Long-term effects of coronavirus disease 2019 on the cardiovascular system, CV COVID registry: A structured summary of a study protocol.

BACKGROUND: Patients presenting with the coronavirus-2019 disease (COVID-19) may have a high risk of cardiovascular adverse events, including death from cardiovascular causes. The long-term cardiovascular outcomes of these patients are entirely unknown. We aim to perform a registry of patients who have undergone a diagnostic nasopharyngeal swab for SARS-CoV-2 and to determine their long-term cardiovascular outcomes. STUDY AND DESIGN: This is a multicenter, observational, retrospective registry to be conducted at 17 centers in Spain and Italy (ClinicalTrials.gov number: NCT04359927). Consecutive patients older than 18 years, who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions, will be included since March 2020, to August 2020. Patients will be classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome will be cardiovascular mortality at 1 year. The secondary outcomes will be acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias, at 1 year. Outcomes will be compared between the two groups. Events will be adjudicated by an independent clinical event committee. CONCLUSION: The results of this registry will contribute to a better understanding of the long-term cardiovascular implications of the COVID19.

[Myocardial injury in coronavirus disease 19 (Covid-19): main pathophysiological mechanisms and clinical utility of cardiac biomarkers]. / Atteintes myocardiques au cours de la maladie à coronavirus 19 (Covid-19) : principaux mécanismes physiopathologiques et utilité clinique des biomarqueurs cardiaques.

Covid-19 is responsible for myocardial injury in many infected patients, which is associated with severe disease and critical illness. The mechanisms by which SARS-CoV-2 may cause myocardial damage involve direct effect of the virus in cardiac cells and indirect effect due to the clinical consequences of Covid-19. Cardiomyocytes are well known to express Angiotensin-Converting Enzyme-2 receptors (ACE-2) to facilitate the virus cell entry, which could explain the occurrence of myocarditis, functional alterations in the myocardium, and more rarely, myocardial infarction. Myocardial injury may also be secondary to systemic inflammation or coagulopathy due to complicated Covid-19. The existence of a cardio-intestinal axis with alteration of tryptophan metabolism in the small bowel leading first to colitis and then to systemic inflammation has also been evoked to explain the myocardial injury. Morphological and metabolic disturbances of the heart during the Covid-19 are associated with elevated concentrations of cardiac blood biomarkers, mainly troponins and natriuretic peptides. The determination of these biomarkers has proven to be very useful for diagnosis, prognosis, and risk stratification. Indeed, recent data demonstrated that about 20% of infected patients admitted to the hospital have elevated troponin or BNP levels, and Covid-19 patients with elevated troponin concentrations beyond the diagnostic threshold (99th percentile) were associated with a higher risk of in-hospital mortality. In conclusion, after more than a year of a unique global pandemic, it is now clearly established that myocardial injury during Covid-19 is frequent and strongly contributes to the severity of the disease. Cardiac alterations secondary to direct infection of cardiac cells by SARS-CoV-2 or to the clinical consequences of Covid-19 are associated with elevated levels of cardiac biomarkers in blood, whose measurement is crucial in clinical decision making.

Microthrombi as a Major Cause of Cardiac Injury in COVID-19: A Pathologic Study.

BACKGROUND: Cardiac injury is common in patients who are hospitalized with coronavirus disease 2019 (COVID-19) and portends poorer prognosis. However, the mechanism and the type of myocardial damage associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain uncertain. METHODS: We conducted a systematic pathological analysis of 40 hearts from hospitalized patients dying of COVID-19 in Bergamo, Italy, to determine the pathological mechanisms of cardiac injury. We divided the hearts according to presence or absence of acute myocyte necrosis and then determined the underlying mechanisms of cardiac injury. RESULTS: Of the 40 hearts examined, 14 (35%) had evidence of myocyte necrosis, predominantly of the left ventricle. Compared with subjects without necrosis, subjects with necrosis tended to be female, have chronic kidney disease, and have shorter symptom onset to admission. The incidence of severe coronary artery disease (ie, >75% cross-sectional narrowing) was not significantly different between those with and without necrosis. Three of 14 (21.4%) subjects with myocyte necrosis showed evidence of acute myocardial infarction, defined as ≥1 cm2 area of necrosis, whereas 11 of 14 (78.6%) showed evidence of focal (>20 necrotic myocytes with an area of ≥0.05 mm2 but <1 cm2) myocyte necrosis. Cardiac thrombi were present in 11 of 14 (78.6%) cases with necrosis, with 2 of 14 (14.2%) having epicardial coronary artery thrombi, whereas 9 of 14 (64.3%) had microthrombi in myocardial capillaries, arterioles, and small muscular arteries. We compared cardiac microthrombi from COVID-19-positive autopsy cases to intramyocardial thromboemboli from COVID-19 cases as well as to aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19-infected patients presenting with ST-segment-elevation myocardial infarction. Microthrombi had significantly greater fibrin and terminal complement C5b-9 immunostaining compared with intramyocardial thromboemboli from COVID-19-negative subjects and with aspirated thrombi. There were no significant differences between the constituents of thrombi aspirated from COVID-19-positive and -negative patients with ST-segment-elevation myocardial infarction. CONCLUSIONS: The most common pathological cause of myocyte necrosis was microthrombi. Microthrombi were different in composition from intramyocardial thromboemboli from COVID-19-negative subjects and from coronary thrombi retrieved from COVID-19-positive and -negative patients with ST-segment-elevation myocardial infarction. Tailored antithrombotic strategies may be useful to counteract the cardiac effects of COVID-19 infection.

