Diagnosis of Acute Myocarditis Following mRNA Vaccines against SARS-CoV-2: A Methodological Review.

The occurrence of acute myocarditis following the administration of mRNA vaccines against SARS-CoV-2 remains relatively rare, and it is associated with a very low mortality rate. The incidence varied by vaccine type, sex, and age and after the first, second, or third vaccination dose. However, the diagnosis of this condition often remains challenging. To further elucidate the relationship between myocarditis and SARS-CoV-2 mRNA vaccines, starting with two cases observed at the Cardiology Unit of the West Vicenza General Hospital located in the Veneto Region, which was among the first Italian areas hit by the COVID-19 pandemic, we performed a review of the available literature to highlight the clinical and diagnostic elements that could contribute to suspicion of myocarditis as an adverse event of SARS-CoV-2 immunization.

Risk of Incident New-Onset Arterial Hypertension After COVID-19 Recovery: A Systematic Review and Meta-analysis.

INTRODUCTION: Arterial Hypertension (HT) has been described as a common comorbidity and independent risk factor of short-term outcome in COVID-19 patients. However, data regarding the risk of new-onset HT during the post-acute phase of COVID-19 are scant. AIM: We assess the risk of new-onset HT in COVID-19 survivors within one year from the index infection by a systematic review and meta-analysis of the available data. METHODS: Data were obtained searching MEDLINE and Scopus for all studies published at any time up to February 11, 2023, and reporting the long-term risk of new-onset HT in COVID-19 survivors. 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 I2 statistic. RESULTS: Overall, 19,293,346 patients (mean age 54.6 years, 54.6% males) were included in this analysis. Of them, 758,698 survived to COVID-19 infection. Over a mean follow-up of 6.8 months, new-onset HT occurred to 12.7 [95% CI 11.4-13.5] out of 1000 patients survived to COVID-19 infection compared to 8.17 [95% CI 7.34-8.53] out of 1000 control subjects. Pooled analysis revealed that recovered COVID-19 patients presented an increased risk of new-onset HT (HR 1.70, 95% CI 1.46-1.97, p < 0.0001, I2 = 78.9%) within seven months. This risk was directly influenced by age (p = 0.001), female sex (p = 0.03) and cancer (p < 0.0001) while an indirect association was observed using the follow-up length as moderator (p < 0.0001). CONCLUSIONS: Our findings suggest that new-onset HT represents an important post-acute COVID-19 sequelae.

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.

Excess of heart failure-related deaths during the 2020 COVID-19 pandemic in Unites States.

BACKGROUND: HF can be encountered at different stages in the course of COVID-19 disease. However, data regarding the HF-related mortality during COVID-19 pandemic are scant OBJECTIVE: We investigate the heart failure (HF)-related mortality rate in the US among patient with or without COVID-19 infection during the first two pandemic waves in 2020 and to compare them to those of previous years (2014-2019). METHODS: Age-adjusted mortality rates (AAMR) per 100.000 person-years, with relative 95% confidence interval (CI) were determined using the free-available dataset for Multiple cause-of-death, provided by the Center for Disease Control. RESULTS: Throughout the 2020, the first year of the COVID-19 pandemic, 522.848 HF-related deaths were registered (461.594 and 61.254 in subjects without and with COVID-19 infection, respectively). The overall HF-related AAMR was 124.6 (65% CI 123.4-125.6), reflecting an increased HF-related mortality of 13.2% and 25.9% compared to 2019 and 2018 (p < 0.0001). HF-related AAMR was 111.0 (95% CI: 110.7-111.4) and 14.8 (95% CI: 14.6-14.9) per 100.000 population for decedents without and with COVID-19 disease, respectively. The proportionate mortality of HF in COVID-19 patients was 11.7%. HF-related AAMR in COVID-19 patients was higher in men (18.0 per 100.000, 95% CI: 17.8-18.2), in patients aged more 65 years (104.0 per 100.000, 95% CI: 103.1-104.9), in African Americans (22.5 per 100.000, 95% CI: 22.0-22.3) and in those living in rural counties (18.4 per 100.000, 95% CI: 18.0-18.7). CONCLUSIONS: A significant increase in the HF-related mortality during the 2020 was observed synchronously with the COVID-19 pandemic.

