Nonthyroidal illness syndrome (NTIS) in severe COVID-19 patients: role of T3 on the Na/K pump gene expression and on hydroelectrolytic equilibrium.

BACKGROUND: Nonthyroidal Illness Syndrome (NTIS) can be detected in many critical illnesses. Recently, we demonstrated that this condition is frequently observed in COVID-19 patients too and it is correlated with the severity the disease. However, the exact mechanism through which thyroid hormones influence the course of COVID-19, as well as that of many other critical illnesses, is not clear yet and treatment with T4, T3 or a combination of both is still controversial. Aim of this study was to analyze body composition in COVID-19 patients in search of possible correlation with the thyroid function. METHODS AND FINDINGS: We report here our experience performed in 74 critically ill COVID-19 patients hospitalized in the intensive care unit (ICU) of our University Hospital in Rome. In these patients, we evaluated the thyroid hormone function and body composition by Bioelectrical Impedance Analysis (BIA) during the acute phase of the disease at admission in the ICU. To examine the effects of thyroid function on BIA parameters we analyzed also 96 outpatients, affected by thyroid diseases in different functional conditions. We demonstrated that COVID-19 patients with low FT3 serum values exhibited increased values of the Total Body Water/Free Fat Mass (TBW/FFM) ratio. Patients with the lowest FT3 serum values had also the highest level of TBW/FFM ratio. This ratio is an indicator of the fraction of FFM as water and represents one of the best-known body-composition constants in mammals. We found an inverse correlation between FT3 serum values and this constant. Reduced FT3 serum values in COVID-19 patients were correlated with the increase in the total body water (TBW), the extracellular water (ECW) and the sodium/potassium exchangeable ratio (Nae:Ke), and with the reduction of the intracellular water (ICW). No specific correlation was observed in thyroid patients at different functional conditions between any BIA parameters and FT3 serum values, except for the patient with myxedema, that showed a picture similar to that seen in COVID-19 patients with NTIS. Since the Na+/K+ pump is a well-known T3 target, we measured the mRNA expression levels of the two genes coding for the two major isoforms of this pump. We demonstrated that COVID-19 patients with NTIS had lower levels of mRNA of both genes in the peripheral blood mononuclear cells (PBMC)s obtained from our patients during the acute phase of the disease. In addition, we retrieved data from transcriptome analysis, performed on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM)s treated with T3 and we demonstrated that in these cells T3 is able to stimulate the expression of these two genes in a dose-dependent manner. CONCLUSIONS: In conclusion, we demonstrated that measurement of BIA parameters is a useful method to analyze water and salt retention in COVID-19 patients hospitalized in ICU and, in particular, in those that develop NTIS. Our results indicate that NTIS has peculiar similarities with myxedema seen in severe hypothyroid patients, albeit it occurs more rapidly. The Na+/K+ pump is a possible target of T3 action, involved in the pathogenesis of the anasarcatic condition observed in our COVID-19 patients with NTIS. Finally, measurement of BIA parameters may represent good endpoints to evaluate the benefit of future clinical interventional trials, based on the administration of T3 in patients with NTIS.

265 Incidence, determinants and prognostic relevance of HS-troponin and natriuretic peptides elevation at admission in hospitalized COVID-19 pneumonia patients.

