Social Isolation Decreases Survival and Worsens Cardiac Function in a Novel Murine Model of Coronary Atherosclerosis

Introduction: With more people working from home after the COVID pandemic, it is of utmost importance to further understand the impact of social isolation on outcomes of patients with coronary atherosclerosis. Our preliminary studies have shown that the novel diet-inducible, fatal mouse model of coronary atherosclerosis, SR-BIDELTACT/LDLR KO, tend to die on average around 4-6 weeks after starting a high-fat Paigan diet (HFD). This mouse model can be used to further understand the effect of social isolation on cardiovascular disease. We hypothesize that social isolation will decrease survival and worsen cardiac function. Method(s): Male and female SR-BIDELTACT/LDLR KO mice were put into social isolation (n=11), in a group of 2-3 (n=13), or in a group of 4-5 (n=22). At six-weeks-old, mice were started on a HFD to induce pathology. Echocardiography was performed to assess cardiac function. Analysis was performed using one-way Analysis of Variance tests and hoc-Tukey's Honest Significant Difference tests. A log-rank test was used to calculate the difference in survival distributions. Result(s): Mice living in groups of 1, 2-3, and 4-5 lived for an average of 34.9, 35.6, and 41.5 days, respectively, after starting the HFD (Fig. 1A). The survival distribution is significantly different between the mice in isolation versus the mice in groups of 4-5 (p<;0.01). Mice in social isolation have significantly lower ejection fractions than mice living in groups of 4-5 after two weeks of being on the HFD (Fig. 1B, p=0.028). Conclusion(s): Mice in social isolation exhibited decreased survival and reduced ejection fractions compared to mice in groups of 4-5. More mice would be needed to determine whether single isolation is different from mice in groups of 2-3. Further studies should be performed to understand the mechanism underlying the effect of social isolation on heart function. Such studies may influence future prevention strategies to positively affect outcomes of patients with atherosclerosis. (Figure Presented).

Early Impact of Collaborative Remote Patient Monitoring (C-RPM) for Hypertension on Underserved Populations during the COVID19 Pandemic: A Multicenter Retrospective Observational Study

Introduction: Underserved populations are 40% more likely to have hypertension and three times more likely to die from heart diseases due to uncontrolled blood pressure (BP). Disrupted access to care from the COVID-19 pandemic further puts these populations at higher risks of complications. A C-RPM for hypertension was established in response to this threat. Research Question or Hypothesis: Will C-RPM promote timely BP control among underserved patients during the COVID19 pandemic? Study Design: A retrospective, single-arm observational study conducted in two federally qualified health center sites. Method(s): All adult patients with uncontrolled BP (>=140/90) who received physician or nurse practitioner referral to participate in CRPM were included. Patients who failed to use BP device independently were excluded. All participants received a BP device that transmitted their BP measurements to the institution electronic health records. Clinical pharmacists, under a collaborative practice agreement, followed the readings and provided dose adjustments via telemedicine. Patient demographics were collected at baseline and BP readings were tracked daily for the first three months. Descriptive analysis, ASCVD risk calculator and paired t-test were used accordingly. Result(s): Between August and December 2021, 89 patients were referred, of which 70 (78.7%) monitored BP daily while 19 (21.3%) were lost to follow up. The average age of the patients was 60.8 years with majority being Hispanic (76.4%), female (63%), and diagnosed with type 2 diabetes (52.8%). The average BP improved from 163/82 at baseline to 132/71 at three months (p<0.001) with an average ASCVD risk score reduction of 25%. Approximately 76% achieved BP target (<140/90) within three months. BP of those lost to follow up maintained uncontrolled over the three months. Conclusion(s): C-RPM achieved clinically meaningful and timely improvement in BP control and cardiovascular risks among underserved patients, bypassing the threat of care access disruption due to the COVID19 pandemic.