Risk of venous thromboembolic events after COVID-19 infection: a systematic review and meta-analysis.

Data regarding the occurrence of venous thromboembolic events (VTE), including acute pulmonary embolism (PE) and deep vein thrombosis (DVT) in recovered COVID-19 patients are scant. We performed a systematic review and meta-analysis to assess the risk of acute PE and DVT in COVID-19 recovered subject. Following the PRIMSA guidelines, we searched Medline and Scopus to locate all articles published up to September 1st, 2022, reporting the risk of acute PE and/or DVT in patients recovered from COVID-19 infection compared to non-infected patients who developed VTE over the same follow-up period. PE and DVT risk were evaluated using the Mantel-Haenszel random effects models with Hazard ratio (HR) as the effect measure with 95% confidence interval (CI) while heterogeneity was assessed using Higgins I2 statistic. Overall, 29.078.950 patients (mean age 50.2 years, 63.9% males), of which 2.060.496 had COVID-19 infection, were included. Over a mean follow-up of 8.5 months, the cumulative incidence of PE and DVT in COVID-19 recovered patients were 1.2% (95% CI:0.9-1.4, I2: 99.8%) and 2.3% (95% CI:1.7-3.0, I2: 99.7%), respectively. Recovered COVID-19 patients presented a higher risk of incident PE (HR: 3.16, 95% CI: 2.63-3.79, I2 = 90.1%) and DVT (HR: 2.55, 95% CI: 2.09-3.11, I2: 92.6%) compared to non-infected patients from the general population over the same follow-up period. Meta-regression showed a higher risk of PE and DVT with age and with female gender, and lower risk with longer follow-up. Recovered COVID-19 patients have a higher risk of VTE events, which increase with aging and among females.

Risk of incident heart failure after COVID-19 recovery: a systematic review and meta-analysis.

Patients recovered from COVID-19 have an increased incidence of cardiovascular disease and heart structural changes. The aim of the present manuscript is to assess the risk of incident heart failure (HF) after COVID-19 infection. Data were obtained searching MEDLINE and Scopus for all studies published at any time up to September 1, 2022 reporting the risk of incident HF in COVID-19 recovered patients. The cumulative post-COVID-19 incidence and risk of incident HF were pooled using a random effects model and presented with the corresponding 95% confidence interval (CI). Statistical heterogeneity was measured using the Higgins I2 statistic. Overall, 21,463,173 patients (mean age 54.5 years, 58.7% males) were analyzed. Among them, 1,628,424 had confirmed COVID-19 infection while the remaining 19,834,749 represented the controls. The mean length of follow-up was 9.2 months. A random effect model revealed a pooled incidence of post COVID-19 HF in 1.1% of cases (95% CI: 0.7-1.6, I2: 99.8%). Moreover, recovered COVID-19 patients showed an increased risk of incident HF (HR: 1.90, 95% CI: 1.54-3.24, p < 0.0001, I2 = 96.5%) in the same follow-up period. Meta-regression showed a direct relationship for the risk of incident HF using age (p = 0.001) and hypertension (HT) (p = 0.02) as moderators, while an inverse association was observed when the follow-up length was adopted as moderating variable (p = 0.01). COVID-19 survivors had an additional 90% risk of developing HF after COVID-19 infection in the long-term period. This risk was directly related with age and previous history of HT especially in the early post-acute phase of the infection.

Increased risk of acute myocardial infarction after COVID-19 recovery: A systematic review and meta-analysis.

