Longitudinal Characterization of Immune Response in a Cohort of Children Hospitalized with Multisystem Inflammatory Syndrome.

BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of SARS-CoV-2 infection caused by hyperactivation of the immune system. METHODS: this is a retrospective analysis of clinical data, biochemical parameters, and immune cell subsets in 40 MIS-C patients from hospital admission to outpatient long-term follow-up. RESULTS: MIS-C patients had elevated inflammatory markers, associated with T- and NK-cell lymphopenia, a profound depletion of dendritic cells, and altered monocyte phenotype at disease onset, while the subacute phase of the disease was characterized by a significant increase in T- and B-cell counts and a rapid decline in activated T cells and terminally differentiated B cells. Most of the immunological parameters returned to values close to the normal range during the remission phase (20-60 days after hospital admission). Nevertheless, we observed a significantly reduced ratio between recently generated and more differentiated CD8+ T- and B-cell subsets, which partially settled at longer-term follow-up determinations. CONCLUSIONS: The characterization of lymphocyte distribution in different phases of MIS-C may help to understand the course of diseases that are associated with dysregulated immune responses and to calibrate prompt and targeted treatments.

Cardiac MRI in midterm follow-up of MISC: a multicenter study.

In this multicenter retrospective study we aimed to evaluate the outcome of cardiac involvement in children affected by multisystem inflammatory syndrome (MIS-C), assessed through cardiac magnetic resonance (CMR). Children referring to three Italian tertiary pediatric centers between February 2020 and November 2021 with a diagnosis of MIS-C, who underwent CMR during a follow-up visit, were enrolled. Demographic, clinical, laboratory, treatment, and outcome data were collected. Twenty MIS-C patients (aged 9-17, median 12 years) were included in the study. Heart involvement at onset was testified by hypotension/shock (55%), laboratory evidence of myocardial involvement (100%), reduced LV ejection fraction (EF) on echocardiography (83%), and/or need for inotrope agents (40%); they all presented good clinical, laboratory, and echocardiographic response to treatment. CMR was performed after a median interval of 3 months from discharge. Pericardial effusion and myocardial edema were found in 5% of patients. Mild residual left ventricular (LV) dysfunction was found in 20% of patients, all showing normal echocardiographic LVEF at discharge. Minimal myocardial scars were found in 25% by late gadolinium enhancement (LGE). One patient was evaluated at two consecutive time points, showing partial resolution of a myocardial scar after 7 months from its first finding. CONCLUSION: Despite the severity of heart involvement in the acute MIS-C phase, the mid-term cardiac outcome is good. Direct cardiac tissue viral invasion may be involved in MIS-C pathogenesis. WHAT IS KNOWN: • Heart involvement is common in MIS-C, but conflicting findings have been shown regarding cardiac outcome when assessed through cardiac MRI. WHAT IS NEW: • Midterm cardiac MRI shows mild abnormalities in patients recovered from MIS-C with any grade of severity of cardiac involvement at presentation.

Risk of Cardiovascular Hospitalizations from Exposure to Coarse Particulate Matter (PM10) Below the European Union Safety Threshold.

The association between exposure to air pollution and acute cardiovascular (CV) events is well documented; however, limited data are available evaluating the public health safety of various "doses" of particular matter (PM) below currently accepted safety thresholds. We explored the cross-sectional association between PM with aerodynamic diameter <10 µm (PM10) and daily CV hospitalizations in Brescia, Italy, using Poisson regression models adjusted for age, gender, and meteorologic indices. Average daily exposure to PM10 obtained from arithmetic means of air pollution data were captured by 4 selected monitoring stations. PM10 data were expressed as daily means (lag 0-day) or 3-day moving averages (lag 3-day) and categorized according to the European Union daily limit value of 50 µg/m(3). From September 2004 to September 2007, data from 6,000 acute CV admissions to a tertiary referral center were collected. An increase of 1 µg/m(3) PM10 at lag 0-day was independently associated with higher rates of acute hospitalizations for composite CV-related events (relative risk [RR] 1.004, 95% confidence interval [CI] 1.002 to 1.006), acute heart failure (RR 1.004, 95% CI 1.001 to 1.008), acute coronary syndromes (RR 1.002, 95% CI 0.999 to 1.005), malignant ventricular arrhythmias (RR 1.004, 95% CI 0.999 to 1.010), and atrial fibrillation (RR 1.008, 95% CI 1.003 to 1.012). Similar results were obtained using PM10 lag 3-day data. The excess PM10 CV hospitalization risk (by lag 0-day and lag 3-day) did not vary significantly above and below the 50 µg/m(3) safety threshold or by age and gender. In conclusion, increased levels of PM10, even below the current limits set by the European Union, were associated with excess risk for admissions for acute CV events.