ASYMPTOMATIC SARS-CoV-2 INFECTION IS EXTREMELY COMMON among PEOPLE with HIV

Background: Asymptomatic COVID-19 is common among the general population, but little has been reported on this phenomenon among people with HIV (PWH) globally. Here we present data on a representative subset of 2,464 REPRIEVE participants with blood collected for COVID-19 serology from May 2020 to February 2021. Methods: REPRIEVE is an international primary atherosclerotic cardiovascular disease (ASCVD) prevention RCT of pitavastatin calcium vs. placebo among 7,770 PWH ages 40-75 on antiretroviral therapy (ART). Beginning in April 2020, targeted data on COVID-19 diagnosis and symptoms were collected as part of routine trial visits every 4 months, and blood was collected annually to assess SARS-CoV-2 serology. SARS-CoV-2 infection was defined as either presence of SARS-CoV-2 IgG or IgA RBD protein (anti-spike) antibodies or reporting of confirmed COVID-19 disease prior to the date of antibody sampling in the absence of prior COVID-19 vaccine receipt. We distinguished symptomatic from asymptomatic disease based on completed COVID-19 symptom questionnaire. Demographic, cardiometabolic, and HIV-specific data are described among those with symptomatic versus asymptomatic COVID-19 disease. Results: Participant characteristics (n=2464) included median age 53 years, 35% female sex, 47% Black or African American race, median CD4 count 649 c/mm3, and 97% with HIV VL <400 cp/mL. SARS-CoV-2 infection occurred in 318 persons (13%): 58 with clinical disease diagnosis and 260 with reactive Abs but no reported clinical disease. Of these persons, 304 completed symptom questionnaires: 120 (39%) reported at least 1 symptom of COVID-19 disease, but 184 (61%) reported no symptoms. PWH with asymptomatic infection were more likely to be from non-High Income Regions, of Black or African American race, and to be non-obese (Table). Median ASCVD risk score was <5% (low risk) for the two groups. Potential differences in symptomatic disease based on ART-regimen were noted, but no clinical differences between the groups for CD4 counts or HIV viral suppression were observed. Conclusion: Asymptomatic SARS-CoV-2 infection is very common among ART-treated PWH globally. With Ab testing, we determined that 61% of COVID-19 infections were asymptomatic in the REPRIEVE cohort, similar to rates reported in the general population. HIV clinicians must remain vigilant about COVID-19 testing among PWH to assure that asymptomatic cases are identified.

Phytosterol Therapy Effectively Reduces LDL-C in Middle-Aged, Borderline Risk South Asians

Lead Author's Financial Disclosures: Nothing to disclose. Study Funding: Piper Biosciences. Background/Synopsis: The effectiveness of a plant sterol gummy supplement was studied in a South-Asian (SA) patient population with low to moderate cardiovascular disease (CVD) risk as defined by an Atherosclerotic Cardiovascular Disease (ASCVD) Risk Score of < 7.5%, and a low density lipoprotein (LDL)-C level of 120-189 mg/dl. Statin therapy is often not recommended to patients with ASCVD score < 7.5% even in the presence of risk accelerators such as SA ethnicity, to which the 2018 National Lipid Association (NLA) guidelines call attention. Objective/Purpose: Phytosterols are known to lower LDL-C and are included in NLA and other global guidelines. This study aimed to establish their impact on LDL-C levels in 'borderline' risk SAs. Methods: 50 SAs were recruited during the COVID 19 pandemic, mainly from a preventive cardiology clinic dedicated to reducing SA heart disease risk. Eligible subjects had a 10-year CV risk score (ASCVD) <7.5% and LDL-C level of 120-193mg/dl at study enrollment. Subjects intolerant of or refusing statins were also recruited. The study was administered with a fully decentralized design, leveraging mailed supplements, televisits, remote lab collection, and SMS-based communications. Upon completing baseline labs and surveys, subjects were provided a 90-day supply of 1400mg phytosterol gummy supplements in individual packets (Piper Biosciences, Los Altos, CA) to be ingested twice daily. Subjects were instructed to continue current lifestyle habits and report major dietary pattern deviations. The primary endpoint was LDL-C reduction at 3 months. Pre- and post-study surveys were administered to assess diet and lifestyle. Results: 33 of the 50 subjects successfully completed the protocol. A significant overall reduction in LDL-C of 5.8% was observed (p=0.03) (Table 1, Figure 1). Subgroup A (n=27) completed the protocol with no significant dietary variation, demonstrating a significant LDL-C reduction of 6.5% (p=0.002), as well as a total cholesterol (TC) reduction of 4.4% (p=0.01). There was no significant change in other metrics, including BMI, fasting glucose, or HbA1C. Patients who completed the protocol but reported worsening dietary habits (Subgroup B, n=6) showed an average increase in LDL-C of 6% (p=0.2) and in TC of 8% (p=0.002). Survey responses indicate that 94% of subjects would be interested in long-term supplementation if recommended by physician and 80% would prefer taking it proactively to manage cholesterol levels. Conclusions: Plant sterols are an effective and sustainable means to lower LDL-C in middle-aged SAs, whose CV risk is often underestimated. To our knowledge this study represents the first demonstration of phytosterol effectiveness in the highest coronary disease risk population globally.

