Clinical Profiles and CMR Findings of Young Adults and Pediatrics with Acute Myocarditis Following mRNA COVID-19 Vaccination: A Case Series.

Messenger RNA (mRNA) coronavirus disease of 2019 (COVID-19) vaccines have been recently associated with acute myocarditis, predominantly in healthy young males. Out of 231,989 vaccines administrated in our region (Marche, Italy), we report a case series of six healthy patients (four males and two females, 16.5 years old (Q1, Q3: 15, 18)) that experienced mRNA-COVID-19-vaccines side effects. All patients were hospitalized due to fever and troponins elevation following the second dose of an mRNA-based COVID-19 vaccine. Cardiovascular magnetic resonance (CMR) was performed 72-96 h after vaccination. All patients were treated with colchicine and ibuprofen. Myocarditis was prevalent in males. It was characterized by myocardial edema and late gadolinium enhancement (LGE) in the lateral wall of the left ventricle (LV). One patient showed sole right ventricular involvement, while the females presented with myopericarditis (myocarditis + pericardial effusion). All patients in our series had preserved LV ejection fraction and remained clinically stable during a relatively short inpatient hospital stay. One case presented with atrial tachycardia. At the follow-up, no significant CMR findings were documented after a three-month medical treatment. According to other recently published case series, our report suggests a possible association between acute myocarditis and myopericarditis with mRNA COVID-19 vaccination in healthy young adults and pediatric patients. Not only males are involved, while some arrhythmic manifestations are possible, such as atrial tachycardia. Conversely, we here highlight the benign nature of such complications and the absence of CMR findings after a three-month medical treatment with colchicine and ibuprofen.

Echocardiographic changes and quality of life after surgical unroofing of myocardial bridges.

OBJECTIVE: To examine the echocardiographic changes and quality of life (QoL) after surgical unroofing of myocardial bridges (MBs) involving the left anterior descending (LAD) coronary artery compared with optimal medical therapy (OMT). METHODS: Twenty-two patients (median age, 24 years; interquartile range, 16-40 years) with MBs of the LAD artery and exertional angina from 2018 to 2019 were retrospectively analyzed. Twelve patients underwent OMT and 10 underwent surgery. Both groups underwent clinical and echocardiographic examinations during hospitalization and follow-up (mean, 1.0 ± 0.8 years). QoL was assessed with the Seattle Angina Questionnaire, short version (SAQ-7). RESULTS: Surgery resulted in significantly better QoL than OMT, with a significant improvement in left ventricular global longitudinal strain (GLS) [mean (standard error): 19% (0.19) to 22% (0.34) and 19% (0.15) to 20% (0.24), respectively; delta-change (delta-GLS) of 0.15 vs. 0.067]. In the univariate and multivariable analyses, delta-GLS was positively correlated with the SAQ-7 score and MB length (rho = 0.64 and 0.71, respectively), with a significant interaction between MB length and surgical treatment (beta coefficient, 1.95; 95% confidence interval, 0.14-3.77). CONCLUSIONS: MB unroofing surgery provided benefits in terms of QoL and left ventricular GLS improvement compared with 1 year of OMT.

Echocardiographic screening for the anomalous aortic origin of coronary arteries.

AIMS: We sought to determine the diagnostic performance, clinical profiles and outcomes of anomalous aortic origin of coronary arteries (AAOCA) using a standardised echocardiographic approach in young adults and athletes. METHODS: In 2015-2019, we screened 5998 outpatients (age 16 years (Q1-Q3: 11, 36)), referred for routine echocardiography, using four specific echocardiographic windows: parasternal short/long axis and apical 4/5-chambers view. Coronary CT confirmed AAOCA. For the performance analysis, 300 coronary-CT scans were available; two independent and double-blinded physicians retrospectively reviewed echocardiographic images. RESULTS: A total of 47 AAOCA was diagnosed; the overall prevalence was 0.0078%. Over 5 years, we found a significant increment of AAOCA diagnostic rate (P for trend=0.002). Syncope (n=17/47) and palpitations (n=6/47) were prevalent symptoms. All patients suspended sports activity at the diagnosis. Twenty-seven patients underwent surgery, while 20 underwent a conservative medical treatment. All patients are alive at a median follow-up of 3±1.6 years; only surgical repairs restarted their activity. Our method showed better sensitivity than traditional short-axis evaluation: 93% vs 83%, p=0.0030 (AUC 0.96 (95% CI 0.92, 0.99) and AUC 0.89 (95% CI 0.83, 0.95), respectively), with a good interobserver agreement (95%, k=0.83, p<0.001). CONCLUSIONS: The application of a standardised echocardiographic approach for AAOCA detection led to a significantly increased rate of identified anomalies. This approach demonstrated higher sensitivity than the traditional echocardiographic assessment. Implementing this protocol in clinical practice may help improve the AAOCA diagnosis in young adults and athletes. TRIAL REGISTRATION NUMBER: NCT04224090.