Aims: myocardial involvement in the course of Coronavirus disease 2019 (COVID-19) pneumonia has been reported, though not fully characterized yet. Aim of the present study is to undertake a joint evaluation of hs-Troponin and natriuretic peptides (NP) in patients hospitalized for COVID-19 pneumonia. Methods and results: in this multicenter observational study, we analyzed data from n = 111 COVID-19 patients admitted to dedicated "COVID-19" medical units. Hs-Troponin was assessed in n = 103 patients and NP in n = 82 patients on admission; subgroups were identified according to values beyond reference range. increased hs-Troponin and NP were found in 38% and 56% of the cases respectively. As compared to those with normal cardiac biomarkers, these patients were older, had higher prevalence of cardiovascular diseases (CVD) and more severe COVID-19 pneumonia by higher CRP and D-dimer and lower PaO2/FIO2. Two-dimensional echocardiography performed in a subset of patients (n = 24) showed significantly reduced left ventricular ejection fraction in patients with elevated NP only (p = 0.02), whereas right ventricular systolic function (tricuspid annular plane systolic excursion) was significantly reduced both in patients with high hs-Troponin and NP (p = 0.022 and p = 0.03 respectively). On multivariable analysis, independent associations were found of hs-Troponin with age, PaO2/FIO2 and D-dimer (B = 0.419, p = 0.001; B=-0.212, p = 0.013 and B = 0.179, p = 0.037 respectively), and of NP with age and previous CVD (B = 0.480, p < 0.001 and B = 0.253, p = 0.001 respectively). In patients with in-hospital mortality (n = 23, 21%) hs-Troponin and NP were both higher (p = 0.001 and p = 0.002 respectively), while increasing hs-troponin and NP were associated with worse in-hospital prognosis [OR 4.88 (95% CI 1.9-12.2), p = 0.001 (adjusted OR 3.1 (95% CI 1.2-8.5), p = 0.025) and OR 4.67 (95% CI 2-10.8), p < 0.001 (adjusted OR 2.89 (95% CI 1.1-7.9), p = 0.04) respectively]. Receiver operator characteristic curves showed good ability of hs-Troponin and NP in predicting in-hospital mortality (AUC = 0.869 p < 0.001 and AUC = 0.810, p < 0.001 respectively). Conclusion: myocardial involvement at admission is common in COVID-19 pneumonia and associated to worse prognosis, suggesting a role for cardiac biomarkers assessment in COVID-19 risk stratification. Independent associations of hs-Troponin with markers of disease severity and of NP with underlying CVD might point towards existing different mechanisms leading to their elevation in this setting.

Serum biomarkers evaluation to predict chemotherapy-induced cardiotoxicity in breast cancer patients.

Anti-neoplastic chemotherapy can determine various side effects, including cardiotoxicity, and no real guidelines for its early detection and management have been developed. The aim of this study is to find some plasmatic markers able to identify breast cancer patients that are at greater risk of developing cardiovascular complications during chemotherapy, in particular heart failure. A prospective study on 100 breast cancer patients with mean age of 66 years in adjuvant treatment with anthracyclines, taxanes, and trastuzumab was performed. Patients underwent cardiological examination before starting treatment (T0) and at 3 months (T1), 6 months (T2), and 1 year (T3) after treatment. Evaluation of serum cardiac markers and N-terminal pro-brain natriuretic peptide (NT-proBNP) was performed at T0, T1, T2, and T3, simultaneously to electrocardiogram and echocardiogram, showing a significant increase in NT-proBNP concentration (p > 0.0001) at T1, T2, and T3, before left ventricular ejection fraction decrease became evident. Human epidermal growth factor receptor 2 (HER2)-negative patients were more susceptible to mild hematological cardiotoxicity, while HER2-positive patients were more susceptible to severe cardiotoxicity. A significant correlation between NT-proBNP increased values after chemotherapy and prediction of mortality at 1 year was evidenced. From our experience, serum biomarker detection was able to support an early diagnosis of cardiac damage, also in the absence of left ventricular ejection fraction decrease. Therefore, the evaluation of specific plasmatic markers for cardiac damage is more sensitive than echocardiography in the early diagnosis of chemotherapy-related cardiotoxicity; furthermore, it can also add a prognostic value on outcome.

The measurement of the left ventricle ejection fraction by a bedside FoCUS examination.

The use of point-of-care ultrasound is rapidly increasing in medical practice. This study aims to evaluate the left ventricle systolic function by the bedside focus cardiac ultrasound (FoCUS). We consecutively enrolled n.59 patients of the Emergency Medicine Unit of S. Andrea Hospital. Every patient received a bedside FoCUS examination to estimate the left ventricle (LV) ejection fraction (EF); the LV EF measurements were compared with those obtained by standard echocardiography (as gold standard). The LV EF obtained by the bedside FoCUS examination and the standard echocardiography, resulted, respectively: 50.2 ± 15.1% (by the Quinones equation), 39.5 + 12.0% (by the Lvivo app) and 53.7 + 11.1% (by the standard echocardiography). The correlations between the bedside FoCUS EF measurements versus standard echocardiography were statistically significant: r = + 0.694 p < 1.9 × 10-6 (Quinones equation, Bland-Altman analysis mean = - 2.3%) and r = + 0.571 p < 0.01 (Lvivo app, Bland-Altman analysis mean = - 13.3%). In conclusion, the present study showed a high accuracy of the bedside FoCUS EF evaluations, which may support the diagnosis of the heart failure in an emergency setting without delaying. The EF measurements by the operational method are more precise than those obtained by the unselected images of the software application.

