The indirect consequences of COVID-19

by:
Alice M. Jackson

The direct impact of the COVID-19 pandemic is easily measured, with many countries reporting the daily number of hospitalisations and fatalities attributed to the disease. Excess deaths (deaths within the total death toll above those that would have been expected if the crisis had not occurred) represent both the direct and the indirect impact of a pandemic. The measurement of excess deaths allows objective quantification of the extent and scale of the impact, even when methods for reporting deaths differ between regions or countries; for example, some countries only report COVID-19 deaths that occur in hospitals, while others only report deaths for patients that have tested positive for the virus. Reporting of excess deaths provides information about deaths that may be related to COVID-19, but are not captured through the reporting system, and also, crucially, about whether the pandemic has led to an increase (or decrease) in deaths from other causes.

There has been mounting concern that patients with cardiovascular disease, and in particular those with acute conditions such as ST-elevation myocardial infarction, might avoid seeking medical attention, leading to late presenting sequalae such as ventricular septal rupture or heart failure. In Scotland, the rate of deaths from cardiovascular disease peaked at around 17% higher than the preceding 5-year average shortly after the country’s lockdown measures were implemented, before starting to fall (1). Furthermore, 7% of the total excess deaths over a 5-week period were due to cardiovascular causes (2). Collated data from England and Wales, the Netherlands, Italy and New York State have also highlighted notable levels of excess mortality, not all attributable to COVID-19 (2). What is not clear is whether these excess deaths are due to unconfirmed or unsuspected COVID-19 infection in a high-risk population, whether, as feared, a change in health behaviours has resulted in patients not seeking treatment with symptoms suggestive of an acute cardiac condition, or to what extent both factors may be contributing.

The future impact of the pandemic is difficult to project. Even after immediate transmission is controlled, it is likely that there will be lasting effects on overall population mortality. In an analysis using linked primary and secondary care electronic records for just less than 4 million individuals in the UK, excess 1-year mortality was modelled under 3 different scenarios – full suppression, mitigation and ‘do nothing’ – assuming different levels of risk in each scenario based on underlying comorbidities (3). Excess deaths ranged from 2 in a full suppression scenario with a relative risk of 1.5, to 587 982 in a ‘do nothing’ scenario with a relative risk of 3.0.  Data such as these are essential to policy makers in order to understand and mitigate worst case scenarios.

Reporting of excess deaths provides a more accurate representation of the full effects of the pandemic and a better measure from which to draw international comparisons. Understanding exactly what contributes to these deaths is important if high-risk groups are to be identified and targeted with appropriate risk-modifying interventions. Although health services have been reorganised and redirected in order to cope with the pandemic, it is vital that the public are encouraged to access acute service as normal.

  • Figueroa JD, Brennan P, Theodoratou E et al. Trends in excess cancer and cardiovascular deaths in Scotland during the COVID-19 pandemic 30 December – 20 April suggest underestimation of COVID-19 related deaths. 6 May 2020. https://doi.org/10.1101/2020.05.02.20086231
  • Docherty K, Butt J, de Boer R et al. Excess deaths during the Covid-19 pandemic: an international comparison. 13 May 2020. https://doi.org/10.1101/2020.04.21.20073114
  • Banerjee A, Pasea L, Harris S et al. Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population based cohort study. Lancet. 12 May 2020. https://doi.org/10.1016/S0140-6736(20)30854-0

Ethnicity, cardiovascular disease and COVID-19 in the UK

by:
Alice M. Jackson

Soon after the first death of a UK health care worker linked to COVID-19 was reported at the end of March, an alarming trend quickly appeared – the majority of those dying on the front line were from an ethnic minority. To date, just under two-thirds have been from a Black, Asian or Minority Ethnic (BAME) group (1). By contrast, 14% of the UK population and approximately 20% of the National Health Service workforce are from a BAME group. Whilst the media reports of deaths amongst frontline workers relayed an early warning about ethnic disproportionalities, only more recently have data about the issue in the wider UK public started to emerge.

Last week, the Office for National Statistics (ONS) published an analysis of 14,745 COVID-19 related deaths in England and Wales, stratified by ethnic group, through linkage with patient characteristics captured in the 2011 Census (2). Across all ages, 16% of deaths occurred in BAME groups – predominantly Indian, Bangladeshi, Pakistani and Black patients. Compared to their White counterparts, the age-adjusted likelihood of death for Black men and women was more than 4-times greater, for Bangladeshi or Pakistani men and women was more than 3-times greater and for Indian men and women was more than 2-times greater. After further adjustment for sociodemographic factors (region, rural and urban classification, area deprivation, household composition, socioeconomic position, highest qualification held, household tenure, and health or disability), the association was attenuated by around half for all groups, but not removed.