BACKGROUND: Few studies have analyzed the incidence and the risk of acute myocardial infarction (AMI) during the post-acute phase of COVID-19 infection. OBJECTIVE: To assess the incidence and risk of AMI in COVID-19 survivors after SARS-CoV-2 infection by a systematic review and meta-analysis of the available data. METHODS: Data were obtained searching MEDLINE and Scopus for all studies published at any time up to September 1, 2022 and reporting the risk of incident AMI in patients recovered from COVID-19 infection. AMI risk was evaluated using the Mantel-Haenszel random effects models with Hazard ratio (HR) as the effect measure with 95% confidence interval (CI) while heterogeneity was assessed using Higgins and Thomson I2 statistic. RESULTS: Among 2765 articles obtained by our search strategy, four studies fulfilled the inclusion criteria for a total of 20,875,843 patients (mean age 56.1 years, 59.1% males). Of them, 1,244,604 had COVID-19 infection. Over a mean follow-up of 8.5 months, among COVID-19 recovered patients AMI occurred in 3.5 cases per 1.000 individuals compared to 2.02 cases per 1.000 individuals in the control cohort, defined as those who did not experience COVID-19 infection in the same period). COVID-19 patients showed an increased risk of incident AMI (HR: 1.93, 95% CI: 1.65-2.26, p < 0.0001, I2 = 83.5%). Meta-regression analysis demonstrated that the risk of AMI was directly associated with age (p = 0.01) and male gender (p = 0.001), while an indirect relationship was observed when the length of follow-up was utilized as moderator (p < 0.001). CONCLUSION: COVID-19 recovered patients had an increased risk of AMI.

Excess of heart failure-related deaths during the 2020 COVID-19 pandemic in Unites States

Background HF can be encountered at different stages in the course of COVID-19 disease. However, data regarding the HF-related mortality during COVID-19 pandemic are scant Objective We investigate the heart failure (HF)-related mortality rate in the US among patient with or without COVID-19 infection during the first two pandemic waves in 2020 and to compare them to those of previous years (2014-2019). Methods Age-adjusted mortality rates (AAMR) per 100.000 person-years, with relative 95% confidence interval (CI) were determined using the free-available dataset for Multiple cause-of-death, provided by the Center for Disease Control. Results Throughout the 2020, the first year of the COVID-19 pandemic, 522.848 HF-related deaths were registered (461.594 and 61.254 in subjects without and with COVID-19 infection, respectively). The overall HF-related AAMR was 124.6 (65% CI 123.4-125.6), reflecting an increased HF-related mortality of 13.2% and 25.9% compared to 2019 and 2018 (p<0.0001). HF-related AAMR was 111.0 (95% CI: 110.7-111.4) and 14.8 (95% CI: 14.6-14.9) per 100.000 population for decedents without and with COVID-19 disease, respectively. The proportionate mortality of HF in COVID-19 patients was 11.7%. HF-related AAMR in COVID-19 patients was higher in men (18.0 per 100.000, 95% CI: 17.8-18.2), in patients aged more 65 years (104.0 per 100.000, 95% CI: 103.1-104.9), in African Americans (22.5 per 100.000, 95% CI: 22.0-22.3) and in those living in rural counties (18.4 per 100.000, 95% CI: 18.0-18.7). Conclusions A significant increase in the HF-related mortality during the 2020 was observed synchronously with the COVID-19 pandemic

COVID-19 patients with acute pulmonary embolism have a higher mortality risk: systematic review and meta-analysis based on Italian cohorts.