CARBOPLATIN-PACLITAXEL INDUCED ACUTE MULTI-VESSEL CORONARY THROMBOSIS

Background: Delayed cancer screenings during COVID-19 pandemic are expected to increase use of chemotherapy agents like paclitaxel. Paclitaxel has been implicated in rare cases of acute myocardial infarction from chemotoxicity. We present a rare case and literature review of Paclitaxel-induced acute multiple vessel coronary thrombosis in absence of native coronary artery atherosclerosis. Case: A 68-year-old man with a history of metastatic stage IV non-small cell lung cancer, hypertension, hyperlipidemia, normal baseline left ventricular systolic function and without coronary disease on recent heart catheterization, was found unresponsive with telemetry showing monomorphic ventricular tachycardia six hours post Carboplatin-Paclitaxel infusion. Decision-making: The patient was emergently cardioverted at bedside, intubated, and started on amiodarone, lidocaine, and norepinephrine infusions. The patient was thrombocytopenic at 61K, leukopenic at 1.2K, and anemic at 7.1 with INR of 1.8. ECG showed new ST-elevation in inferior leads. Bedside echocardiogram revealed global hypokinesis with apical akinesis and a newly reduced LVEF 25%. Troponin measured 0.5 ng/mL (normal <0.04 ng/mL), creatinine 1.4, K+ 3.4, and Mg2+ 1.8. After cardio-oncology led multidisciplinary discussion, a decision was made to pursue invasive angiogram. Found to have de novo triple-vessel coronary thrombosis in mid-LAD, proximal OM1 and mid RCA (Figure 2), percutaneous intervention was performed with drug-eluting stents placed in mid-LAD and mid-RCA, with staged PCI planned on proximal OM1 if needed. Patient responded well to the intervention and was extubated the same day. Patient remained medically stable at 3-month follow-up despite continued chemotherapy. Staged PCI to OM1 was not needed. Conclusion: Paclitaxel based therapy can cause ventricular arrhythmias and sudden cardiac death secondary to acute multi-vessel coronary thrombosis in patients without underlying coronary artery disease in the setting of pronounced thrombocytopenia. Prompt recognition of this severe adverse effect and timely utilization of multidisciplinary care models led by a cardio-oncologist achieves optimal outcomes.

Acute coronary syndrome in COVID-19 patients

Acute coronary syndrome (ACS) is caused by an acute mismatch between myocardial oxygen demand and its supply. This mechanism is largely associated with the progression of coronary atherosclerosis in combination with an inflammatory response, hypoxemia, and blood procoagulation. Patients with the coronavirus disease 2019 (COVID-19), aggravated by cardiovascular diseases and comorbidities, are at high risk of ACS. Aim. To analyze the publications, which reflects the development of ACS in patients with COVID-19, its pathogenesis, and clinical course. Material and methods. Literature data were searched using Google Scholar, PubMed, ScienceDirect, and Cyberleninka services. The analysis included data from clinical guidelines on COVID-19, data from clinical studies, reports, and systematic reviews. Results. This literature review summarizes and systematizes the data presented in modern publications, highlights the aspects of the clinical course and pathogenetic mechanisms underlying ACS in patients with COVID-19. Conclusion. The pathogenesis of COVID-19 is inextricably associated with the widespread cytopathic effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uncontrolled immune response that causes systemic inflammation, as well as the coagulation system activation. In patients with COVID-19, along with the atherosclerosis, these mechanisms significantly increase the risk of ACS and can worsen its in-hospital course.

The role of premorbid transthoracic echocardiogram in identifying adverse clinical outcomes in patients admitted with COVID-19

