Outcome and Morpho-Functional Changes on Cardiac Magnetic Resonance in Patient with Acute Myocarditis Following Mrna Covid 19 Vaccination

Background: MessengerRNA (mRNA) COVID-19 vaccination has been associated with a higher-than-expected occurrence of acute myocarditis. Scarce information is available on mid-term prognosis and changes in cardiac function, volumes, and tissue characterization on cardiac magnetic resonance (CMR). Method(s): Retrospective, multicenter study including patients with a definite diagnosis of acute myocarditis within 30 days from mRNA COVID-19 vaccination, with a confirmed myocarditis diagnosis based on endomyocardial biopsy (EMB) or autopsy or by the coexistence of positive biomarkers (troponin >99th upper reference limit or elevated creatine kinase myocardial band [CK-MB]) and cardiac MRI findings consistent with AM according to the 2018 updated Lake Louise Criteria. Result(s): 77 patients (median age 25 years [IQR 20-35], 15% female) were included and followed-up for 147 days [IQR 74-215]. Follow-up CMR was available in n=49 patients and showed no changes in biventricular ejection fraction (EF) as compared to CMR at diagnosis (left ventricular EF: 59%[55-65]vs. 60%[57-64], p=0.507, right ventricular EF: 56%[52-62]vs. 57%[52-61], p=0.563, respectively). Late gadolinium enhancement was present in all patients at diagnosis and persisted in only n=39 (79.6%) at follow-up (p=0.001), generally sparing the anterior wall and the septum. N=10 (20.4%) had a persistent edema based on T2-weighted short tau inversion recovery (STIR) sequences, with predominant involvement of inferior or inferiorlateral walls. The proportion of patients with increased T1 and T2 mapping signals significantly decreased at follow-up (n=13 (68%) vs. n=4 (13%),p<0.001, and n=21 (84%) vs. n=3 (10%),p<0.001, respectively), as well as the presence of pericardial effusion (n=16 (33%) vs. n=3 (6%),p=0.004). No differences in morpho-functional CMR parameters based on the type of vaccine administered were found (BNT162b2 Pfizer/BioNTech, n=36, 73.5%, m-RNA-1273 Moderna, n=13, 26.5%). Among patients with available follow-up (N=75, 97.4%), no major adverse cardiovascular events nor myocarditis recurrence or death were reported. Conclusion(s): At mid-term follow-up, patients who experienced an acute myocarditis after a mRNA COVID-19 vaccine had preserved biventricular EF. The rate and localization of residual scar or edema on CMR is in line with classic viral myocarditis with a good prognosis. This new piece of information should further reassure patients who experience acute myocarditis after mRNA COVID-19 vaccination.

Impact of Female Gender on Acute and Mid-Term Mortality in Patients with St-Segment Elevation Myocardial Infarction during the Pandemic Era

Background: There is still much controversy concerning the impact of gender on mortality during ST-segment elevation myocardial infarction (STEMI). The COVID-19 pandemic deeply affected the clinical history of these patients, both in terms of presentation time and management. The aim of our study was to evaluate the impact of female gender on acute and mid-term mortality in STEMI patients hospitalized during the pandemic period. Material(s) and Method(s): Our study focuses on STEMI patients hospitalized during the darkest period of the pandemic.We retrospectively analyzed consecutive STEMI patients hospitalized from 15 March 2020 to 15 March 2021 in our Hub centre in Milan, Lombardy. All clinical, demographic, and procedural characteristics were collected in a dedicated database. Patient follow-up was carried out through clinical visits, telephone calls and remote monitoring through the "Lombardia Regional Registry". Result(s): From a total of 283 patients, women represented 26.8% of the population, with a mean age of 72 - 11.2 years vs. 64.7 - 12.6 years in men. Anterior STEMI was the most represented with a mildly reduced ejection fraction (EF 48.3 - 11.8%) similar between genders. Coronary angiography showed more extensive disease in man, while women presented with a higher Killip class at admission and a more pronounced anemic status. In-hospital and 1-year mortality of the whole cohort were 11.4% and 7.5%, respectively, with no significant differences between genders (14.5% women vs. 10.6% men, p = ns;9.2% women vs. 7% man, p = ns). EF resulted in being the only independent predictor of mortality in the short-term and at 1-year follow up in both genders. In the acute phase, the only other independent predictor of mortality was COVID-19 infection, secondary to the higher rate of respiratory omplications, without any difference in terms of major adverse cardiac events. The impact of COVID-19 infection on mortality was completely lost at 1-year follow up. Conclusion(s): Our study has shown that female gender in STEMI patients does not represent an independent predictor of mortality both in the short- and in the midterm follow up. Concomitant COVID-19 infection significantly influenced in-hospital mortality due to the higher rate of respiratory complications in both genders. The impact of COVID-19 on mortality was completely lost at follow-up, where age and a reduced EF remained the only independent predictors, regardless of gender.

