Acute Myocardial Infarction and Myocarditis following COVID-19 Vaccination.

BACKGROUND: Emerging reports raise concerns on the potential association between the COVID-19 vaccines and cardiac manifestations. We sought to evaluate cardiac complications associated with COVID-19 vaccination in a pooled analysis from our institution's cohort study and systematic review. METHODS: Consecutive patients admitted in a tertiary hospital in Singapore between 1 January 2021 and 31 March 2021, with onset of cardiac manifestations within 14 days following COVID-19 vaccination were studied. Furthermore, a systematic review was performed, with PubMed, Embase, Research Square, MedRxiv, and LitCovid databases accessed from inception up to 29 June 2021. Relevant manuscripts reporting individual patient data on cardiac complications following COVID-19 vaccination were included. RESULTS: Thirty patients were included in the study cohort, with 29 diagnosed with acute myocardial infarction (AMI) and 1 with myocarditis. Five patients developed heart failure, two had cardiogenic shock, three intubated, and one had cardiovascular-related mortality. In the systematic review, 16 studies were included with 41 myocarditis and six AMI cases. In the pooled analysis of the study cohort and the systematic review, 35 patients had AMI and 42 had myocarditis. Majority were men, and myocarditis patients were younger than AMI patients. Myocarditis patients tended to present 72 hours post-vaccination, while AMI patients were older and typically presented 24 hours post-vaccination. Majority with AMI or myocarditis developed symptoms after the first and second vaccination dose respectively. CONCLUSIONS: This pooled analysis of patients presenting with cardiac manifestations following COVID-19 vaccination highlights the differences between myocarditis and AMI presentations in temporal association with the vaccination.

Impact of COVID-19 pandemic early response measures on myocardial infarctions and acute cardiac care in Singapore.

The COVID -19 pandemic impacted acute myocardial infarction (AMI) attendances, ST-elevation myocardial infarction (STEMI) treatments, and outcomes. We collated data from majority of primary percutaneous coronary intervention (PPCI)-capable public healthcare centres in Singapore to understand the initial impact COVID-19 had on essential time-critical emergency services. We present data comparisons from 'Before Disease Outbreak Response System Condition (DORSCON) Orange', 'DORSCON Orange to start of circuit breaker (CB)', and during the first month of 'CB'. We collected aggregate numbers of weekly elective PCI from four centres and AMI admissions, PPCI, and in-hospital mortality from five centres. Exact door-to-balloon (DTB) times were recorded for one centre; another two reported proportions of DTB times exceeding targets. Median weekly elective PCI cases significantly decreased from 'Before DORSCON Orange' to 'DORSCON Orange to start of CB' (34 vs 22.5, P = 0.013). Median weekly STEMI admissions and PPCI did not change significantly. In contrast, the median weekly non-STEMI (NSTEMI) admissions decreased significantly from 'Before DORSCON Orange' to 'DORSCON Orange to start of CB' (59 vs 48, P = 0.005) and were sustained during CB (39 cases). Exact DTB times reported by one centre showed no significant change in the median. Out of three centres, two reported significant increases in the proportion that exceeded DTB targets. In-hospital mortality rates remained static. In Singapore, STEMI and PPCI rates remained stable, while NSTEMI rates decreased during DORSCON Orange and CB. The severe acute respiratory syndrome (SARS) experience may have helped prepare us to maintain essential services such as PPCI during periods of acute healthcare resource strain. However, data must be monitored and increased pandemic preparedness measures must be explored to ensure that AMI care is not adversely affected by continued COVID fluctuations and future pandemics.

Age-Related Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI: Results of the ISACS-STEMI COVID-19 Registry.