Prognostic value of serial measurements of blood urea nitrogen in ambulatory patients with chronic heart failure.

BACKGROUND: Elevated blood urea nitrogen (BUN) in chronic heart failure (CHF) patients may represent increased neurohormonal activation. The purpose of this work was to evaluate the prognostic value of BUN and its variation in ambulatory patients with stable CHF. METHODS: In a retrospective analysis we included 241 outpatients with stable CHF (NYHA class I-III). We evaluated patients at baseline and at 6 months, then they have been followed for one year. The population was divided in four groups according to the median value of BUN at baseline and BUN change (percentage) at 6 months (group 1 BUN <25.2 mg/dL and variation <3.4%, group 2 BUN <25.2 mg/dL and ≥3.4 %, group 3 BUN ≥25.2 mg/dL and <3.4%, group 4 BUN ≥25.2 mg/dL and ≥3.4%). During a median follow-up of one year, 3 (1.3%) patients died and 49 (20.3%) were hospitalized due to worsening heart failure HF. RESULTS: The Kaplan-Meier curve showed that group 3 and group 4 had worse prognosis compared with group 1 and 2 and that a greater change in BUN, was associated with a further worsening of the prognosis (group 4). Multivariable models confirmed that cardiovascular mortality and HF hospitalizations were more frequent in patients who had an increase of BUN (HR 1.011 [IC 95% 1.002-1.021]; P=0.015). CONCLUSIONS: In ambulatory patients with stable chronic heart failure the increment of BUN is associated with increased cardiovascular mortality and heart failure hospitalizations at one-year.

[Chronic heart failure therapy: where we are and where we are going to]. / Terapia farmacologica dello scompenso cardiaco cronico: realtà e prospettive.

Despite significant advances in pharmacological and non-pharmacological therapy, epidemiological data from European and US hospitals show that the prevalence of heart failure (HF) hospitalization, especially for patients >65 years, continues to rise. Hospitalization for worsening HF is one of the most important predictors of short- and long-term outcomes in patients with chronic HF. There is therefore a clear need for new therapies that can work synergistically with standard medications to reverse the progression of the disease and improve myocardial efficiency. In the last years, researches in chronic HF focused on drugs that can exert a greater attenuation of neurohormonal activation and that can improve cardiac energy and substrate utilization.

Six-year prognosis of diabetic patients with coronary artery disease.

BACKGROUND: Diabetes is associated with increased cardiovascular mortality. The aim of our study was to determine the prognostic factors for mortality in patients with type 2 diabetes (T2DM) and coronary artery disease (CAD) who underwent coronary angiography and percutaneous coronary intervention. MATERIALS AND METHODS: Four hundred and forty-five consecutive T2DM patients with significant CAD (≥ 75% stenosis) were included in our analysis. All patients underwent standard clinical examination, laboratory tests and transthoracic echocardiography with measurement of the left ventricular ejection fraction. Severity of CAD at the coronary angiography was evaluated using the Gensini score. Clinical follow-up was completed at 1, 3 and 6 years. RESULTS: During a mean follow-up of 73·3 ± 22·1 months, 109 patients died (24·5%). Significant determinants of an increased risk of death at multivariable analysis were age (p < 0·001), serum creatinine (p = 0·001), peripheral vascular disease (p = 0·002), serum glucose (p = 0·004), serum fibrinogen (p = 0·011) and history of heart failure (HF, p = 0·011). When all the variables were entered as categorical variables, with continuous variables split at their median value, only history of HF, estimated glomerular filtration rate, serum glucose, serum fibrinogen (all p < 0·0001) and beta-blocker therapy at discharge (p = 0·027) were selected. CONCLUSIONS: Our study shows a relatively good prognosis of patients with T2DM. Comorbidities, namely HF and renal impairment, are main determinants of survival.

Effects of supplementation with polyunsaturated fatty acids in patients with heart failure.

Despite the clinical and prognostic improvement obtained with the current medical treatment, heart failure (HF) continues to have high morbidity and mortality and its prevalence is increasing in most regions of the world. Thus, there is a need for novel adjunctive therapies that act independently of current neurohormonally and haemodynamically oriented drugs. Nutritional approaches are particularly attractive because they could work additively with established therapies without negative hemodynamic effects. There is growing evidence that omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation positively impacts established pathophysiological mechanisms in HF and thus has a potential role for preventing and treating HF. The results of the GISSI-HF trial have indicated that, in patients with chronic HF on evidence-based therapy, long term treatment with PUFAs reduced mortality and hospitalizations for cardiovascular reasons, irrespective of etiology and left ventricular (LV) ejection fraction (EF). The purpose of this review is to summarize the evidence emerged from studies conducted so far on the effect of n-3 PUFAs in HF.

n-3 polyunsaturated fatty acids in the prevention of atrial fibrillation recurrences after electrical cardioversion: a prospective, randomized study.

