Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy.

AIMS: To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy. METHODS AND RESULTS: The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020. Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease. Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease. Mean age was 67 ± 12 years, and 80 (81%) patients were males. No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients. During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock. Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08-5.09). The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively). CONCLUSIONS: Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.

Irreversible proteasome inhibition with carfilzomib as first line therapy in patients with newly diagnosed multiple myeloma: Early in vivo cardiovascular effects.

Patients who experienced cardiovascular side effects during cancer therapy with carfilzomib for multiple myeloma had relapsed multiple myeloma, so have be previously treated with other cancer therapies. The present is a single center cohort study to evaluate early cardiovascular effects of administration of irreversible proteasome inhibitor carfilzomib in naïve patients. We included 24 patients and collected cardiovascular side effects, echocardiographic parameters and endothelial function at baseline and after 4 cycles. At early follow up we observed increase in blood arterial pressure values (mean change in systolic pressure of 10 mmHg (P-value < 0.01; diastolic arterial pressure and mean arterial pressure of 3.3 mmHg and 5.4 mmHg, both P-value < 0.01). Reactive hyperemia PAT index was reduced in the whole cohort by a mean of 0.46 points (P-value < 0.01); diastolic function was changed: E-wave-deceleration-time (EDT) was reduced by 49,96 ±â€¯31 ms, P-value < 0.05 and early diastolic tissue Doppler velocity (e') by a mean value of 1.46 cm/s, P - value 0.04. At early follow up we did not observe events of grade 3 or 4. We observe correlation between events and endothelial dysfunction at baseline and age (OR 1.9, CI 95% 0.05-5.804, P- value: 0.038 for RHI<1.67; OR 1,4, CI 95%0.99-2.56, P- value: 0.04 for age). Our results suggest that therapy with carfilzomib when used as first line therapy is responsible for increase in systemic blood pressure, alteration of endothelium-mediated vascular dilatation and early myocardial diastolic dysfunction.

Echocardiographic evaluation of diastolic dysfunction in young and healthy patients with psoriasis: A case-control study.

Psoriasis is a systemic inflammatory disease with a great prevalence in general population. The inappropriate activation of the cellular immune system has been hypothesized to be an independent cardiovascular risk factor, given the higher incidence of cardiovascular disorders in psoriatic patients. Echocardiographic abnormalities have been demonstrated too: the aim of our study was to evaluate the presence of preclinical cardiac dysfunction in a cohort of psoriatic patients without cardiovascular risk factors. We enrolled 52 patients with the diagnosis of chronic plaque psoriasis, compared with a control group not affected by any relevant systemic diseases and inflammatory disorders. In all patients and control group, echocardiographic conventional and tissue Doppler (TDI) studies were conducted. The analysis of echocardiographic parameters revealed normal dimension, mass and systolic function of the left ventricle. Left ventricular diastolic dysfunction was found in 36.5% patients in the psoriasis group versus 0% in control group, and significant reduction of the E/A ratio was found also for the right ventricle. A significant increase of mitral regurgitation has been found in psoriatic patients (p=0.005). The early recognition of cardiovascular pre-clinic disease in psoriatic patients may guide a strict follow up and an early treatment, potentially improving cardiovascular prognosis.

Mechanism of cardiovascular toxicity by proteasome inhibitors: New paradigm derived from clinical and pre-clinical evidence.

Proteasome Inhibitors (PI) have now become the cornerstone of treatment of multiple myeloma (MM). Carfilzomib has been demonstrated to cause more frequent cardiovascular side effects such as dyspnea, hypertension, and heart failure. Recent pre-clinical studies have investigated the effects of proteasome on myocardial and vascular cells, but the pathogenic mechanism underlying the effects of proteasome inhibition on these cells is poorly understood. We reviewed the evidence from clinical trials, post-hoc analysis and small observational studies currently available and summarized the data from experimental, focusing on the pathogenic mechanisms potentially implicated in the cardiovascular toxicity of proteasome inhibitor, particularly of carfilzomib that is most responsible for cardiovascular side effects. Finally, we tried to suggest future perspectives for diagnostic and therapeutic approach to this type of cardiovascular damage.

