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Insulin resistance (IR) and the associated hyperinsulinemia are early pathophysiological changes which, if not well treated, can lead to type 2 diabetes, endothelial dysfunction and cardiovascular disease. While diabetes care is fairly well standardized, the prevention and treatment of IR lacks a single pharmaceutical approach and many lifestyle and dietary interventions have been proposed, including a wide range of food supplements. Among the most interesting and well-known natural remedies, alkaloid berberine and the flavonol quercetin have particular relevance in the literature, while silymarin—the active principle of the Silybum marianum thistle—was traditionally used for lipid metabolism disorders and to sustain liver function. This review describes the major defects of insulin signaling leading to IR and the main properties of the three mentioned natural substances, their molecular targets and synergistic action mechanisms. The actions of berberine, quercetin and silymarin are partially superimposable as remedies against reactive oxygen intermediates generated by a high-lipid diet and by NADPH oxidase, which is triggered by phagocyte activation. Furthermore, these compounds inhibit the secretion of a battery of pro-inflammatory cytokines, modulate intestinal microbiota and are especially able to control the various disorders of the insulin receptor and post-receptor signaling systems. Although most of the evidence on the effects of berberine, quercetin and silymarin in modulating insulin resistance and preventing cardiovascular disease derive from experimental studies on animals, the amount of pre-clinical knowledge strongly suggests the need to investigate the therapeutic potential of these substances in human pathology. [ABSTRACT FROM AUTHOR]

Recently, in Italy, a flowchart to be used by General Practitioners for the at-home treatment of patients with COVID-19, has been released. It states that early at-home treatment for SARS-CoV-2 infection is possible due to the availability of specific antiviral drugs to be used in at-risk patients, and that non-steroidal anti-inflammatory drugs (NSAIDs) have an important function in combating the virus. Therefore, the use of NSAIDs is not only rational but also effective in cases that cannot be treated using antivirals. These seemingly simple concepts have been applied in Italy since the beginning of the pandemic by doctors that belong to Italian groups created in order to help COVID-19 patients early at home, at a time of organizational difficulties within Italian health institutions and government. However, this approach was largely boycotted by both the Italian Ministry of Health and medical institutions, which mainly suggested the use of paracetamol as symptomatic, and a wait-and-watch approach for the first three days from the onset of symptoms. In this article, we analyze the rationale for the use of NSAIDs and, in particular, the multi-targeted approach including indomethacin in synergism with flavonoids and low-dose aspirin, as early at-home treatment of patients with COVID-19. Applying these simple concepts from the beginning could have reduced the high lethality of the disease during the first two years of the pandemic and prevented hospital overload. In perspective, it is still necessary to systematically address the comparison between different therapeutic approaches to this viral disease on an experimental basis. [ABSTRACT FROM AUTHOR]

Over 1 year has passed since the beginning of the coronavirus disease 2019 (COVID-19) pandemic outbreak. In addition, our experience also raises several questions: Should anticoagulation (e.g., LMWH) be administered in all mild-to-moderate COVID-19 patients or at least in those who exhibit elevated D-dimer (implying that in all patients D-dimer should be measured), and for how long?. [Extracted from the article]

Device therapy for advanced heart failure has become increasingly employed in the last 10 years. Several retrospective studies have postulated a harmful effect of implantable cardioverter-defibrillator (ICD) lead placement on tricuspid valve function and right heart hemodynamics, in particular among patients with preexisting pulmonary vascular overload and both left and right ventricular remodeling/dysfunction. This functional hypothesis is also supported by long-term clinical follow-up analyses of ICD and cardiac resynchronization therapy recipients. In this viewpoint, we propose that the possibility of worsening tricuspid regurgitation and consequent hemodynamic deterioration following device implantation should be considered in future studies, as well as in the preimplant evaluation of individual candidates among other clinical factors. (PACE 2011; 34:1181-1184) [ABSTRACT FROM AUTHOR]

Authors Guido Carlomagno and Serafino Fazio respond to a letter to the editor submitted in response to their article "The Importance of Tricuspid Regurgitation and Right Ventricular Overload in ICD/CRT Recipients: Beside the Left, Beyond the Left".

A reply is presented by Dr. Serafino Fazio to letters to the editor about the article "A preliminary study of growth hormone in the treatment of dilated cardiomyopathy."