Acute rheumatic fever prophylaxis in high-income countries: clinical observations from an Italian multicentre, retrospective study.

OBJECTIVES: The aim of the study is to evaluate the compliance rate to secondary prophylaxis and the presence of rheumatic heart disease (RHD) in a cohort of Italian patients with acute rheumatic fever (ARF). METHODS: This is a multicentre retrospective study. The patients were divided into two groups by the presence or absence at last follow-up of RHD. Clinical features, ARF recurrences and the rate of compliance to secondary prophylaxis were evaluated. RESULTS: Two-hundred and ninety patients were enrolled (137 females; 153 males). Carditis at onset was present in 244 patients (84.7%). At the end of follow-up, 173 patients manifested RHD. Adherence to secondary prophylaxis was low in 26% of patients. The presence of RHD at follow-up was associated with the presence of carditis and its severity at onset (p=0.001), but it was not related to secondary prophylaxis adherence (p=NS). No association between prophylaxis adherence and ARF recurrence was found (p=NS) nor between ARF recurrence and RHD at the end of follow-up (p=NS). CONCLUSIONS: Poor adherence to secondary prophylaxis does not seem to be associated with increased risk of RHD in developed countries. Further studies are needed to confirm our data in a larger population.

Prognostic value of cardiopulmonary exercise testing in Idiopathic Dilated Cardiomyopathy.

BACKGROUND: Although cardiopulmonary exercise testing (CPET) is considered as an important tool in risk stratification of patients with heart failure (HF), prognostic data in the specific setting of Idiopathic Dilated Cardiomyopathy (iDCM) are still undetermined. The aim of the study was to test the prognostic value of CPET in a large cohort of iDCM patients. METHODS AND RESULTS: We analyzed 381 iDCM patients who consecutively performed CPET. The study end-point was a composite of cardiovascular death/urgent heart transplantation (CVD/HTx). In the overall population the average values of peak oxygen consumption (peak VO2/kg) and percent-predicted peak VO2 (peak VO2%) were 17.1±5.1ml/kg/min and 59±15%, respectively. Mean VE/VCO2 slope was 29.8±6.1. During a median follow-up of 47months (interquartile range 23-84), 83 patients experienced CVD/HTx. Peak VO2% (Area Under the Curve [AUC] 0.74; 95% CI 0.71-0.85, p<0.001) and VE/VCO2 slope (AUC 0.78; 95% CI 0.74-0.84, p<0.001) were more accurate in predicting CVD/HTx compared to peak VO2/kg (AUC 0.60; 95% CI 0.54-0.68, p=0.003) (p<0.001 for both comparisons). The most accurate threshold values for outcome prediction in our iDCM cohort were <60% for peak VO2% and >29 for VE/VCO2 slope. At multivariable analysis peak VO2% and VE/VCO2 slope were the strongest predictors of CVD/HTx, either as continuous and categorical variables, whereas peak VO2/kg was not independently related with prognosis. CONCLUSION: In a large population of iDCM patients peak VO2% and VE/VCO2 slope emerged as the strongest prognostic CPET variables. Prospective studies will be necessary to confirm these data.

Up-regulation of the monocyte chemotactic protein-3 in sera from bone marrow transplanted children with torquetenovirus infection.