BACKGROUND: Acute pulmonary embolism has been recognized as a frequent complication of COVID-19 infection influencing the clinical course and outcomes of these patients. OBJECTIVES: We performed a systematic review and meta-analysis to evaluate the mortality risk in COVID-19 Italian patients complicated by acute pulmonary embolism in the short-term period. METHODS: The study was performed in accordance with the Preferred Report Items for Systematic Reviews and Meta-analyses guidelines. PubMed-MEDLINE and Scopus databases were systematically searched for articles, published in the English language and enrolling Italian cohorts with confirmed COVID-19 infection from inception through 20 October 2021. Mortality risk data were pooled using the Mantel-Haenszel random effects models with odds ratio as the effect measure with 95% confidence interval. Heterogeneity among studies was assessed using Higgins and Thomson I2 statistic. RESULTS: Eight investigations enrolling 1.681 patients (mean age 64.9 years, 1125 males) met the inclusion criteria and were considered for the analysis. A random-effect model showed that acute pulmonary embolism was present in 19.0% of Italian patients with COVID-19 infection. Moreover, these patients were at higher mortality risk compared with those without (odds ratio: 1.76, 95% confidence interval: 1.26-2.47, P  = 0.001, I2  = 0%). Sensitivity analysis confirmed yielded results. CONCLUSION: In Italian patients with COVID-19 infection, acute pulmonary embolism was present in about one out of five and significantly associated with a higher mortality risk in the short-term period. The identification of acute pulmonary embolism in these patients remains critical to promptly identify vulnerable populations who would require prioritization in treatment and prevention and close monitoring.

Takotsubo Syndrome during COVID-19 Pandemic in the Veneto Region, Italy.

Background: During the COVID-19 pandemic, the risk of SARS-CoV-2 infection, the public health measures of social distancing, the freedom limitations, quarantine, and the enforced homeworking under the lockdown period, as well as medical causes including COVID-19 infection per se, may have caused major emotional distress, especially in the most vulnerable patients. We aimed to evaluate the variations in the number of admissions due to Takotsubo syndrome (TTS) during the COVID-19 pandemic in the Veneto region. Methods: We retrospectively reviewed and analyzed the number of admissions because of TTS in 13 Divisions of Cardiology located in the Veneto region, the northeastern area of Italy, covering a population of more than 2.5 million inhabitants, during the two major pandemic waves of COVID-19 (the first between 15 March and 30 April 2020 and the second between 15 November and 30 December 2020) that occurred in 2020. Results: In total, 807 acute coronary syndromes were admitted in the 13 enrolling hospitals. Among these, 3.9% had TTS. Compared to the corresponding 2018 and 2019 time periods, we observed a significant increase in the number of TTS cases (+15.6%, p = 0.03 and +12.5%, p = 0.04, comparing 2018 to 2020 and 2019 to 2020, respectively). Geographical distribution of the TTS cases reflected the broad spread of the SARS-CoV-2 infection with a significant direct relationship between TTS incidence and the number of COVID-19 infections according to Pearson's correlation (r = 0.798, p < 0.001). Conclusions: The higher incidence of TTS during the 2020 COVID-19 pandemic waves, especially in the areas that were hit hardest in terms of morbidity and mortality by the SARS-CoV-2 infection, suggest a strong direct and/or indirect role of COVID-19 in the pathogenesis of TTS.

Decline of Admission for Acute Coronary Syndromes and Acute Cardiovascular Conditions during COVID-19 Pandemic in Veneto Region.

BACKGROUND: The present study aimed to examine longitudinal trends in hospitalizations for acute coronary syndrome (ACS) before and during the COVID-19 pandemic, by reviewing the data from 13 hospitals of the Veneto Region, in the north-east of Italy. METHODS: We performed a multicenter, retrospective analysis including all the consecutive patients presenting with ACS and other acute cardiovascular (CV) conditions (defined as heart failure, arrhythmias, cardiac arrest and venous thromboembolism) hospitalized in 13 different hospitals of the Veneto Region covering a population of 2,554,818 inhabitants, during the first (between 15 March 2020 and 30 April 2020) and second (between 15 November 2020 and 30 December 2020) COVID-19 pandemic waves (the 2020 cohort). Data were compared with those obtained at the same time-windows of years 2018 and 2019 (the historical cohorts). RESULTS: Compared to the historical cohorts, a significant decrease in the number of ACS cases was observed in 2020 (-27.3%, p = 0.01 and -32%, p < 0.001, comparing 2018 versus 2020 and 2019 and 2020, respectively). The proportion of patients hospitalized for acute CV conditions decreased during the first and second wave COVID-19 pandemic when compared to the historical cohorts (-36.5%, p < 0.001 and -40.6%, p < 0.001, comparing 2018 versus 2020 and 2019 and 2020, respectively). Pearson's correlation evidenced a significant inverse relationship between the number of COVID-19 cases and both ACS hospital admissions (r = -0.881, p = 0.005) and hospitalizations for acute CV conditions (r = -0.738, p = 0.01), respectively. CONCLUSIONS: The decrease in hospitalizations for ACS and other acute CV conditions will strongly affect future patients' management since undiagnosed nonfatal CV events represent a source of increased (and unknown) CV morbidity and mortality.

