Type 2 myocardial infarction in patients with coronavirus disease 2019

To the Editor The recent outbreak of coronavirus disease 2019 (COVID-19) has rapidly become a pandemic.1 In this setting, although the respiratory picture is prevalent, a complex relationship of SARS-CoV-2 with the cardiovascular system promptly emerged2,3 and myocardial injury, observed in a relevant subset of COVID-19 patients, has been associated with an unfavorable outcome.4 Among different forms of myocardial injury, type 2 myocardial infarction (T2MI) is usually a poorly studied clinical entity,5 with no dedicated guidelines or consensus documents.6 As a matter of fact, there are no data regarding COVID-19 patients experiencing a T2MI during hospitalization. Methods We performed a retrospective, observational, single-center study of 60 consecutive patients with T2MI. Twelve consecutive T2MI patients (admitted in our hospital between 1 March and 15 April 2020) with COVID-19 were compared with 48 consecutive T2MI patients (admitted in the same period in 2019) without COVID-19. T2MI diagnosis was performed in the presence of acute myocardial injury associated with clinical evidence (symptoms or ECG/imaging evidence) of myocardial ischemia in the context of imbalance between oxygen supply and demand.4 Troponin determinations were not performed on a routine basis but requested only in the presence of clinical suspicion of MI. No patient showed persistent ST-segment elevation by ECG and pulmonary embolism was excluded in all COVID-19 patients by chest computed tomography scan. Endomyocardial biopsy was not performed in any patient, given the high-profile risk and the frailty of the participants. Thus, clinical judgment along with available laboratory/instrumental data and epidemiological probability were used to exclude myocarditis on a case-by-case basis. The primary endpoint of the study was in-hospital mortality. Results Patients with COVID-19-related T2MI had a significantly higher rate of hypoxemia as compared with control T2MI patients (67 vs. 40%), as well as a trend toward a higher heart rate (HR) (67 vs. 27%). Moreover, blood test showed significantly higher values of hemoglobin (median: 12.5 vs. 10.4 g/dl), ferritin (median: 850 vs. 127 ng/ml), d-dimer (median: 5.2 vs. 1.7 μg/ml) and C-reactive protein (median: 10.6 vs. 6.0 mg/dl) in patients with COVID-19 as compared with those without. On the contrary, patients with COVID-19 had significantly lower peak troponin I values than noninfected patients (median: 0.16 vs. 0.66 ng/ml). Left ventricular (LV) systolic function by echocardiography was similar in the two study groups (Table 1). Among pharmacological treatment in patients with COVID-19-related T2MI, the use of statins was significantly lower as compared with that of control T2MI patients, as well as a trend for a less frequent use of angiotensin converting enzyme inhibitors was observed in COVID-19 patients. No differences in the use of beta-blockers were reported. Coronary angiography was performed in a minority of patients (8%) regardless of the infective status, and no patient underwent myocardial revascularization (neither with percutaneous coronary intervention nor with coronary artery bypass graft); angiographic findings are reported in Table 1. Finally, patients with COVID-19-related T2MI showed a two-fold higher in-hospital mortality (50 vs. 23%; P = 0.025) as compared with the control T2MI patients (Table 2). Table 1 - Baseline characteristics of 60 patients with type 2 myocardial infarction All T2MI, N = 60 T2MI with COVID-19, N = 12 T2MI without COVID-19, N = 48 P value Age (years) 77 (71–83) 76 (73–78) 79 (70–83) 0.444 Male sex 33 (55) 10 (83) 23 (48) 0.060 Caucasian race 60 (100) 12 (100) 48 (100) 1.000 Comorbidities Hypertension 35 (58) 10 (83) 25 (52) 0.101 Diabetes mellitus 21 (35) 6 (50) 15 (31) 0.379 Chronic pulmonary disease 10 (17) 1 (8) 9 (19) 0.665 Chronic kidney disease 12 (20) 1 (8) 11 (23) 0.467 History of heart failure 10 (17) 2 (17) 8 (17) 1.000 Previous stroke/TIA 7 (12) 1 (8) 6 (12) 0.687 History of malignant neoplasm 7 (12) 2 (17) 5 (10) 0.919 Atrial fibrillation/flutter 19 (35) 4 (33) 15 (35) 0.889 Previous myocardial infarction 15 (25) 3 (25) 12 (25) 1.000 Previous PCI 4 (7) 0 (0) 4 (8) 0.697 Previous CABG 4 (7) 1 (8) 3 (6) 0.795 Symptoms at the time of T2MI Chest pain 43 (72) 9 (75) 34 (71) 0.774 Dyspnea 25 (42) 10 (83) 15 (31) 0.003 Fever 18 (30) 5 (42) 13 (27) 0.649 Vital signs SBP (mmHg) 125 (120–130) 125 (97–130) 125 (120–130) 0.730 Hypoxemia (SpO2 ≤ 92%) 27 (45) 8 (67) 19 (40) 0.040 Heart rate (bpm) 90 (75–112) 95 (85–117) 87 (72–106) 0.076 Heart rate >100 21 (35) 8 (67) 13 (27) 0.010 