Impact of the COVID-19 pandemic on total, sex- and age-specific all-cause mortality in 20 countries worldwide during 2020: results from the C-MOR project.

BACKGROUND: To understand the impact of the COVID-19 pandemic on mortality, this study investigates overall, sex- and age-specific excess all-cause mortality in 20 countries, during 2020. METHODS: Total, sex- and age-specific weekly all-cause mortality for 2015-2020 was collected from national vital statistics databases. Excess mortality for 2020 was calculated by comparing weekly 2020 observed mortality against expected mortality, estimated from historical data (2015-2019) accounting for seasonality, long- and short-term trends. Crude and age-standardized rates were analysed for total and sex-specific mortality. RESULTS: Austria, Brazil, Cyprus, England and Wales, France, Georgia, Israel, Italy, Northern Ireland, Peru, Scotland, Slovenia, Sweden, and the USA displayed substantial excess age-standardized mortality of varying duration during 2020, while Australia, Denmark, Estonia, Mauritius, Norway, and Ukraine did not. In sex-specific analyses, excess mortality was higher in males than females, except for Slovenia (higher in females) and Cyprus (similar in both sexes). Lastly, for most countries substantial excess mortality was only detectable (Austria, Cyprus, Israel, and Slovenia) or was higher (Brazil, England and Wales, France, Georgia, Italy, Northern Ireland, Sweden, Peru and the USA) in the oldest age group investigated. Peru demonstrated substantial excess mortality even in the <45 age group. CONCLUSIONS: This study highlights that excess all-cause mortality during 2020 is context dependent, with specific countries, sex- and age-groups being most affected. As the pandemic continues, tracking excess mortality is important to accurately estimate the true toll of COVID-19, while at the same time investigating the effects of changing contexts, different variants, testing, quarantine, and vaccination strategies.

Exercise Training in Post-COVID-19 Patients: The Need for a Multifactorial Protocol for a Multifactorial Pathophysiology.

The battle against COVID-19 has entered a new phase with Rehabilitation Centres being among the major players, because the medical outcome of COVID-19 patients does not end with the control of pulmonary inflammation marked by a negative virology test, as many patients continue to suffer from long-COVID-19 syndrome. Exercise training is known to be highly valuable in patients with cardiac or lung disease, and it exerts beneficial effects on the immune system and inflammation. We therefore reviewed past and recent papers about exercise training, considering the multifactorial features characterizing post-COVID-19 patients' clinical conditions. Consequently, we conceived a proposal for a post-COVID-19 patient exercise protocol as a combination of multiple recommended exercise training regimens. Specifically, we built pre-evaluation and exercise training for post-COVID-19 patients taking advantage of the various programs of exercise already validated for diseases that may share pathophysiological and clinical characteristics with long-COVID-19.

Impact of the COVID-19 pandemic on prescription of sacubitril/valsartan in Italy.

AIMS: The present study sought to examine the effect of the COVID-19 pandemic and lockdown measures on the prescription of sacubitril/valsartan in patients with heart failure (HF) in Italy. METHODS AND RESULTS: Data from Italian Medicines Agency (AIFA) monitoring registries were analysed. The sacubitril/valsartan monitoring registry is based on 6-month prescriptions. A monthly aggregation on new activations throughout the observational period was computed. From March to December 2020, the initiation of new HF patients on sacubitril/valsartan decreased by nearly 40% with prescriptions dropping to values similar to 2018 when the registry was still operated off-line. A slight increase in prescriptions was observed after the lockdown measures were lifted, but prescriptions remained constantly below the pre-lockdown period. CONCLUSION: A marked and worrisome decline during the COVID-19 pandemic in the activation of a life-saving treatment such as sacubitril/valsartan was observed. This decline was clearly linked to the lockdown measures instated to counteract the COVID-19 pandemic. Upcoming studies should analyse the occurrence of new cases of HF as well as the severity of patients admitted to hospitals and their mortality compared to pre-pandemic levels.

Worldwide differences of hospitalization for ST-segment elevation myocardial infarction during COVID-19: A systematic review and meta-analysis.

