Cardiovascular Damage in COVID-19: What We Know Two Years Later.

PURPOSE OF THE REVIEW: The Coronavirus disease 2019 (COVID-19) pandemic has profoundly influenced cardiological clinical and basic research in the past two years. In the present review, we summarize the current knowledge on myocardial involvement in COVID-19, providing an overview on the incidence, the pathogenetic mechanisms, and the clinical implications of cardiac injury in this setting. RECENT FINDINGS: The possibility of heart involvement in patients with COVID-19 has received great attention since the beginning of the pandemic. After more than two years, several steps have been taken in understanding the mechanisms and the incidence of cardiac injury during COVID-19 infection. Similarly, studies globally have clarified the implications of co-existing heart disease and COVID-19. Severe COVID-19 infection may be complicated by myocardial injury. To date, a direct damage from the virus has not been demonstrated. The presence of myocardial injury should be systematically assessed for a prognostication purpose and for possible therapeutic implications.

Reshaping care in the aftermath of the pandemic. Implications for cardiology health systems.

In the last two years, the COVID-19 pandemic has undeniably changed everyday life and significantly reshaped the healthcare systems. Besides the direct effect on daily care leading to significant excess mortality, several collateral damages have been observed during the pandemic. The impact of the pandemic led to staff shortages, disrupted education, worse healthcare professional well-being, and a lack of proper clinical training and research. In this review we highlight the results of these important changes and how can the healthcare systems can adapt to prevent unprecedented events in case of future catastrophes.

One-Year Risk of Myocarditis After COVID-19 Infection: A Systematic Review and Meta-analysis.

BACKGROUND: Acute myocarditis has been described as a relatively rare cardiovascular complication of COVID-19 infection. However, data regarding the risk of myocarditis during the post-acute phase of COVID-19 are scant. We assess the risk of incident myocarditis in COVID-19 survivors within 1 year from the index infection by a systematic review and meta-analysis of the available data. METHODS: Data were obtained by searching Medline and Scopus for all studies published at any time up to September 1, 2022, and reporting the long-term risk of incident myocarditis in COVID-19 survivors. Myocarditis risk data were pooled using the Mantel-Haenszel random-effects models with hazard ratio (HR) as the effect measure with 95% confidence interval (CI). Heterogeneity among studies was assessed using the Higgins-Thompson I2 statistic. RESULTS: Overall, 20,875,843 patients (mean age 56.1 years, 59.1% male) were included in this analysis. Of them, 1,245,167 experienced (and survived) COVID-19 infection. Over a mean follow-up of 9.5 months, myocarditis occurred to 0.21 (95% CI 0.13-0.42) out of 1000 patients survived to COVID-19 infection compared with 0.09 [95% CI 0.07-0.12) out of 1000 control subjects. Pooled analysis revealed that recovered COVID-19 patients presented an increased risk of incident myocarditis (HR 5.16, 95% CI 3.87-6.89; P < 0.0001; I2 = 7.9%) within 1 year from the index infection. The sensitivity analysis confirmed yielded results. CONCLUSIONS: Our findings suggest that myocarditis represents a relatively rare but important post-acute COVID-19 sequelae.

Machine learning for prediction of in-hospital mortality in coronavirus disease 2019 patients: results from an Italian multicenter study.