Systematic review and meta-analysis on coronary calcifications in COVID-19.

Chest CT is valuable to detect alternative diagnoses/complications of COVID-19, while its role for prognostication requires further investigation. Non-pulmonary radiological findings such as cardiovascular calcifications could increase the predictivity of clinical outcomes of COVID-19 patients beyond pulmonary involvement. Several observational studies have reported mixed results on the role of coronary calcifications in COVID-19 patients as a predictor of hospitalization, ventilatory support, and mortality. The purpose of the study is to systematically review the available evidence on the predictive role of cardiovascular calcifications in SARS-CoV2 disease. The meta-analysis confirms the prognostic significance of coronary calcifications on hospital mortality, and coronary calcifications (CAC ≠ 0) were associated with an OR for mortality of 2.19 (95% CI 1.36-3.52). CAC was neutral on respiratory outcomes, but it was associated with an increased trend of cardiovascular events. Coronary calcium appears as a promising biomarker imaging even in short-term outcomes (MACEs, hospital mortality) in a non-cardiovascular disease such as Sars-CoV2 infection. Further large studies are needed to confirm promising results of this imaging biomarker in non-cardiovascular disease.

Platypnea-orthodeoxia syndrome years after acute pulmonary embolism: Two consecutive cases

Platypnea-Orthodeoxia syndrome (POS) is a rare condition in which dyspnoea and arterial oxygen desaturation are present in the upright position, while in the supine position, they are alleviated. It is observed in the presence of an anatomical (intra-or extracardiac) communication between the right and left heart causing a right-to-left shunt. POS is most frequently caused by a patent foramen ovale (PFO) and usually, the clinical assessment and a transthoracic echocardiograms with bubble study are enough to reach the diagnosis. The only possible treatment of POS is the percutaneous closure of the defect. We describe two cases of POS due to a PFO which manifested itself years after an episode of acute pulmonary embolism (PE), a finding never reported to date in the literature. Few cases describe the relationship between PE and POS, but these conditions may be more closely related than we currently think.

Machine learning for prediction of in-hospital mortality in COVID-19 patients: Results from an Italian multicentre study