BACKGROUND: The constraints in the management of patients with ST-segment elevation myocardial infarction (STEMI) during the COVID-19 pandemic have been suggested to have severely impacted mortality levels. The aim of the current analysis is to evaluate the age-related effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI within the registry ISACS-STEMI COVID-19. METHODS: This retrospective multicenter registry was performed in high-volume PPCI centers on four continents and included STEMI patients undergoing PPCI in March-June 2019 and 2020. Patients were divided according to age (< or ≥75 years). The main outcomes were the incidence and timing of PPCI, (ischemia time longer than 12 h and door-to-balloon longer than 30 min), and in-hospital or 30-day mortality. RESULTS: We included 16,683 patients undergoing PPCI in 109 centers. In 2020, during the pandemic, there was a significant reduction in PPCI as compared to 2019 (IRR 0.843 (95%-CI: 0.825-0.861, p < 0.0001). We found a significant age-related reduction (7%, p = 0.015), with a larger effect on elderly than on younger patients. Furthermore, we observed significantly higher 30-day mortality during the pandemic period, especially among the elderly (13.6% vs. 17.9%, adjusted HR (95% CI) = 1.55 [1.24-1.93], p < 0.001) as compared to younger patients (4.8% vs. 5.7%; adjusted HR (95% CI) = 1.25 [1.05-1.49], p = 0.013), as a potential consequence of the significantly longer ischemia time observed during the pandemic. CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures, with a larger reduction and a longer delay to treatment among elderly patients, which may have contributed to increase in-hospital and 30-day mortality during the pandemic.

Gender Difference in the Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI: Results of the ISACS-STEMI COVID-19 Registry.

BACKGROUND: Several reports have demonstrated the impact of the COVID-19 pandemic on the management and outcome of patients with ST-segment elevation myocardial infarction (STEMI). The aim of the current analysis is to investigate the potential gender difference in the effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI patients within the ISACS-STEMI COVID-19 Registry. METHODS: This retrospective multicenter registry was performed in high-volume primary percutaneous coronary intervention (PPCI) centers on four continents and included STEMI patients undergoing PPCIs in March-June 2019 and 2020. Patients were divided according to gender. The main outcomes were the incidence and timing of the PPCI, (ischemia time ≥ 12 h and door-to-balloon ≥ 30 min) and in-hospital or 30-day mortality. RESULTS: We included 16683 STEMI patients undergoing PPCIs in 109 centers. In 2020 during the pandemic, there was a significant reduction in PPCIs compared to 2019 (IRR 0.843 (95% CI: 0.825-0.861, p < 0.0001). We did not find a significant gender difference in the effects of the COVID-19 pandemic on the numbers of STEMI patients, which were similarly reduced from 2019 to 2020 in both groups, or in the mortality rates. Compared to prepandemia, 30-day mortality was significantly higher during the pandemic period among female (12.1% vs. 8.7%; adjusted HR [95% CI] = 1.66 [1.31-2.11], p < 0.001) but not male patients (5.8% vs. 6.7%; adjusted HR [95% CI] = 1.14 [0.96-1.34], p = 0.12). CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures similarly observed in both genders. Furthermore, we observed significantly increased in-hospital and 30-day mortality rates during the pandemic only among females. Trial registration number: NCT 04412655.

SARS-CoV-2 Positivity, Stent Thrombosis, and 30-day Mortality in STEMI Patients Undergoing Mechanical Reperfusion.

SARS-Cov-2 has been suggested to promote thrombotic complications and higher mortality. The aim of the present study was to evaluate the impact of SARS-CoV-2 positivity on in-hospital outcome and 30-day mortality in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) enrolled in the International Survey on Acute Coronary Syndromes ST-segment elevation Myocardial Infarction (ISACS-STEMI COVID-19 registry. The 109 SARS-CoV-2 positive patients were compared with 2005 SARS-CoV-2 negative patients. Positive patients were older (P = .002), less often active smokers (P = .002), and hypercholesterolemic (P = .006), they presented more often later than 12 h (P = .037), more often to the hub and were more often in cardiogenic shock (P = .02), or requiring rescue percutaneous coronary intervention after failed thrombolysis (P < .0001). Lower postprocedural Thrombolysis in Myocardial Infarction 3 flow (P = .029) and more thrombectomy (P = .046) were observed. SARS-CoV-2 was associated with a significantly higher in-hospital mortality (25.7 vs 7%, adjusted Odds Ratio (OR) [95% Confidence Interval] = 3.2 [1.71-5.99], P < .001) in-hospital definite in-stent thrombosis (6.4 vs 1.1%, adjusted Odds Ratio [95% CI] = 6.26 [2.41-16.25], P < .001) and 30-day mortality (34.4 vs 8.5%, adjusted Hazard Ratio [95% CI] = 2.16 [1.45-3.23], P < .001), confirming that SARS-CoV-2 positivity is associated with impaired reperfusion, with negative prognostic consequences.

