Natalia Fabin

Background: Empiric antimicrobial therapy with azithromycin is highly used in patients admitted to the hospital with COVID‐19, despite prior research suggesting that azithromycin may be associated with increased risk of cardiovascular events. Methods and Results: This study was conducted using data from the ISACS‐COVID‐19 (International Survey of Acute Coronavirus Syndromes‐COVID‐19) registry. Patients with a confirmed diagnosis of SARS‐CoV‐2 infection were eligible for inclusion. The study included 793 patients exposed to azithromycin within 24 hours from hospital admission and 2141 patients who received only standard care. The primary exposure was cardiovascular disease (CVD). Main outcome measures were 30‐day mortality and acute heart failure (AHF). Among 2934 patients, 1066 (36.4%) had preexisting CVD. A total of 617 (21.0%) died, and 253 (8.6%) had AHF. Azithromycin therapy was consistently associated with an increased risk of AHF in patients with preexisting CVD (risk ratio [RR], 1.48 [95% CI, 1.06–2.06]). Receiving azithromycin versus standard care was not significantly associated with death (RR, 0.94 [95% CI, 0.69–1.28]). By contrast, we found significantly reduced odds of death (RR, 0.57 [95% CI, 0.42–0.79]) and no significant increase in AHF (RR, 1.23 [95% CI, 0.75–2.04]) in patients without prior CVD. The relative risks of death from the 2 subgroups were significantly different from each other ( P _interaction =0.01). Statistically significant association was observed between AHF and death (odds ratio, 2.28 [95% CI, 1.34–3.90]). Conclusions: These findings suggest that azithromycin use in patients with COVID‐19 and prior history of CVD is significantly associated with an increased risk of AHF and all‐cause 30‐day mortality. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05188612.

Coronary artery disease (CAD) is the leading cause of mortality globally. Although sub-stantial advances have been made in the diagnosis, management, and risk stratification of CAD, there is still a need for novel diagnostic biomarkers and new therapeutic targets to prevent the epi-demic of the disease. Recently, growing evidence has linked dysregulated microRNAs (miRNAs) to cardiovascular diseases, including CAD. miRNAs are endogenous, stable, single-stranded, short, non-coding RNAs, and may have utility as diagnostic and prognostic biomarkers for CAD. Dysreg-ulated miRNAs are involved in regulating lipid and glucose homeostasis pathways, renin-angiotensin-aldosterone pathways, inflammation, endothelial and vascular smooth cell phenotypes promoting atherosclerotic plaque development, progression, and instability. Additionally, miRNAs are stable and easily accessible in the extracellular space, may reside in microvesicles, and are de-tectable in serum or plasma, making them attractive biomarkers for the diagnosis and prognosis of cardiovascular disease. Accumulating studies suggest that miRNAs could be useful biomarkers for early discrimination of patients presenting with myocarditis or Takotsubo syndrome from those with a diagnosis of acute myocardial infarction, early prognostication of patients presenting with acute coronary syndromes, and accurate detection of left ventricular remodeling after a chronic or acute ischemic event. Moreover, miRNAs represent potential novel therapeutic targets for CAD or other cardiovascular diseases. This review provides an overview of the effects of the entire spec-trum of CAD, its major risk factors, and complications on levels of circulating miRNAs, as well as the limitations and challenges of their potential clinical applications.