Aims: Several risk factors have been identified to predict worse outcomes in patients affected by SARS-CoV-2 infection. Prediction models are needed to optimize clinical management and to early stratify patients at a higher mortality risk. Machine learning (ML) algorithms represent a novel approach to identify a prediction model with a good discriminatory capacity to be easily used in clinical practice. Methods and results: The Cardio-COVID is a multicentre observational study that involved a cohort of consecutive adult Caucasian patients with laboratory-confirmed COVID-19 [by real time reverse transcriptase-polymerase chain reaction (RT-PCR)] who were hospitalized in 13 Italian cardiology units from 1 March to 9 April 2020. Patients were followed-up after the COVID-19 diagnosis and all causes in-hospital mortality or discharge were ascertained until 23 April 2020. Variables with more than 20% of missing values were excluded. The Lasso procedure was used with a λ=0.07 for reducing the covariates number. Mortality was estimated by means of a Random Forest (RF). The dataset was randomly divided in two subsamples with the same percentage of death/alive people of the entire sample: training set contained 80% of the data and test set the remaining 20%. The training set was used in the calibration procedure where a RF models in-hospital mortality with the covariates selected by Lasso. Its accuracy was measured by means of the ROC curve, obtaining AUC, sensitivity, specificity, and related 95% confidence interval (CI) computed with 10 000 stratified bootstrap replicates. From the RF the relative Variable Importance Measure (relVIM) was extracted to understand which of the selected variables had the greatest impact on outcome, providing a ranking from the most (relVIM=100) to the less important variable. The model obtained was compared with the Gradient Boosting Machine (GBM) and with the logistic regression, where the predictions were cross validated. Finally, to understand if each model has the same performance in sample (training) and out of sample (test), the two AUCs were compared by means of the DeLong's test. Among 701 patients enrolled (mean age 67.2±13.2 years, 69.5% males), 165 (23.5%) died during a median hospitalization of 15 (IQR, 9-24) days. Variables selected by the Lasso were: age, Oxygen saturation, PaO2/FiO2, Creatinine Clearance and elevated Troponin. Compared with those who survived, deceased patients were older, had a lower blood oxygenation, a lower creatinine clearance levels and higher prevalence of elevated Troponin (all P<0.001). Training set included 561 patients and test set 140 patients. The best performance out of sample was provided by the RF with an AUC of 0.78 (95% CI: 0.68-0.88) and a sensitivity of 0.88 (95% CI: 0.58-1.00). Moreover, RF is the unique methodology that provided similar performance in sample and out of sample (DeLong test P=0.78). On the contrary, prediction model was less accurate by using GBM and logistic regression. The relVIM ranked the variables from the most to the less important in predicting the outcome as follows: clearance creatinine, PaO2/FiO2, age, oxygen saturation, and elevated Troponin. Conclusions: In a large COVID-19 population, we showed that a customizable MLbased score derived from clinical variables, is feasible and effective for the prediction of in-hospital mortality.

Position paper of the Italian Society of Cardiology SIC): Technical, instrumental and reporting requirements for resting electrocardiography, ambulatory electrocardiographic monitoring according to Holter, ambulatory blood pressure monitoring in telemedicine

The current COVID-19 pandemic has renewed interest in providing healthcare services based on the implementation of innovative technologies. Such strategy capillarizes the therapeutic opportunities for larger urban areas, mostly when people are living under extraordinarily difficult circumstances. Improving care delivery in cardiovascular diseases appears particularly feasible when telemedicine is pursued, especially with regard to baseline standard 12-lead electrocardiography, ambulatory electrocardiographic monitoring, and 24-hour ambulatory blood pressure monitoring. Nowadays, these first-line cardiovascular examinations are also available in health centers and pharmacies, and in recent months, there has been an increasing demand of such local services in the absence of specific rules and regulations regarding technical requirements and standards of interpretation that ensure a high quality clinical consultation. The purpose of this position paper is to provide critical requirements for the type/model of devices to be used, training dedicated to healthcare personnel, ensuring security of sensitive data, highlighting type of platforms to be used, as well as for maintaining high reporting quality and standards.

Consequences on the right ventricular to pulmonary circulation coupling of COVID-19 infection

