The Heart in the Time of COVID-19

The long cardiovascular tail of the pandemic

The countries which have been unable to suppress SARS-CoV-2 infection rate have had to focus health systems and resources on the acute hospitalised phase of COVID-19, particularly in the intensive care unit. However, most hospital care of COVID is not in intensive care, and most COVID patients, even in high-income settings, are not seen in hospital. Moreover, it is now clear that a great deal of the burden of COVID-19 is outside the acute phase.

Consideration of cardiovascular disease (CVD) has followed the same trajectory, where much of the debate and concern has been about direct effects such as myocarditis and pericarditis. Myocarditis may not be as common as initially thought. Where it occurs, it appears to be mild and usually recovers, based on current literature, but further follow-up and more representative data are required.

However, the indirect impact of the pandemic on CVD and its care are likely to represent a greater burden for individuals, populations and health systems. A systematic review included 103 observational studies of CVD care during the pandemic. Most studies assessed hospitalisations for acute CVD, e.g. acute coronary syndrome, ischaemic strokes and heart failure. 89% of studies reported reduced hospitalisations during the pandemic compared to pre-pandemic times, with reductions ranging from 20.2 to 73%. CVD and its care needs to be prioritised, especially in times of global health emergency, when we know that underlying conditions such as CVD increase the severity and mortality of COVID-19. This can be achieved by reducing infection rate at population level (a “zero COVID” strategy) which ensures that non-COVID services can be maintained, and education of patients, public and health professionals to recognise and seek help for CVD symptoms. Following acute COVID-19, it has been clear since May 2020, that some patients have persistent symptoms and functional impairment. In 47 780 post-hospitalised COVID-19 patients , four months after initial SARS-CoV2 infection, we showed that major adverse cardiovascular events, chronic liver disease, chronic kidney disease, and diabetes after discharge from hospital were 3.0 (2.7 to 3.2), 2.8 (2.0 to 4.0), 1.9 (1.7 to 2.1), and 1.5 (1.4 to 1.6) times more frequent, respectively, than in a matched control group. Even in non-hospitalised patients, cardiorespiratory symptoms are common and have resource implications in terms of investigations and specialist input. The mechanism of the increased risk of CVD is not clear and needs to be further investigated. However, it is clear that CVD has played a role in the COVID-19 pandemic as a risk factor, a potential long-term consequence and an indirect effect. Therefore, CVD management is crucial during and after the pandemic.

Do COVID STEMIs have a higher thrombus burden? More questions & implications

by:
Aaysha Cader

Whilst much has been written about COVID-19 and its inflammation-thrombosis-hypercoagulability cascade, this has to a large extent focused on venous thromboembolism (VTE). As more data emerges, it is evident that the intense inflammatory response associated with SARS-COV-2 infection may trigger thrombosis across multiple vascular beds, with large thrombus burden in ST-segment elevation myocardial infarction (STEMI) being one of many potential manifestations (1,2).

In a single-center, observational study published in the Journal of American College of Cardiology, Choudry et al. (1) reported a strong signal toward higher thrombus burden and poorer outcomes among COVID-19-positive STEMI patients undergoing primary percutaneous coronary intervention (PCI), in comparison with those who were COVID-negative.

Representing the largest comparative data-set of real-world consecutive STEMI patients during the COVID-19 pandemic, this study compared patient characteristics, laboratory variables, procedural characteristics and outcomes between 39 COVID-positive and 76 COVID-negative cases presenting at the Barts Heart Centre in London, United Kingdom between March 1, 2020, and May 20, 2020.

The median age of the 115 patients was 62 years, and included 48.7% from Black, Asian, or minority ethnic (BAME) groups. 78% were male. The predominant conclusion derived from the analysis was the unique burden of coronary thrombus leading to greater technical complexity during primary PCI in COVID-related STEMIs.

Angiographic data analysis showed significantly higher rates of multivessel coronary thrombosis in COVID-19 STEMI patients (17.9% vs 0%; p= 0.0003). This was consistent with a previously reported case of STEMI from Spain, published earlier-on during the pandemic, in which a critical thrombotic stenosis of the right coronary artery, and concomitant non-occlusive thrombus in the left anterior descending artery were observed, without underlying atherosclerotic plaque and confirmed by optical coherence tomography (OCT) imaging (3).