A substantial part of the inequality in outcomes from COVID-19 is explained by differences in geographic and socioeconomic factors. This is not only the case in the UK, but also in America, where similar disparities have been reported. However, other drivers not accounted for in the analyses by ONS, such as health behaviours, employment (i.e. higher-risk occupations), specific underlying health conditions and, possibly, genetic factors, are likely to be important and the relationship between these factors complex.

Differences in the prevalence of cardiovascular diseases, which adversely affect prognosis, may also be relevant. Amongst Italian patients who died, 71% had a history of hypertension, 28% of coronary artery disease and 16% of heart failure (3). The development of cardiovascular disease is driven by an extensive number of risk factors, and ethnicity is well-established as one of these. Coronary artery disease is more common in South Asians than in Europeans (4), and Black men and women more frequently develop hypertension than other groups (5). Multimorbidity, which itself is more common in BAME than in White patients, further increases the risk of adverse cardiovascular events and death from any cause in patients with established cardiovascular disease (6).  Although not accounted for by ONS, two UK-based groups have reported the effect of adjusting for comorbidities on the association between ethnicity and risk of death from COVID-19. In one population study, national primary care electronic health record data was linked to in-hospital death data for more than 17 million patients (7), and in the other, specific data was collected from the electronic health records of 2217 patients (8). In both studies, despite adjusting for comorbidities, the point estimates for the risk of death remained well above 1.0 for patients from BAME groups (although in some cases, due to small numbers of events, the confidence intervals were wide).

Better understanding the interplay between ethnicity and cardiovascular disease within the context of COVID-19 is important. However, although this may account for part of the ethnicity trend observed, there remains factors that are, as yet, unexplained. Research into identifying what these are is urgently needed. Whether the observations in the UK population extend to other ethnically diverse countries remains to be seen.

  • Williamson E, Walker AJ, Bhaskaran K et al. OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients. medRxiv preprint 7 May 2020. https://doi.org/10.1101/2020.05.06.20092999
  • Sapay E, Gallier S, Mainey C et al. Ethnicity and risk of death in patients hospitalised for COVID-19 infection: an observational cohort study in an urban catchment area. medRxiv preprint 9 May 2020. https://doi.org/10.1101/2020.05.05.20092296

Do hypertension patients have high risk for COVID-19 ?

by:
Eduardo Chuquiure-Valenzuela

Recent studies about COVID-19 patients have reported that hypertension is associated with higher in-hospital complications and mortality. Also, worse results in angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) were hypothesized.  There was uncertainty about initial clinical studies solidity. Most of cardiologic societies around the world, advise to continue ACEI and ARBs treatment, according to guidelines recommendations and proposed further clinical studies to assess safety in antihypertensive drugs use.

The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension.   Comorbidities, drug safety, in-hospital mortality, and high-risk predictors in cardiovascular patients with COVID-19 were evaluated in two clinical studies.

Zhang et al, on 17 Apr 2020, ahead to print published  in Circulation Research   https://doi.org/10.1161/CIRCRESAHA.120.317134 an association between in-hospital use of ACEI/ARB and all-cause mortality in COVID-19 patients with hypertension.

A retrospective study, in nine hospitals in Hubei, China, from December  2019 to February  2020. They included 1128 adult hypertensive patients with COVID-19.  Authors analyzed two groups: A taking ACEI/ARB (188 patients) group and 940 without treatment (non-ACEI/ARB group). Clinical characteristics were similar in both groups, but the non-ACEI/ARB group had higher prevalence of fever, dyspnea, and bilateral lung lesion at presentation. Unadjusted mortality rate was lower in the ACEI/ARB group versus the non- ACEI/ARB group (3.7% vs. 9.8%; P = 0.01).  All- cause mortality risk was observed in age, gender, coronary heart disease and cerebrovascular disease.