Impact of chronic obstructive pulmonary disease on short-term outcome in patients with ST-elevation myocardial infarction during COVID-19 pandemic: insights from the international multicenter ISACS-STEMI registry.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study. METHODS: In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents. RESULTS: A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658-1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620-1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups. CONCLUSION: This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity. TRIAL REGISTRATION NUMBER: NCT04412655 (2nd June 2020).

A review of COVID-19 vaccination and the reported cardiac manifestations.

In Singapore, 9.03 million doses of the mRNA COVID-19 vaccines by Pfizer-BioNTech and Moderna have been administered, and 4.46 million people are fully vaccinated. An additional 87,000 people have been vaccinated with vaccines in World Health Organization's Emergency Use Listing. The aim of this review is to explore the reported cardiac adverse events associated with different types of COVID-19 vaccines. 42 studies that reported cardiac side effects after COVID-19 vaccination were included in this study. Reported COVID-19 vaccine-associated cardiac adverse events were mainly myocarditis and pericarditis, most commonly seen in adolescent and young adult male individuals after mRNA vaccination. Reports of other events such as acute myocardial infarction, arrhythmia and stress cardiomyopathy were rare. Outcomes of post-vaccine myocarditis and pericarditis were good. Given the good vaccine efficacy and the high number of cases of infection, hospitalisation and death that could potentially be prevented, COVID-19 vaccine remains of overall benefit, based on the current available data.

Post-ST-Segment Elevation Myocardial Infarction Follow-Up Care During the COVID-19 Pandemic and the Possible Benefit of Telemedicine: An Observational Study.

Background: Infectious control measures during the COVID-19 pandemic have led to the propensity toward telemedicine. This study examined the impact of telemedicine during the pandemic on the long-term outcomes of ST-segment elevation myocardial infarction (STEMI) patients. Methods: This study included 288 patients admitted 1 year before the pandemic (October 2018-December 2018) and during the pandemic (January 2020-March 2020) eras, and survived their index STEMI admission. The follow-up period was 1 year. One-year primary safety endpoint was all-cause mortality. Secondary safety endpoints were cardiac readmissions for unplanned revascularisation, non-fatal myocardial infarction, heart failure, arrythmia, unstable angina. Major adverse cardiovascular events (MACE) was defined as the composite outcome of each individual safety endpoint. Results: Despite unfavorable in-hospital outcomes among patients admitted during the pandemic compared to pre-pandemic era, both groups had similar 1-year all-cause mortality (11.2 vs. 8.5%, respectively, p = 0.454) but higher cardiac-related (14.1 vs. 5.1%, p < 0.001) and heart failure readmissions in the pandemic vs. pre-pandemic groups (7.1 vs. 1.7%, p = 0.037). Follow-up was more frequently conducted via teleconsultations (1.2 vs. 0.2 per patient/year, p = 0.001), with reduction in physical consultations (2.1 vs. 2.6 per patient/year, p = 0.043), during the pandemic vs. pre-pandemic era. Majority achieved guideline-directed medical therapy (GDMT) during pandemic vs. pre-pandemic era (75.9 vs. 61.6%, p = 0.010). Multivariable Cox regression demonstrated achieving medication target doses (HR 0.387, 95% CI 0.164-0.915, p = 0.031) and GDMT (HR 0.271, 95% CI 0.134-0.548, p < 0.001) were independent predictors of lower 1-year MACE after adjustment. Conclusion: The pandemic has led to the wider application of teleconsultation, with increased adherence to GDMT, enhanced medication target dosing. Achieving GDMT was associated with favorable long-term prognosis.

COVID-19 pandemic, mechanical reperfusion and 30-day mortality in ST elevation myocardial infarction.