BACKGROUND: Torquetenovirus (TTV) represents a commensal human virus producing life-long viremia in approximately 80% of healthy individuals of all ages. A potential pathogenic role for TTV has been suggested in immunocompromised patients with hepatitis of unknown etiology sustained by strong proinflammatory cytokines. OBJECTIVES: The aim of this study was to investigate the sera immunological profile linked to TTV infection in bone marrow transplant (BMT) children with liver injury. STUDY DESIGN: TTV infection was assessed in sera from 27 BMT patients with altered hepatic parameters and histological features, by the use of quantitative real-time PCR, along with TTV genogroups and coinfection with HEV. The qualitative and quantitative nature of soluble inflammatory factors was evaluated studying a large set of cytokines using the Bioplex platform. As controls, sera from 22 healthy children negative for serological and molecular hepatitis markers including TTV and HEV, and for autoimmune diseases, were selected. RESULTS AND CONCLUSIONS: TTV was detected in 81.4% of BMT patients with a viral load ranging from 10(5) to 10(9) copies/mL. All samples were HEV-RNA negative. A pattern of cytokines, IFN-γ, TNF-α, FGF-basic (p<0.01) and MCP-3 (p<0.001) was found significantly highly expressed in TTV-positive patients compared to TTV-negative and controls. Of note, MCP-3 chemokine showed the highest sera concentration independently of the amount of TTV load and the status of immune system deregulation (p<0.001). In this pilot study for the first time, a positive association was found between TTV and increased level of MCP-3 suggesting a indirect role of TTV in liver injury.

The resurgence of rheumatic fever in a developed country area: the role of echocardiography.

OBJECTIVES: The annual incidence of ARF ranges from 5 to 51/100, 000 population worldwide in the 5- to 15-year age group. In the past, there was a decline in the incidence of ARF; however, focal outbreaks have been reported. This study evaluated the incidence of ARF in 2007-08 in a region of a developed country compared with the previous decade. METHODS: A retrospective review of all admission records for ARF in Trieste between January 2007 and December 2008 was undertaken. The diagnosis of ARF was established by the Jones criteria according to the 1992 revision. RESULTS: Between January 2007 and December 2008: 13 cases of ARF were recorded, 11 females and 2 males. The estimated incidence was 23 and 27/100, 000 population new cases each year, respectively, in the 5- to 15-year age group. Migratory polyarthritis occurred in 6/13, chorea in 7/13 and clinical carditis in 5/13 cases. Five out of 13 patients had only echocardiographic abnormalities, with no clinical cardiac manifestations. Another two patients did not fulfil diagnostic criteria for ARF, presenting with only three minor criteria, but they revealed silent carditis at echocardiography evaluation. During the follow-up, in one case the carditis receded and in the other it significantly improved. CONCLUSIONS: Our experience underlines that ARF has not yet disappeared in industrialized countries. We observed a high incidence of chorea, always associated with mild carditis. Echocardiographic assessment should be routinely performed in all patients with suspected ARF in order to identify those subclinical cases of valvulitis that would otherwise pass undiagnosed without receiving proper prophylaxis.

Permanent atrial fibrillation affects exercise capacity in chronic heart failure patients.

AIMS: The influence of permanent atrial fibrillation on exercise tolerance and cardio-respiratory function during exercise in heart failure (HF) is unknown. METHODS AND RESULTS: We retrospectively compared the results of 942 cardiopulmonary exercise tests, performed consecutively at seven Italian laboratories, in HF patients with atrial fibrillation (n = 180) and sinus rhythm (n = 762). By multivariable logistic regression analysis, peak VO(2) (OR 0.376, 95% CI 0.240-0.588, P < 0.0001), O(2)pulse (VO(2)/heart rate, HR) (OR 0.236, 95% CI 0.152-0.366, P < 0.0001), VCO(2) (OR 3.97, 95% CI 2.163-7.287, P < 0.0001), and ventilation (OR 1.38, 95% CI 1.045-1.821, P = 0.0231) were independently associated with atrial fibrillation. Anaerobic threshold (AT) was identified in 132 of 180 (73%) atrial fibrillation and in 649 of 762 (85%) sinus rhythm patients (P = 0.0002). By multivariable logistic regression analysis, only peak VO(2) (OR 0.214, 95% CI 0.155-0.296, P < 0.0001) was independently associated with unidentified AT. At AT, atrial fibrillation HF patients had higher HR (P < 0.0001) and higher VO(2) (P < 0.001) compared with sinus rhythm HF patients. Among AT variables, by multivariable logistic regression analysis, only HR was an independent predictor of atrial fibrillation. CONCLUSION: In HF patients with permanent atrial fibrillation, exercise performance is reduced as reflected by reduced peak VO(2). The finding of unidentified AT is associated with a poor performance. In atrial fibrillation patients, VO(2) is higher at AT whereas lower at peak. This last observation raises uncertainties about the use of AT data to define performance and prognosis of HF patients with atrial fibrillation.