In-hospital use of ACEI/ARB was associated with lower risk of all-cause mortality (adjusted HR, 0.29; 95%CI, 0.12-0.69; P = 0.005) due to COVID-19. After adjusting for age, gender, comorbidities, and in-hospital medications, risk for all-cause mortality was lower in the ACEI/ARB group

Mehra et al published in NEJM.org.DOI:10.1056/NEJMoa2007621, (May 1th, 2020) an observational study in 8,910 COVID-19 patients from 169 hospitals in Asia, Europe, and North America, between December 2019, and March 2020. They contrasted cardiovascular disease and drug therapy history with in-hospital mortality.

In this collaborative database, investigators described that in-hospital  global mortality was 5.8%, factors associated with an increased mortality were: age greater than 65 years (10.0%, vs. 4.9%;) coronary artery disease (10.2%, vs. 5.2%)¸ heart failure (15.3%, vs. 5.6%); cardiac arrhythmia (11.5%, vs. 5.6%); chronic obstructive pulmonary disease (14.2%, vs. 5.6%).

No increased risk of in-hospital death was found to be associated with use of ACEI (2.1% vs. 6.1%); ARBs (6.8% vs. 5.7%) and female gender (5.0% vs 6.35)

Comments

As clinical data progresses, we can have a better guidance  to address these research questions.  

Both prospective and consecutive clinical studies revised had non comparable populations, but in common, the pair evaluate mortality, risks of the history of comorbidities  and cardiovascular treatment.  The impact on hypertensive patients and the use of ACEI/ARB was described by Zhang et al,  instead comparisons  based on survivors and non survivors were analyzed by Mehra et al.

In my consideration, both clinical studies are complementary because safety of antihypertensive drugs were analyzed, and high risk in cardiovascular history with COVID-19 patients was determined.

What do we learn from these studies?

  • Beneficial effects observed with continued use of ACEI/ARB therapy.
  • ACEI/ARB was associated with lower risk of all-cause mortality.
  • Elderly, heart failure and coronary artery disease have high risk.

Limitations

  • Both are retrospective and consecutive studies.
  • Antihypertensive drugs were not controlled.
  • They could be biased by residual confounders.
  • Studies were evaluated at different time periods.

Eduardo Chuquiure-Valenzuela
Clinical cardiologist
Instituto Nacional de Cardiología
Mexico City
@cardinvest

EMPTY HOSPITALS: ARE WE CREATING A TICKING TIME BOMB FOR CARDIOVASCULAR DISEASE PATIENTS

by:
Lilian Mbau

A lot has been discussed about the interaction between coronavirus disease of 2019 (COVID-19) and Cardiovascular Diseases (CVDs) with more focus on the effect of COVID-19 on patients with CVDs as well as the cardiovascular (CV) complications resulting from COVID-19 infection. Patients with underlying conditions such as CVD or associated risk factors have increased mortality from COVID-19 infection (European Society of cardiology, 2020). Covid-19 infection on the other hand has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias and venous thromboembolism (Xiong et al., 2020).

It is however important that we also focus on the implications of the pandemic on CVD patients without COVID-19 infection. It is estimated that up to 80% of elective admissions and procedures in most countries have been postponed (Gori et al., 2020). In addition, in some countries there has been a drop of up to 30% of visits to the emergency departments (Gori et al., 2020). A study carried out in Hongkong, China looking at the effect of COVID-19 on Acute ST-segment–elevation myocardial infarction (STEMI) patients seeking care at one of the treatment centers found an increase in time from onset of symptoms to seeking medical care as well as an increase in the time from arrival to the hospital to the completion primary percutaneous coronary intervention (PPCI).

Not seeking care or delays in seeking care can result in negative outcomes especially among patients with CVDs and other chronic illnesses. Patients with CVDs and other comorbidities have been made aware of their increased risk of infection as well as the poorer outcomes. They have been urged to take more seriously hygiene and social distancing measures. The European Society of Cardiology (ESC) recommends patients with hypertension to monitor their blood pressure at home and receive videoconference and telephone consultation as required (European Society of cardiology, 2020). The American College of Cardiology recommends that in-person clinic visits should be replaced with telehealth visits in areas with active COVID-19 to minimize nosocomial infections (ACC, 2020). The risk of these recommendations occurs when patients are not adequately able to monitor their conditions at home or are not educated on when they should seek care.