OBJECTIVE: The initial data of the International Study on Acute Coronary Syndromes - ST Elevation Myocardial Infarction COVID-19 showed in Europe a remarkable reduction in primary percutaneous coronary intervention procedures and higher in-hospital mortality during the initial phase of the pandemic as compared with the prepandemic period. The aim of the current study was to provide the final results of the registry, subsequently extended outside Europe with a larger inclusion period (up to June 2020) and longer follow-up (up to 30 days). METHODS: This is a retrospective multicentre registry in 109 high-volume primary percutaneous coronary intervention (PPCI) centres from Europe, Latin America, South-East Asia and North Africa, enrolling 16 674 patients with ST segment elevation myocardial infarction (STEMI) undergoing PPPCI in March/June 2019 and 2020. The main study outcomes were the incidence of PPCI, delayed treatment (ischaemia time >12 hours and door-to-balloon >30 min), in-hospital and 30-day mortality. RESULTS: In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio 0.843, 95% CI 0.825 to 0.861, p<0.0001). This reduction was significantly associated with age, being higher in older adults (>75 years) (p=0.015), and was not related to the peak of cases or deaths due to COVID-19. The heterogeneity among centres was high (p<0.001). Furthermore, the pandemic was associated with a significant increase in door-to-balloon time (40 (25-70) min vs 40 (25-64) min, p=0.01) and total ischaemia time (225 (135-410) min vs 196 (120-355) min, p<0.001), which may have contributed to the higher in-hospital (6.5% vs 5.3%, p<0.001) and 30-day (8% vs 6.5%, p=0.001) mortality observed during the pandemic. CONCLUSION: Percutaneous revascularisation for STEMI was significantly affected by the COVID-19 pandemic, with a 16% reduction in PPCI procedures, especially among older patients (about 20%), and longer delays to treatment, which may have contributed to the increased in-hospital and 30-day mortality during the pandemic. TRIAL REGISTRATION NUMBER: NCT04412655.

Renin-angiotensin system inhibitors and mortality among diabetic patients with STEMI undergoing mechanical reperfusion during the COVID-19 pandemic.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been arisen on the use of renin-angiotensin system inhibitors (RASI) due to the potentially increased expression of Angiotensin-converting-enzyme (ACE)2 and patient's susceptibility to SARS-CoV2 infection. Diabetes mellitus have been recognized favoring the coronavirus infection with consequent increase mortality in COVID-19. No data have been so far reported in diabetic patients suffering from ST-elevation myocardial infarction (STEMI), a very high-risk population deserving of RASI treatment. METHODS: The ISACS-STEMI COVID-19 registry retrospectively assessed STEMI patients treated with primary percutaneous coronary intervention (PPCI) in March/June 2019 and 2020 in 109 European high-volume primary PCI centers. This subanalysis assessed the prognostic impact of chronic RASI therapy at admission on mortality and SARS-CoV2 infection among diabetic patients. RESULTS: Our population is represented by 3812 diabetic STEMI patients undergoing mechanical reperfusion, 2038 in 2019 and 1774 in 2020. Among 3761 patients with available data on chronic RASI therapy, between those ones with and without treatment there were several differences in baseline characteristics, (similar in both periods) but no difference in the prevalence of SARS-CoV2 infection (1.6% vs 1.3%, respectively, p = 0.786). Considering in-hospital medication, RASI therapy was overall associated with a significantly lower in-hospital mortality (3.3% vs 15.8%, p < 0.0001), consistently both in 2019 and in 2010. CONCLUSIONS: This is first study to investigate the impact of RASI therapy on prognosis and SARS-CoV2 infection of diabetic patients experiencing STEMI and undergoing PPCI during the COVID-19 pandemic. Both pre-admission chronic RASI therapy and in-hospital RASI did not negatively affected patients' survival during the hospitalization, neither increased the risk of SARS-CoV2 infection. TRIAL REGISTRATION NUMBER: NCT04412655.

The Global Effect of the COVID-19 Pandemic on STEMI Care: A Systematic Review and Meta-analysis.