High-dose atorvastatin versus moderate dose on early vascular protection after ST-elevation myocardial infarction.

BACKGROUND AND AIM: Clinical benefits of early high-dose statin therapy after acute coronary syndromes are widely known; however, there is poor evidence on the specific setting of ST-elevation myocardial infarction (STEMI) and dose-dependent effects of this therapy on endothelial function and inflammatory biomarkers in the most vulnerable phase after acute coronary syndromes: the postdischarge period. In our study, we compared the short-term effects of high (80 mg) vs moderate doses of atorvastatin (20 mg) in patients with STEMI undergoing primary percutaneous coronary intervention on endothelial function and vascular inflammation. The aim of our study was the evaluation of dose-dependent short-term effects. SUBJECTS AND METHODS: We enrolled 52 patients within 48 hours of a STEMI to atorvastatin 80 mg (n=26) or 20 mg (n=26). Every patient underwent endothelial function evaluation by the reactive hyperemia-peripheral arterial tonometry (RH-PAT) index on the first day and 1 month after the STEMI. At the same time, we measured lipid profile and serum levels of high-sensitivity CRP, IL6, TNFα, and oxidized LDL. RESULTS: After 1 month of therapy, we observed differences in high-sensitivity CRP levels (0.04±0.02 mg/dL vs 0.36±0.3 mg/dL, P=0.001), IL6 (1.12±0.93 pg/mL vs 3.13±2.84 pg/mL, P=0.03), and improvement in RH-PAT index (1.96±0.16 vs 1.72±0.19, P=0.002) in the group treated with high-dose vs moderate-dose atorvastatin. There was no significant difference in levels of TNFα or oxidized LDL with atorvastatin 20 mg, while there was a reduction in these variables in the group treated with atorvastatin 80 mg. We observed a correlation between high-sensitivity polymerase chain reaction and RH-PAT index on the 30th day after STEMI (r=0.5, P=0.001). CONCLUSION: Higher dose statin therapy in patients with STEMI undergoing primary percutaneous coronary intervention showed early greater vascular protective effects that moderate dose.

Prognostic value of the absolute lymphocyte count in patients admitted for acute heart failure.

BACKGROUND: Low relative lymphocyte count is an important prognostic marker in acute heart failure (AHF); however, it could be influenced by other abnormalities in white cells count. Our purpose is to evaluate if low absolute lymphocyte count (ALC) is an independent predictor of events in patients with AHF. METHODS: In a retrospective analysis, we included 309 patients with AHF, divided into two groups according to the median value of ALC at admission (1410 cells/µl). The primary end point was all-cause mortality or urgent heart transplantation within 1 year. RESULTS: Patients with low ALC were older and had more comorbidity, namely atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease and anemia. Low ALC was associated with higher all-cause mortality or urgent heart transplantation at 1 year (24.3 vs 13.0%; P = 0.012). In a multivariable model, the independent predictors of mortality at 1 year were ALC 1410 cells/µl or less at admission [hazard ratio 2.04; CI (confidence interval) 95% (1.06-3.95); P = 0.033], age [hazard ratio 1.08; CI 95% (1.04-1.12); P < 0.001], baseline serum creatinine [hazard ratio 1.25; CI 95% (1.05-1.50); P = 0.012] and baseline serum Na [hazard ratio 0.91; CI 95% (0.85-0.98); P = 0.013]. CONCLUSION: Low ALC in patients with AHF is associated with higher in-hospital mortality during the hospitalization and is an independent predictor of long-term mortality.

In-hospital worsening heart failure in patients admitted for acute heart failure.