The impact of COVID-19 on health outcomes of chronic disease patients in low- and middle-income countries (LMIC) may be worse. A significant proportion of these patients are often poorly managed due to inability to access quality health services including affordable medication. In addition, due to poor health seeking behavior and competing priorities, patients with chronic disease such as hypertension tend to stop their medication when they feel better and even abandon their routine clinic visits altogether.  Poor health accessibility brought about by the COVID-19 pandemic is likely to worsen the situation resulting in poorer outcomes (Kretchy et al., 2020). It is also likely that the global restriction in imports and exports will affect supply of medication for chronic diseases resulting in shortages and subsequent increase in cost.

In Kenya for example, as soon as the initial patients with COVID-19 were diagnosed, a number of both private and public CVD and other routine clinics rushed to close requiring patients who needed care to visit the accident and emergency department or consult the doctor through their mobile phones. Some private practices and hospitals were able to quickly put in place telemedicine and drug delivery services however majority of Kenyans seeking care in the public hospitals were left out. Several public hospitals are reporting significant decline in both acute and chronic care visits. Cognizant of the danger many chronic disease patients were exposed to by restrictions in access to health services, the Ministry of Health issued a directive to all health facilities in the public sector to ensure services for patients with non-communicable diseases such as hypertension and diabetes clinics remain open.

The true impact of the pandemic on CVD care will become evident after the containment of the pandemic. It is however important that as policy makers put in place measure to contain the infection, they take into consideration the effect of these measure on delivery of routine services especially for chronic disease patients (Tam et al., 2020).

Table of Contents

Can the fear of COVID-19 lead to harmful delays in seeking care for cardiovascular emergencies?
by: Darryl Leong

Should cardiovascular disease comorbidity scare you during the COVID-19 season?
by: Jeemon Panniyammakal

Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China
by: Lucrecia M. Burgos

The link between smoking and COVID 19; should we wait for more evidence to quit smoking?
by: Jeemon Panniyammakal

Cardiovascular implications of fatal outcomes of patients with Coronavirus disease 2019 (COVID-19)
by: Lucrecia M. Burgos

Cardiac Biomarkers and COVID19
by: Darryl Leong

The Implications of Viral Particles in the Myocardium
by: Darryl Leong

Impact of the COVID-19 pandemic on interventional cardiology activity
by: Lucrecia M. Burgos

Association of renin-angiotensin system inhibitors with severity and outcomes of COVID-19 infection in hospitalized patients with hypertension
by: Lucrecia M. Burgos

Multimorbidity and COVID 19: A catastrophic combination
by: Jeemon Panniyammakal

COVID-19 and critical care admissions in the UK: using routine data during a pandemic.
by: Alice M. Jackson

EMPTY HOSPITALS: ARE WE CREATING A TICKING TIME BOMB FOR CARDIOVASCULAR DISEASE PATIENTS
by: Lilian Mbau

Do hypertension patients have high risk for COVID-19?
by: Eduardo Chuquiure-Valenzuela

Ethnicity, cardio-vascular disease and COVID-19 in the UK
by: Alice M. Jackson

The indirect consequences of COVID-19
by: Alice M. Jackson

COVID-19 and critical care admissions in the UK: using routine data during a pandemic.

by:
Alice M Jackson

The Intensive Care National Audit and Research Centre (ICNARC) collates, reports and audits data for all National Health Service adult critical care admissions in the UK (England, Wales and Northern Ireland). Since the beginning of March 2020, 245 critical care units across the UK have submitted data on 6720 patients admitted with confirmed COVID-19, with data on outcomes in 4078 (61%) (1). In the report, patient demographics, markers of disease severity, length of stay, requirement for organ support and death or discharge from critical care are presented. Approximately a third of patients are from critical care units in London.

The mean age of patients was 59.4 (±12.5) years, 72% were men, half were in the two highest deprivation quintiles (where a higher number equates to more deprivation) and race was reported as Black, Asian or was unspecified (but non-White) in 34% of patients. In the 2011 England and Wales census, 14% of the whole population and 40% of people living in London identified as non-White (2). The burden of comorbidity is not well-described in the report, which only provides data about ‘very severe comorbidities’; in the case of cardiovascular disease, this is defined as cardiovascular disease with symptoms at rest in the six months prior to admission to critical care, and was present in 0.4% of patients.