The Role of Anticoagulation in Post-COVID-19 Concomitant Stroke, Myocardial Infarction, and Left Ventricular Thrombus: A Case Report.

BACKGROUND Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the lungs but can involve any organ. The medical community is struggling to cope with the critical illness associated with the disease. On top of that, patients who have recovered from COVID-19 have presented with complications such as thrombotic episodes in various organs both during and after being infected with SARS-CoV-2. A COVID-19-associated prothrombotic state has been mentioned in multiple recent research articles. The role of anticoagulants is debatable, because even after receiving them prophylactically, many patients have experienced thrombotic episodes. The situation, therefore, represents a challenge to the medical community. CASE REPORT We report on a COVID-19-associated prothrombotic state in a 65-year-old man with no history of comorbid illness. Initially, he presented with right-sided weakness and was found to have had an acute ischemic stroke. Urgent imaging after the stroke revealed changes on electrocardiography that were remarkable for left bundle branch block. The patient's elevated cardiac enzyme levels correlated with a silent acute myocardial infarction (MI). His echocardiogram revealed a left ventricular (LV) thrombus. He was managed with a multidisciplinary approach involving Neurology, Cardiology, and Medicine. CONCLUSIONS COVID-19-associated prothrombotic episodes involving arterial and venous systems have been reported in the literature. But concomitant stroke, acute MI, and LV thrombus rarely have been documented. The role of prophylactic or therapeutic anticoagulation is still unclear because even when patients are on these drugs, they continue to develop thrombotic episodes. Indeed, further studies are required to develop a standard management plan for what can be a fatal situation.

Acute myocardial infarction and large coronary thrombosis in a patient with COVID-19.

This is a case report of a 60-year-old male, without any cardiovascular risk factor and no cardiac history admitted to hospital with a diagnosis of interstitial pneumonia caused by coronavirus disease 2019 (COVID-19). After 7 days, the blood tests showed a significant rise of inflammatory and procoagulant markers, along with a relevant elevation of high-sensitivity Troponin I. Electrocardiogram and transthoracic echocardiogram (TTE) were consistent with a diagnosis of infero-posterolateral acute myocardial infarction and the patient was transferred to the isolated Cath Lab for primary percutaneous coronary intervention (PCI). The angiography showed an acute massive thrombosis of a dominant right coronary artery without clear evidence of atherosclerosis. Despite the optimal pharmacological therapies and different PCI techniques, the final TIMI flow was 0/1 and after 3 hr the clinical condition evolved in cardiac arrest for pulseless electric activity. Acute coronary syndrome-ST-elevation myocardial infarction is a relevant complication of COVID-19. Due to high levels of proinflammatory mediators, diffuse coronary thrombosis could occur even in patients without cardiac history or comorbidities. This clinical case suggests that coronary thrombosis in COVID-19 patients may be unresponsive to optimal pharmacological (GP IIb-IIIa infusion) and mechanical treatment (PCI).

SARS-CoV-2 and myocardial injury: Few answers, many questions.

Acute cardiac injury, defined as an elevated high-sensitivity troponin I or troponin T upon admission or during hospitalization, is common in patients with COVID-19, occurring in 10% to 35% of patients depending on the assay used and the population studied. Even though the mechanisms of SARS-CoV-2 myocardial injury are not well defined, type 1 myocardial infarction and fulminant myocarditis are rare. Often, acute cardiac injury occurs in patients with elevated inflammatory markers, and both are associated with worse outcomes. However, the extent to which treatments should differ for patients with acute cardiac injury, heightened systemic inflammation, or both, is unknown.