BACKGROUND: Discrepant data were reported about hospital admissions for ST-segment elevation myocardial infarction (STEMI) during COVID-19 pandemic. We reviewed studies reporting STEMI hospitalizations during COVID-19 pandemic, investigating whether differences in COVID-19 epidemiology or public health-related factors could explain discrepant findings in different countries. METHODS: Search through MedLine, Embase, Scopus, Web-of-Science, Cochrane Register of Controlled Trials, of studies comparing STEMI admissions during COVID-19 pandemic with a reference period, without language restrictions, as registered in PROSPERO International Prospective Register of Systematic Reviews. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed. Data independently extracted by multiple investigators were pooled using a random-effects model. Health-related metrics were from publicly-available sources. RESULTS: We included 79 articles (111,557 STEMI cases, from 57 countries). During peak COVID-19 pandemic, overall incidence rate-ratio (IRR) of STEMI hospitalizations over reference period decreased (0.80; 95% CI 0.76-0.84; p < 0.05). Although wide variations and significant heterogeneity were detected among studies (I2 = 89%; p < 0.0001), no significant differences were observed by report methodology (survey vs registry), or observation/reference period. However, large differences emerged at country level not explained by COVID-related epidemiological data, nor by public health strategies. Instead, IRRs for STEMI admissions were inversely related to hospital bed availability in each country (p < 0.05). CONCLUSIONS: During COVID-19 pandemic hospitalization for STEMI significantly decreased, although to a smaller extent than initially reported. Large variability emerged across countries, unrelated to COVID-related epidemiology or social containment measures. Disparities in healthcare organization likely contributed, indicating that proper organization of emergency medicine should be preserved during pandemics.

Mechanical concordance between left atrium and left atrial appendage in nonvalvular atrial fibrillation: can it be exploited to avoid transesophageal echocardiography prior to electrical cardioversion during Covid-19 pandemic?

Transesophageal echocardiography (TEE) is the gold standard for assessing left atrial appendage (LAA) mechanic and thrombosis (LAAT); however, TEE is a high-risk procedure for viral transmission during coronavirus disease 2019 (COVID-19) pandemic. We investigated whether deformation indices of left atrium (LA) at transthoracic echocardiography (TTE) correlate with those of LAA assessed by TEE in nonvalvular atrial fibrillation (NVAF) patients undergoing electrical cardioversion (ECV). Consecutive patients with NVAF of ≥ 48 h or unknown duration, who underwent TEE and TTE at our Institution before ECV were retrospectively investigated. Standard echo-Doppler and LA and LAA myocardial strain and strain rate parameters were analyzed. A total of 115 NVAF patients (71.3 ± 8.1 yr/o, 59.1% men) were included: LAAT was diagnosed in 25 (21.7%) patients. Compared to patients without LAAT, those with LAAT had significantly higher CHA2DS2-VASc Risk score (4.5 ± 1.4 vs. 3.5 ± 1.1, p < 0.001), and lower ejection fraction (46.0 ± 14.8 vs. 57.6 ± 8.6%, p < 0.001). In LAAT patients, global strain of LA (8.7 ± 2.6 vs. 16.3 ± 4.5%, p < 0.001) and LAA (7.0 ± 1.7 vs. 11.7 ± 2.0%, p < 0.001) was significantly reduced compared to non-LAAT patients. A close relationship between left atrial strain reservoir (LASr) and LAA-global strain was demonstrated (r = 0.81). By univariable analysis, CHA2DS2-VASc Risk Score (OR 2.01, 95%CI 1.34-3.00), NT-proBNP (OR 1.36, 95%CI 1.19-1.54), ejection fraction (OR 0.92, 95%CI 0.88-0.96), E/e' ratio (OR 2.07, 95%CI 1.51-2.85), and LASr (OR 0.39, 95%CI 0.25-0.62) were strongly associated with LAAT presence at TEE. By multivariable analysis, only LASr (OR 0.40, 95%CI 0.24-0.70) retained statistical significance. ROC curve analysis revealed that an LASr cut-off value ≤ 9.3% had 98.9% sensibility and 100% specificity to identify LAAT by TEE (AUC = 0.98). In patients with NVAF of ≥ 48 h or unknown duration, scheduled to undergo ECV, LA deformation assessment by TTE might substitute invasive measurement of LAA function by TEE, simplifying diagnostic approach and possibly contributing to reduce COVID-19 infection diffusion.

Excess all-cause mortality and COVID-19-related mortality: a temporal analysis in 22 countries, from January until August 2020.

BACKGROUND: This study aimed to investigate overall and sex-specific excess all-cause mortality since the inception of the COVID-19 pandemic until August 2020 among 22 countries. METHODS: Countries reported weekly or monthly all-cause mortality from January 2015 until the end of June or August 2020. Weekly or monthly COVID-19 deaths were reported for 2020. Excess mortality for 2020 was calculated by comparing weekly or monthly 2020 mortality (observed deaths) against a baseline mortality obtained from 2015-2019 data for the same week or month using two methods: (i) difference in observed mortality rates between 2020 and the 2015-2019 average and (ii) difference between observed and expected 2020 deaths. RESULTS: Brazil, France, Italy, Spain, Sweden, the UK (England, Wales, Northern Ireland and Scotland) and the USA demonstrated excess all-cause mortality, whereas Australia, Denmark and Georgia experienced a decrease in all-cause mortality. Israel, Ukraine and Ireland demonstrated sex-specific changes in all-cause mortality. CONCLUSIONS: All-cause mortality up to August 2020 was higher than in previous years in some, but not all, participating countries. Geographical location and seasonality of each country, as well as the prompt application of high-stringency control measures, may explain the observed variability in mortality changes.