Background: Cardiac hypertrophy is a physiologic response that allows the heart to adapt to an excess hemodynamic load. We hypothesized that inducing cardiac hypertrophy with recombinant human growth hormone might be an effective approach to the treatment of idiopathic dilated cardiomyopathy, a condition in which compensatory cardiac hypertrophy is believed to be deficient. Methods: Seven patients with idiopathic dilated cardiomyopathy and moderate-to-severe heart failure were studied at base line, after three months of therapy with human growth hormone, and three months after the discontinuation of growth hormone. Standard therapy for heart failure was continued throughout the study. Cardiac function was evaluated with Doppler echocardiography, right-heart catheterization, and exercise testing. Results: When administered at a dose of 14 IU per week, growth hormone doubled the serum concentrations of insulin-like growth factor I. Growth hormone increased left-ventricular-wall thickness and reduced chamber size significantly. Consequently, end-systolic wall stress (a function of both wall thickness and chamber size) fell markedly (from a mean [±SE] of 144±11 to 85±8 dyn per square centimeter, P<0.001). Growth hormone improved cardiac output, particularly during exercise (from 7.4±0.7 to 9.7±0.9 liters per minute, P = 0.003), and enhanced ventricular work, despite reductions in myocardial oxygen consumption (from 56±6 to 39±5 ml per minute, P = 0.005) and energy production (from 1014±100 to 701±80 J per minute, P = 0.002). Thus, ventricular mechanical efficiency rose from 9±2 to 21±5 percent (P = 0.006). Growth hormone also improved clinical symptoms, exercise capacity, and the patients' quality of life. The changes in cardiac size and shape, systolic function, and exercise tolerance were partially reversed three months after growth hormone was discontinued. Conclusions: Recombinant human growth hormone administered for three months to patients with idiopathic dilated cardiomyopathy increased myocardial mass and reduced the size of the left ventricular chamber, resulting in improvement in hemodynamics, myocardial energy metabolism, and clinical status. (N Engl J Med 1996;334:809-14.) [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic is a highly dramatic concern for mankind. In Italy, the pandemic exerted its major impact throughout the period of February to June 2020. To date, the awkward amount of more than 134,000 deaths has been reported. Yet, post‐mortem autopsy was performed on a very modest number of patients who died from COVID‐19 infection, leading to a first confirmation of an immune‐thrombosis of the lungs as the major COVID‐19 pathogenesis, likewise for SARS. Since then (June–August 2020), no targeted early therapy considering this pathogenetic issue was approached. The patients treated with early anti‐inflammatory, anti‐platelet, anticoagulant and antibiotic therapy confirmed that COVID‐19 was an endothelial inflammation with immuno‐thrombosis. Patients not treated or scarcely treated with the most proper and appropriate therapy and in the earliest, increased the hospitalization rate in the intensive care units and also mortality, due to immune‐thrombosis from the pulmonary capillary district and alveoli. The disease causes widespread endothelial inflammation, which can induce damage to various organs and systems. Therapy must be targeted in this consideration, and in this review, we demonstrate how early anti‐inflammatory therapy may treat endothelia inflammation and immune‐thrombosis caused by COVID‐19, by using drugs we are going to recommend in this paper. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about tadalafil as a treatment for primary pulmonary arterial hypertension.

Objective. Anorexia nervosa is a condition of reduced hemodynamic load, characterized by varying degrees of cardiac remodelling, only in part related to reduced body mass; the mechanism for such variability, as well as its clinical significance, remains unknown. Aim of the study was to assess the possible influence of a great number of clinical, biochemical, and endocrine factors on cardiovascular parameters in restrictive anorexia nervosa. Method. Twenty-five female patients hospitalized for restrictive anorexia nervosa underwent extensive cardiovascular, clinical, and biochemical evaluation. Results. Height-adjusted and cardiac workload-matched left ventricular mass was significantly related to several endocrine parameters, blood pressure, and vasoreactivity. On multivariate analysis, IGF/GH ratio and systolic blood pressure were the only independent predictors of height-adjusted ventricular mass (adj-R² = 0 585; P = 0 001); when matching for cardiac workload, left ventricular mass was independently predicted only by GH and FT3 levels. All effects were independent of patient's weight and BMI. Conclusions. Indices of endocrine impairment seem to be the most relevant determinants of left ventricular hypotrophy in anorectic patients, apparently independent of reduced hemodynamic load and BMI. In particular, IGF/GH ratio and FT3 seem to particularly affect left ventricular mass in this population. [ABSTRACT FROM AUTHOR]