Strong and independent prognostic value of peak circulatory power in adults with congenital heart disease.

BACKGROUND: The identification of patients with adult congenital heart disease (ACHD) who are at higher risk of death is challenging. Peak circulatory power (CircP; expressed as peak exercise oxygen uptake multiplied for peak mean arterial blood pressure) is a strong predictor of death in adults with acquired heart disease. We sought to establish the distribution and the prognostic value of peak CircP across a wide spectrum of patients with ACHD. METHODS: Four hundred thirty-two consecutive patients with ACHD of varying diagnosis underwent cardiopulmonary exercise testing at a single laboratory between 1996 and 2005. Patient age was 32 +/- 10 years. RESULTS: A gradual variation in peak CircP was found across the spectrum of congenital heart defects (P < .0001 at analysis of variance). Reduced peak CircP values were associated with the presence of heart failure symptoms (P < .0001), absence of sinus rhythm (P = .010), and use of antiarrhythmic medications (P = .0013). At a follow-up of 4.4 +/- 2.4 years, 23 patients (5.3%) had died. Peak CircP was a strong predictor of mortality when univariate analysis was used and the strongest independent predictor of mortality among exercise parameters. A peak CircP < or = 1476 mm Hg mlO2 min(-1) kg(-2) was associated with a 15.4-fold increase in the 4-year risk of death. CONCLUSIONS: Peak CircP is abnormal across the spectrum of ACHD. Peak CircP appears as the strongest predictor of adverse outcome in ACHD.

Non-invasive evaluation of gas exchange during a shuttle walking test vs. a 6-min walking test to assess exercise tolerance in COPD patients.

Walking tests, such as the "shuttle" incremental walking test (SWT) and the 6-min walking test (6'WT), are commonly utilized in evaluating exercise intolerance in patients with chronic obstructive pulmonary disease (COPD) and the distance covered is the variable usually considered. Because lung gas exchange indexes are not measured, little is known about the physiological response elicited by different walking protocols. We compared exercise adaptation during the 6'WT and SWT in 13 male stable COPD patients [mean (SE) age: 70 (1) years; forced expiratory volume in 1 s (FEV(1)): 1.2 (0.1) l; arterial O(2) tension (PaO(2)): 72 (2) mmHg; arterial CO(2) tension (PaCO(2)): 41 (1) mmHg]. Oxygen uptake (.VO(2)), CO(2) output (.VCO(2)), minute ventilation (.V(E)), and heart rate (HR) were monitored by a portable telemetric system. During the SWT a linear response in lung gas exchange indexes was observed while, during the 6'WT, the response was exponential. During the 6'WT, .VO(2), .VCO(2), .V(E), and HR values at steady-state (SS) were significantly lower compared to SWT peak values. For SWT, distance covered correlated with .VO(2PEAK), (R=0.86, p<0.001), .VCO(2PEAK), (R=0.87, p<0.001) and .V(EPEAK) (R=0.74, p<0.01); moreover, distance and .VO(2PEAK) were significantly correlated with peak .VO(2) values obtained during cycle ergometer incremental exercise (R=0.72, p<0.01 and R=0.92, p<0.0001, respectively). For 6'WT, the distance covered did not correlate with any pertinent physiological index. The two walking protocols reveal substantial differences in pathophysiologic adaptations and provide evidence that SWT is more accurate than the 6'WT in the evaluation of maximal exercise tolerance in COPD patients.