Preexisting coronary artery disease among coronavirus disease 2019 patients: a systematic review and meta-analysis.

AIMS: The prevalence and prognostic implications of coronary artery disease (CAD) in patients infected by the novel coronavirus 2019 (COVID-19) disease remain unclear. METHODS: We conducted a systematic review and meta-analysis to investigate the prevalence and mortality risk in COVID-19 patients with preexisting CAD. We searched Medline and Scopus to locate all articles published up to December 8, 2021, reporting data of COVID-19 survivors and nonsurvivors with preexisting CAD. Data were pooled using the Mantel-Haenszel random effects models with odds ratio (OR) as the effect measure with the related 95% confidence interval (CI). RESULTS: Thirty-eight studies including 27 435 patients (mean age 61.5 and 70.9 years) were analysed. The pooled prevalence of preexisting CAD was 12.6% (95% CI: 11.2-16.5%, I2 : 95.6%), and resulted as higher in intensive care unit patients (17.5%, 95% CI: 11.9-25.1, I2 : 88.4%) and in European cohorts (13.1%, 95% CI: 7.8-21.6%, P  < 0.001, I2 : 98.4%). COVID-19 patients with preexisting CAD had a two-fold risk of short-term mortality (OR 2.61, 95% CI 2.10-3.24, P  < 0.001, I2  = 73.6%); this risk was higher among Asian cohorts (OR: 2.66, 95% CI: 1.79-3.90, P  < 0.001, I2 : 77.3%) compared with European (OR: 2.44, 95% CI: 1.90-3.14, P  < 0.001, I2 : 56.9%) and American (OR: 1.86, 95% CI: 1.41-2.44, P  < 0.001, I2 : 0%) populations. The association between CAD and poor short-term prognosis was influenced by age, prevalence of hypertension (HT), DM and CKD. CONCLUSIONS: Preexisting CAD is present in approximately 1 in 10 patients hospitalized for COVID-19 and significantly associated with an increased risk of short-term mortality, which is influenced by age, HT, DM and CKD.

Prevalence of pre-existing peripheral artery disease in COVID-19 patients and relative mortality risk: Systematic review and meta-analysis.

INTRODUCTION: This study aims to assess prevalence and prognostic implications of pre-existing peripheral artery disease (PAD) in patients infected by the SARS-CoV-2 by means of a systematic review and meta-analysis. MATERIAL AND METHODS: We searched MEDLINE and Scopus to locate all the articles published up to 10 December 2021, reporting data on pre-existing PAD among COVID-19 survivors (S) and non survivors (NS). The pooled prevalence of pre-existing PAD in COVID-19 patients was calculated using a random effects model and presenting the related 95% confidence interval (CI), while the mortality risk was estimated using the Mantel-Haenszel random effects models with odds ratio (OR) and related 95% CI. Statistical heterogeneity was measured using the Higgins I2 statistic. RESULTS: Eight investigations, enrolling 13,776 COVID-19 patients (mean age: 67.1 years, 3.863 males), met the inclusion criteria and were included in the final analysis. The pooled prevalence of pre-existing PAD was 5.7% of cases (95% CI: 3.8-8.4%, p < 0.0001), with high heterogeneity (I2 = 84.5%), which was directly correlated with age (p < 0.0001), previous hypertension (p = 0.003), and dyslipidaemia (p = 0.02) as demonstrated by the meta-regression. Moreover, pre-existing PAD was significantly associated with higher risk of short-term death in patients with SARS-CoV-2 infection (OR: 2.78, 95% CI: 2.37-3.27, p < 0.0001 I2 = 0%); the sensitivity analysis confirmed yielded results. CONCLUSIONS: Pre-existing PAD represents a comorbidity in about 1 out of 6 COVID-19 patients, but it is associated with a twofold higher risk of short-term mortality.