The London registry also reported significantly higher rates of stent thrombosis in the COVID-19 positive STEMI group in comparison to those testing negative (10.3% vs. 1.2%; p= 0.0445). Furthermore, large thrombus burden (post first device modified thrombus grade 4/5) was more than twice as likely in patients with COVID-19 STEMI compared with those without COVID-19 (75.0% vs. 31.4%; p= 0.0006). Laboratory findings indicated significantly higher median peak plasma hs-troponin (p=0.0028) and D-dimer levels (p= 0.0012) in COVID STEMI cases; these patients also had a lower left ventricular ejection fraction (p=0.019).

In the setting of higher thrombotic burden, there was also significantly greater use of aspiration thrombectomy (17.9% vs. 1.3%; p= 0.0021) and GP IIb/IIIa inhibitors (59.0% vs. (9.2%; p<0.0001) in patients with COVID-19. Although no significant differences were observed in the total dose of heparin administered, there was a suggestion of higher heparin doses required to achieve therapeutic activated clotting times (ACTs) in the COVID-positive cohort.

In terms of procedural success, TIMI flow grade 3 was achieved at similarly high levels in both groups, however myocardial blush grade was significantly lower in the COVID-19 group (myocardial blush grade of 2 to 3 in 54% vs. 93% for COVID-positive and COVID-negative respectively, p < 0.0001).

Despite more thrombotic STEMI, only numerically higher rates of in-hospital mortality were observed among the COVID-19 STEMI patients (17.9% vs. 6.5%, p =0.10). However, COVID-19 STEMI group had longer in-patient admission (p = 0.0004) and higher rates of intensive care admission (p = 0.003).

The findings in this UK registry are in contrast to data that emerged at the beginning of the pandemic, where much emphasis was placed on the presence of the so-called “STEMI-mimickers”, with two early registries, one from New York and another from Lombardy, Italy both reporting a significant percentage of COVID-positive STEMI patients with no obstructive culprit lesion on angiography (≥50% from New York and 39.3% in the Lombardy registry) (4,5).

Also of note, is the 10-fold higher incidence of stent thrombosis reported among COVID STEMIs in the London registry. Prieto-Lobato et al similarly reported an increase in stent thrombosis during the COVID-19 pandemic peak at their centre in Albacete, Spain (5). They described a series of four cases: one acute and 3 cases of very late stent thrombosis. The case of acute ST was seen in a 49-year-old, where OCT demonstrated in-stent mixed thrombus with mild proximal stent under expansion, and was effectively managed with intracoronary tirofiban and proximal over-expansion of the stent. The 3 cases of very late stent thrombosis all occurred in patients over the age of 70 years, two of them requiring aspiration thrombectomy and tirofiban infusions. The authors also used more potent P2Y12 inhibitors (ticagrelor and prasugrel) in these patients. These cases potentially demonstrate the SARS-CoV-2 hypercoagulable state leading to a stent thrombosis trigger in the presence of other mechanical and biological risk factors (6).

While none of these registry associations nor case series can adequately prove causality for a coronavirus-inflammation-thrombosis–mediated mechanism of STEMI, the increased thrombotic burden and resulting angiographic complexity observed in these COVID STEMI subsets have led to important questions and implications regarding optimum therapeutic strategies, particularly the use of thrombectomy, Glycoprotein IIb/IIIa inhibitors and more potent P2Y12 inhibitors in these patients.

References:

1. Choudry FA, Hamshere SM, Rathod KS, et al. High thrombus burden in patients with COVID-19 presenting with ST-segment elevation myocardial infarction. J Am Coll Cardiol 2020; 76:1168–76.

2. Dauerman HL. The Unbearable Thrombus of COVID-19: Primary PCI, Thrombus, and COVID-19. J Am Coll Cardiol. 2020;76(10):1177-1180.

3. Dominguez-Erquicia P, Dobarro D, Raposeiras-Roubín S, et al. Multivessel coronary thrombosis in a patient with COVID-19 pneumonia. Eur Heart J. 2020 Jun 7;41(22):2132.

4. Bangalore S, Sharma A, Slotwiner A, et al. ST-segment elevation in patients with COVID-19—a case series. N Engl J Med 2020; 382:2478–80.

5. Stefanini GG, Montorfano M, Trabattoni D, et al. ST-elevation myocardial infarction in patients with COVID-19: clinical and angiographic outcomes. Circulation 2020;141:2113–6.