Prevalence and characteristics of distress in a sample of large hospital's workers in Rome in a period between two peaks of the covid-19 pandemic.

AIM: The aim of this study has been to measure the distress of workers at a large hospital in Rome, immediately after the lockdown with relaxed national restrictions except the indication to wear masks FP2 and to maintain the interpersonal distance of at least one meter. METHOD: A web-based anonymous survey has been conducted. Of the 324 responders (23-69 years; 78.09% females), 41.05% was nurse, 31.17% medical doctor, 7.72% employee with administrative function, 3.09% psychologist, 1.54% biologist, 13.58% grouped in the "other" category. 60.49% worked in a no-covid-19 ward, 20.37% in the covid-19 ward, 13.58% in outpatient clinics, and 5.56% outside the hospital. 45.06% have been exposed to covid-19 and 7.72% tested positive for covid-19. 66.67% were satisfied with the safety measures taken by the hospital. Post-traumatic stress disorder (PTSD) symptoms, as measured by IES-R, and peritraumatic distress, measured by CPDI, were frequently reported (41.05% and 43.21%, respectively). PTSD resulted independently associated with peritraumatic distress (Adjusted Odds Ratio, AOR 49.83), perception of being avoided by family and/or friends due to work performed (AOR= 4.05), low hope for the future (AOR= 2.25) and female gender (AOR= 2.90). Age and profession were considered confounding variables. RESULTS: These results showed that even in times of reduced restrictions, the prevalence of peritraumatic distress and PTSD is high, regardless of work and professional specialization, length of service, more or less direct contact with covid-19 patients. CONCLUSIONS: Since the biological damage resulting from a PTSD is known, it is important to activate screening programs followed by specific interventions to reduce long-term risks to mental health.

CHA2DS2-VASc score in patients with COVID-19 pneumonia and its relationship with biomarkers of thrombosis, inflammation and myocardial injury.

CHA2DS2-VASC score associates with worse prognosis in coronavirus-disease-19 (COVID-19). This study investigated laboratory correlates of increasing CHA2DS2- VASc in patients with COVID-19. Patients with COVID-19 were stratified by CHA2DS2-VASc (Group 1: CHA2DS2-VASc 0-1; Group 2: CHA2DS2-VASc 2-3; Group 3: CHA2DS2-VASc ≥4). We found stepwise increase of D-dimer, hs-Troponin and in-hospital mortality across groups (all P < 0.01). D-dimer and hs-Troponin remained independently associated with CHA2DS2-VASc (B = 0.145, P = 0.03; B = 0.320, P < 0.001, respectively). We found significant correlations between D-dimer and C-reactive protein (CRP) in Group 1 and 2, not in Group 3 (r2 = 0.103, P = 0.005; r2 = 0.226, P = 0.001; r2 = 0.021, P = 0.253 respectively), and between D-dimer and hs-Troponin in group 2 and 3, not in Group 1 (r2 = 0.122, P = 0.003; r2 = 0.120, P = 0.007; r2 = 0.006, P = 0.514 respectively). In our cohort, CHA2DS2- VASc was independently associated with D-dimer and hs- Troponin increase. Variable relationships of D-dimer with hs-Troponin and CRP within different CHA2DS2-VASc strata suggest multiple mechanisms to be responsible for D-dimer increase in COVID-19.

[18F]FDG PET/CT in Patients Affected by SARS-CoV-2 and Lymphoproliferative Disorders and Treated with Tocilizumab.