Background/Introduction: The novel coronavirus disease (COVID-19) inpatient mortality rate is approximately 20% in the United States. Reports have described a wide pattern of abnormalities in echocardiograms performed in patients admitted with COVID-19. The role of premorbid transthoracic echocardiogram (TTE) in the prediction of COVID-19 severity and mortality is yet to be fully assessed. Purpose: To assess whether a pre-COVID TTE can identify patients at high risk of adverse outcomes who are admitted with COVID-19. Methods: All patients who underwent a TTE from one year to one month prior to an index inpatient admission for COVID-19 were retrospectively enrolled across five clinical sites. Demographic information, medical history, and laboratory data were included for analysis. Echocardiograms were analyzed by an observer blinded to clinical data. Linear and logistic regressions were performed to detect the association of variables with death, invasive mechanical ventilation, initiation of dialysis, and a composite of these endpoints during the COVID-19 admission. Outcomes were then adjusted for a risk score using inverse propensity weighting incorporating age, sex, diabetes, hypertension, obstructive sleep apnea, history of atherosclerotic cardiovascular disease, atrial fibrillation, diuretic use, and angiotensinconverting enzyme inhibitor or angiotensin receptor blocker use. Results: There were 104 patients (68±15 years old, 49% male, BMI 31.4±9.1kg/m2) who met inclusion criteria (baseline characteristics in Table 1). Mean time from TTE to positive SARS-CoV-2 PCR test was 139±91 days. Twenty-nine (28%) participants died during the index COVID-19 admission. There was no association of pre-COVID echocardiographic measures of systolic ventricular function with any endpoint. Diastolic function, as assessed by LV e', was associated with mortality (Table 2). There were 25 patients (24%) with a normal lateral e' (≥10cm/s);none died. There were 35 (34%) patients with LV e' lateral velocity <8 cm/s, of whom 15 (43%) died. LV e' lateral velocity <8 cm/s was associated with an unadjusted odds ratio of 7.69 (95% confidence interval [CI] 2.26-26.19) for death and 3.25 (95% CI 1.11-9.54) for the composite outcome. The odds ratio for death was 4.76 (95% CI 1.10-20.61) and 3.78 (95% CI 0.98-14.6) for the composite outcome after adjustment for clinical risk factors (Table 2). Conclusion: In patients with an echocardiogram prior to COVID-19, impaired diastolic function as represented by an abnormal LV e' lateral velocity was associated with both inpatient COVID-19 mortality and a composite outcome of death, mechanical ventilation, and initiation of dialysis, even after adjustment for multiple co-morbidities and medication use. Knowledge of the pre-COVID TTE results may help clinicians identify patients at higher risk of adverse outcomes during an admission for COVID-19. (Figure Presented).

Post-COVID myocarditis diagnosed by endomyocardial biopsy and/or magnetic resonance imaging 2-9 months after acute COVID-19

Purpose: To study clinical features of myocarditis and its possible mechanisms (including persistence of SARS-Cov-2 in the myocardium) in the long-term period after acute COVID-19. Methods: Fifteen patients (8 male and 7 female, mean age 47.8±13.4, 24-65 years) diagnosed with postcovid myocarditis were included in the study. The diagnosis of COVID-19 was confirmed by positive PCR results in 40%, and seroconversion in all patients. The average time of admission after COVID-19 was 4 [3;7] months, from 2 to 9 months. The diagnosis of myocarditis was confirmed by cardiac MRI in 10 patients and by right ventricular endomyocardial biopsy (EMB) in 6 patients. The PCR for cardiotropic viruses and PCR with immunohistochemical study for SARSCov2 detection were used. All patients had study for anti-heart antibodies (AHA), EchoCG, and Holter ECG. Coronary atherosclerosis was excluded in all patients over 40 years (7 coronary angiography, 4 cardiac CT). Results: A clear association of the cardiac symptoms with a previous new coronavirus infection was noted in all patients. The symptoms started 1-5 months following COVID-19. MRI showed subepicardial and intramyocardial LGE, signs of hyperemia, increased T1 relaxation time, edema. AHA levels were increased 3-4-fold in 73%. Two variants of postcovid myocarditis were observed. 1. Arrhythmic variant (n=6) - newly developed frequent supraventricular or ventricular extrasystole, recurrent atrial fibrillation in the absence of systolic dysfunction. 2. Decompensated variant with biventricular heart failure (n=9): the mean LV EF was 34.1±7.8% (23 to 46%), LV EDD 5.8±0.7 cm, EDV 153.8±46.1 ml, pulmonary artery systolic pressure 40.7±11.2 mmHg. In one case, myocarditis was accompanied by IgG4- and ANCA-negative aortitis. SARS-Cov-2 RNA was detected in 4 of 5 myocardial biopsies (in one case the material in the study). The longest period of virus persistence after COVID-19 was 9 months. By using spike and nucleocapsid antibodies, coronavirus was detected in cardiomycytes and macrophages. Data of patients with morphologically proved myocarditis are presented in Table 1. Lymphocytic myocarditis was diagnosed and confirmed immunohistochemically (n=5);giant cell myocarditis with atrial standstill was detected in one more case (Fig. 1). Three patients had also signs of endocarditis, in two cases with parietal thrombosis. Conclusions: COVID-19 can lead to the subacute and chronic myocarditis of varying severity. Post-COVID myocarditis manifests itself in two main clinical forms - isolated arrhythmias and systolic dysfunction with heart failure. Post-COVID myocarditis is characterized by prolonged persistence of coronavirus (up to 9 months in this study, in most patients with decompensated variant) in combination with high immune activity (high titers of AHA), which should be considered as the main mechanisms of its longterm course. Treatment approaches for such myocarditis require investigation. (Figure Presented).