6. Prieto-Lobato A, Ramos-Martínez R, Vallejo-Calcerrada N, et al. A Case Series of Stent Thrombosis During the COVID-19 Pandemic. JACC Case Rep. 2020;2(9):1291-1296.

Cardiac rehabilitation in the time of COVID19

by:
Abraham Samuel Babu

Cardiac rehabilitation (CR) is an integral part of cardiovascular care. Yet, it is one of the most underutilised evidence based intervention across the world.¹ With uptake to CR varying greatly around the world, the novel 2019 coronavirus (COVID19), has been no help to this. Nevertheless, this has brought the entire CR community together to work towards alternate forms of delivery of CR, and move away from traditional institution/supervised CR.

Over the years, home-based CR and telerehabilitation have been gaining some prominence, but not to the extent one would expect it to. With the start of the COVID19 and the cessation of all on-site programs, the need to expand home-based CR and technology driven CR models has hastened the expansion for these models. A proposed technology driven approach to facilitate a complete delivery of CR from assessment to intervention to follow up, has been suggested by two authors. ^2,3 One suggested the use of accessibility of information through social media or online sources for education and the digitisation of patient support groups², while the other focused on its use for assessment and follow-up.³ However, both did recommend the use of various technologically driven methods for exercise prescription.^2,3

From these preliminary reports, professional organisations began to respond to the need for continual delivery of CR across the world during the COVID19 pandemic. Three position statements from leading cardiovascular organisations in Australia⁴, Italy⁵ and Europe⁶ have recommended various strategies to ensure a smooth transition for the delivery of CR for secondary prevention. Specific technology driven recommendations for the delivery of CR from these guidelines are for:

Patient assessment (history, symptoms, adherence to medications), physical examination and investigations
Assessment of physical activity, frailty and exercise capacity
Delivery of patient education
Provision of psychosocial support

From these recommendations, it would seem that technology can be used to ensure the delivery of CR services through home-based delivery models. The use of home-based models is most crucial as patients with cardiovascular disease (with or without comorbidities) places them at a greater risk for COVID19 infection. Considering that the COVID19 is here to stay, CR programs around the world would need to consider long term transition to technologically driven CR method to improve and sustain CR services. A recent statement has provided three simple steps to adapt and transition to virtual CR over a period of year,⁷ which could be worth considering by CR programs.

For those being admitted to hospitals for acute cardiovascular events, delivery of CR may be limited due to relocation of CR staff to COVID duties. However, where CR can be provided on-site for acute cardiac events, protective equipment should be used as recommended for safe delivery of CR.^5,8 Regular assessments of this dynamic situation, should be carried out by the CR team to ensure safety for both patient and the CR team members.

Even though many of the recommendations for virtual CR are applicable across most settings, low resource settings could have their own challenges. Nevertheless, the use of simple technological methods like a phone call, would be more than adequate to ensure the continuity of care for patients with cardiovascular diseases. In addition, home-based delivery models, which are common in low resource settings, should be continued with monitoring through technological methods such as messaging, phone calls and video calls, where feasible.

In conclusion, CR is an essential service for ensuring the continuity of care for patients with cardiovascular disease. Technology driven strategies should be used to facilitate uptake, delivery and monitoring of CR. Simple methods like messaging and phone calls could be considered useful tools in low resource settings, while more advanced technological methods could be considered in high resource settings and where access to technology is not limited by purchasing capacity of an individual.

References:

1. Turk-Adawi K, Supervia M, Lopez-Jimenez F, et al. Cardiac Rehabilitation Availability and Density around the Globe. EClinicalMedicine 2019; 13: 31-45.

2. Yeo TJ, Wang YL, Low TT. Have a heart during the COVID-19 crisis: Making the case for cardiac rehabilitation in the face of an ongoing pandemic. Eur J Prev Cardiol 2020: 2047487320915665.

3. Babu AS, Arena R, Ozemek C, Lavie CJ. COVID-19: A Time for Alternate Models in Cardiac Rehabilitation to Take Center Stage. Can J Cardiol 2020.

4. Nicholls SJ, Nelson M, Astley C, et al. Optimising Secondary Prevention and Cardiac Rehabilitation for Atherosclerotic Cardiovascular Disease During the COVID-19 Pandemic: A Position Statement from the Cardiac Society of Australia and New Zealand (CSANZ). Heart, lung & circulation 2020.

