studies have demonstrated an increased mortality from cardiovascular causes in patients with Klinefelter Syndrome (KS). Little information is available about the nature of the underlying cardiovascular abnormalities. Aim of the study was to investigate exercise performance, left ventricular architecture and function, vascular reactivity, and carotid intima-media thickness in a group of patients with KS. Materials and methods: Sixty-nine patients with KS and 48 age-matched controls participated in our population-controlled study. Forty-eight Klinefelter subjects were on testosterone treatment at the time of the investigation while 21 were naive and underwent a complete Doppler echocardiographic examination, a cardiopulmonary exercise test as well as a vascular study including measures of carotid intima-media thickness and endothelial function with flow-mediated dilation of the brachial artery. Patients with KS on testosterone therapy (n=48) were also matched against a population of men with treated secondary hypogonadism (n=21). Results: Patients with KS exhibited a wide array of cardiovascular abnormalities including left ventricular diastolic dysfunction, reduced maximal oxygen consumption (pb 0.01), increased intima-media thickness (p b 0.05) (−34% and +42% vs. controls, respectively) and a high prevalence of chronotropic incompetence (55% of patients, pb 0.01). No significant difference was found between treated and untreated KS in variance with men treated for secondary hypogonadism. Conclusion: Left ventricular diastolic dysfunction, impaired cardiopulmonary performance, chronotropic incompetence, and increased intima-media thickness suggest that cardiovascular abnormalities are a common finding in KS that is not reversed by testosterone replacement therapy and may represent the pathophysiological underpinnings of the increased risk of dying from heart disease.
European Journal of Nuclear Medicine, 1991
We tested the feasibility of endobronchial administration of radiolabelled monoclonal antibodies ... more We tested the feasibility of endobronchial administration of radiolabelled monoclonal antibodies (MoAbs) and the biodistribution of the radiotracer. Ten patients with histological confirmed adenocarcinoma or squamous cell carcinoma were studied. Nine received 470 gCi (103 gg) of Iodine-131-B72.3, a monoclonal antibody reacting against TAG 72 antigen, while one patient received 502 gCi (291 gg) of 131I-4C4, an indifferent antibody used for comparison in a negative control study. The radiolabelled antibody was administered through a flexible fiberoptic bronchoscope and placed on the tumour mass under visual monitoring. Scans with a large field-of-view gamma-camera showed retention of 131I-B72.3 at the tumour site up to 6-9 days in six of eight patients. No other organs were visualized with the exception of faint activity in the gastrointestinal tract, bladder and thyroid. On the contrary, the indifferent antibody 13~I-4C4 was not retained at the tumour site 6 days after MoAb administration, and more prominent activity was found in the gastrointestinal tract. In one patient the study was not technically adequate because of failure of the delivery system. The vascular compartment contained less than 3% of the administered dose. We conclude that endobronchial administration is a feasible technique and allows stable and specific targetting of bronchial tumours. Furthermore, the low activity found in the plasma and other organs suggests that this approach may be used to deliver therapeutic doses of MoAbs to lung cancers.