Objective. Anorexia nervosa is a condition of reduced hemodynamic load, characterized by varying degrees of cardiac remodelling, only in part related to reduced body mass; the mechanism for such variability, as well as its clinical significance, remains unknown. Aim of the study was to assess the possible influence of a great number of clinical, biochemical, and endocrine factors on cardiovascular parameters in restrictive anorexia nervosa. Method. Twenty-five female patients hospitalized for restrictive anorexia nervosa underwent extensive cardiovascular, clinical, and biochemical evaluation. Results. Height-adjusted and cardiac workload-matched left ventricular mass was significantly related to several endocrine parameters, blood pressure, and vasoreactivity. On multivariate analysis, IGF/GH ratio and systolic blood pressure were the only independent predictors of height-adjusted ventricular mass (adj-R² = 0 585; P = 0 001); when matching for cardiac workload, left ventricular mass was independently predicted only by GH and FT3 levels. All effects were independent of patient's weight and BMI. Conclusions. Indices of endocrine impairment seem to be the most relevant determinants of left ventricular hypotrophy in anorectic patients, apparently independent of reduced hemodynamic load and BMI. In particular, IGF/GH ratio and FT3 seem to particularly affect left ventricular mass in this population. [ABSTRACT FROM AUTHOR]

Abstract: Background: The relationship between peripheral circulation and blood pressure (BP) response to maximal exercise is an intriguing and not yet well defined topic. Aims: Aims of the present study were to investigate in well trained young healthy males the possible relationships between the endothelial or the smooth muscle component of the peripheral circulation and 1) the BP response to physical exercise on treadmill 2) the body mass composition. Subjects and methods: Fifteen subjects (18–36 years), regularly performing physical activity 3 times weekly underwent the following examinations: body composition by bioelectrical impedance analysis; measurement of the forearm blood flow (FBF) at rest and during post-ischemic hyperemia by strain-gauge plethysmography at the upper arm; measurement of brachial artery diameter (BAD) at rest and after 4-min ischemia by echography; BP response to maximal exercise on treadmill with the determination of maximal oxygen consumption and the measurement of lactic acid serum concentration. Results: BAD was significantly increased during post-ischemic hyperemia up to the 4th minute of observation with a peak at 60 s (+8.5%); FBF increased at 30 s after ischemia (+210%) and returned to baseline levels at the 2nd minute. In the linear correlation analysis, systolic BP increase at the end of the maximal exercise was significantly and inversely related to the increase in FBF (r =−0.663, p <0.01) and to the early FMD (r =0.503, p <0.05). In the multiple regression analysis, however, only FBF independently affected SBP increase during exercise (t =−3.268, p <0.02). Systolic BP increase at the end of the maximal exercise was significantly related to the increase in FBF but not to that of BAD. Among parameters of body composition, fat-free mass was closely related to changes only in BAD. Conclusions: These data indicate that FBF, which depends on the smooth muscle component of the peripheral circulation, is closely related to BP response to exercise while the endothelial function, which has been determined as changes in BAD, is related to the fat-free mass of the body, possibly through the peripheral insulin sensitivity. [Copyright &y& Elsevier]

In older healthy men, aerobic exercise capacity is related to postischemic flow-mediated dilation of the brachial artery (FMD), but corresponding data in a younger population is not available. In addition, whether submaximal aerobic exercise performance also correlates with this kind of vasomotor reactivity is not known. Therefore, in 15 nonsmoking young healthy men [age 27 (5) years; body mass index: 24 (2) kg/m(2); mean (SD)] with different levels of ordinary physical activity, but not performing upper-extremity training, we measured FMD at 1 min after reactive hyperemia, and pulmonary oxygen uptake (VO(2)) at ventilatory anaerobic threshold (VO(2)AT) and at peak effort (peak VO(2)) during an incremental exercise on a treadmill. In our participants, FMD was 9.1 (3.4)%, VO(2)AT was 40.72 (5.92) ml/kg per min, and peak VO(2) was 52.95 (8.13) ml/kg per min. Using bivariate Pearson's correlation, and in separate multivariate regression analyses, VO(2)AT and peak VO(2) showed a significant and reasonably good correlation with FMD (r = 0.84, P < 0.001 and r = 0.77, P = 0.001, respectively), independent of age, body mass index and serum total cholesterol (beta = 0.77, P < 0.001, R(2) of the overall model = 0.79 and beta = 0.70, P < 0.005, R(2) of the overall model = 0.69, respectively). Our data provide evidence suggesting that in young healthy men a higher submaximal and maximal aerobic exercise performance is associated with a greater FMD of peripheral conduit arteries. [ABSTRACT FROM AUTHOR]