OBJECTIVES: Interstitial pneumonia is a severe complication induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Several treatments have been proposed alone or, more often, in combination, depending, also, on the presence of other organ disfunction. The most frequently related, well-described, and associated phenomenon is pan-lymphopenia with circulating, high levels of cytokines. We report, here, on two patients with COVID-19 and lymphoproliferative disorders treated with Tocilizumab (a humanized monoclonal antibody against the interleukin-6 receptor) and followed by an [18F]FDG PET/CT to early evaluate the therapy's efficacy. METHODS: One patient with angioimmunoblastic T-lymphoma (A), one with Hodgkin lymphoma (A), and both with positive RT-PCR for SARS-CoV-2 and with similar clinical findings of interstitial pneumonia at the CT scan, were imaged by [18F]FDG PET/CT before and 14 days after a single dose of Tocilizumab. RESULTS: In both patients, the basal [18F]FDG PET/CT showed a diffused lung parenchyma uptake, corresponding to the hyperdense areas at the CT scan. After 2 weeks of a Tocilizumab infusion, patient B had an improvement of symptoms, with normalization of the [18F]FDG uptake. By contrast, patient A, who was still symptomatic, showed a persisting and abnormal distribution of [18F]FDG. Interestingly, both patients showed a low bone marrow uptake of [18F]FDG at the diagnosis and after 15 days, while the spleen uptake was low only in lymphopenic patient A; both are indirect signs of an immune deficiency. CONCLUSIONS: In conclusion, in these two patients, interstitial pneumonia was efficiently treated with Tocilizumab, as demonstrated by the [18F]FDG PET/CT. Our results confirm that interleukin-6 (IL6) has a role in the COVID-19 disease and that anti-cytokine treatment can also be performed in patients with lymphoproliferative disorders.

Coronavirus disease 2019 in patients with cardiovascular disease: clinical features and implications on cardiac biomarkers assessment.

INTRODUCTION: Previous cardiovascular disease (CVD) and myocardial involvement are common in coronavirus disease-19 (COVID-19). We investigated relationships between CVD, cardiac biomarkers and outcome in COVID-19. METHODS: We analyzed n = 252 patients from a multicenter study and provided comparison according to the presence or absence of underlying CVD. Cardiac biomarkers high-sensitivity Troponin [upper reference of normality (URN) 35 pg/ml for Troponin I and 14 pg/ml for Troponin T] and natriuretic peptides (Nt-pro-B-type natriuretic peptide, URN 300 pg/ml and B-type natriuretic peptide, URN 100 pg/ml) were both available in n = 136. RESULTS: Mean age was 69 ±â€Š16 years (56% men, 31% with previous CVD). Raised hs-Troponin and natriuretic peptides were detected in 36 and 50% of the cases respectively. Age, chronic obstructive pulmonary disease, hemoglobin, hs-Troponin and natriuretic peptides were independently associated with underlying CVD (P < 0.05 for all). Compared with the normal biomarkers subgroups, patients with isolated hs-Troponin elevation had higher in-hospital mortality (31 vs. 4%, P < 0.05), similar CVD prevalence (15 vs. 11%) and trend towards higher D-dimer (930 vs. 397 ng/ml, P = 0.140). Patients with both biomarkers elevated had higher age, D-dimer, CVD and in-hospital mortality prevalence compared with other subgroups (all P < 0.05 for trend). Outcome analysis revealed previous CVD [model 1: OR 2.72 (95% CI 1.14-6.49), P = 0.024. model 2: OR 2.65 (95% CI 1.05-6.71), P = 0.039], hs-Troponin (log10) [OR 2.61 (95% CI 1.21-5.66), P = 0.015] and natriuretic peptides (log10) [OR 5.84 (95%CI 2.43-14), P < 0.001] to be independently associated with in-hospital mortality. CONCLUSION: In our population, previous CVD was part of a vulnerable phenotype including older age, comorbidities, increased cardiac biomarkers and worse prognosis. Patients with isolated increase in hs-Troponin suffered higher mortality rates despite low prevalence of CVD, possibly explained by higher COVID-19-related systemic involvement.

Multi-omic approach identifies a transcriptional network coupling innate immune response to proliferation in the blood of COVID-19 cancer patients.