BACKGROUND: In-hospital worsening heart failure (WHF) is predictive of worse post-discharge outcomes and has been recently used as an endpoint in clinical trials in acute heart failure (AHF). METHODS: We described the clinical and prognostic significance of WHF in consecutive patients hospitalized for AHF at our institute. WHF was defined as worsening signs and symptoms of HF requiring treatment intensification. We compared WHF events by day 7 (early WHF) with WHF occurring at any time during admission. The primary endpoint was cardiovascular (CV) death and HF rehospitalizations through day 60. RESULTS: We included 387 consecutive patients. Median length of stay was 11days (interquartile range 8-18days). Forty-five patients (11.6%) had WHF, HF rehospitalization, or death through day 7 whereas 90 (23.3%) had WHF or died at any time during initial hospitalization. Patients with WHF occurring any time during admission were more symptomatic, had lower systolic blood pressure, worse renal function, and higher troponins at baseline. Both early WHF and WHF at any time during hospitalization were associated with a longer length of stay and higher CV death and HF rehospitalization rates at day 60, but only WHF at any time was associated with all-cause death at day 180 (adjusted HR 2.42 95% CI 1.30, 4.52; p=0.0055) and with all-cause death any time during the follow-up period (adjusted HR 1.60 95% CI 1.02, 2.53; p=0.0425). CONCLUSIONS: Our study confirms the prognostic significance of WHF and shows the independent prognostic value of WHF also for long-term mortality when assessed throughout hospitalization.

Cardiorenal Interactions.

Recently, there has been increased appreciation of the identification and management of comorbidities in heart failure patients, and for therapies targeting conventional heart failure signs and symptoms. Renal dysfunction is common in patients with heart failure and is associated with high morbidity and mortality. Early identification of renal damage through novel biomarkers and the use of new pharmacological strategies aimed at preserving renal function may represent an important objective in the treatment. This article reviews the epidemiology and pathophysiology of cardiorenal syndrome in heart failure, and highlights novel biomarkers and improved therapies targeting renal dysfunction.

Nutritional Deficiency in Patients with Heart Failure.

Heart failure (HF) is the main cause of mortality and morbidity in Western countries. Although evidence-based treatments have substantially improved outcomes, prognosis remains poor with high costs for health care systems. In patients with HF, poor dietary behaviors are associated with unsatisfactory quality of life and adverse outcome. The HF guidelines have not recommended a specific nutritional strategy. Despite the role of micronutrient deficiency, it has been extensively studied, and data about the efficacy of supplementation therapy in HF are not supported by large randomized trials and there is limited evidence regarding the outcomes. The aim of the present review is to analyze the state-of-the-art of nutritional deficiencies in HF, focusing on the physiological role and the prognostic impact of micronutrient supplementation.

Nutrition and Cardiovascular Disease: Finding the Perfect Recipe for Cardiovascular Health.

The increasing burden of cardiovascular disease (CVD) despite the progress in management entails the need of more effective preventive and curative strategies. As dietary-associated risk is the most important behavioral factor influencing global health, it appears the best target in the challenge against CVD. Although for many years, since the formulation of the cholesterol hypothesis, a nutrient-based approach was attempted for CVD prevention and treatment, in recent years a dietary-based approach resulted more effective in reducing cardiovascular risk worldwide. After the publication of randomized trials on the remarkable effects of the Mediterranean diet and the Dietary Approach to Stop Hypertension (DASH) diet on CVD, new efforts were put on research about the effects of complex dietary interventions on CVD. The purpose of this paper is to review the evidence on dietary interventions in the prevention and disease modification of CVD, focusing on coronary artery disease and heart failure, the main disease responsible for the enormous toll taken by CVD worldwide.

N-terminal pro-B-type natriuretic peptide-guided therapy in patients hospitalized for acute heart failure.