Amongst 4078 patients with data on outcomes, advanced cardiovascular support (defined as the use of pharmacological inotropic or chronotropic support, or continuous cardiac output monitoring, or insertion of an intra-aortic balloon pump, or temporary cardiac pacing) was required in 27%, for a median duration of 3 (IQR 1-5) days –  5% more than required the same support when admitted to critical care with viral pneumonia from 2017-2019. As expected, nearly all of these patients (98.6%) required some form other additional organ support. Of those who required advanced cardiovascular and advanced respiratory support (n=613, 15%), the case-fatality rate during the critical care admission was 73%, increasing to 87% when renal replacement therapy was also required (n=440, 11%).

In the UK, routinely collected data like these are a rich source of information and can provide a comprehensive description of the emerging epidemiology of a new disease early in its course, such as with COVID-19. In England and Wales, population-level mortality datasets are collated and reported by the Office for National Statistics, and in Scotland by National Records for Scotland. Linkage of mortality datasets with other routine datasets, such as hospital admissions, is also possible. In Scotland, this is done through a combination of deterministic matching, which involves matching a unique patient identifier assigned to each individual in Scotland at birth, and probabilistic matching, which involves the use of other variables (such as name, date of birth or postcode) to determine whether the records belong to the same individual (3). In recent weeks, this existing infrastructure has allowed the UK to produce regular reports on health outcomes relating to COVID-19 in a timely and cost-effective fashion. Going forward, routine data such as these will not only facilitate research on the direct health effects of COVID-19, but also on the wider consequences of the pandemic.

References
1) https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports. ICNARC report on COVID-19 in critical care 24 April 2020. (Accessed 28 April 2020)

2) http://www.nomisweb.co.uk/census/2011/dc2101ew. Ethnic group by sex and age. (Accessed 28 April 2020)

3) Fleming M, Kirby B, Penny K. Record linkage in Scotland and its applications to health research. J Clin Nurs. 2012;21(19-20):2711-2721.

Multimorbidity and COVID 19: A catastrophic combination

by:
Jeemon Panniyammakal

Multimorbidity is the existence of multiple long-term mental, physical, and cognitive disorders in one patient. These could include diabetes, hypertension, lung diseases, heart attacks, stroke, kidney failure, mental health conditions, and liver problems or other chronic conditions. Multimorbid conditions often share common disease causes and consequences. The disease pattern, progression and trajectories in multimorbidity are path-dependent in nature and often determined by age, sex and socio-demographic characteristics. However, addition of COVID 19 dramatically changes the disease progression pathways and cut-short the trajectories to immediate clinical end-points in individual with multimorbidity.

Richardson et al, presented the characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area. (doi:10.1001/jama.2020.6775). Hypertension (57%), obesity (42%) and diabetes (34%) were the most common comorbid conditions in this group of patients with median age of 63 years. Nearly, 9 of 10 COVID 19 patients had more than one comorbidities. The median number of comorbid conditions were 4. Similarly, the median score on the Charlson Comorbidity Index was 4 points (Inter Quartile Range, 2-6). In short, the comorbidity burden was substantial in the affected COVID 19 cases in the New York City area. For example, the cumulative comorbidity burden corresponds to a 53% estimated 10-year survival.

Richardson and colleagues reported mortality rates only for patients with definite outcomes (discharge or death). Of the total 2634 patients with one of the definite outcomes, 553 died (21%). Nearly three of four deaths were reported in individuals with >65 years of age. There were no deaths in the age group of <18 years. Nearly, 70% of patients died in the hospital had hypertension as a comorbidity. However, only 47% of discharged patients had hypertension as a comorbidity. Diabetes was present in 40% of patients died in the hospital, while it was 26% in those who were discharged from the hospital. It is reasonably clear that individuals with comorbid conditions have poor prognosis when affected by COVID 19. Although the data are not presented separately by multmorbidity pattern, it is probably appropriate to assume that multimorbidity is associated with poor survival outcomes in COVID 19 patients.

In comparison to people with single health problems and no other comorbid conditions, people with multimorbidity are more likely to have worse general health and an increased risk of premature death. Available data indicate that COVID 19 further increases the risk of mortality in individuals with multimorbidity. We may have to devise effective public health strategies to protect individuals with multimorbidity from COVID 19. Further, such individuals may require prioritised testing and management for COVID 19. They also need to get access to their regular medications and health services essential to manage their comorbid conditions. Ignoring their immediate medical needs may lead to catastrophic consequences even if they escape from COVID 19. 