Clinical outcomes of COVID-19 patients are worsened by the presence of co-morbidities, especially cancer leading to elevated mortality rates. SARS-CoV-2 infection is known to alter immune system homeostasis. Whether cancer patients developing COVID-19 present alterations of immune functions which might contribute to worse outcomes have so far been poorly investigated. We conducted a multi-omic analysis of immunological parameters in peripheral blood mononuclear cells (PBMCs) of COVID-19 patients with and without cancer. Healthy donors and SARS-CoV-2-negative cancer patients were also included as controls. At the infection peak, cytokine multiplex analysis of blood samples, cytometry by time of flight (CyTOF) cell population analyses, and Nanostring gene expression using Pancancer array on PBMCs were performed. We found that eight pro-inflammatory factors (IL-6, IL-8, IL-13, IL-1ra, MIP-1a, IP-10) out of 27 analyzed serum cytokines were modulated in COVID-19 patients irrespective of cancer status. Diverse subpopulations of T lymphocytes such as CD8+T, CD4+T central memory, Mucosal-associated invariant T (MAIT), natural killer (NK), and γδ T cells were reduced, while B plasmablasts were expanded in COVID-19 cancer patients. Our findings illustrate a repertoire of aberrant alterations of gene expression in circulating immune cells of COVID-19 cancer patients. A 19-gene expression signature of PBMCs is able to discriminate COVID-19 patients with and without solid cancers. Gene set enrichment analysis highlights an increased gene expression linked to Interferon α, γ, α/ß response and signaling which paired with aberrant cell cycle regulation in cancer patients. Ten out of the 19 genes, validated in a real-world consecutive cohort, were specific of COVID-19 cancer patients independently from different cancer types and stages of the diseases, and useful to stratify patients in a COVID-19 disease severity-manner. We also unveil a transcriptional network involving gene regulators of both inflammation response and proliferation in PBMCs of COVID-19 cancer patients.

Right ventricular dysfunction in patients with end-stage renal disease.

BACKGROUND: While chronic dialysis treatment has been suggested to increase pulmonary pressure values, right ventricular dysfunction (RVD) is a major cause of death in patients with end-stage renal disease. We investigated the impact of different dialysis treatments on right ventricular function. METHODS: We examined 220 subjects grouped as follows: healthy controls (n = 100), peritoneal dialysis (PD; n = 26), hemodialysis (HD) with radial arteriovenous fistula (AVF; n = 62), and HD with brachial AVF (n = 32). Echocardiography including tissue Doppler imaging (TDI) of the right ventricle was performed in all patients. RESULTS: Pulmonary pressure values progressively rose from controls across the 3 dialysis groups (21.7 ± 6.8, 29.7 ± 6.7, 37.9 ± 6.7 and 40.8 ± 6.6 mm Hg, respectively; p < 0.001). TDI indices of right ventricular function were more impaired in HD patients, particularly in those with brachial AVF. RVD, assessed by TDI myocardial performance index, was higher in HD patients compared with PD patients (71.3 vs. 34.6%, p < 0.001). Moreover, the prevalence of RVD further increased in patients with brachial AVF compared with the radial access (90.6 vs. 61.3%, p < 0.001). CONCLUSIONS: Compared to DP, HD increases the risk of RVD, particularly in the presence of brachial AVF. TDI may detect early functional failure of the right ventricle in HD patients.

Longitudinal changes of left and right cardiac structure and function in patients with end-stage renal disease on replacement therapy.