[Incidence of acute pulmonary embolism in hospitalized COVID-19 Italian patients. A pooled meta-analysis]. / Tasso di embolia polmonare acuta nei pazienti ospedalizzati per COVID-19 in Italia. Metanalisi aggregata.

BACKGROUND: Acute pulmonary embolism (PE) represents a frequent and prognostically relevant complication of COVID-19. METHODS: We performed a systematic review and meta-analysis, according to the PRISMA guidelines to determine the in-hospital incidence of acute PE, based on Italian studies published on this issue. We searched PubMed and Scopus to locate all articles published between February 2020 to October 15, 2021, reporting the incidence of acute PE in Italian COVID-19 patients. The pooled in-hospital incidence of acute PE was calculated using a random-effect model and presented with relative 95% confidence interval (CI). RESULTS: We analysed data from 3287 Italian COVID-19 patients (mean age 65.7 years) included in 20 studies. The pooled in-hospital incidence of acute PE was 20% (95% CI 13.4-28.7%; I2 = 95.1%); the incidence was lower among patients hospitalized in intensive care unit (ICU) (32.3%; 95% CI 20.2-44.0%; I2 = 77.2%) compared to those admitted in general wards (47.6%; 95% CI 18.7-78.2%; I2 = 94.4%). Meta-regression showed a significant direct correlation of acute PE incidence using age, male gender and previous coronary artery disease as moderating variables. Conversely, an inverse correlation was observed in relation to the use of anticoagulation at therapeutic dose. Prophylactic and therapeutic anticoagulation was administered in 80.2% of patients (95% CI 72.5-86.2%; I2 = 91.0%); the former regimen was more frequently used compared to the latter (63.5% vs 14.3%; p<0.001). Computed tomography angiography (CTPA) was used only in 10.7% of infected patients across 7 studies. CONCLUSIONS: One in five COVID-19 patients experienced acute PE as complication of the infection during hospitalization. The in-hospital incidence of acute PE was lower in ICU compared to general wards. CTPA was scantly used. Early prophylactic anticoagulation was associated with a lower incidence of acute PE.

Prevalence of Acute Pulmonary Embolism at Autopsy in Patients With COVID-19.

To date, the actual prevalence of acute pulmonary embolism (PE) in patients with SARS-CoV-2 infection remains unknown, as systematic screening for PE is cumbersome. We performed a systematic review and meta-analysis on autoptic data to estimate the prevalence of histopathologic findings of acute PE and its relevance as a cause of death on patients with COVID-19. We searched MEDLINE-PubMed and Scopus to locate all articles published in the English language, up to August 10, 2021, reporting the autoptic prevalence of acute PE and evaluating PE as the underlying cause of death in patients with COVID-19. The pooled prevalence for both outcomes was calculated using a random-effects model and presenting the related 95% confidence interval (CI). Statistical heterogeneity was measured using the Higgins I2 statistic. We analyzed autoptic data of 749 patients with COVID-19 (mean age 63.4 years) included in 14 studies. In 10 studies, based on 526 subjects (mean age 63.8 years), a random-effect model revealed that autoptic acute PE findings were present in 27.5% of cases (95% CI 15.0 to 45.0%, I2 89.9%). Conversely, in 429 COVID-19 subjects (mean age 64.0 years) enrolled in 9 studies, acute PE was the underlying cause of death in 19.9% of cases (95% CI 11.0 to 33.3%, I2 83.3%). Autoptic findings of acute PE in patients with COVID-19 are present in about 30% of subjects, whereas a venous thromboembolic event represents the underlying cause of death in about 1 of 4 patients.