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The elderly population is the most susceptible to SARS-CoV-2 infection and develops the worst clinical phenotype with severe pneumonia and cardiac complications. Older COVID-19 patients are also at higher risk of sudden death, mainly attributable to electrolyte disorders and to an uncontrolled inflammatory response. After the identification of ACE 2 as the receptor of SARS-CoV-2 in human cells, several research studies have focused on the role of the activation of Renin Angiotensin System in COVID-19 clinical course. In the present opinion paper, we discuss the role of hyperaldosteronism in the increasing risk of cardiac complications in COVID-19 older patients. In particular, we focus on the immunoregulatory activity of aldosterone, as the last mediator of the Renin Angiotensin System cascade, in activating the innate and adaptive immune response related to SARS-CoV-2 infection in the elderly. Aldosterone may stimulate dendritic cells and the recruitment of monocytes/macrophages in the endothelium of coronary vessels, favoring the production of pro-inflammatory mediators and T-cells response. Higher basal levels of aldosterone together with SARS-CoV-2-induced production may explain the unfavorable course of COVID-19 in the elderly. [ABSTRACT FROM AUTHOR]

Given the epidemiologic increase of aged population in the world, aortic stenosis (AS) represents now the most common valvular heart disease in industrialized countries. It is a very challenging disease, representing an important cause of morbidity, hospitalization and death in the elderly population. It is widely recognized that AS is the result of a very complex active process, driven by inflammation and involving multifactorial pathological mechanisms promoting valvular calcification and valvular bone deposition. Several evidence suggest that epicardial adipose tissue (EAT), the visceral fat depot of the heart, represents a direct source of cytokines and could mediate the deleterious effects of systemic inflammation on the myocardium. Importantly, obesity and metabolic disorders are associated with chronic systemic inflammation leading to a significant increase of EAT amount and to a pro-inflammatory phenotypic shift of this fat depot. It has been hypothesized that the EAT inflammatory state can influence the structure and function of the heart, thus contributing to the pathogenesis of several cardiac diseases, including calcific AS. The current review will discuss the recently discovered mechanisms involved in the pathogenesis of AS, with particular attention to the role of inflammation, metabolic risk factors and pro-fibrotic and pro-osteogenic signal pathways promoting the onset and progression of the disease. Moreover, it will be explored the potential role of EAT in the AS pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is often managed by geriatricians. Few data are available on their knowledge and attitudes about this condition. Aims: To compare perceptions and knowledge on HF of specialists/fellows in geriatrics working in Italy. Methods: This nation-wide survey carried out by the Italian Society of Gerontology and Geriatrics in May–June 2019 enrolled 283 specialists/fellows in geriatrics in Italy. Results were stratified by qualification (specialist/fellow) and performance (lower/higher quartile of correct answers). Results: About half (55.5%) of the participants worked in acute care wards, 190 were residents, and 93 specialists. The overall proportion of correct answers was 70.8%, with no differences between specialists and fellows. There was a poor knowledge, with no differences between groups, about the target doses of ACE-inhibitors (36% of correct answers), the pharmacological treatment of HF with preserved ejection fraction (HFpEF) (37% of correct answers), and the inotropes indicated in acute HF (35% of correct answers). Compared to specialists, fellows performed better on indication (88% vs 76%, P = 0.019) and mechanism of action (93% vs 84%, P = 0.023) of sacubitril/valsartan, and on therapeutic indications of patients with atrial fibrillation (92% vs 75%, P < 0.001). Conclusions: Globally, there was a good knowledge of the latest guidelines on the diagnosis and management of HF. However, for some important topics, such as HFpEF, that is the most common HF manifestation in older adults, the observed performance was relatively poor, indicating the need for focused educational campaigns. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) and heart failure (HF) are frequent comorbidities among elderly patients. HF, a leading cause of mortality and morbidity worldwide, is characterized by sympathetic nervous system hyperactivity. The prevalence of diabetes mellitus (DM) is rapidly growing and the risk of developing HF is higher among DM patients. DM is responsible for several macro- and micro-angiopathies that contribute to the development of coronary artery disease (CAD), peripheral artery disease, retinopathy, neuropathy and diabetic nephropathy (DN) as well. Independently of CAD, chronic kidney disease (CKD) and DM increase the risk of HF. Individuals with diabetic nephropathy are likely to present a distinct pathological condition, defined as diabetic cardiomyopathy, even in the absence of hypertension or CAD, whose pathogenesis is only partially known. However, several hypotheses have been proposed to explain the mechanism of diabetic cardiomyopathy: increased oxidative stress, altered substrate metabolism, mitochondrial dysfunction, activation of renin-angiotensin-aldosterone system (RAAS), insulin resistance, and autonomic dysfunction. In this review, we will focus on the involvement of sympathetic system hyperactivity in the diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Purpose: Sympathetic nervous system (SNS) hyperactivity is a salient characteristic of chronic heart failure (HF) and contributes to the progression of the disease. Iodine-123 meta-iodobenzylguanidine (I-mIBG) imaging has been successfully used to assess cardiac SNS activity in HF patients and to predict prognosis. Importantly, SNS hyperactivity characterizes also physiological ageing, and there is conflicting evidence on cardiac I-mIBG uptake in healthy elderly subjects compared to adults. However, little data are available on the impact of ageing on cardiac sympathetic nerve activity assessed by I-mIBG scintigraphy, in patients with HF. Methods and results: We studied 180 HF patients (age = 66.1 ± 10.5 years [yrs]), left ventricular ejection fraction (LVEF = 30.6 ± 6.3 %) undergoing cardiac I-mIBG imaging. Early and late heart to mediastinum (H/M) ratios and washout rate were calculated in all patients. Demographic, clinical, and echocardiographic data were also collected. Our study population consisted of 53 patients aged >75 years (age = 77.7 ± 4.0 year), 67 patients aged 62-72 years (age = 67.9 ± 3.2 years) and 60 patients aged ≤61 year (age = 53.9 ± 5.6 years). In elderly patients, both early and late H/M ratios were significantly lower compared to younger patients ( p < 0.05). By multivariate analysis, H/M ratios (both early and late) and washout rate were significantly correlated with LVEF and age. Conclusions: Our data indicate that, in a population of HF patients, there is an independent age-related effect on cardiac SNS innervation assessed by I-mIBG imaging. This finding suggests that cardiac I-mIBG uptake in patients with HF might be affected by patient age. [ABSTRACT FROM AUTHOR]