BACKGROUND: Several risk factors have been identified to predict worse outcomes in patients affected by SARS-CoV-2 infection. Machine learning algorithms represent a novel approach to identifying a prediction model with a good discriminatory capacity to be easily used in clinical practice. The aim of this study was to obtain a risk score for in-hospital mortality in patients with coronavirus disease infection (COVID-19) based on a limited number of features collected at hospital admission. METHODS AND RESULTS: We studied an Italian cohort of consecutive adult Caucasian patients with laboratory-confirmed COVID-19 who were hospitalized in 13 cardiology units during Spring 2020. The Lasso procedure was used to select the most relevant covariates. The dataset was randomly divided into a training set containing 80% of the data, used for estimating the model, and a test set with the remaining 20%. A Random Forest modeled in-hospital mortality with the selected set of covariates: its accuracy was measured by means of the ROC curve, obtaining AUC, sensitivity, specificity and related 95% confidence interval (CI). This model was then compared with the one obtained by the Gradient Boosting Machine (GBM) and with logistic regression. Finally, to understand if each model has the same performance in the training and test set, the two AUCs were compared using the DeLong's test. Among 701 patients enrolled (mean age 67.2 ±â€Š13.2 years, 69.5% male individuals), 165 (23.5%) died during a median hospitalization of 15 (IQR, 9-24) days. Variables selected by the Lasso procedure 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, lower creatinine clearance levels and higher prevalence of elevated troponin (all P < 0.001). The best performance out of the samples was provided by Random Forest 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, Random Forest was the unique model that provided similar performance in sample and out of sample (DeLong test P = 0.78). CONCLUSION: In a large COVID-19 population, we showed that a customizable machine learning-based score derived from clinical variables is feasible and effective for the prediction of in-hospital mortality.

The impact of COVID-19 on myocardial infarctions, strokes and out-of-hospital cardiopulmonary arrests: an observational retrospective study on time-sensitive disorders in the Friuli Venezia Giulia region (Italy).

The COVID-19 global pandemic has changed considerably the way time-sensitive disorders are treated. Home isolation, people's fear of contracting the virus and hospital reorganisation have led to a significant decrease in contacts between citizens and the healthcare system, with an expected decrease in calls to the Emergency Medical Services (EMS) of the Friuli-Venezia Giulia (FVG) region. However, mortality in clinical emergencies like acute ST-elevation myocardial infarction (STEMI), stroke and out-of-hospital cardiopulmonary arrest (OHCA) remained high. An observational retrospective cross-sectional study was carried out in FVG, taking into account the period between March 1, 2020, and May 31, 2020, the first wave of the COVID-19 pandemic, and comparing it with the same period in 2019. The flow of calls to the EMS was analysed and COVID-19 impact on time-sensitive disorders (STEMIs, ischemic strokes and OHCPAs) was measured in terms of hospitalisation, treatment and mortality. Despite a -8.01% decrease (p value ˂0.001) in emergency response, a 10.89% increase in calls to the EMS was observed. A lower number of advanced cardiopulmonary resuscitations (CPR) (75.8 vs 45.2%, p=0.000021 in April) and ROSC (39.1 vs 11.6%, p=0.0001 in April) was remarked, and survival rate dropped from 8.5 to 5%. There were less strokes (-27.5%, p value=0.002) despite a more severe onset of symptoms at hospitalisation with NHISS˃10 in 38.47% of cases. Acute myocardial infarctions decreased as well (-20%, p value=0.05), but statistical significances were not determined in the variables considered and in mortality. Despite a lower number of emergency responses, the number of calls to the EMS was considerably higher. The number of cardiac arrests treated with advanced CPR (ALS) was lower, but mortality was higher. The number of strokes decreased as well, but at the time of hospitalisation the clinical picture of the patient was more severe, thus affecting the outcome when the patient was discharged. Finally, STEMI patients decreased; however, no critical issues were observed in the variables taken into account, neither in terms of response times nor in terms of treatment times.

Coronavirus disease 2019 vaccination-related pericarditis: a single tertiary-center experience.

AIMS: Vaccination represents a cornerstone of prevention in the COVID-19 pandemic. Rare adverse events including acute pericarditis and myopericarditis have been reported. METHODS: All consecutive patients referred to our referral center for pericardial diseases following COVID-19 vaccination from 1 April 2021 to 15 April 2022 were included. Acute pericarditis and myopericarditis were diagnosed according to ESC guidelines. Patients with SARS-CoV-2 infection were excluded from the study. RESULTS: Twenty-four patients (79% men) aged 39.7 ±â€Š19.8 years were referred to our center with pericarditis after receiving COVID-19 vaccination. Thirteen (54%) patients were diagnosed with myopericarditis. The mean time between vaccination and symptoms onset was 7.0 ±â€Š4.9 days, and the most frequent symptom was pericarditic chest pain (83%). Respectively, 50 and 33% of patients presented after the second and the third dose of the vaccine. Almost all patients were treated with both nonsteroidal anti-inflammatory drugs and colchicine. Five patients (21%) experienced a recurrence of pericarditis. No patient died or developed constrictive pericarditis. Mean follow-up was 8.0 ±â€Š3.2 months. CONCLUSION: COVID-19 vaccine-related pericarditis typically manifest with mild clinical signs, in young male individuals, a few days after the second or third vaccine dose and are commonly characterized by a rapid complete recovery.