5. Mureddu GF, Ambrosetti M, Venturini E, et al. Cardiac rehabilitation activities during the COVID-19 pandemic in Italy. Position Paper of the AICPR (Italian Association of Clinical Cardiology, Prevention and Rehabilitation). Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace 2020; 90(2).

6. Scherrenberg M, Wilhelm M, Hansen D, et al. The future is now: a call for action for cardiac telerehabilitation in the COVID-19 pandemic from the secondary prevention and rehabilitation section of the European Association of Preventive Cardiology. Eur J Prev Cardiol 2020: 2047487320939671.

7. Moulson N, Bewick D, Selway T, et al. Cardiac Rehabilitation during the COVID-19 Era: Guidance on Implementing Virtual Care. Can J Cardiol 2020.

8. ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic. 2020. https://www.escardio.org/Education/COVID-19-and-Cardiology/ESC-COVID-19-Guidance#p05 (accessed 7th July 2020).

Heart failure and COVID-19: A dynamic and changing interaction

by:
Eduardo Chuquiure-Valenzuela

In several COVID-19 cases, acute myocarditis results in focal or global myocardial inflammation, necrosis¹. Clinically presents ventricular dysfunction and tachyarrhythmias^2-3. Also, may influence in cardiac contractile worsening with a severe impact on Heart Failure (HF).

It is postulated that Heart Failure risk is mediated by a decrease in myocardial oxygen supply caused by hypoxia and severe respiratory distress. Worsening in myocardial oxygen is exaggerated by sympathetic stimulation. Myocarditis, myocardial depression, and myocyte necrosis is mediated by an increase in proinflammatory cytokines^3-4.

Acute myocardial injury during COVID-19 may be asymptomatic and can be detected only by laboratory markers. The clinical presentation of COVID-19 is extremely variable. It may be asymptomatic or cause mild symptoms such as fever, dry cough, and fatigue¹^,2,4,5. On the other side of the spectrum, a severe pneumonic distress with clinical deterioration and cardiogenic shock may be present.

A frequent cause of hospital admission among cardiac patients is COVID-19 pneumonia⁶, but the most common cause of hospitalization due to cardiovascular decompensation is HF. Prevalence of HF in COVID-19 patients^7,9-12 was dynamic and changing, according to the time of presentation and region (Figure 1). Bromage et al¹³reported a significantly lower hospitalization rate for acute HF during the COVID‐19 pandemic, but hospitalized patients had higher rates of NYHA III or IV symptoms and severe peripheral edema at admission. Heart Failure patients may be at increased risk for severe disease and complications associated to COVID-19 and can worsen HF ⁸. Mortality was reported, Shi⁹et al and Inciardi¹⁴ et al described an increment in HF mortality rates (51.2%, 63.2% respectively). Confirming the high risk of HF mortality.

With a higher risk for severe infection, worsening and complications, general recommendation for HF outpatients are social isolation, telemedicine, guideline-directed medical therapy, and self-daily care also protective measures to prevent infection⁸. Limiting hospital care and admissions based on health systems have been reorganized or reconverted. Reza et al¹⁵ and DeFilippis⁸ et al hypothesizedsevere consequences in socioeconomically disadvantaged populations especially in HF outpatients, who live in low-middle income countries in which health systems are challenged with limited access to remote care, therapeutics, and may endure disproportionate cardiovascular morbidity and mortality¹⁵.

Limitations

Variability in current reports may indicate a different clinical pattern of HF associated with COVID-19 that shows limitations of observational data, inclusion criteria heterogeneity, temporality and geographic biases, residual confounding factors that potentially affect external validity and results may not be generalizable.

Summary

Heart failure in COVID-19 pandemic has a dynamic and changing process

Clinical feature can be broad and assorted.
Leading cause of cardiovascular hospitalization is HF
HF Increases morbidity and mortality risk especially in LMIC countries.

References

1.- Tavazzi doi:10.1002/ejhf.1828

2.- Shi doi:10.1093/eurheartj/ehaa408

3.- Dong https://doi.org/10.1016/j.jchf.2020.04.001

4.- Tersalvi Journal of Cardiac Failure Vol. 00 No. 00 2020

5.-Hendren 10.1161/CIRCULATIONAHA.120.047349

6.-Tomasoni 10.1002/ejhf.1871

7.-Chen https://doi.org/10.1136/bmj.m1091

8.- DeFilippis. JACC Heart Fail ; 2020 Jun 02.