Background: Right Ventricular (RV) dysfunction and pulmonary hypertension (PH) are two very likely acute and long term targets of COVID-19 pneumonia, with a potential prognostic implications. Purpose: To determine the COVID-19 pneumonia effects on the right ventricular to pulmonary circulation coupling through bedside echocardiography and extend its implications to prognostic assessment. Methods: Single-centre study including consecutive subjects hospitalized for COVID-19 pneumonia who underwent a clinical indicated echocardiogram between March 2020 and December 2020. Extensive analysis of cardiac function was performed offline by an operator blinded to clinical data, laboratory findings and CT scans. Results: 133 patients were enrolled (mean age 69±12 years, 57% men), 38% of whom already had cardiac disease in their medical history. Inhospital mortality was 26% (35 pts), during a mean hospital stay of 26±16 days. Non survivors had higher pulmonary artery systolic pressure (PASP) and worse RV function, assessed with both standard parameters (i.e. TAPSE) and with the novel speckle tracking analysis by RV-Global Longitudinal Strain (RV-GLS) and RV-Free Wall Longitudinal Strain (RV-FWLS). The combination of these two variables in TAPSE/PASP ratio allows assessment of RV to pulmonary circulation (Pc) coupling and was strongly associated with in-hospital death (HR 0.73, 95% CI 0.59-0.89, p=0.003) and patients with TAPSE/PASP<0.57 mm/mmHg had a more than 4-fold increased risk of in-hospital death (HR 4.8, 95% CI 1.7-13.1, p=0.003). In patients where speckle tracking analysis was feasible, we examined RVGLS/ PASP and RV-FWLS/PASP and found that it was associated with inhospital mortality. The best cut-offs for predicting in-hospital mortality was 0.51 for RV-GLS/PASP (94% sensitivity and 59% specificity) and 0.49 for RV-free wall LS (87% sensitivity and 70% specificity). At the multivariable analysis RV to Pc remained associated with in-hospital death after adjustments for age, PaO2/FiO2, LVEF, and severity of lung involvement at the CT. Conclusions: Either PH and RV dysfunction predict in-hospital mortality in patients with COVID-19 pneumonia. The assessment of RV to Pc coupling, however, better describes the adaptive RV response to increased PASP and gives additional prognostic information in a population with a relevant prevalence of comorbidities. (Figure Presented).

Different COVID19 pandemic phases & STEMI: experience from an Italian hub centre

Introduction and methods: During Coronavirus disease 2019 (COVID- 19) pandemic a reduction in ST-elevation acute myocardial infarction with an increase in in-hospital mortality has been observed. In our region the pandemic temporal trend was sinusoidal with peaks and valleys. A first outbreak (phase-peak 1 P-P1) was in March 2020 (248.12 cases for 100,000 inhabitants), a reduction (phase-valley 1 P-V1) in May 2020 (16.68 cases for 100,000 inhabitants) and a second outbreak (phase-peak 2 P-P2) in November 2020 (540.17 cases for 100,000 inhabitants;data from Italian Health Ministry). Our hospital was reorganized as one of the 13 Macro- Hubs identified in Lombardy for the treatment of STEMI. Here we describe our experience in the treatment of STEMI patients in the three different phases of COVID-19 pandemic. Results: In the three different phases the groups were superimposable for mean characteristics, but they differ for COVID-19 infection incidence (table). At multivariate analysis for the entire population COVID-19 infection (OR 45.8 [95% CI] 1.39-1511.79;p=0.03) was the only independent predictor of in-hospital mortality. Focusing on COVID-19 patients (figure) they experienced a 5-time increased incidence of in-hospital mortality (COVID- 19pos vs COVID-19neg, 50% vs 11.1%;p=0.02). Moreover, the compresence of COVID-19 infection induced an 8 times increased risk of death (OR 8;[95% CI] 1.85-34.60;p=0.005) determined by a higher incidence respiratory complications (COVID-19pos vs COVID-19neg, 33.3% vs 8.9%;p=0.03) with a similar incidence of cardiac death (COVID-19pos vs COVID- 19neg, 16.7% vs 11.17%;p=0.60). Conclusions: In conclusion our data suggest the crucial necessity of an early and precise diagnosis of COVID-19 infection in STEMI to establish a correct management of this very high risk patients. STEMI mortality in COVID+ vs COVID-.

Influence of different covid-19 pandemic phases on stemi: Experience from an Italian hub centre