Background: Patients with cancer represent a uniquely vulnerable population not only with higher susceptibility to COVID-19 but also at increased risk for death. However, detailed information on causes of death and the contribution of pre-existing health conditions to death yet is missing. Purpose: This study focuses on the implications of COVID-19 in the cardiovascular health of patients with cancer by assessing the relation between cancer and de novo acute heart failure (AHF) with in-hospital mortality. Methods: The initial population consisted of 3968 patients included in the ISACS COVID-19 registry between March 2020 and February 2022. Of these, 546 patients with chronic HF were excluded, leaving a final population of 3422. Patients were divided in two groups according to the presence or absence of a cancer diagnosis at the time of hospitalization for COVID-19. Primary outcomes were incidence of in-hospital mortality or AHF during hospitalization. Association between cancer and outcomes was estimated using multivariable logistic regression analyses. Subsidiary analysis was conducted to evaluate differences between patients with prior vs active cancer. Results: Of the 3422 patients included in the study, 468 patients had cancer (8.2% active, 5.5% past cancer). Cancer patients were older (68.9±13.4 vs 63.3±15.6, p-value <0.001) and more likely to be female (50.4% vs 39.1%, p-value <0.001). They presented more frequently with a history of chronic obstructive pulmonary disease (12.3% vs 7.6%, p-value = 0.001). When considering outcomes, cancer patients had a significantly higher incidence of in-hospital mortality (27.7% vs 19.2%; p-value <0.001). This despite the presence of a numerically higher mean PiO2/FiO2 (281±108.8 vs 267.05±122.5, p-value = 0.11) on admission and a lower rate of X-ray findings of interstitial pneumonia (60% vs 70.5%, p-value <0.001) than their non-oncological counterparts, as well as similar use of mechanical ventilation (30.6% vs 35.0%, p value=0.14). The association between cancer and death persisted when adjusting for demographic, laboratory findings and in-hospital treatment (OR: 1.46; 95% CI: 1.11–1.94; p value=0.01). Cancer patients also had higher rates of AHF (9.6% vs 4.7%, p-value <0.001) during hospitalization. This association was independent from presence of cardiovascular risk factors or comorbidities (OR: 1.61; 95% CI: 1.07–2.43; p value=0.02). When restricting the analysis to the cancer population, AHF appeared to be significantly associated with death (OR: 2.41; 95% CI 1.18–4.95; p-value = 0.01), but this correlation persisted only in patients affected by active cancer in age and sex adjusted analyses (OR: 4.27; 95% CI: 1.51–12.07; p value=0.01 vs 1.20; 95% CI: 0.38–3.76; p-value = 0.75). Conclusions: The incidence of AHF in cancer patients with COVID-19 is high. Patients with active cancer are also at high risk for mortality. This has implications for cardiac monitoring and chemotherapy administration during COVID-19. Funding Acknowledgement: Type of funding sources: None.

Cardiovascular diseases and cancer are the leading cause of morbidity and mortality globally. Cardiotoxicity from chemotherapeutic agents results in substantial morbidity and mortality in cancer survivors and patients with active cancer. Cardiotoxicity induced by 5-fluorouracil (5-FU) has been well established, yet its incidence, mechanisms, and manifestation remain poorly defined. Ischemia secondary to coronary artery vasospasm is thought to be the most frequent cardiotoxic effect of 5-FU. The available evidence of 5-FU-induced epicardial coronary artery spasm and coronary microvascular dysfunction suggests that endothelial dysfunction or primary vascular smooth muscle dysfunction (an endothelial-independent mechanism) are the possible contributing factors to this form of cardiotoxicity. In patients with 5-FU-related coronary artery vasospasm, termination of chemotherapy and administration of nitrates or calcium channel blockers may improve ischemic symptoms. However, there are variable results after administration of nitrates or calcium channel blockers in patients treated with 5-FU presumed to have myocardial ischemia, suggesting mechanisms other than impaired vasodilatory response. Clinicians should investigate whether chest pain and ECG changes can reasonably be attributed to 5-FU-induced cardiotoxicity. More prospective data and clinical randomized trials are required to understand and mitigate potentially adverse outcomes from 5-FU-induced cardiotoxicity.

In Italy, more than 116 doctors died due to the SARS-CoV-2 infection since the beginning of the pandemic.¹ We collected data on each one of them, using local newspapers and obituaries as sources. We found out that 110 were male (95%) and only 6 were female (5%), the youngest was 49 years old, the oldest 94 years old and the average age was 70 years old. Five of these doctors had returned from retirement to help with the emergency, only 21 were retired. Eighty-two per cent of the deceased worked closely with patients at the time of the infection.