9.-Shi doi:10.1001/jamacardio.2020.0950

10.-Mancia www.nejm.org/doi/full/10.1056/NEJMoa2006923

11.-Reynolds DOI: 10.1056/NEJMoa2008975

12.-Richardson doi:10.1001/jama.2020.6775

13.- Bromage https://doi.org/10.1002/ejhf.1925

14.-Inciardi https://doi.org/10.1093/eurheartj/ehaa388

15.- Reza Circ Heart Fail ; 13(5): e007219, 2020 05.

by Eduardo Chuquiure-Valenzuela

Clinical Cardiologist

National Heart Instituto of Mexico

EL-19 Word Heart Federation

Figure 1 Prevalence of Heart Failure in COVID-19 patients

Virtual health and COVID-19: Is this the future of cardiovascular disease care delivery?

by:
Lilian Mbau

With the ongoing COVID-19 pandemic, virtual health is being embraced more than ever (1). This is especially so for cardiovascular disease (CVD) care because patients with underlying conditions such as CVD or associated risk factors have an increased risk of dying from COVID-19 infection (2). In addition, virtual health provides an option for physicians who are older or have underlying conditions and therefore at higher risk of severe illness if infected by Coronavirus to continue providing their much-needed services during this time. Virtual health refers to the use of digital and telecommunication technologies to deliver health care. The application varies from complementing to totally substituting health service delivery depending on the needs of the patients and resources available (3). The scale-up in the use of virtual health presents a lot of opportunities. Still, at the same time, several issues need to be addressed, such as regulatory and ethical considerations.

The use of telemedicine and similar virtual health platforms has been ongoing for decades, but the scale of implementation has been unprecedented with the advent of the COVID-19 pandemic. The pandemic has reduced barriers to virtual health care adoption and accelerated the enactment of regulations to guide its implementation. In the United States, most consultations are currently happening virtually. In China, virtual health was embraced soon after the pandemic began with significant government support, which paid for the online physician consultations. Other countries that have embraced virtual health include Canada and Scotland. In Scotland, it is estimated that the use of videoconferencing has increased by 1000% (1).

Virtual health has also been embraced in Africa, although the pace is slower. For a long time, telemedicine has been explored to solve the shortage of human resources, especially specialists, including cardiologists. However, its use remains limited due to technological and non-technological factors. Non-technological factors include lack of adequate political support, lack of regulatory frameworks, and lack of funding (4). There is a minimal investment from governments, and often these services are paid for out of pocket. This limits their uptake and sustainability. Technology barriers have also hindered the scale-up of virtual health in Africa; however, mobile phones which have a broad penetration are now providing a suitable alternative (1).

An example successful deployment of telemedicine is at the adult congenital heart disease program, Massachusetts General Hospital in Boston. There has been a significant drop in the workload from 400 patients a day to less than 40. Dr. Ami Bhatt, the director of the program reported positive benefits of telecardiology on the physician-patient relationship. Patients are made to feel like they are equal partners in the relationship and that their needs are respected. On the other hand, the health provider is freed from the hustle of running a clinic and focuses more on listening and educating the patient. The result is improved satisfaction which can help address the high burnout and suicide rates experienced by overworked physicians (5).

In Kenya, several private hospitals in Nairobi, the country’s capital city, have initiated online consultation services. Unfortunately, these services are still limited to major towns. The Kenya Healthcare Federation estimates that there are 41 registered e-health providers in Kenya some of whom provide online consultation services. Online consultations platforms such as AskADoc and Daktari Africa are gaining popularity. Daktari Africa, for example, has been in existence since 2015 and currently has 512 doctors and serves more than 10,000 patients across the country. The platform has experienced increased use since the pandemic began especially by patients with chronic diseases such as diabetes and hypertension. Following a consultation, the patient has the option of getting medication delivered to their home. The platform has however faced challenges expanding to the rural areas due to unstable internet access. Patients using the platform report that they spend less money overall due to reduced consultation fees as well as savings in transportation (6).