Long-term effect of SARS-CoV-2 infection on cardiovascular outcomes and all-cause mortality.

Since the very beginning of the coronavirus disease 2019 (COVID-19) pandemic in early 2020, it was evident that patients with cardiovascular disease (CVD) were at an increased risk of developing severe illness, and complications spanning cerebrovascular disorders, dysrhythmias, acute coronary syndrome, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure, thromboembolic disease, stroke, and death. Underlying these was excessive systemic inflammation and coagulopathy due to SARS-COV-2 infection, the effects of which also continued long-term as evidenced by post-COVID-19 cardiovascular complications. The acute and chronic cardiovascular effects of COVID-19 occurred even among those who were not hospitalized and had no previous CVD or those with mild symptoms. This comprehensive review summarizes the current understanding of molecular mechanisms triggered by the SARS-CoV-2 virus on various cells that express the angiotensin-converting enzyme 2, leading to endothelial dysfunction, inflammation, myocarditis, impaired coagulation, myocardial infarction, arrhythmia and a multisystem inflammatory syndrome in children or Kawasaki-like disease.

Leflunomide-induced pulmonary arterial hypertension: Case report and review of literature.

Leflunomide, an isoxazole derivative, is a disease-modifying antirheumatic drug, that has successfully been used for the treatment of rheumatoid arthritis and psoriatic arthritis as a feasible alternative to methotrexate. Among side effects, pulmonary arterial hypertension (PAH) has been described in a few case reports.We present a 55-year-old woman treated with leflunomide for psoriatic spondyloarthritis who consulted our hospital because of progressive exertional dyspnea. Clinical examination found signs of right heart failure and severe pre-capillary pulmonary hypertension (PH) was diagnosed by right heart catheterization. All investigations for pre-capillary PH were negative and a diagnosis of severe PAH was thus established. Due to previous evidence of the association of leflunomide with PAH, the drug was stopped and upfront dual combination therapy with pulmonary vasodilators was initiated. The patient's condition rapidly improved with significant improvement in exercise tolerance and normalization of echocardiographic right ventricular systolic pressure within three months of treatment. Learning objective: Pulmonary arterial hypertension (PAH) is a rare disease and drug-induced causes account for only a small percentage of these patients. In recent years, new drugs have been identified or suspected as potential risk factors for PAH. Among these, leflunomide, a disease-modifying antirheumatic drug, has been associated with PAH only in a few case reports. An accurate drug history is strongly recommended for all patients in which a PAH is newly diagnosed.

[Italian Society of Cardiology (SIC) Expert consensus document: Post-acute cardiovascular sequelae of SARS-CoV-2 infection]. / Expert consensus document della Società Italiana di Cardiologia (SIC): Sequele cardiovascolari post-acute dell'infezione da SARS-CoV-2.