In older healthy men, aerobic exercise capacity is related to postischemic flow-mediated dilation of the brachial artery (FMD), but corresponding data in a younger population is not available. In addition, whether submaximal aerobic exercise performance also correlates with this kind of vasomotor reactivity is not known. Therefore, in 15 nonsmoking young healthy men [age 27 (5) years; body mass index: 24 (2) kg/m2; mean (SD)] with different levels of ordinary physical activity, but not performing upper-extremity training, we measured FMD at 1 min after reactive hyperemia, and pulmonary oxygen uptake (V?O2) at ventilatory anaerobic threshold (V?O2AT) and at peak effort (peakV?O2) during an incremental exercise on a treadmill. In our participants, FMD was 9.1 (3.4)%,V?O2AT was 40.72 (5.92) ml/kg per min, and peakV?O2 was 52.95 (8.13) ml/kg per min. Using bivariate Pearson’s correlation, and in separate multivariate regression analyses,V?O2AT and peakVO2 showed a significant and reasonably good correlation with FMD (r=0.84,P<0.001 andr=0.77,P=0.001, respectively), independent of age, body mass index and serum total cholesterol (ß=0.77,P<0.001,R2 of the overall model=0.79 and ß=0.70,P<0.005,R2 of the overall model=0.69, respectively). Our data provide evidence suggesting that in young healthy men a higher submaximal and maximal aerobic exercise performance is associated with a greater FMD of peripheral conduit arteries. [ABSTRACT FROM AUTHOR]

Echocardiography can be used to estimate myocardial contractility by the assessment of the circumferential end-systolic stress-corrected left ventricular (LV) fractional shortening measured at midwall level (stress-corrected MWS). Whether stress-corrected MWS at rest predicts exercise peak oxygen uptake (peak VO2) is unknown. Also, it is not known whether the propagation rate of the early LV filling wave (E wave propagation rate, Vp), a new pre-load insensitive index of LV diastolic function, and echocardiographically assessed indices of arterial stiffness correlate to peak VO2. Accordingly, we performed echocardiographic studies and exercise tests with respiratory gas analysis in 15 young healthy male subjects (mean age 27 years, range 18–36). Neither stress-corrected-MWS (r=0.20, P=NS) nor ejection fraction (r=-0.05, P=NS) correlated significantly with peak VO2. Adjustment for age and resting heart rate had no effect on the results. In separate multiple regression models adjusting for standard covariates (age, LV size and heart rate), peak VO2 correlated with Vp (beta=0.98, P<0.01), as well as with E/A (beta=0.85, P<0.01), and with the isovolumic relaxation time (indicator of LV relaxation) (beta=-0.59, P<0.05). Arterial stiffness indices showed no significant relation to peak VO2. We conclude that in young healthy male subjects, resting myocardial contractility and arterial stiffness are not significant correlates of peak VO2, whereas LV diastolic function, and in particular Vp, influences the variability of peak VO2. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the incidence of vascular events during a 7-year followup evaluation in a group of 34 hypertensive patients with kinking of the internal carotid artery and 36 well-matched hypertensive control subjects. The carotid intima-media thickness (IMT) was measured at three points of the carotid bifurcation and at three points of carotid kinking on the ultrasonographic posterior wall. The mean IMT measured in the segment of the angular bending was lower than the mean values detected at the bifurcation in normal subjects and in hypertensives without carotid elongation (p < 0.01 ). At the carotid bifurcation of the same side of the kinking, there was an arterial IMT that was significantly lower as compared to the contralateral axis and to the measurements obtained in other hypertensive subjects. During a 7-year follow-up study, 10 vascular events occurred in the hypertensives with carotid kinking and 14 in the controls, without significant differences between the 2 groups. In hypertensives with carotid kinking, the mean IMT measured on the angular bending and at the ipsilateral carotid bifurcation was significantly lower than the values obtained at the contralateral bifurcation and in the other hypertensive subjects. In the 7-year follow-up study, moreover, the presence of carotid kinking does not impact the incidence of vascular events in the hypertensive population. Thus, the presence of carotid kinking in hypertensive subjects may not be considered a further risk factor for ischemic events. [ABSTRACT FROM AUTHOR]