BACKGROUND: In patients with acute heart failure, high levels of N-terminal-pro-brain natriuretic peptide (NT-proBNP) at discharge are associated with worse outcomes. We hypothesized that NT-proBNP-guided therapy may improve prognosis. METHODS AND RESULTS: Two hundred and seventy-one consecutive patients, admitted for acute heart failure, were prospectively randomized to NT-proBNP-guided therapy or control group. The NT-proBNP-guided therapy group underwent medical treatment intensification when predischarge NT-proBNP was at least 3000 pg/ml. The primary endpoint was cardiovascular death or cardiovascular rehospitalization at day 182. The secondary endpoints were all-cause death, cardiovascular death, cardiovascular rehospitalization, heart failure rehospitalization, and cardiovascular death or heart failure rehospitalization at day 182. Treatment intensification in the NT-proBNP-guided therapy group regarded mainly diuretics. The NT-proBNP strategy was not associated with a significant reduction of the primary endpoint [43% intervention vs. 39% controls, hazard ratio 1.22 (0.84, 1.76), P = 0.305] and of any secondary endpoint. The change of NT-proBNP from predischarge to discharge was associated with the risk of cardiovascular death or cardiovascular rehospitalization through day 182, even after multivariable adjustment. CONCLUSION: NT-proBNP-guided therapy resulted mainly in an increase of diuretics in acute setting and compared with clinical evaluation alone did not improve prognosis. However, the reduction of NT-proBNP at discharge was an independent predictor of outcomes.

School and family-based interventions for promoting a healthy lifestyle among children and adolescents in Italy: a systematic review.

AIMS: Cardiovascular diseases affect adult population but risk factors develop as a result of known or assumed behavior since childhood. In Italy, up to 22.2% of children are overweight, 10.6% are obese, and 2.5% have severe obesity. METHODS: We performed a systematic review of the literature to identify studies and initiatives addressing health promotion among children in Italy. Given the high heterogeneity of interventions and outcomes assessed we opted to perform a qualitative synthesis of the results. We described also nonrandomized trial where the intervention of primary prevention was very innovative, explained in detail, and reached an improving outcome for participants. RESULTS: We identified 11 projects since 1983, only five were randomized control trials. Three involved children and teachers of primary and secondary schools and were based on specific curricular lectures about health. One was based on a game developed for high schools with the purpose to promote healthy lifestyle and physical activity. The fifth project was based on an enhanced physical activity program. CONCLUSION: Our results show that school and family should be considered as the privileged places for health promotion. In Italy, the development of scientific-validated lifestyle interventions for children is still an unmet need.

Family-Based Approaches to Cardiovascular Health Promotion.

Cardiovascular disease is the leading cause of mortality in the world, and the increasing burden is largely a consequence of modifiable behavioral risk factors that interact with genomics and the environment. Continuous cardiovascular health promotion and disease prevention throughout the lifespan is critical, and the family is a central entity in this process. In this review, we describe the potential rationale and mechanisms that contribute to the importance of family for cardiovascular health promotion, focusing on: 1) mutual interdependence of the family system; 2) shared environment; 3) parenting style; 4) caregiver perceptions; and 5) genomics. We conclude that family-based approaches that target both caregivers and children, encourage communication among the family unit, and address the structural and environmental conditions in which families live and operate are likely to be the most effective approach to promote cardiovascular health. We describe lessons learned, future implications, and applications to ongoing and planned studies.

Seaweed floating in the pericardium: a rare case of primary dedifferentiated liposarcoma.

Primary cardiac tumors are uncommon and primary liposarcoma of the pericardium is extremely rare. We describe the case of a 55-year-old Caucasian woman without significant medical history, who presented with 3weeks complain of dyspnea, peripheral edema, and gain weight. Echocardiography revealed a huge pericardial mass confirmed by computed tomography and by magnetic resonance. The lesion was primitive of the pericardium but the surgery was not able to cut it off because of the absence of cleavage planes. Histopathologic analysis detected a dedifferentiated liposarcoma. Mediastinum compression syndrome brought the patient to the exitus in a few days.

Role of the old and new echocardiographic technologies in cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is an important tool for the treatment of patients with chronic heart failure, as it can correct the heterogeneity of regional left ventricular mechanical contraction, known as dyssynchrony. Although this therapy is strongly indicated in patients with both heart failure with left ventricular systolic dysfunction and wide Q-, R- and S-waves (QRS) on electrocardiogram, about one-third of these patients are non-responders. Since the degree of mechanical dyssynchrony can vary greatly, it is interesting to quantify dyssynchrony by means of imaging methods, such as echocardiography, which might be able to lead to a better selection of CRT candidates. This article will review the role of old and new echocardiographic techniques to predict CRT response.