Association of renin-angiotensin system inhibitors with severity and outcomes of COVID-19 infection in hospitalized patients with hypertension

by
Lucrecia M. Burgos

Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are not associated with severity and outcomes of coronavirus disease 2019 (COVID-19) infection in hospitalized patients with hypertension  in Wuhan, China according to a recent study in JAMA Cardiology1.

In this retrospective single-centre analysis, the authors analysed hospitalized patients with COVID-19 at the Central Hospital of Wuhan China from January 15, 2020, to March 15, 2020. There were 1178 patients hospitalized with COVID-19 (mean age 55.5 years; 46.3% men). Among them, 30,7% had hypertension. Patients with hypertension were older and had greater prevalence of chronic diseases; they also had more severe manifestations of COVID-19, including higher rates of acute respiratory distress syndrome and greater in-hospital mortality (21.3% vs 6.5%; P < .001). Around one-third were taking an ACEI or ARB.

Patients with and without ACEI/ARB treatment had similar comorbidities, with the exception of higher prevalence of coronary artery disease in those taking ACEIs/ARBs (23.5% vs 14.2%).  They also presented similar laboratory profile results including blood cell counts, inflammatory markers, renal and liver function tests, and cardiac biomarkers.  The frequency of severity of illness and acute respiratory distress syndrome did not differ with respect to ACEI/ARB therapy.  ACEIs/ARBs use was similar for those who died and those who survived (27.3% vs 33.0%; P = 0.34).

In this study, the authors report data demonstrating that there was no difference in the disease progression and risk of death during hospitalization for COVID-19 with respect to various antihypertensive drugs and in the use of ACEIs/ARBs. They also confirm that patients with hypertension had more severe illness and higher mortality rates than those without hypertension, however, these previous reports did not indicate how many patients were taking ACEIs or ARBs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) use the ACE2 receptor to enter the host cells, and ACE2 negatively regulates the renin-angiotensin system by inactivating angiotensin II and likely plays a protective role against the development and progression of acute lung failure 2,3.  Animal studies have shown that expression of ACE2 is substantially increased in patients treated with ACEIs/ARBs4.  In contrast to available animal models, there are few studies in humans regarding the effects of RAAS inhibition on ACE2 expression. In a study circulating ACE2 levels were increased in patients with diabetes treated with ACEIs5. Based on these observations, some experts have speculated that use of ACEIs/ARBs leading to increased expression of ACE2 could potentially facilitate infection with COVID-19. A recent study showed that serum angiotensin II levels in patients with COVID-19 pneumonia was significantly higher compared with healthy individuals and were linearly associated with viral load and lung injury6.  Based on this, it can be postulated that SARS-CoV-2 binding to ACE2 may attenuate residual ACE2 activity, skewing the ACE/ACE2 balance to a state of heightened angiotensin II activity leading to pulmonary vasoconstriction and inflammatory and oxidative organ damage, which increases the risk for acute lung injury7.

The clinical role of this pathway in COVID-19 complications and any effect from possible modulation of this receptor is not yet fully known and going to be tested in upcoming clinical trials. A multicenter, double-blind, placebo-controlled phase 2 randomized clinical trial of starting losartan in patients with COVID-19 in outpatient settings (ClinicalTrials.gov identifier: NCT04311177) and in in-patient settings (ClinicalTrials.gov identifier: NCT04312009) is currently being planned7.

Presently, there are no data regarding a favorable effect of RAS blockade on pulmonary outcome in SARS-CoV-2-infected patients. Whether or not infectivity to viral infection is increased in patients treated with RAS blockers remains unknown8. There are no peer-reviewed experimental or clinical data demonstrating a specific benefit or risk from using ACE inhibitors, ARBs, or renin-angiotensin-aldosterone system antagonists in COVID-19 9. However, recent news media coverage of this issue have provoked concern and unfortunately even motivated some patients to discontinue RAS blockers all together.

Several professional societies have put forward their guidance regarding the use of ACEIs/ARBs in patients with COVID-19. A joint statement by the Heart Failure Society of America, American College of Cardiology, and American Heart Association recommends that these medications can be continued in patients with COVID-19 without interruption in compliance with available clinical guidelines10.

Study authors mention as a limitation that the current findings may not be generalizable to all patients with hypertension, and it is possible that ACEIs/ARBs could affect the chance of hospitalization. In addition, it is not certain whether the ACEI/ARB treatment at baseline was maintained throughout the hospitalization for all patients. Furthermore, the authors did not mention whether the inclusion of patients was consecutive. In China most patients are on ARB as opposed to an ACE inhibitor, because  the prevalence of cough requiring discontinuation of ACE inhibitor therapy was found to be significantly higher among subjects with Chinese ethnicity11,12.