Although the clinical course of COVID-19 in its acute phase is now delineated, less known is its late phase characterized by a heterogeneous series of sequelae affecting various organs and systems, including the cardiovascular system, which continue after the acute episode or arise after their resolution. This syndrome, now referred with the new acronym "PASC" (post-acute sequelae of SARS-CoV-2 infection) has been formally recognized by various scientific societies and international organizations that have proposed various definitions. The World Health Organization defines PASC, distinguishing it from "ongoing symptomatic COVID-19", as a condition that arises few weeks after infection, persists at least 8 weeks, and cannot be explained by alternative diagnoses.There are multiple mechanisms responsible for PASC: inflammation, immune activation, viral persistence, activation of latent viruses, endothelial dysfunction, impaired response to exercise, and profound cardiac deconditioning following viral infection. The key symptoms of PASC are palpitations, effort dyspnea, chest pain, exercise intolerance, and postural orthostatic tachycardia syndrome.For PASC treatment, it may be useful to take salt and fluid loading, to reduce symptoms such as tachycardia, palpitations, and/or orthostatic hypotension, or in some subjects the use of drugs such as beta-blockers, non-dihydropyridine calcium channel blockers, ivabradine, and fludrocortisone.Finally, in PASC a gradual resumption of physical activity is recommended, starting with recumbent or semi-recumbent exercise, such as cycling, swimming, or rowing, and then moving on to exercise in an upright position such as running when the ability to stand improves without dyspnea appearance. Exercise duration should also be short initially (5 to 10 min per day), with gradual increases as functional capacity improves.

[2022 Update on myocarditis and pericarditis following COVID-19 vaccination. Expert Opinion of the Italian Society of Cardiology]. / Update 2022 dell'Expert Opinion della Società Italiana di Cardiologia su miocarditi, pericarditi e vaccini contro il COVID-19.

Vaccine-associated myocarditis and pericarditis usually develop within 14 days of COVID-19 vaccination, are exceptionally rare, manifest with mild clinical pictures and are commonly characterized by a favorable evolution. Young men inoculated with two doses of an mRNA vaccine are the subgroup at higher risk. Recent epidemiological studies evaluated the incidence and risk of vaccine-associated myocarditis and pericarditis among men and women, in different ranges of age and specific types of vaccines. Long-term population analyses demonstrated that the cardiovascular risk conferred by COVID-19 extends beyond the acute phase, representing the rationale for implementing prevention strategies for SARS-CoV-2 infection, monitoring specific populations at higher risk and pursuing the completion of the vaccination campaign. This document provides an update on the most recent scientific evidence and critical interpretation of available data in constant evolution towards personalized strategies of immunization.

Sex-related differences in patients with coronavirus disease 2019: results of the Cardio-COVID-Italy multicentre study.

INTRODUCTION: The role of sex compared to comorbidities and other prognostic variables in patients with coronavirus disease (COVID-19) is unclear. METHODS: This is a retrospective observational study on patients with COVID-19 infection, referred to 13 cardiology units. The primary objective was to assess the difference in risk of death between the sexes. The secondary objective was to explore sex-based heterogeneity in the association between demographic, clinical and laboratory variables, and patients' risk of death. RESULTS: Seven hundred and one patients were included: 214 (30.5%) women and 487 (69.5%) men. During a median follow-up of 15 days, deaths occurred in 39 (18.2%) women and 126 (25.9%) men. In a multivariable Cox regression model, men had a nonsignificantly higher risk of death vs. women (P = 0.07).The risk of death was more than double in men with a low lymphocytes count as compared with men with a high lymphocytes count [overall survival hazard ratio (OS-HR) 2.56, 95% confidence interval (CI) 1.72-3.81]. In contrast, lymphocytes count was not related to death in women (P = 0.03).Platelets count was associated with better outcome in men (OS-HR for increase of 50 × 103 units: 0.88 95% CI 0.78-1.00) but not in women. The strength of association between higher PaO2/FiO2 ratio and lower risk of death was larger in women (OS-HR for increase of 50 mmHg/%: 0.72, 95% CI 0.59-0.89) vs. men (OS-HR: 0.88, 95% CI 0.80-0.98; P = 0.05). CONCLUSIONS: Patients' sex is a relevant variable that should be taken into account when evaluating risk of death from COVID-19. There is a sex-based heterogeneity in the association between baseline variables and patients' risk of death.