BACKGROUND: n-3 polyunsaturated fatty acids (n-3 PUFAs) exert antiarrhythmic effects and reduce sudden cardiac death. However, their role in the prevention of atrial fibrillation remains controversial. We aimed to determine the effect of n-3 PUFAs in addition to amiodarone and a renin-angiotensin-aldosterone system inhibitor on the maintenance of sinus rhythm after direct current cardioversion in patients with persistent atrial fibrillation. METHODS AND RESULTS: We conducted a randomized, double-blind, placebo-controlled, parallel-arm trial in patients with persistent atrial fibrillation, with at least 1 relapse after cardioversion, and treated with amiodarone and a renin-angiotensin-aldosterone system inhibitor. Participants were assigned to placebo or n-3 PUFAs 2 g/d and then underwent direct current cardioversion 4 weeks later. The primary end point was the probability of maintenance of sinus rhythm at 1 year after cardioversion. Of 254 screened patients, 199 were found to be eligible and randomized. At the 1-year follow up, the probability of maintenance of sinus rhythm was significantly higher in the n-3 PUFAs-treated patients compared with the placebo group (hazard ratio, 0.62 [95% confidence interval, 0.52 to 0.72] and 0.36 [95% confidence interval, 0.26 to 0.46], respectively; P=0.0001). CONCLUSIONS: In patients with persistent atrial fibrillation on amiodarone and a renin-angiotensin-aldosterone system inhibitor, the addition of n-3 PUFAs 2 g/d improves the probability of the maintenance of sinus rhythm after direct current cardioversion. Our data suggest that n-3 PUFAs may exert beneficial effects in the prevention of atrial fibrillation recurrence. Further studies are needed to confirm and expand our findings. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01198275.

Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy.

OBJECTIVES: This study was designed to test the effects of n-3 polyunsaturated fatty acids (PUFAs) on left ventricular (LV) systolic function in chronic heart failure (HF) due to nonischemic dilated cardiomyopathy (NICM). BACKGROUND: One hundred thirty-three patients with NICM and minimal symptoms on standard therapy were randomized to 2 g of n-3 PUFAs or placebo. LV function and functional capacity were assessed prospectively by echocardiography and cardiopulmonary exercise testing at baseline and at 12 months after randomization. METHODS: Patients with chronic HF due to NICM and minimal symptoms while receiving evidence-based therapy were enrolled. LV function and functional capacity were assessed prospectively by echocardiography, cardiopulmonary exercise test, and New York Heart Association functional class at baseline and at 12 months after randomization to either 2 g of n-3 PUFAs or placebo. RESULTS: At 12 months after randomization, the n-3 PUFAs group and the placebo group differed significantly (p <0.001) in regard to: 1) LV ejection fraction (increased by 10.4% and decreased by 5.0%, respectively); 2) peak VO(2) (increased by 6.2% and decreased by 4.5%, respectively); 3) exercise duration (increased by 7.5% and decreased by 4.8%, respectively); and 4) mean New York Heart Association functional class (decreased from 1.88 ± 0.33 to 1.61 ± 0.49 and increased from 1.83 ± 0.38 to 2.14 ± 0.65, respectively). The hospitalization rates for HF were 6% in the n-3 PUFAs and 30% in the placebo group (p = 0.0002). CONCLUSIONS: In patients with NICM and minimal symptoms in response to evidence-based medical therapy, n-3 PUFAs treatment increases LV systolic function and functional capacity and may reduce hospitalizations for HF. Given these promising results, larger studies are in order to confirm our findings.

n-3 PUFAs and cardiovascular disease prevention.

Today, there are several observational and experimental studies, especially clinical randomized trials, that have proven the beneficial effects of n-3 polyunsaturated fatty acids (PUFAs). The most compelling evidence for the cardiovascular benefits of n-3 PUFAs comes from studies of primary prevention in patients following myocardial infarction, and most recently, in patients with heart failure. In this review, we analyze the evidence from epidemiologic studies and from large randomized controlled trials showing the benefits of n-3 PUFAs, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in primary and secondary cardiovascular prevention. Further studies are needed to determine optimal dosing and the relative ratio of DHA and EPA that provide maximal cardioprotection.