Diagnostic findings ECG abnormalities 44 (73) 7 (58) 37 (77) 0.342 Preserved LV function by echo 45 (74) 9 (75) 36 (75) 1.000 Echo LV wall-motion abnormality 11 (19) 3 (27) 8 (17) 0.802 Coronary angiography 5 (8) 1 (8)a 4 (8)b 1.000 Laboratory values White blood cell (μl) 9.52 (6.3–12.5) 8.8 (6.4–16.0) 9.5 (8.0–16) 0.146 Neutrophil (μl) 7.9 (5.1–11.8) 8.4 (5.2–14.4) 7.9 (5.1–10.3) 0.096 Lymphocyte (μl) 1.15 (0.9–1.7) 0.8 (0.5–1.1) 1.2 (0.9–1.7) 0.953 Hemoglobin (g/dl) 10.6 (8.6–13.5) 12.5 (9.9–15.4) 10.4 (8.6–13.1) 0.030 Hemoglobin <13 g/dl 44 (73) 6 (50) 38 (79) 0.040 Peak cardiac troponin I (ng/ml) 0.452 (0.08–1.84) 0.16 (0.09–0.70) 0.66 (0.73–2.03) 0.031 Creatinine (mg/dl) 1.2 (0.8–1.7) 1.1 (0.9–1.4) 1.2 (0.8–1.8) 0.407 Ferritin (ng/ml) 203 (98–476) 850 (456–2611) 127 (89–256) 0.001 d-Dimer (μg/ml) 2.3 (1.1–6.22) 5.2 (1.8–10.2) 1.7 (1.1–3.3) 0.036 C-reactive protein (mg/dl) 6.6 (2.19–12) 10.6 (3.0–23.1) 6.0 (1.8–8.4) 0.017 Procalcitonin (μg/ml) 1.2 (0.2–2.3) 0.4 (0.1–1.6) 1.6 (0.2–8) 0.500 NT-pro-BNP (pg/ml) 6936 (3442–25 195) 8941 (3442–35 000) 6042 (3386–25 195) 0.328 Acute infection 36 (60) 12 (100) 24 (50) 0.145 Data are presented as median values (interquartile ranges) or numbers (percentage). CABG, coronary artery bypass graft; COVID-19, coronavirus disease 2019; LV, left ventricular; NT-pro-BNP, N-terminal pro-B type natriuretic peptide; PCI, percutaneous coronary intervention; T2MI, type 2 myocardial infarction; TIA, transient ischemic attack.aAngiography showed significant stenosis of the intermediate and the first diagonal branches.bAngiography showed significant coronary artery disease for two patients: respectively significant stenosis of the first diagonal branches (first patient) and significant stenosis of the distal segment of the circumflex artery (second patient). The remaining two patients had no critical coronary disease on angiography. Table 2 - Treatment and outcome of 60 patients with type 2 myocardial infarction All T2MI, N = 60 T2MI with COVID-19, N = 12 T2MI without COVID-19, N = 48 P value Respiratory treatment Oxygen inhalation 19 (31) 4 (33) 15 (31) 0.889 Noninvasive ventilation 18 (30) 10 (83) 8 (17) 0.001 Orotracheal intubation 3 (5) 1 (8) 2 (4) 0.553 Treatment PCI 0 (0) 0 (0) 0 (0) 1.000 CABG 0 (0) 0 (0) 0 (0) 1.000 Medical therapy 5 (8) 1 (8) 4 (8) 1.000 Beta blockers 28 (47) 6 (50) 22 (46) 0.795 ACE inhibitors 35 (58) 3 (25) 32 (67) 0.088 Statins 25 (42) 2 (17) 23 (48) 0.024 DAPT 3 (5) 1 (8) 2 (4) 0.276 Clinical outcome Death in hospital 17 (28) 6 (50)a 11 (23)b 0.025 Data are presented as median values (interquartile ranges) or numbers (percentage). ACE, angiotensin converting enzyme; CABG, coronary artery bypass graft; COVID-19, coronavirus disease 2019; DAPT, dual antiplatelet therapy; PCI, percutaneous coronary intervention; T2MI, type 2 myocardial infarction.aThree (50%) patients died of respiratory failure, two (33%) of multiorgan failure and one (17%) of arrhythmic storm.bSix (54%) patients died of multiorgan failure, three (27%) of respiratory failure and two (18%) of sepsis. Comment Our data underline that T2MI may occur in the context of COVID-19 syndrome due to the imbalance between oxygen supply and demand, which can be secondary to hypoxemia, increased HR, inflammatory status and/or decompensated heart failure, whereas in T2MI without COVID-19, anemia seems to be a more prevalent mechanism of oxygen supply/demand imbalance leading to myocardial ischemia. Despite the lower degree of myocardial damage and similar systolic LV function, COVID-19-related T2MI patients showed a significantly higher in-hospital mortality than control patients. Of note, T2MI outcome is known to be characterized by an extremely high risk of both cardiovascular and noncardiovascular mortality (50% after 2 years).7,8 Thus, given the medical complexity and the other associated comorbidities and the high expected rate of noncardiovascular mortality, a multidisciplinary approach is mandatory in COVID-19 patients with T2MI.6,7 Our study confirms the very low rate of coronary angiography and myocardial revascularization procedures in T2MI patients despite the potential contribution to myocardial ischemia of preexisting obstructive coronary artery disease. However, cardiac catheterization almost certainly is associated with significant risk in such critically ill patients. Finally, the optimal medical treatment of T2MI is still unknown, since therapeutic agents currently used for type 1 MI have not been tested in T2MI so far.6,9–11 Accordingly, in our study we observed a very low use of such pharmacological treatments in COVID-19 patients. Conflicts of interest There are no conflicts of interest.