COVID-19 cardiological research in France: A nationwide perspective

In this issue of Archives in Cardiovascular Diseases, a series of nine articles provides an important perspective of the current impact of the COVID-19 pandemic in France with a focus on cardiovascular diseases and the organization of cardiology centres.

At the time of this writing, the European toll in terms of deaths, hospitalizations, economic and societal impacts has been unprecedented since the end of World War II. Within the European Union, the death toll has been highest for Italy (120,544), with France following close (104,253). In terms of detected COVID-19 cases, France has the highest number (5,592,390), followed by Italy (4,009,208) and Spain (3,514,942) (https://www.ecdc.europa.eu/en/cases-2019-ncov-eueea, last accessed 1 May 2021). In Europe outside of the European Union, the sad record of death is attributed to the United Kingdom (151,243 deaths with COVID-19 on the death certificate) (https://coronavirus.data.gov.uk/details/deaths, last accessed 1 May 2021). This treacherous pandemic, unprecedented in modern times, is affecting societies around the world at all levels, imposing structural changes in the health-system organizations and changing the epidemiology and management of all non-COVID-19 diseases, including cardiovascular disease. The series of articles appearing in this monographic issue of the journal now provides new elements of knowledge on the impact of COVID-19 on the epidemiology and management of cardiovascular disease in France, and contains lessons that go beyond the perspective of a single country.

Bonnet et al. [1] report data from the Critical COVID-19 France (CCF) study, highlighting the characteristics and outcomes of patients hospitalized for COVID-19 in France. The CCF study is a French nationwide study including all consecutive adults with a diagnosis of severe acute respiratory syndrome COVID-19 hospitalized in 24 centres right at the beginning of the pandemic, between 26 February and 20 April 2020, excluding patients admitted direct to intensive care units (ICU). Clinical, biological and imaging parameters were systematically collected at hospital admission. The primary outcome was in-hospital death. Of 2878 patients included (mean age 66.6 years and 57.8% men), 12.5% died in hospital, 20.7% after being transferred to ICU before death. The majority of patients had at least one (72.6%) or two (41.6%) cardiovascular risk factors, mostly hypertension (50.8%), obesity (30.3%), dyslipidaemia (28.0%) and diabetes (23.7%). In multivariable analysis, older age, male sex, diabetes, chronic kidney failure, elevated troponin and B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide, and quick Sequential Organ Failure Assessment score ≥ 2 were independently associated with in-hospital death. This study therefore documents the important association of cardiovascular comorbidities and risk factors with a substantial morbidity/mortality burden, and sets the stage for the other articles in this series.

In a second paper, also by Bonnet et al. [2], the authors report that during the first peak of the COVID-19 pandemic in France, there was a decrease in admissions for ST-elevation myocardial infarction (STEMI), associated with longer ischaemic time, driven exclusively by an increase in patient-related delays and an increase in mechanical complications. These findings are quite similar to those reported early in the pandemic in Italy by De Rosa et al. [3], who also documented an increase in STEMI case-fatality rates in 2020 compared with 2019, and a parallel increase in complications. Rather than a unique mechanism, several factors likely contributed to the phenomenon. The fear of contagion at the hospital probably discouraged access to emergency medical services, particularly after the media diffused the news that the infection was largely spread across hospitalized patients and healthcare personnel due to the lack of personal protection equipment. However, a second factor may have been that the emergency medical system was at that time practically entirely focused on COVID-19, with most healthcare resources relocated to manage the pandemic. This induced an attitude towards deferral of less urgent cases, as shown by data that the reduction in hospitalizations for STEMI (26.5%) was less striking than for NSTEMI (65.1%) [3]. In any case, these findings altogether suggest the need to encourage the population to seek medical help in case of symptoms, because the deferral to treatment in the hospital setting is likely to affect morbidity and mortality after the onset of an acute myocardial infarction.

Complementary to these findings, a paper by Olié et al. [4] reports on the emergency department admissions for myocardial infarction and stroke in France during the first wave of the COVID-19 pandemic. The paper also concludes that the decrease in emergency department admissions for myocardial infarction and stroke observed during the lockdown was probably caused by the fear of COVID-19 and was augmented by the lockdown. Interestingly, however, the phenomenon was quite heterogeneous across France, and it will be interesting to correlate disease occurrence with different patterns of patients’ attitudes and health-system organizations throughout the country. Emergency department admissions were slow to return to the usual levels of previous years, without a compensatory increase. The paper again underlines the need to reinforce messages directed at the population, encouraging people to seek medical care without delay in case of cardiovascular symptoms [4].