To conclude, renin–angiotensin system blockade treatment should be continued.  Present evidence is insufficient to recommend use of RAS blockade prophylactically in subjects at risk or therapeutically in those infected with SARS-CoV-2. In this preliminary assessment ACEI/ARB was not associated with severity and worse outcomes of COVID-19 infection in hospitalized patients with hypertension.

Further epidemiological studies and prospective trials are urgently needed to investigate if use of ACEIs/ARBs can reduce the incidence, severity and or mortality associated with COVID-19.

References

1. Li J, Wang X, Chen J, et al. Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China. JAMA Cardiol. 2020 Apr 23. doi: 10.1001/jamacardio.2020.1624.

2. Li  F.  Structure, function, and evolution of coronavirus spike proteins.  Annu Rev Virol. 2016;3:237-261. doi:10.1146/annurev-virology-110615-042301

3. Imai  Y, Kuba  K, Rao  S,  et al.  Angiotensin-converting enzyme 2 protects from severe acute lung failure.  Nature. 2005;436:112-116. doi:10.1038/nature03712

4. Klimas  J , Olvedy  M , Ochodnicka-Mackovicova  K ,  et al.  Perinatally administered losartan augments renal ACE2 expression but not cardiac or renal Mas receptor in spontaneously hypertensive rats.   J Cell Mol Med. 2015;19:1965-1974. doi:10.1111/jcmm.12573

5. Soro-Paavonen  A , Gordin  D , Forsblom  C ,  et al; FinnDiane Study Group.  Circulating ACE2 activity is increased in patients with type 1 diabetes and vascular complications.   J Hypertens. 2012;30:375-383. doi:10.1097/HJH.0b013e32834f04b6

6. Liu  Y , Yang  Y , Zhang  C ,  et al.  Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury.   Sci China Life Sci. 2020;63:364-374. doi:10.1007/s11427-020-1643-8

7. Bavishi C, Maddox TM, Messerli FH. Coronavirus Disease 2019 (COVID-19) Infection and Renin Angiotensin System Blockers. JAMA Cardiol. 2020 Apr 3. doi: 10.1001/jamacardio.2020.1282. 

8. Messerli FH, Siontis GCM2, Rexhaj E. COVID-19 and Renin Angiotensin Blockers: Current Evidence and Recommendations. Circulation. 2020 Apr 13. doi: 10.1161/CIRCULATIONAHA.120.047022.

9. Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System: A Review. JAMA Cardiol. Published online March 27, 2020. doi:10.1001/jamacardio.2020.1286

10. HFSA/ACC/AHA statement addresses concerns re: using RAAS antagonists in COVID-19. Accessed March 19, 2020.

https://professional.heart.org/professional/ScienceNews/UCM_505836_HFSAACCAHA-statement-addresses-concerns-re-using-RAAS-antagonists-in-COVID-19.jsp

11. Woo KS, Nicholls MG. High prevalence of persistent cough with angiotensin converting enzyme inhibitors in Chinese. Br J Clin Pharmacol. 1995;40:141–4.

12. Tseng DS, Kwong J, Rezvani F, Coates AO. Angiotensin-converting enzyme-related cough among Chinese-Americans. Am J Med. 2010;123:183, e11–5


Impact of the COVID-19 pandemic on interventional cardiology activity

by:
Lucrecia Maria Burgos

An important reduction in the activity in interventional cardiology has been observed during the COVID-19 epidemic according to a recent study in REC Interventional Cardiology1.

The authors carried out a survey in 81 centres involved in ST-elevation myocardial infarction (STEMI) networks in the 17 autonomous communities of Spain. Information was collected on diagnostic activity, percutaneous coronary intervention (PCI), structural interventions, and PCI in STEMI on changes in the organization of STEMI networks, and on the prevalence of COVID-19 among interventional cardiologists. Data was compared for the week of February 24 through March 1 (before the outbreak) and for the week of March 16 through March 22 (during the outbreak).  A significant decrease in the number of diagnostic procedures (─57%), PCI (─48%), structural interventions (─81%) and PCI in STEMI (─40%) has been observed. A slight increase in the use of pharmacological thrombolysis has been reported, although primary angioplasty remains the leading reperfusion strategy. Of 339 medical professionals who perform primary angioplasty procedures, 17 presented COVID-19 infection (5%).