BACKGROUND: Few data are available regarding longitudinal changes of cardiac structure and function in end-stage chronic kidney disease (CKD). Aim of the present study is to describe serial echocardiographic findings in a cohort of dialyzed CKD patients. METHODS: In this retrospective longitudinal study, we included n = 120 dialyzed CKD patients who underwent at least 2 echocardiograms either 1, 2 or 3 years apart. After baseline echocardiogram, n = 112 had a further examination at year 1, n = 76 at year 2 and n = 45 at year 3. Echocardiographic examination included Tissue Doppler Imaging of both left (LV) and right (RV) ventricle. RESULTS: LV geometry and LV mass index did not significantly change over time. RV progressively dilated (mean change +1.3 mm, +1.1 mm and +3.1 mm at year 1, 2 and 3 respectively, p = 0.002, adjusted p = 0.003). Tissue Doppler parameters showed significant changes with regard to both LV (mean change of E/E' +0.7, +1.3, +1.7 at year 1, 2 and 3 respectively p<0.001, adjusted p = 0.079) and RV (mean change of S wave (cm/sec) -1, -1.7, -2 at year 1, 2 and 3 respectively, p <0.001, adjusted p = 0.041). Decrease of RV S wave negatively correlated with E/E' changes (r=-0.303, p = 0.002; r=-0.246, p = 0.049; r=-0.265, p = 0.089; at year 1, 2 and 3 respectively). LV ejection fraction (LVEF) progressively declined (p = 0.034, adjusted p = 0.140), albeit being significant lower against baseline only at year 3 (mean change -4.3%, p<0.05). CONCLUSIONS: In dialyzed CKD patients we observed parallel worsening of LV diastolic and RV systolic function accompanied by RV dilation. LVEF decreased less sharply.

[Grey zones on dual antiplatelet therapy. Expert opinion]. / Grey zones sulla duplice terapia antipiastrinica. Opinioni degli esperti.

Clinical guidelines, while representing an objective reference to perform appropriate treatment choices, contain grey zones, where recommendations are not supported by solid evidence. In a conference held in Bergamo in October 2018, an attempt was made to highlight some of the main gray zones in Cardiology and, through a comparison between experts, to draw shared conclusions that can illuminate our clinical practice. This manuscript contains the statements of the symposium concerning the controversies regarding dual antiplatelet therapy (DAPT). The manuscript represents the organization of the meeting, with an initial review of current guidelines on this topic, followed by an expert presentation of pros (white) and cons (black) related to the identified "gaps of evidence". For every issue is then reported the response derived from the votes of the experts and the public, the discussion and, finally, the highlights, which are intended as practical "take home messages" to be used in everyday clinical practice. The first topic concerns the utility of scores to shorten the duration of DAPT in patients at high bleeding risk. The second issue examines the appropriateness of the level of evidence to prolong DAPT beyond 1 year in patients at high ischemic risk. The last "gap in evidence" concerns the possibility of adopting the single antiplatelet therapy plus an anticoagulant vs the triple therapy in patients with atrial fibrillation and acute coronary syndrome. The work has also been implemented with evidences deriving from important randomized studies published after the date of the Conference.

Risk stratifying asymptomatic left ventricular systolic dysfunction in the community: beyond left ventricular ejection fraction.

AIMS: Midwall fractional shortening (MWFS) is a measure of left ventricular (LV) systolic function that is more reliable in case of concentric LV geometry compared to LV ejection fraction (LVEF). We hypothesized that MWFS might predict heart failure (HF) and death in a high-risk asymptomatic population, beyond other echocardiographic parameters. METHODS AND RESULTS: Among 4047 subjects aged ≥55/≤80 years followed by 10 general practitioners in northern Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic outpatients at increased risk for HF. Baseline evaluation included clinical visit, electrocardiogram, N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiogram. Mean age of the population was 69 ± 7 years, 56% were men, 88% had hypertension, mean LVEF was 61 ± 9%, and mean MWFS 16.2 ± 3.3. During a median follow-up of 5.7 years, 95 subjects experienced HF/death events. At Cox analysis, lower MWFS was the only echocardiographic parameter, among structural/functional ones, associated with higher risk of HF/death [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.84-0.95, Padjusted < 0.001]. The risk of HF/death related to clinical data and NT-proBNP (baseline model) was reclassified by echocardiography only when MWFS was included into the model (baseline C-statistics 0.761; adding conventional structural/functional echocardiographic data 0.776, P = 0.09; adding MWFS 0.791, P = 0.007). Compared to subjects with normal LVEF and MWFS, only subjects with combined systolic dysfunction (11% of the population) were at higher risk (P = 0.001 for both abnormal; P > 0.24 for either LVEF or MWFS abnormal). CONCLUSION: DAVID-Berg data suggest to include MWFS assessment in clinical practice, a simple and reliable echocardiographic parameter able to improve risk stratification in subjects at high risk for HF.

Incidence and determinants of high-sensitivity troponin and natriuretic peptides elevation at admission in hospitalized COVID-19 pneumonia patients.