The COVID-19 pandemic affected all organizations involved in the care of cardiovascular patients, including cardiac surgery activities, as described by Nader et al. [5]. This led to the postponement of operations and the need for a complex and still largely insufficient restructuring of organizations related to cardiac surgery. This is just another example of the profound hospital-reorganizational problems imposed by the pandemic [5].

Regarding sex-related disparities in access to health care during the COVID-19 pandemic, Weizman et al. [6] report that female sex was associated with a lower risk of transfer to ICU or in-hospital death than male sex. COVID-19 remained, however, associated with considerable morbidity/mortality in women, especially in those with cardiovascular diseases [6].

Regarding disease mechanisms, the paper by Chocron et al. [7] reports that D-dimer concentration > 1128 ng/mL, reflecting a marked activation of coagulation, is a relevant predictor for in-hospital mortality in patients hospitalized for COVID-19, regardless of the occurrence of venous thromboembolism. This report is in line with several others in the literature pointing to the activation of haemostasis as an important amplifying mechanism leading to morbidity/mortality in COVID-19, and with the now widespread use of anticoagulants, mostly with subcutaneous low-molecular-weight heparins, since the early phases of the disease. It is sobering, however, that at this time we still do not know the best options for anticoagulation in COVID-19 patients, whether prophylactic or therapeutic doses of heparins should be used, or whether vitamin K antagonists or non-vitamin K antagonist oral anticoagulants might play a role as alternatives to heparins [8].

COVID-19 also affected the incidence of cardiac arrhythmias, as detected in recipients of implantable cardioverter defibrillators followed by remote monitoring. Indeed, Galand et al. [9] report an increase in the incidence of ventricular arrhythmias in the 2 weeks before lockdown – at the time of major governmental measures – and then a dramatic decrease during the lockdown. No correlation was observed between the incidence of ventricular arrhythmias and the incidence of COVID-19. No changes were observed regarding atrial fibrillation/atrial tachycardia episodes over time. The authors mainly hypothesize that this variation in the incidence of ventricular arrhythmias could be related to the stress generated in the overall population at the onset of the COVID-19 outbreak, due to the stressful media coverage of the pandemic in France; and that the subsequent decrease in ventricular arrhythmias during the lockdown was related to the sharp decline in physical activity forced by the confinement, together with a sharp decline in perceived stress during the quarantine [9].

Contrary to most common respiratory viruses, children seem less susceptible to COVID-19 and generally develop a mild disease with low mortality. However, as described in another article of the series by Mercier et al. [10], clusters of severe shock associated with high levels of cardiac biomarkers and unusual vasoplegia requiring inotropes, vasopressors and volume loading have recently been described. Both clinical symptoms (high and persistent fever, gastrointestinal disorders, skin rash, conjunctival injection and dry cracked lips) and biohumoral signs (elevated C-reactive protein, procalcitonin and ferritin) resemble Kawasaki disease. In most such instances, intravenous immunoglobin therapy improved cardiac function and led to full recovery within a few days. Adjunctive steroid therapy and sometimes therapy with anti-interleukin-1 receptor (anakinra) and anti-interleukin-6 (tocilizumab) monoclonal antibodies were often necessary. Although almost all children fully recovered within a week, some later developed coronary artery dilation or aneurysms, mimicking Kawasaki disease [10]. The pathogenesis of this occurrence still remains to be uncovered.

Finally, the paper by Roncalli et al. [11] shows how the prognosis of patients with congestive heart failure is greatly jeopardized in case of SARS-CoV-2 infection due to the poor outcomes associated with comorbidities. Indeed, heart failure patients are among the most fragile patient categories at risk of death during the pandemic. These considerations support the prioritization of vaccination against COVID-19 in this at-risk population [11].

Indeed, vaccination currently appears to be the best weapon in our hands to combat COVID-19. The same statistics regarding the above-reported patterns of COVID-19 impact in Europe are now showing the benefits of fast, responsible and accurately planned vaccination campaigns, whereby priorities given to the elderly and fragile patients appear key to drive the decline in morbidity and mortality associated with the pandemic. It will be important, in this regard, to correlate the quicker or slower decline in morbidity and mortality by COVID-19 in the countries and regions in Europe with the different choices of vaccination priorities selected by the various European governments. This will be an important lesson for tackling similar disasters in the future, and will vouch for more coordinated efforts across countries to capitalize from the best possible knowledge and experiences.

Disclosure of interest

The author declares that he has no competing interest.