Background: Mounting evidence indicates that subclinical thyroid dysfunction has important clinical effects and prognostic implications, supporting the view that it is not a compensated biochemical change sensu strictu.Purpose: To review clinical information on the effects of subclinical thyroid dysfunction on the heart.Data Sources: English-language articles identified from files and a MEDLINE search (1970-September 2001), references of relevant articles, textbooks, and meeting abstracts.Study Selection: Reports on the effects of subclinical hypothyroidism and subclinical hyperthyroidism on the cardiovascular system in humans.Data Extraction: Data on cardiac structure and performance, arrhythmias, and risk for coronary artery disease were independently assessed by all authors and summarized.Data Synthesis: Subclinical hypothyroidism is associated with impaired left ventricular diastolic function at rest, systolic dysfunction on effort, and enhanced risk for atherosclerosis and myocardial infarction. Subclinical hyperthyroidism is associated with increased heart rate, atrial arrhythmias, increased left ventricular mass with marginal concentric remodeling, impaired ventricular relaxation, reduced exercise performance, and increased risk for cardiovascular death. All abnormalities were reversed by restoration of euthyroidism (subclinical hypothyroidism) or were blunted by beta-blockade and tailoring of the l -thyroxine dose (subclinical hyperthyroidism).Conclusion: The heart responds to the minimal but persistent changes in circulating thyroid hormone levels typical of subclinical thyroid dysfunction. Thus, the condition is not a compensated biochemical change sensu strictu, and timely treatment should be considered in an attempt to avoid adverse cardiovascular effects. [ABSTRACT FROM AUTHOR]

: ObjectivesThe goal of this study was to test the hypothesis that growth hormone (GH) administration to patients with chronic heart failure (CHF) corrects their vascular dysfunction.: BackgroundEndothelial dysfunction is a prominent feature of CHF. Recent evidence indicates that GH plays a role in vascular reactivity.: MethodsWe studied vascular reactivity in 16 patients with CHF (New York Heart Association class II to III) before and after three months of GH (4 IU subcutaneously every other day) or placebo administration in a randomized, double-blind trial. We measured forearm blood flow (FBF) by strain-gauge plethysmography during intrabrachial, graded infusion of acetylcholine (ACh) and sodium nitroprusside (NP). We also measured the forearm balance of nitrite and cyclic guanosine monophosphate (cGMP) before and during ACh infusion. Maximal oxygen uptake (VO2max) was measured by breath-to-breath respiratory gas analysis.: ResultsBefore treatment, the response of FBF to ACh was flat (p = NS). Growth hormone, but not placebo, greatly improved this response (p = 0.03) and, concomitantly, increased the forearm release of nitrite and cGMP (p < 0.05). Growth hormone also potentiated the FBF response to NP (p = 0.013). Growth hormone interacted with ACh response (p = 0.01) but not with the response to NP (p = NS). Accordingly, GH enhanced the slope of the dose-response curve to ACh (p < 0.05) but not to NP. The VO2max increased significantly after GH treatment (20 ± 2 and 26 ± 2 ml ·Kg−1· min−1 before and after GH treatment, respectively, p < 0.05) but not after placebo.: ConclusionsA three-month treatment with GH corrected endothelial dysfunction and improved non-endothelium-dependent vasodilation in patients with CHF. The data highlight the potential role of GH in the progression of congestive heart failure. [Copyright &y& Elsevier]

Abstract: Pulmonary arterial hypertension has a poor prognosis quoad vitam et valitudinem. Herein, we report on a middle-aged woman affected by idiopathic pulmonary arterial hypertension whose quality of life and exercise tolerance improved remarkably after a six-month course of treatment with the long-acting phosphodiesterase-5 inhibitor tadalafil. [Copyright &y& Elsevier]

Presents a letters to the editor which focuses on effects of subclinical thyroid dysfunction on the heart. Rate of atrial fibrillation in patients with subclinical hyperthyroidism; Finding that appropriate thyroid hormone replacement therapy prevented progression of angiographic coronary artery disease; Assertion that subclinical hypothyroidism is a mild type of tissue hypothyroidism.