BACKGROUND: Myocardial involvement in the course of coronavirus disease 2019 (COVID-19) pneumonia has been reported, though not fully characterized yet. The aim of the present study is to undertake a joint evaluation of hs-Troponin and natriuretic peptides (NP) in patients hospitalized for COVID-19 pneumonia. METHODS: In this multicenter observational study, we analyzed data from n = 111 patients. Cardiac biomarkers subgroups were identified according to values beyond reference range. RESULTS: Increased hs-Troponin and NP were found in 38 and 56% of the cases, respectively. As compared to those with normal cardiac biomarkers, these patients were older, had higher prevalence of cardiovascular diseases (CVD) and had more severe COVID-19 pneumonia by higher CRP and D-dimer and lower PaO2/FIO2. Two-dimensional echocardiography performed in a subset of patients (n = 24) showed significantly reduced left ventricular ejection fraction in patients with elevated NP (p = 0.02), whereas right ventricular systolic function (tricuspid annular plane systolic excursion) was significantly reduced both in patients with high hs-Troponin and NP (p = 0.022 and p = 0.03, respectively). Both hs-Troponin and NP were higher in patients with in-hospital mortality (p = 0.001 and p = 0.002, respectively). On multivariable analysis, independent associations were found of hs-Troponin with age, PaO2/FIO2 and D-dimer (B = 0.419, p = 0.001; B = - 0.212, p = 0.013; and B = 0.179, p = 0.037, respectively) and of NP with age and previous CVD (B = 0.480, p < 0.001; and B = 0.253, p = 0.001, respectively). CONCLUSIONS: Myocardial involvement at admission is common in COVID-19 pneumonia. Independent associations of hs-Troponin with markers of disease severity and of NP with underlying CVD might point toward existing different mechanisms leading to their elevation in this setting.

Effects of different statin types and dosages on systolic/diastolic blood pressure: Retrospective analysis of 24-hour ambulatory blood pressure database.

We previously demonstrated lower diastolic blood pressure (BP) levels under statin therapy in adult individuals who consecutively underwent 24-hour ambulatory BP monitoring and compared their levels to untreated outpatients. Here we evaluated systolic/diastolic BP levels according to different statin types and dosages. 987 patients (47.5% female, age 66.0 ± 10.1 years, BMI 27.7 ± 4.6 kg/m2 , clinic BP 146.9 ± 19.4/86.1 ± 12.1 mm Hg, 24-hour BP 129.2 ± 14.4/74.9 ± 9.2 mm Hg) were stratified into 4 groups: 291 (29.5%) on simvastatin 10-80 mg/d, 341 (34.5%) on atorvastatin 10-80 mg/d, 187 (18.9%) on rosuvastatin 5-40 mg/d, and 168 (17.0%) on other statins. There were no significant BP differences among patients treated by various statin types and dosages, except in lower clinic (P = .007) and daytime (P = .013) diastolic BP in patients treated with simvastatin and atorvastatin compared to other statins. Favorable effects of statins on systolic/diastolic BP levels seem to be independent of types or dosages, thus suggesting a potential class effect of these drugs.

Reduced levels of N-terminal-proatrial natriuretic peptide in hypertensive patients with metabolic syndrome and their relationship with left ventricular mass.

OBJECTIVES: The metabolic syndrome (MS) is associated with left ventricular hypertrophy (LVH). Previous evidence has shown that LVH is favoured by low levels of atrial natriuretic peptide (ANP), independently from blood pressure (BP), in hypertension. Although levels of natriuretic peptides are known to be lower in obesity, plasma ANP levels have not yet been assessed in MS. We aimed to assess the ANP levels and their relationship with left ventricular mass (LVM) in patients affected by MS. METHODS: One hundred and twenty-eight essential hypertensive patients were included in the study: 51 with MS and 77 without MS. Clinical, echocardiographical and biochemical parameters, and levels of both N-terminal (NT)-proANP and alphaANP were assessed. RESULTS: Hypertensive patients affected by MS had higher LVM and increased frequency of LVH. NT-proANP levels were significantly lower in MS, independent of waist circumference (WC). Log(NT-proANP) levels were significantly inversely related to left ventricular mass index (LVMI) (beta = -0.360, P < 0.001) and LVM/height (beta = -0.370, P < 0.001) in the whole hypertensive population by multiple linear regression analysis. The relationship of log(NT-proANP) with LVM was more enhanced in patients with MS. CONCLUSIONS: The present study demonstrates that levels of NT-proANP are significantly reduced in hypertensive patients affected by MS, and they are significantly inversely related to the increased LVM observed in these patients. Our findings, while supporting previous experimental and clinical evidence of the antihypertrophic role of ANP in hypertension, may help to identify one of the possible mechanisms directly underlying LVH in MS.