Purpose: Myocardial contractile function is under the control of cardiac sympathetic activity. Three-dimensional speckle tracking echocardiography (3D-STE) and cardiac imaging with I-metaiodobenzylguanidine (I-MIBG) are two sophisticated techniques for the assessment of left ventricular (LV) deformation and sympathetic innervation, respectively, which offer important prognostic information in patients with heart failure (HF). The purpose of this investigation was to explore, in patients with systolic HF, the relationship between LV deformation assessed by 3D-STE and cardiac sympathetic derangement evaluated by I-MIBG imaging. Methods: We prospectively studied 75 patients with systolic HF. All patients underwent a 3D-STE study (longitudinal, circumferential, area and radial) and I-MIBG planar and SPECT cardiac imaging. Results: 3D-STE longitudinal, circumferential and area strain values were correlated with I-MIBG late heart to mediastinum (H/M) ratio and late SPECT total defect score. After stratification of the patients according to ischaemic or nonischaemic HF aetiology, we observed a good correlation of all 3D-STE measurements with late H/M ratio and SPECT data in the ischaemic group, but in patients with HF of nonischaemic aetiology, no correlation was found between LV deformation and cardiac sympathetic activity. At the regional level, the strongest correlation between LV deformation and adrenergic innervation was found for the left anterior descending coronary artery distribution territory for all four 3D-STE values. In multivariate linear regression analyses, including age, gender, LV ejection fraction, NYHA class, body mass index, heart rate and HF aetiology, only 3D-STE area and radial strain values significantly predicted cardiac sympathetic derangement on I-MIBG late SPECT. Conclusion: This study indicated that 3D-STE measurements are correlated with I-MIBG planar and SPECT data. Furthermore, 3D-STE area and radial strain values, but not LVEF, predict cardiac sympathetic derangement in human postischaemic HF. [ABSTRACT FROM AUTHOR]

The human prothymosin alpha (PTα) gene encodes a 12.5 kDa highly acidic nuclear protein that is widely expressed in mammalian tissues including the heart and importantly, is detectable also in blood serum. During apoptosis or necrosis, PTα changes its nuclear localization and is able to exert an important cytoprotective effect. Since the role of PTα in the heart has never been evaluated, the aim of the present study was to investigate the effects of PTα on cardiomyocytes during ischemic injury. Our data show that seven after myocardial infarction (MI), PTα expression levels are significantly increased both in blood serum and in cardiac tissue, and notably we observe that PTα translocates from the nuclei to cytoplasm and plasma membrane of cardiomyocytes following MI. Furthermore, in vitro experiments in cardiomyocytes, confirm that after 6 h of simulated ischemia (SI), PTα protein levels are upregulated compared to normoxic cells. Importantly, treatment of cardiomyocytes with a recombinant PTα (rPTα), during SI results in a significant decrease in the apoptotic response and in a robust increase in cell survival. Moreover, these effects are accompanied to a significant preservation of the activated levels of the anti-apoptotic serine-threonine kinase Akt. Consistent with our in vitro observation, rPTα-treated MI mice exhibit a strong reduction in infarct size at 24 h, compared to the MI control group and at the molecular level, PTα treatment induces activation of Akt. The present study provides for the first time the demonstration that PTα offers cardioprotection against ischemic injury by an Akt-dependent mechanism. [ABSTRACT FROM AUTHOR]