Phrenic nerve neuropathy discovered with cardiopulmonary exercise test in long-COVID-19 syndrome

Corona virus disease of 2019 (COVID19) is an ongoing global pandemic caused by SARS-CoV-2 virus. COVID-19 typically involves the respiratory tract with a wide spectrum of disease severity. Long-Covid19 syndrome refers to a series of symptoms that sometimes persist after COVID-19 infection. We describe a case of unilateral phrenic nerve palsy in a young woman with Long-COVID-19 syndrome. a 28-year-old woman admitted for COVID-19 presented persistent exertional dyspnoea. All the examinations performed were normal. At Cardiopulmonary exercise test (CPET) however, the ventilation plot was characterized by a lack of increase of the tidal volume compensated with a premature and continuous rise in respiratory frequency. Suspecting a ventilation abnormality, an electroneurography of the diaphragmatic nerves was conducted showing a right phrenic nerve palsy. Long-COVID-19 syndrome is a growing entity in clinical practice and dyspnoea is one of the most common symptoms. In this setting, phrenic nerve palsy should be ruled out, especially in patients with unexplained dyspnoea. CPET is a complete technique that assesses both pulmonary and cardiac performance. Since it might give important clues in the recognition of the cause of persistent symptoms after COVID-19 it should be extensively performed in these patients.

[Italian Society of Cardiology (SIC) Position paper: Technical, instrumental and standards of interpretation for electrocardiography, ambulatory electrocardiographic and blood pressure monitoring in telemedicine]. / Position paper della Società Italiana di Cardiologia (SIC): Requisiti tecnici, strumentali e di refertazione per elettrocardiografia a riposo, monitoraggio elettrocardiografico ambulatoriale secondo Holter, monitoraggio ambulatoriale della pressione arteriosa in telemedicina.

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.

Effects of the COVID-19 pandemic on the formation of fellows in training in cardiology.

CoronaVIrus Disease-19 (COVID-19) had a huge impact on human health and economy. However, to this date, the effects of the pandemic on the training of young cardiologists are only partially known. To assess the consequences of the pandemic on the education of the cardiologists in training, we performed a 23-item national survey that has been delivered to 1443 Italian cardiologists in training, registered in the database of the Italian Society of Cardiology (SIC). Six hundred and thirty-three cardiologists in training participated in the survey. Ninety-five percent of the respondents affirmed that the training programme has been somewhat stopped or greatly jeopardized by the pandemic. For 61% of the fellows in training (FITs), the pandemic had a negative effect on their education. Moreover, 59% of the respondents believe that they would not be able to fill the gap gained during that period over the rest of their training. A negative impact on the psycho-physical well being has been reported by 86% of the FITs. The COVID-19 pandemic had an unparalleled impact on the education, formation and mental state of the cardiologists in training. Regulatory agencies, universities and politicians should make a great effort in the organization and reorganization of the teaching programs of the cardiologists of tomorrow.

[Myocarditis and pericarditis following mRNA COVID-19 vaccination. Expert opinion of the Italian Society of Cardiology]. / Miocarditi, pericarditi e vaccino a mRNA contro il COVID-19. Expert opinion della Società Italiana di Cardiologia.

The coronavirus disease (COVID-19) pandemic has caused 2.69 million deaths and 122 million infections. Great efforts have been made worldwide to promptly develop effective vaccines and reduce morbidity and mortality rates from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Available vaccines have proven highly effective at preventing symptomatic disease in clinical trials and real-world reports and are playing an essential role in flattening the epidemiology curve and, mostly, in reducing COVID-19 hospitalizations. Some concerns have been raised after very rare cases of myocarditis and pericarditis recently reported by the Centers for Disease Control and Prevention (CDC) as potentially associated with COVID-19 mRNA vaccinations, namely the Pfizer-BioNTech mRNA vaccine (BNT162b2) and the Moderna mRNA vaccine (mRNA-1273). Therefore, the aim of this document is to explore the possible link between COVID-19 mRNA vaccination and the development of myocarditis and/or pericarditis by performing a critical analysis of available data and to provide indications for specific subgroups of individuals.

Biomarkers in the management of acute heart failure: state of the art and role in COVID-19 era.