As clinicians quickly put mechanisms in place to incorporate telehealth, questions still remain regarding the lack of physical examination and human contact, which has for a long time been regarded as a core component of the patient-physician relationship (6). It is still not clear what implications this will have on the quality of care (1). The American College of Cardiology (ACC) has issued guidance on establishing telecardiology services. One of the critical elements to consider includes the choice of patients eligible for telecardiology services. Patients who are too ill, unstable, or challenging to assess must be directed to face-to-face consults (7). It is also essential to consider critical elements that need to be put in place when setting up telecardiology services. Such services include remote monitoring of implanted devices as well as access to noninvasive monitoring equipment (e.g., blood pressure cuffs, weighing scales, or oxygen saturation monitors). Patients can share their results either before or during the consult, depending on the systems in place. In most cases, prescriptions can be given virtually except for controlled substances. However, if diagnostic tests are required, an in-person visit will be necessary (7).

Questions remain as to the future of virtual health and the role it will continue playing in the delivery of cardiovascular health services after the containment of the pandemic. For countries in Africa, I believe this is the best time to lobby for more investment towards this, the benefits of which will be reaped long after the pandemic has been contained.

References

1. Webster P. Virtual health care in the era of COVID-19. Lancet [Internet]. 2020;395(10231):1180–1. Available from: http://dx.doi.org/10.1016/S0140-6736(20)30818-7

2. European Society of cardiology. ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic. 2020;1–115.

3. Deloitte. Transforming care delivery through virtual health | Deloitte US [Internet]. 2017 [cited 2020 May 25]. Available from: https://www2.deloitte.com/us/en/pages/life-sciences-and-health-care/articles/virtual-health-health-care-providers.html

4. Wamala D, Augustine K. A meta-analysis of telemedicine success in Africa. J Pathol Inform. 2013;4(1):6.

5. ACC. Adopting Telemedicine During the COVID-19 Pandemic: A Return to Patient-Focused Care – American College of Cardiology [Internet]. 2020 [cited 2020 May 25]. Available from: https://www.acc.org/latest-in-cardiology/articles/2020/03/01/08/42/feature-adopting-telemedicine-during-the-coronavirus-2019-covid-19-pandemic-a-return-to-patient-focused-care

6. Ngila F. Just a click away: Apps bring doctors to your home [Internet]. Daily Nation. 2020 [cited 2020 Jun 1]. Available from: https://www.nation.co.ke/dailynation/healthy-nation/just-a-click-away-apps-bring-doctors-to-your-home-302612

7. ACC. Telehealth: Rapid Implementation For Your Cardiology Clinic [Internet]. 2020 [cited 2020 May 25]. Available from: https://www.acc.org/latest-in-cardiology/articles/2020/03/01/08/42/feature-telehealth-rapid-implementation-for-your-cardiology-clinic-coronavirus-disease-2019-covid-19

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.

Cook T, Kursumovic E, Lennane S. Exclusive: deaths of NHS staff from covid-19 analysed. Health Serv J 2020 Apr 22. https://www.hsj.co.uk/exclusive-deaths-of-nhs-staff-from-covid-19-analysed/7027471.article.
Coronavirus (COVID-19) related deaths by ethnic group, England and Wales: 2 March 2020 to 10 April 2020. https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/articles/coronavirusrelateddeathsbyethnicgroupenglandandwales/2march2020to10april2020
Characteristics of SARS-CoV-2 patients dying in Italy. Report based on available data on April 13 2020. https://www.epicentro.iss.it/en/coronavirus/bollettino/Report-COVID-2019_13_april_2020.pdf
Tillin T, Hughes AD, Mayet J et al. The Relationship Between Metabolic Risk Factors and Incident Cardiovascular Disease in Europeans, South Asians, and African Caribbeans: SABRE (Southall and Brent Revisited)—A Prospective Population-Based Study. J Am Coll Cardiol. 2013;61(17):1777-1786. https://doi.org/10.1016/j.jacc.2012.12.046
Spence JD, Rayner BL. Hypertension in Blacks. Hypertension. 2018;72(2):263-269. https://doi.org/10.1161/HYPERTENSIONAHA.118.11064
Glynn LG, Buckley B, Reddan D, et al. Multimorbidity and risk among patients with established cardiovascular disease: a cohort study. Br J Gen Practice. 2008;58(552):488-494. 10.3399/bjgp08X319459

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 1^th, 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).