[Intramyocardial bridges: anatomo-pathological characteristics, diagnosis, and therapeutic strategies]. / I ponti intramiocardici: caratteristiche anatomo-patologiche, diagnosi e strategie terapeutiche.

Intramyocardial bridge is defined as the segment of a major epicardial coronary artery that runs within the cardiac muscle wall (coronary tunneling). Usually, this kind of anatomic variant is asymptomatic but sometimes it may lead to acute coronary syndrome and/or arrhythmias, and more rarely to sudden cardiac death. Treatment for symptomatic patients is pharmacological, using beta-blockers.

[New pharmacological approaches to ischemic heart disease]. / Nuovi approcci farmacologici nella cardiopatia ischemica.

Major steps have been made in the treatment of ischemic heart disease from the discovery of nitrates as antianginal medication to the techniques of percutaneous angioplasty. This incredible therapeutic progress has resulted in a reduced incidence of ischemic heart disease and related mortality and morbidity. However, statistical and epidemiological data indicate that in ischemic heart disease, despite the achievement of great success, there is a necessity for a further step toward treatment, considering the fact that the characteristics of this population are changing (increased prevalence of subendocardial infarction compared with classic transmural infarction, especially in the elderly population). Furthermore, the need for alternative therapeutic approaches to traditional ones is recognized. Ranolazine is a selective inhibitor of Na channels that prevents pathological extension of late Na current developing in the ischemic myocardial cell. This current is responsible for calcium overload, with consequent impairment of diastolic relaxation. Ranolazine reduces Na overload induced by calcium and improves diastolic relaxation and coronary subendocardial flow, without affecting hemodynamic parameters such as blood pressure, heart rate, or inotropic state of the heart, avoiding undesirable side effects. Efficacy of ranolazine has been evaluated in several trials, using clinical and instrumental endpoints (MARISA and CARISA) or, more recently, using endpoints such as mortality and reinfarction (ERICA and MERLIN-TIMI 36). Ivabradine acts through the inhibition of late Na current (also known as If), which controls the spontaneous diastolic depolarization of sinus node cells. The partial inhibition of these channels reduces the frequency of sinus node action potential initiation, resulting in decreased heart rate without effects on contractility, atrio-ventricular conduction, or repolarization. The BEAUTIFUL trial has tested whether the effect of ivabradine in lowering heart rate is able to reduce mortality and cardiovascular morbidity in patients with coronary artery disease and left ventricular systolic dysfunction. The most significant results were obtained in the subgroup of patients with life-limiting exertional angina. In this group, ivabradine significantly reduced the primary endpoint, a composite of cardiovascular death, hospitalization for fatal and nonfatal acute myocardial infarction (AMI) or heart failure, by 24%, and hospitalizations for AMI by 42%. In the subgroup of patients with baseline heart rate >70 bpm, hospitalizations for AMI and revascularization were reduced by 73% and 59%, respectively.

Biological drugs: classic adverse effects and new clinical evidences.

The last 20 years was characterized by great improvements in the efficacy and tolerability of anticancer therapies. Most of these changes are related to the introduction of targeted drugs, which presents a better activity on the biology of cancer and less toxicity. Nevertheless, the initial enthusiasm was cooled by the emerging evidences of cardiac side effects. The aim of this review is to describe the actual knowledge about the possible cardiotoxicity of targeted drugs. The most important need is the detection of early cardiotoxicity and the evidence of subtle myocardial dysfunction that allows to begin a protective therapy. In our review we analyzed the non invasive imaging techniques to early predict myocardial dysfunction. Echocardiography seems to be the ideal method for her availability, safety and clinical usefulness, in particular the new echocardiographic techniques like speckle tracking.