In this study, the time to reperfusion, the clinical characteristics, as well as in-hospital complications, were not analysed. And the report of the use of lithic, was made with a non-quantitative method, asking each centre if more thrombolytic therapy has been performed.

The COVID-19 pandemic caused by infection with the SARS-CoV-2 virus has put the Spanish health system in a situation of serious overload. On March 14, 2020, the state of alarm was declared in Spain with a house confinement of the population with the aim of slowing down the progression of the epidemic. As a consequence, attention to other pathologies could have been affected, and among them the treatment of cardiovascular diseases. This is especially important in emergencies such as STEMI. In a recently reviewed study in the Heart Blog, Tam, et al 2. described the timeliness of primary percutaneous coronary intervention for STEMI in a single centre in Hong Kong, China. They reported an approximately 3-fold increase in the time from symptom onset to medical contact.

Scientific societies and health authorities have to promote that patients presenting STEMI compatible symptoms should proceed with no delay to access the health system to receive reperfusion treatment.

More studies are needed to assess whether this phenomenon occurs in other parts of the world, and to explore the factors that could explain the decrease of coronary interventions, especially in STEMI. From the World Heart Federation, we encourage to start studies that evaluate the impact of the pandemic on the health care of other cardiovascular diseases. To identify the barriers to cardiovascular disease care, and find possible solutions such as telephone advice lines or telemedicine.

References

1. Rodríguez-Leor O, Cid Alvarez B, Ojeda S et al. Impacto de la pandemia de COVID-19 sobre la actividad asistencial en cardiología intervencionista en España. REC Interv Cardiol. 2020. https://doi.org/10.24875/RECIC.M20000120

2. Tam CF, Cheung KS, Lam S, et al. Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on ST-Segment-Elevation Myocardial Infarction Care in Hong Kong, China. Circ Cardiovasc Qual Outcomes. 2020:CIRCOUTCOMES120006631.


The Implications of Viral Particles in the Myocardium

by.
Darryl Leong

Systolic left ventricular dysfunction in the absence of obstructive coronary artery disease has been described in several anecdotes and case reports in patients with COVID-19. The mechanisms underlying the cardiomyopathy is unclear. In a case report, Tavazzi, et al. describe the first instance of coronavirus-like particles seen by electron microscopy in the myocardium of a patient with COVID-19 who exhibited marked impairment in systolic left ventricular function1. These particles were seen within interstitial cytopathic macrophages and not within myocytes under electron microscopy of a single endomyocardial biopsy. In addition, only low-grade myocardial inflammation was observed, with no evidence of myocyte necrosis.

While this report is valuable in that it is the first to demonstrate likely SARS-CoV-2 localization within the heart, the authors prudently avoid ascribing a causal relationship between the viral particles and the left ventricular dysfunction. Previous research has shown that viral (e.g. parvovirus B19) genomes can be found in cardiac tissue in patients with no evidence of myocarditis2. Therefore, it remains unknown whether the localization of SARS-CoV-2 in cardiac tissue is simply the result of viremia or translocation of infected macrophages, or whether it has a direct pathogenic effect on the myocardium. Further evidence of a causal relationship, such as the demonstration of active myocarditis or histologic myonecrosis is needed to build the case that SARS-CoV-2 can directly cause myocardial damage. Numerous randomized, clinical trials of antiviral therapies in patients with COVID-19 are underway or being planned. If a reduction in adverse cardiac outcomes were shown in these trials, it would strengthen the evidence of a direct causal role of COVID-19 in left ventricular dysfunction.

1.           Tavazzi G, Pellegrini C, Maurelli M, Belliato M, Sciutti F, Bottazzi A, Sepe PA, Resasco T, Camporotondo R, Bruno R, Baldanti F, Paolucci S, Pelenghi S, Iotti GA, Mojoli F and Arbustini E. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail. 2020.

2.           Kuhl U, Pauschinger M, Noutsias M, Seeberg B, Bock T, Lassner D, Poller W, Kandolf R and Schultheiss HP. High prevalence of viral genomes and multiple viral infections in the myocardium of adults with “idiopathic” left ventricular dysfunction. Circulation. 2005;111:887-93.