Acute heart failure (AHF) affects millions of people worldwide, and it is a potentially life-threatening condition for which the cardiologist is more often brought into play. It is crucial to rapidly identify, among patients presenting with dyspnoea, those with AHF and to accurately stratify their risk, in order to define the appropriate setting of care, especially nowadays due to the coronavirus disease 2019 (COVID-19) outbreak. Furthermore, with physical examination being limited by personal protective equipment, the use of new alternative diagnostic and prognostic tools could be of extreme importance. In this regard, usage of biomarkers, especially when combined (a multimarker approach) is beneficial for establishment of an accurate diagnosis, risk stratification and post-discharge monitoring. This review highlights the use of both traditional biomarkers such as natriuretic peptides (NP) and troponin, and emerging biomarkers such as soluble suppression of tumourigenicity (sST2) and galectin-3 (Gal-3), from patients' emergency admission to discharge and follow-up, to improve risk stratification and outcomes in terms of mortality and rehospitalization.

Heart failure in COVID-19: the multicentre, multinational PCHF-COVICAV registry.

AIMS: We assessed the outcome of hospitalized coronavirus disease 2019 (COVID-19) patients with heart failure (HF) compared with patients with other cardiovascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia). We further wanted to determine the incidence of HF events and its consequences in these patient populations. METHODS AND RESULTS: International retrospective Postgraduate Course in Heart Failure registry for patients hospitalized with COVID-19 and CArdioVascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia) was performed in 28 centres from 15 countries (PCHF-COVICAV). The primary endpoint was in-hospital mortality. Of 1974 patients hospitalized with COVID-19, 1282 had cardiovascular disease and/or risk factors (median age: 72 [interquartile range: 62-81] years, 58% male), with HF being present in 256 [20%] patients. Overall in-hospital mortality was 25% (n = 323/1282 deaths). In-hospital mortality was higher in patients with a history of HF (36%, n = 92) compared with non-HF patients (23%, n = 231, odds ratio [OR] 1.93 [95% confidence interval: 1.44-2.59], P < 0.001). After adjusting, HF remained associated with in-hospital mortality (OR 1.45 [95% confidence interval: 1.01-2.06], P = 0.041). Importantly, 186 of 1282 [15%] patients had an acute HF event during hospitalization (76 [40%] with de novo HF), which was associated with higher in-hospital mortality (89 [48%] vs. 220 [23%]) than in patients without HF event (OR 3.10 [2.24-4.29], P < 0.001). CONCLUSIONS: Hospitalized COVID-19 patients with HF are at increased risk for in-hospital death. In-hospital worsening of HF or acute HF de novo are common and associated with a further increase in in-hospital mortality.

Determinants of the protective effect of glucocorticoids on mortality in hospitalized patients with COVID-19: Insights from the Cardio-COVID-Italy multicenter study.

BACKGROUND: Glucocorticoid therapy has emerged as an effective therapeutic option in hospitalized patients with coronavirus disease 2019 (COVID-19). This study aimed to focus on the impact of relevant clinical and laboratory factors on the protective effect of glucocorticoids on mortality. METHODS: A sub-analysis was performed of the multicenter Cardio-COVID-Italy registry, enrolling consecutive patients with COVID-19 admitted to 13 Italian cardiology units between 01 March 2020 and 09 April 2020. The primary endpoint was in-hospital mortality. RESULTS: A total of 706 COVID-19 patients were included (349 treated with glucocorticoids, 357 not treated with glucocorticoids). After adjustment for relevant covariates, use of glucocorticoids was associated with a lower risk of in-hospital mortality (adjusted HR 0.44; 95% CI 0.26-0.72; p = 0.001). A significant interaction was observed between the protective effect of glucocorticoids on mortality and PaO2/FiO2 ratio on admission (p = 0.042), oxygen saturation on admission (p = 0.017), and peak CRP (0.023). Such protective effects of glucocorticoids were mainly observed in patients with lower PaO2/FiO2 ratio (<300), lower oxygen saturation (<90%), and higher CRP (>100 mg/L). CONCLUSIONS: The protective effects of glucocorticoids on mortality in COVID-19 were more evident among patients with worse respiratory parameters and higher systemic inflammation.