ACC Health Policy Statement on Cardiovascular Disease Considerations for COVID-19 Vaccine Prioritization

PREFACEThe American College of Cardiology (ACC) has a long history of developing documents (e.g., decision pathways, health policy statements [HPS], appropriate use criteria) to provide members with guidance on both clinical and nonclinical topics relevant to cardiovascular care. In most circumstances, these documents have been created to complement clinical practice guidelines and to inform clinicians about areas where evidence may be new and evolving or where sufficient data may be more limited. Despite this, numerous care gaps continue to exist, highlighting the need for more streamlined and efficient processes to implement best practices in service to improved patient care.Central to the ACC's strategic plan is the generation of "actionable knowledge"-a concept that places emphasis on making clinical information easier to consume, share, integrate, and update. To this end, the ACC has evolved from developing isolated documents to developing integrated "solution sets." Solution sets are groups of closely related activities, policy, mobile applications, decision support, and other tools necessary to transform care and/or improve heart health.Solution sets address key questions facing care teams and attempt to provide practical guidance to be applied at the point of care. They use both established and emerging methods to disseminate information for cardiovascular conditions and their related management. The success of the solution sets rests firmly on their ability to have a measurable impact on the delivery of care. Because solution sets reflect current evidence and ongoing gaps in care, the associated tools will be refined over time to best match changing evidence and member needs.HPS represent a key component of solution sets. The methodology for HPS is grounded in assembling a group of experts to develop content that addresses key policy issues facing our members. Topics selected for HPS vary widely, but connect to scientific, quality, and/or advocacy efforts within the ACC. HPS are not written to provide clinical guidance; rather, they are intended to advocate a position, be informational in nature, and apprise stakeholders of the ACC's stance on healthcare policies and programs.

# Methodology
To provide this policy document, the American College of Cardiology convened a writing group with expertise in CVD, epidemiology, and risk assessment. We conducted a literature review of published reports relating to CVD and COVID-19. Where the literature was absent, we achieved consensus among the writing group. However, in some cases, there was insufficient evidence and/or experience to present an informed opinion, which needs to be considered in the interpretation of this document.
We attempted to include data from geographically diverse areas, when available, recognizing that variability in COVID-19 testing, treatment strategies, and the prevalence of CV conditions can affect estimates of prevalence.
It is also noteworthy that most published data have been retrospective in nature and have been conducted at various timepoints during the pandemic. As such, we attempted to emphasize data from larger meta-analyses, when available. It should be noted that our recommendations are based on limited data collected since the pandemic onset. Future recommendations may change over time with higher-quality data.

## Overall considerations for vaccine allocation decisions
Although the focus of this document is the specific clinical risk associated with CV risk factors and disease in COVID- [bib_ref] Potential effects of coronaviruses on the cardiovascular system: a review, Madjid [/bib_ref] vulnerable, but not frail; 5 to 6 14 initial signs of frailty but with some degree of independence; and 7 to 9 14 severe or very severe frailty) found that higher levels of frailty were associated with worse adjusted 7-day mortality,

## Central illustration considerations for prioritization of covid-19 vaccination allocation
Poorly controlled hypertension is defined as >140/90 mm Hg. Poorly controlled diabetes is defined using A 1c >10%. Overweight is defined as BMI 25-29 kg/m 2 ; obese as BMI 30-40 kg/m 2 , and morbidly obese as BMI >40 kg/m 2 . Obstructive CAD is defined using $70% obstruction in major epicardial arteries, $50% in left main coronary artery. High-grade PAD is defined using ABI $0.5. Malignant tachyarrhythmia includes atrial fibrillation with poor rate control and/or VT with prior ICD therapy or antiarrhythmic medication. ACHD 14 adult congenital heart disease; ABI 14 ankle brachial index; BMI 14 body mass index; CAD 14 coronary artery disease; CVD 14 cardiovascular disease; NYHA 14 New York Heart Association; PAD 14 peripheral arterial disease; VT 14 ventricular tachycardia.
Driggin et al.