High sensitivity C-reactive protein: a predictor for recurrence of atrial fibrillation after successful cardioversion.

Atrial fibrillation (AF) is often associated, more or less indirectly, with an inflammatory acute or chronic process. So it is probable that the inflammation could contribute to the genesis and the perpetuation of this dysrhythmia. Phlogistic test indexes in patients (pts) with AF will be positive and have prognostic significance in patients treated with electrical cardioversion with restoration of a sinus rhythm. We evaluated 106 pts affected by AF of recent onset without known cardiovascular disease. We measured the plasma concentration of C-reactive protein (CRP) through a high sensibility method, in addition to routine blood samples. We performed an ECG 1 week and a Holter ECG monitoring 1 and 6 months after the electrical cardioversion. The CRP values were high (5.8 +/- 10.7 U/L), with values above the normal range in 60 pts. After electrical cardioversion, we obtained restoration of sinus rhythm in all the patients. One week after cardioversion, 85 pts (80%) were in sinus rhythm, while after 6 months 60 pts (56%) maintained a sinus rhythm. In total 46 (43%) patients had a recurrence of atrial fibrillation within 6 months, and 41 of these 46 patients (89%) had elevated values of CRP (P < 0.001 with respect to the patients who maintained a sinus rhythm). 18/21 patients (86%) with an AF relapse in the first week and 23/25 patients (92%) with AF recurrences at 6 months later had elevated values of CRP. The patients with AF may have elevated values of CRP, and the assessment of this increase may be predictive of early relapses of AF after electrical cardioversion.

The role of n-3 PUFAs in preventing the arrhythmic risk in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: N-3 polyunsaturated fatty acids (n-3 PUFAs) intake is associated with a reduction in sudden cardiac death in patients with ischemic heart disease. Their effects in patients with heart failure caused by idiopathic dilated cardiomyopathy (IDC) are unknown. METHODS: We compared with placebo the effects of n-3 PUFAs administration in 44 patients with IDC and with frequent or repetitive ventricular arrhythmias at Holter monitoring using a randomized, double-blind design. Arrhythmic risk was assessed by microvolt T-wave analysis (MTWA), signal averaged ECG (SAECG), Holter monitoring, power spectral analysis of heart rate (HR) variability, catecholamine and cytokine plasma levels, at baseline and after 6 months. RESULTS: At MTWA, 7/12 patients (58%) initially positive became negative after n-3 PUFAs while one patient became positive after placebo (p = 0.019). N-3 PUFAs administration was also associated to normalization of SAECG (11/15 patients, p < 0.0015), decrease in non-sustained ventricular tachycardia (NSVT) episodes (p = 0.0002) and NSVT HR (p = 0.0003), improvement in HR variability and decrease in catecholamine and cytokine plasma levels. The ratio of plasma n-6 PUFAs to n-3 PUFAs decreased from 12.01 to 3.48 after n-3 PUFAs. CONCLUSIONS: N-3 PUFAs administration is associated with favorable effects on parameters related to arrhythmic risk in patients with idiopathic dilated cardiomyopathy. These results are consistent with antiarrhythmic activity independent from their antiischemic effects.

Endocannabinoids and cardiovascular prevention: real progress?

The prevalence of obesity continues to increase and represents one of the principal causes of cardiovascular morbidity and mortality. After the discovery of a specific receptor of the psychoactive principle of marijuana, the cannabinoid receptors and their endogenous ligands, several studies have demonstrated the role of this system in the control of food intake and energy balance and its overactivity in obesity. Recent studies with the CB1 receptor antagonist rimonabant have demonstrated favorable effects such as a reduction in body weight and waist circumference and an improvement in metabolic factors (cholesterol, triglycerides, glycemia etc). Therefore, the antagonism of the endocannabinoid (EC) system, if recent data can be confirmed, could be a new treatment target for high risk overweight or obese patients. Obesity is a growing problem that has epidemic proportions worldwide and is associated with an increased risk of premature death (1-3). Individuals with a central deposition of fats have elevated cardiovascular morbidity and mortality (including stroke, heart failure and myocardial infarction) and, because of a growing prevalence not only in adults but also in adolescents, it was reclassified in AHA guidelines as a "major modifiable risk factor" for coronary heart disease (4, 5). Although first choice therapy in obesity is based on correcting lifestyle (diet and physical activity) in patients with abdominal obesity and high cardiovascular risk and diabetes, often it is necessary to use drugs which reduce the risks. The EC system represents a new target for weight control and the improvement of lipid and glycemic metabolism (6, 7).