Cardiac resynchronization therapy increases plasma levels of the endogenous inotrope apelin.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been introduced to treat drug refractory chronic heart failure (CHF). Apelin, the endogenous ligand of the APJ receptor, is under evaluation for its potential role in human CHF pathophysiology. This study aims to assess whether biventricular pacing affects plasma apelin levels in patients with severe CHF. METHODS AND RESULTS: Fourteen patients (9 men, 5 women, mean age 68+/-13 years) undergoing biventricular pace-maker/ICD implantation were studied. Patients underwent baseline clinical and echocardiographic evaluation, and assessment of plasma apelin and NT-proBNP levels. The evaluation was repeated 48 h and 9+/-2 months after device implantation to assess the acute and chronic effects of CRT on apelin and NT-proBNP levels. Eight healthy age- and sex-matched subjects served as controls. In CHF patients, baseline apelin levels were reduced and NT-proBNP increased compared to control subjects (apelin: 0.47+/-0.2 vs. 0.97+/-0.3 ng/mL, p<0.001; NT-proBNP: 2007+/-114 vs. 229+/-72 pmol/L, p<0.001). Short-term evaluation did not reveal any effect of CRT on apelin or NT-proBNP levels. By contrast, at 9+/-2 months follow-up, CRT responders showed left ventricular reverse remodelling and an increase in ejection fraction, together with a significant increase in plasma apelin levels (0.99+/-0.1 vs. 0.47+/-0.2 ng/mL, p<0.001) and decrease in NT-proBNP (938+/-591 vs. 2007+/-114 pmol/L, p<0.05). CONCLUSIONS: Long-term CRT increases plasma levels of the endogenous inotrope apelin in patients with CHF.

Markers of inflammation and fibrosis are related to cardiovascular damage in hypertensive patients with metabolic syndrome.

BACKGROUND: Previous studies have shown that metabolic syndrome (MS) is associated with an increased susceptibility to develop cardiovascular damage (CD). Experimental evidence indicates that inflammation and fibrosis could play a critical role in the development of CD in hypertension. This issue has not been clarified yet in patients with MS. The aim of our study was to investigate the relationship between markers of inflammation and fibrosis with CD in hypertensive patients with and without MS. METHODS: One hundred twenty-eight essential hypertensive patients were included in the study: 51 with MS and 77 without MS. Clinical, biochemical parameters, 24-h urinary albumin excretion rate (UAER), levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and procollagen type 1 carboxy-terminal propeptide (PICP) were measured. All patients underwent an echocardiographic examination with transmitral Doppler and tissue Doppler imaging (TDI). RESULTS: Left ventricular mass indexed by height(2.7) (LVM/h(2.7)) (P < .001), early diastolic peak flow velocity/early myocardial diastolic velocity ratio (E/Em ratio), a TDI index of diastolic function (P < .001), and 24-h UAER (P < .05) were significantly higher in the group with MS, whereas peak myocardial systolic velocity (Sm), a TDI index of systolic function (P < .001), was lower. Serum levels of CRP (P < .001), TNF-alpha (P < .05), TGF-beta (P < .01), and PICP (P < .001) were significantly increased in MS. These markers were significantly related to higher LVMI(2.7), higher E/Em ratio, and increased 24-h UAER and a lower Sm in the whole population, with a further significant enhancement in MS. CONCLUSIONS: Cardiovascular damage is more frequent in hypertensives with MS than in hypertensives without MS, and this is significantly related to the increased levels of inflammation and fibrosis found in hypertensives with MS.