## Cvd and covid-19 vaccination
A P R I L 2 0 , 2 0 2 1 : 1 9 3 8 -4 8 independent of age and comorbidity [bib_ref] The effect of frailty on survival in patients with COVID-19 (COPE): a..., Hewitt [/bib_ref]. Given this collective evidence, older patients with multiple comorbidities, including CV conditions, and/or frailty should be considered at high risk and thus prioritized for COVID-19
vaccination.
Finally, it is imperative to recognize the racial, ethnic, and socioeconomic disparities that may influence the risk for adverse outcomes, including mortality, in COVID-19 [bib_ref] Racial disparities in COVID-19 mortality are driven by unequal infection risks, Zelner [/bib_ref] [bib_ref] Disparities in the population at risk of severe illness from COVID-19 by..., Raifman [/bib_ref]. Reports from the CDC show that compared with age-adjusted standardized mortality rates, the risk of death from COVID-19 increased by nearly 3-fold in Blacks, non-Black Hispanics/Latinos, and American Indians/ Alaskan Natives (12). The reasons behind these disparities are multifactorial. First, the exposure risk among these populations tends to be higher, given the higher prevalence of multigenerational households and "essential" jobs necessitating more frequent contact with the public.
Second, patients in racial and ethnic minority populations have a higher prevalence of CV risk factors and disease and therefore are at higher clinical risk compared with those without comorbidity [bib_ref] Association of race and ethnicity with comorbidities and survival among patients with..., Kabarriti [/bib_ref] [bib_ref] Hospitalization and mortality among black patients and white patients with Covid-19, Price-Haywood [/bib_ref]. Higher transmission rates are also observed among those who experience social inequalities [bib_ref] COVID-19 and the impact of social determinants of health, Abrams [/bib_ref]. Third, healthcare accessibility is another important driver of these disparities. 1.1 to 2.7) (28). Additionally, the presence of CVD is a key risk factor for the CV complications of COVID-19, which are also associated with increased morality (29,30).
Below, we review the available data regarding the prevalence and association of specific CV conditions and risk factors with outcomes in patients with COVID-19.

## Hypertension
Since the earliest cohort studies from China, hypertension has been consistently reported as a common CV comorbidity in patients with COVID-19 (31-34). In a large U.S. cohort study using hospital claims data for 11,721 patients across 38 states, pre-existing hypertension was noted in 46.7% of COVID-positive patients [bib_ref] Patient characteristics and outcomes of 11,721 patients with COVID19 hospitalized across the..., Fried [/bib_ref]. In a critically ill cohort of 257 patients from New York City, the prevalence of pre-existing hypertension among patients in the ICU was even higher, at 63.0% (35).
Although the baseline prevalence of hypertension varies significantly by geographic region, multinational data have consistently demonstrated worse outcomes associated with COVID-19 in patients with pre-existing hypertension (23,33). In a large meta-analysis from Driggin et al.
A P R I L 2 0 , 2 0 2 1 : 1 9 3 8 -4 8 especially those with poorly controlled disease with older age and additional comorbidities, should be considered to have elevated risk of adverse outcomes associated with COVID-19.

## Diabetes
Diabetes mellitus is a highly prevalent CV risk factor among patients with COVID-19. In a large cohort study using medical record data including 31,461 patients from 24 U.S. healthcare systems, diabetes was present in 15% of patients with COVID-19. In this analysis, diabetes was the second most common medical comorbidity overall, aside from pre-existing pulmonary disease, which was prevalent in 17.5% of patientsAccordingly, we recognize obesity as an important CV risk factor and postulate the risk of obesity to be incremental, such that patients with morbid obesity are at the highest risk for poor outcomes associated with COVID-19.
Furthermore, it is important to recognize that obesity contributes to other risks such as hypertension, diabetes, sleep apnea, and secondary pulmonary hypertension.

## Atherosclerotic cardiovascular disease
Although the data from China demonstrated pre-existing atherosclerotic cardiovascular disease (ASCVD) in only a small minority of patients with COVID-19, studies from the United States demonstrate ASCVD to be a more common CV comorbidity, likely due to higher baseline prevalence (40). Data from inpatients and outpatients with COVID-19 in a large New York City health system reported an 8.6% prevalence of pre-existing coronary artery Nonetheless, the presence of ASCVD appears to be a clear risk factor for poor outcomes in COVID-19. Furthermore, we believe that patients with extensive, high-risk ASCVD are the most susceptible to adverse outcomes.

## Cardiac dysrhythmia
The risk of COVID-19 infection to patients with preexisting cardiac dysrhythmias has not been well defined.
However, patients with marginally controlled heart rhythm disorders may be at increased risk for exacerbations of their underlying conditions if infected with COVID-19. Interestingly, an association between atrial fibrillation (AF) and elevated angiotensin-converting enzyme 2 (ACE2) levels has led to speculation that patients with known AF may have a higher risk for morbidity and mortality associated with COVID-19 (51-53). Certain populations with AF have a higher risk for morbidity and mortality from arrhythmia recurrence, which COVID-19 seems to provoke (54,55).