BACKGROUND: The COVID-19 pandemic has affected patients with ST-segment elevation myocardial infarction (STEMI) requiring primary percutaneous coronary intervention (PCI) worldwide. In this review we examine the global effect of the COVID-19 pandemic on incidence of STEMI admissions, and relationship between the pandemic and door to balloon time (D2B), all-cause mortality, and other secondary STEMI outcomes. METHODS: We performed a systematic review and meta-analysis to primarily compare D2B time and in-hospital mortality of STEMI patients who underwent primary PCI during and before the pandemic. Subgroup analyses were performed to investigate the influence of geographical region and income status of a country on STEMI care. An online database search included studies that compared the aforementioned outcomes of STEMI patients during and before the pandemic. RESULTS: In total, 32 articles were analyzed. Overall, 19,140 and 68,662 STEMI patients underwent primary PCI during and before the pandemic, respectively. Significant delay in D2B was observed during the pandemic (weighted mean difference, 8.10 minutes; 95% confidence interval [CI], 3.90-12.30 minutes; P = 0.0002; I2 = 90%). In-hospital mortality was higher during the pandemic (odds ratio [OR], 1.27; 95% CI, 1.09-1.49; P = 0.002; I2 = 36%), however this varied with factors such as geographical location and income status of a country. Subgroup analysis showed that low-middle-income countries observed a higher rate of mortality during the pandemic (OR, 1.52; 95% CI, 1.13-2.05; P = 0.006), with a similar but insignificant trend seen among the high income countries (OR, 1.17; 95% CI, 0.95-1.44; P = 0.13). CONCLUSIONS: The COVID-19 pandemic is associated with worse STEMI performance metrics and clinical outcome, particularly in the Eastern low-middle-income status countries. Better strategies are needed to address these global trends in STEMI care during the pandemic.

One-year outcomes of patients with ST-segment elevation myocardial infarction during the COVID-19 pandemic.

The pandemic has led to adverse short-term outcomes for patients with ST-segment elevation myocardial infarction (STEMI). It is unknown if this translates to poorer long-term outcomes. In Singapore, the escalation of the outbreak response on February 7, 2020 demanded adaptation of STEMI care to stringent infection control measures. A total of 321 patients presenting with STEMI and undergoing primary percutaneous coronary intervention at a tertiary hospital were enrolled and followed up over 1-year. They were allocated into three groups based on admission date-(1) Before outbreak response (BOR): December 1, 2019-February 6, 2020, (2) During outbreak response (DOR): February 7-March 31, 2020, and (3) control group: November 1-December 31, 2018. The incidence of cardiac-related mortality, cardiac-related readmissions, and recurrent coronary events were examined. Although in-hospital outcomes were worse in BOR and DOR groups compared to the control group, there were no differences in the 1-year cardiac-related mortality (BOR 8.7%, DOR 7.1%, control 4.8%, p = 0.563), cardiac-related readmissions (BOR 15.1%, DOR 11.6%, control 12.0%, p = 0.693), and recurrent coronary events (BOR 3.2%, DOR 1.8%, control 1.2%, p = 0.596). There were higher rates of additional PCI during the index admission in DOR, compared to BOR and control groups (p = 0.027). While patients admitted for STEMI during the pandemic may have poorer in-hospital outcomes, their long-term outcomes remain comparable to the pre-pandemic era.

Impact of the COVID-19 Pandemic on Door-to-Balloon Time for Primary Percutaneous Coronary Intervention　- Results From the Singapore Western STEMI Network.

BACKGROUND: Little is known about the effect of the coronavirus disease 2019 (COVID-19) pandemic and the outbreak response measures on door-to-balloon time (D2B). This study examined both D2B and clinical outcomes of patients with STEMI undergoing primary percutaneous coronary intervention (PPCI).Methods and Results:This was a retrospective study of 303 STEMI patients who presented directly or were transferred to a tertiary hospital in Singapore for PPCI from October 2019 to March 2020. We compared the clinical outcomes of patients admitted before (BOR) and during (DOR) the COVID-19 outbreak response. The study outcomes were in-hospital death, D2B, cardiogenic shock and 30-day readmission. For direct presentations, fewer patients in the DOR group achieved D2B time <90 min compared with the BOR group (71.4% vs. 80.9%, P=0.042). This was more apparent after exclusion of non-system delay cases (DOR 81.6% vs. BOR 95.9%, P=0.006). Prevalence of both out-of-hospital cardiac arrest (9.5% vs. 1.9%, P=0.003) and acute mitral regurgitation (31.6% vs. 17.5%, P=0.006) was higher in the DOR group. Mortality was similar between groups. Multivariable regression showed that longer D2B time was an independent predictor of death (odds ratio 1.005, 95% confidence interval 1.000-1.011, P=0.029). CONCLUSIONS: The COVID-19 pandemic and the outbreak response have had an adverse effect on PPCI service efficiency. The study reinforces the need to focus efforts on shortening D2B time, while maintaining infection control measures.