Cardiovascular involvement during COVID-19 and clinical implications in elderly patients. A review.

SARS-CoV-2 betacoronavirus is responsible for the Corona Virus Disease 2019 (COVID-19) which has relevant pathogenic implications for the cardiovascular system. Incidence and severity of COVID-19 are higher in the elderly population (65 years and older). This may be due to higher frequency of comorbidities, but increased frailty and immunosenescence linked with aging may also contribute. Moreover, in elderly individuals, SARS-CoV-2 may adopt different molecular strategies to strongly impact on cardiac aging that culminate in exacerbating a pro-inflammatory state (cytokine storm activation), which, in turn, may lead to pulmonary vascular endothelialitis, microangiopathy, diffuse thrombosis, myocarditis, heart failure, cardiac arrhythmias, and acute coronary syndromes. All these events are particularly relevant in elderly patients, and deserve targeted cardiovascular treatments and specific management of repurposed drugs against COVID-19. We discuss current evidence about the cardiovascular involvement during COVID-19, and elaborate on clinical implications in elderly patients.

Potential role of incretins in diabetes and COVID-19 infection: a hypothesis worth exploring.

Patients with diabetes mellitus have been reported to be at a high risk of complications from SARS-CoV2 virus infection (COVID-19). In type 2 diabetes, there is a change in immune system cells, which shift from an anti-inflammatory to a predominantly pro-inflammatory pattern. This altered immune profile may induce important clinical consequences, including increased susceptibility to lung infections; and enhanced local inflammatory response. Furthermore, dipeptidyl peptidase 4 (DPP4) enzyme is highly expressed in the lung, and that it may have additional actions besides its effects on glucose metabolism, which might exert profound pro-inflammatory effects. We briefly review the impact on the inflammatory system of DPP4 for its possible detrimental effect on COVID-19 syndrome, and of DPP4 inhibitors (gliptins), currently used as glucose lowering agents, which may have the potential to exert positive pleiotropic effect on inflammatory diseases, in addition to their effects on glucose metabolism. Thanks to these ancillary effects, gliptins could potentially be "repurposed" as salutary drugs against COVID-19 syndrome, even in non-diabetic subjects. Clinical studies should be designed to investigate this possibility.

Management of heart failure patients with COVID-19: a joint position paper of the Chinese Heart Failure Association & National Heart Failure Committee and the Heart Failure Association of the European Society of Cardiology.

The coronavirus disease 2019 (COVID-19) pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is causing considerable morbidity and mortality worldwide. Multiple reports have suggested that patients with heart failure (HF) are at a higher risk of severe disease and mortality with COVID-19. Moreover, evaluating and treating HF patients with comorbid COVID-19 represents a formidable clinical challenge as symptoms of both conditions may overlap and they may potentiate each other. Limited data exist regarding comprehensive management of HF patients with concomitant COVID-19. Since these issues pose serious new challenges for clinicians worldwide, HF specialists must develop a structured approach to the care of patients with COVID-19 and be included early in the care of these patients. Therefore, the Heart Failure Association of the European Society of Cardiology and the Chinese Heart Failure Association & National Heart Failure Committee conducted web-based meetings to discuss these unique clinical challenges and reach a consensus opinion to help providers worldwide deliver better patient care. The main objective of this position paper is to outline the management of HF patients with concomitant COVID-19 based on the available data and personal experiences of physicians from Asia, Europe and the United States.

[New insights into the seriousness of acute myocardial injury during COVID-19]. / Nuove acquisizioni sulla gravità del danno cardiaco acuto in corso di COVID-19.

Retrospective data from Chinese cohorts published in the last few days have placed a strong emphasis on the possibility that acute myocardial injury represents a critical component in the development of serious complications in patients hospitalized with COVID-19. These analyses showed that 19-27% of hospitalized patients with moderate/severe COVID-19 developed acute myocardial injury, defined as an increase in troponin levels. Fifty-sixty percent of these patients died. The highest mortality rate was detected among patients with both progressively incremental troponin levels and a history of cardiovascular disease. Some pathophysiological reasons have been hypothesized regarding the frequently observed increase in troponin levels in patients hospitalized with COVID-19, but, at the moment, these data could already suggest some clinical management implications, also with the aim of prospectively collecting research data: a troponin dosage should be considered, as a prognostic indicator, in all patients with moderate/severe COVID-19 at hospital admission, periodically during hospitalization, and in the case of clinical deterioration. In those patients with increased troponin levels, serial determinations should be carried out to define the enzymatic trajectory and therefore also the degree of clinical attention that must necessarily be closer in those who turn out to have persistently high or increasing troponin levels. In order to reduce the overdiagnosis risk of acute myocardial injury in critically ill patients, detection of increased troponin levels should always be contextualized into a multi-parametric evaluation.