## Heart failure
In distinction to many other CVDs, there is robust evidence for poor outcomes in COVID-19 in the presence of pre-existing heart failure. Among a cohort of 31,461 patients with COVID-19 across the United States, 7.3% had a history of heart failure (9). Compared with those who survived, those who died had a significantly higher proportion of pre-existing heart failure (30.8% vs. 6.3%). In a multivariable model controlling for relevant demographic and CV risk factors, pre-existing heart failure was independently associated with death in this cohort (OR: 1.42; 95% CI: 1.21 to 1.67). These findings have been replicated in 2 large New York City cohorts as well (49,59). In an analysis of 1,212,153 patients with heart failure who were included in the Premier health care database, patients with heart failure who were hospitalized for COVID-19 had markedly greater risk for in-hospital mortality in multivariable analysis (OR: 14.48; 95% CI: 12.23 to 17.12) [bib_ref] Clinical outcomes in patients with heart failure hospitalized with COVID-19, Bhatt [/bib_ref]. In multivariable models for the outcomes of death or mechanical ventilation, pre-existing heart failure was also a significant independent risk factor (OR: 8.04; 95% CI: 7.10 to 9.12). Notably, these associations were persistent over 2 distinct time periods in the pandemic, although overall mortality was lower later in the pandemic. Therefore, heart failure is a clear, established risk factor for poor outcomes, and patients who are decompensated and/or those with poor functional status should be considered at the highest risk.

## Prior heart transplant
Patients who have undergone heart transplantation are at Pregnant women with CVD should also be considered high risk, given the potential for pregnancy to decompensate certain CVDs, such as heart failure, that may be exacerbated in the setting of COVID-19 infection. In addition to other non-CV comorbidities, other behaviors may amplify CV risk, such as smoking, medical noncompliance, and alcohol or substance abuse. Although these interactions are all important to consider, more data are needed to make recommendations for these specific populations.
[fig] INTRODUCTION: The coronavirus disease 2019 (COVID-19) has had a devastating impact on healthcare systems around the world, with nearly 99 million cases and 2.1 million associated deaths as of January 2021 (1). As such, the rapid development and availability of multiple vaccines are welcome in the long and arduous fight against COVID-19. A coherent vaccine allocation policy promoting the greatest benefit for the greatest number would prioritize individuals with the highest risk for adverse outcomes of COVID-19 ahead of lower-risk populations. There are numerous factors that influence the risk for adverse outcomes in COVID-19, including the exposure risk for contracting COVID-19 and the clinical risk for adverse health outcomes with infection. The phased rollout of the vaccines by the Centers for Disease Control and Prevention (CDC) mirrors this framework by prioritizing older age groups and patients with significant medical comorbidities (2). The guidance specifies that during the Phase 1c allocation, all patients from 16 to 64 years of age with medical conditions that increase the risk for severe COVID-19 infection should receive the vaccine. Although the guidance specifies that heart conditions, hypertension, diabetes, obesity, and smoking are examples of such high-risk medical conditions, further delineation of varying levels of risk among patients with cardiovascular disease (CVD) is absent. As the largest professional society of cardiovascular (CV) professionals in the United States, the ACC aims to offer specific guidance about how CV conditions contribute to the risk for adverse outcomes with COVID-19 infection to inform its membership and the patients they serve. In this policy document, we: 1) outline the overall considerations of both exposure and clinical risk needed for vaccine allocation efforts; 2) present the specific evidence and risk considerations related to CVD and COVID-19; and 3) propose a schema of CV risk to incorporate into vaccine allocation decisions. [/fig]
[fig] 47: Tartof SY, Qian L, Hong V, et al. Obesity and mortality among patients diagnosed with COVID-19: results from an integrated health care organization. Ann Intern Med. 2020;173:773-81. 48. Hamer M, Gale CR, Kivimaki M, Batty GD. Overweight, obesity, and risk of hospitalization for COVID-19: A community-based cohort study of adults in the United Kingdom. Proc Natl Acad Sci U S A. 2020;117: 21011-3. 49. Kuno T, Takahashi M, Obata R, Maeda T. Cardiovascular comorbidities, cardiac injury, and prognosis of COVID-19 in New York City. Am Heart J. 2020;226:24-5. 50. Chen R, Liang W, Jiang M, et al. Risk factors of fatal outcome in hospitalized subjects with Coronavirus Disease 2019 from a nationwide Analysis in China. Chest. 2020;158:97-105. 51. Walters TE, Kalman JM, Patel SK, Mearns M, Velkoska E, Burrell LM. Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling. Europace. 2017;19: 1280-7. [/fig]
[fig] 52: Wallentin L, Lindback J, Eriksson N, et al. Angiotensin-converting enzyme 2 (ACE2) levels in relation to risk factors for COVID-19 in two large cohorts of patients with atrial fibrillation. Eur Heart J. 2020;41: 4037-46. 53. Sanchis-Gomar F, Perez-Quilis C, Lavie CJ. Should atrial fibrillation be considered a cardiovascular risk factor for a worse prognosis in COVID-19 patients? Eur Heart J. 2020;41:3092-3. 54. Lakkireddy DR, Chung MK, Gopinathannair R, et al. [/fig]