Purpose: Exercise training might exert its beneficial effects on myocardial perfusion by inducing coronary vascular adaptations or enhancing collateralization. We evaluated whether long-term exercise-based cardiac rehabilitation started early after ST-elevation acute myocardial infarction (STEMI) improves myocardial perfusion and left ventricular (LV) function. Methods: Forty-six patients with recent STEMI and residual inducible hypoperfusion were randomized into two groups: 25 enrolled in a 6-month outpatient exercise-based cardiac rehabilitation programme (group T) and 21 discharged with generic instructions for maintaining physical activity and correct lifestyle (group C). All patients underwent cardiopulmonary exercise test and dipyridamole rest gated myocardial perfusion single photon emission computed tomography within 1 week after STEMI and at 6-month follow-up. Results: At follow-up, group T showed an improvement in peak oxygen consumption, oxygen pulse and in the slope of increase in ventilation over carbon dioxide output (all p < 0.01) associated with a reduction of stress-induced hypoperfusion ( p < 0.01) and an improvement in resting and post-stress wall motion score indexes (both p < 0.01), resting and post-stress wall thickening score indexes (both p < 0.05) and resting and post-stress LV ejection fraction (both p < 0.05). On the contrary, no changes in cardiopulmonary indexes, myocardial perfusion and LV function parameters were observed in group C at follow-up. Conclusion: Exercise training started early after STEMI reduces stress-induced hypoperfusion and improves LV function and contractility. Exercise-induced changes in myocardial perfusion and function were associated with the absence of unfavourable LV remodelling and with an improvement of cardiovascular functional capacity. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the impact of type 2 diabetes, in the presence of other major cardiovascular risk factors, on coronary microvascular function and myocardial perfusion in patients without obstructive coronary artery disease (CAD). Methods: In this prospective study, 23 patients with type 2 diabetes and 26 nondiabetic patients matched for age, sex and other cardiovascular risk factors underwent a cold pressure test (CPT) and dipyridamole transthoracic echocardiography to determine their coronary flow (CF) ratio. Within 2 weeks, all diabetic patients also underwent dipyridamole-rest myocardial perfusion single-photon emission (MPS) CT. None of the patients with or without diabetes had significant CAD on invasive coronary angiography. Results: The CPT-CF ratio was significantly lower in diabetic patients than in nondiabetic patients (1.46 ± 0.26 vs. 1.71 ± 0.32, p = 0.006) and was correlated significantly with fasting glycaemia ( r = −0.35, p = 0.01), but not with glycated haemoglobin. The dipyridamole-CF ratio was also lower in diabetic patients than in nondiabetic patients (2.38 ± 0.74 vs. 2.75 ± 0.49, p = 0.04). On MPS imaging, 5 diabetic patients (22%) had stress-induced ischaemia and the remaining 18 (78%) had normal myocardial perfusion. The dipyridamole-CF ratio was not different in patients with and without reversible defects (2.3 ± 1.1 vs. 2.4 ± 0.6, p = 0.97). Conclusion: Coronary microvascular function is impaired in type 2 diabetic patients without significant CAD, compared to nondiabetic patients with similar other cardiovascular risk factors. In the majority of diabetic patients, microvascular dysfunction is associated with normal myocardial perfusion. [ABSTRACT FROM AUTHOR]

The study evaluated the effect of Losartan in preventing nitrate tolerance during continuous transdermal nitroglycerin (TD-GTN) therapy in patients with coronary disease. Fifteen subjects with chronic stable ischemia evaluated by exercise test, were randomized to 28 days of TD-GTN 20 mg once a day without free interval plus Losartan 100 mg or Losartan-placebo with a double blind crossover design. Myocardial ischemic parameters during stress test were evaluated after each test period and results of Losartan therapy were compared to those with placebo. Time to onset 1 mm ST-depression was significantly higher after acute TD-GTN 20 mg with respect to placebo run-in, sustained TD-GTN 20 mg plus Losartan 100 mg or Losartan-placebo ( p < 0.001). ST-depression at peak exercise and time to recovery of ST segment were markedly lower after acute TD-GTN 20 mg compared to placebo run-in ( p < 0.05), sustained TD-GTN 20 mg plus Losartan 100 mg ( p < 0.001) or Losartan-placebo ( p < 0.05). At 1 mm-ST depression and at peak exercise, systolic blood pressure and rate-pressure product significantly decreased after sustained TD-GTN 20 mg plus Losartan 100 mg ( p < 0.001, p < 0.05 respectively) with respect to placebo run-in, acute and sustained TD-GTN 20 mg plus Losartan-placebo. Moreover at peak exercise, these data were also observed after acute TD-GTN 20 mg compared to placebo run-in and sustained TD-GTN 20 mg plus Losartan-placebo ( p < 0.001). The AT1 antagonist Losartan administration does not prevent the development of nitrate tolerance during continuous TD-GTN therapy. [ABSTRACT FROM AUTHOR]