Introduction. During the coronavirus disease 2019 (COVID-19) pandemic a reduction in ST-elevation acute myocardial infarction with an increase in in-hospital mortality has been observed. In our region the pandemic temporal trend was sinusoidal with peaks and valleys. A first outbreak was in March 2020 (248.12 cases for 100000 inhabitants), a reduction in May 2020 (16.68 cases for 100000 inhabitants) and a second outbreak in November 2020 (540.17 cases for 100000 inhabitants;data from Italian Health Ministry). Methods. Our hospital was reorganized as one of the 13 Macro-Hubs identified in Lombardy and we retrospectively analysed consecutive STEMI patients hospitalized in the three different phases of COVID-19 pandemic. Results. Despite no presence of COVID patients in the second phase we did not registered any difference in the number of STEMI hospitalized in the three phases (38 vs 34 vs 27;incidence STEMI/die: 1.19 vs 1.06 vs 0.90;p=ns). At multivariate analysis for the entire population COVID-19 infection was the strongest independent predictor of in-hospital mortality (OR 12.6 [95% CI] 2.18-72.77;p = 0.005). Focusing on COVID-19 patients they experienced a 5-time increased incidence of in-hospital mortality (COVID-19pos vs COVID-19ne9, 47.1% vs 8.6%;p <0.0001) mainly driven by a higher incidence of respiratory complications (COVID-19pos vs COVID-19neg, 41.2% vs 6.2%;p<0.0001 with a similar incidence of cardiac death (COVID-IQ5 vs COVID-19n 11.8% vs 6.2%;p=ns) (Fig. 1). Among STEMI admitted during different phases of pandemic, this study found an increased mortality in patients affected by COVID-19;the co-presence of COVID-19 infection leads to an increase of mortality mostly related to respiratory complications. Interestingly the different incidence in the general population of COVID-19 did not influenced the incidence of STEMI. Conclusion. In conclusion our data suggest the crucial need for an early and precise diagnosis of COVID-19 infection in STEMI to establish a correct management of this very high-risk patients.

Prognostic utility of quantitative offline 2D-echocardiography in hospitalized patients with COVID-19

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared as a pandemic by the World Health Organization (WHO) on 11 March 2020. Clinical presentation ranges from asymptomatic to acute respiratory distress syndrome (ARDS) that can lead to death. Patients with concomitant cardiac diseases have an extremely poor prognosis, and SARS-CoV-2 may cause direct acute and chronic damage to the cardiovascular system. Echocardiography may provide useful information, especially in critical care patients, because it can be performed quickly at the bedside. However, the recommendations relating to the use of echocardiography in the COVID-19 pandemic must be considered only as expert suggestions due to the lack of evidence-based scientific outcome data. To date, there is no means to predict the impact of the virus on patient outcome probably because the pathophysiology of COVID-19 remains unexplained. Purpose: To assess the prognostic utility of quantitative 2D-echocardiography, including strain, in patients with COVID-19 disease. Methods: COVID-19 patients admitted to the San Paolo University Hospital of Milan, that underwent a clinically indicated echocardiographic exam were included in the study. To limit contamination all measurements were performed offline. Quantitative measurements were obtained by an operator blinded to the clinical data. Results: Among the 49 patients, non-survivors (33%) had worse respiratory parameters, index of multiorgan failure and worse markers of lung involvement. Right Ventricular (RV) dysfunction (as assessed by conventional and 2-dimensional speckle tracking, fig. 1) was a common finding and a powerful independent predictor of mortality. At the ROC curve analyses, RV free-wall longitudinal strain (LS) showed an AUC 0.77 ± 0.08 in predicting death, p = 0.008, and global RV LS (RV-GLS) showed an AUC 0.79 ± 0.04, p = 0.004. This association remained significant after correction for age (OR= 1.16, 95%CI 1.01-1.34, p = 0.029 for RV free-wall LS and OR = 1.20, 95%CI 1.01-1.42, p = 0.033 for RV-GLS), for oxygen partial pressure at arterial gas analysis/fraction of inspired oxygen (OR= 1.28, 95%CI 1.04-1.57, p = 0.021 for RV free wall-LS and OR = 1.30, 95%CI 1.04-1.62, p = 0.020 for RV-GLS) and for the severity of pulmonary involvement measured by a computed tomography lung score (OR = 1.27, 95%CI 1.02-1.19, p = 0.034 for RV free-wall LS, and OR = 1.30, 95%CI 1.04-1.63, p = 0.022 for RV-GLS). Conclusions: In patients hospitalized with COVID-19, offline quantitative 2D-echocardiographic assessment of cardiac function is feasible. Parameters of RV function are frequently abnormal and have an independent prognostic value over markers of lung involvement. Early identification of RV dysfunction with speckle tracking might be useful not only to guide management acutely (i.e. fluid management, monitoring high-PEEP response in intubated patients) but also to tailor follow-up subsequently.