Myocardial Injury Portends a Higher Risk of Mortality and Long-Term Cardiovascular Sequelae after Hospital Discharge in COVID-19 Survivors.

Background: Cardiovascular sequelae after COVID-19 are frequent. However, the predictors for their occurrence are still unknown. In this study, we aimed to assess whether myocardial injury during COVID-19 hospitalization is associated to CV sequelae and death after hospital discharge. Methods: In this prospective observational study, consecutive patients who were admitted for COVID-19 in a metropolitan COVID-19 hub in Italy, between March 2021 and January 2022, with a ≥ 1 assessment of high sensitivity cardiac troponin I (hs-cTnI) were included in the study, if they were alive at hospital discharge. Myocardial injury was defined as elevation hs-cTnI > 99th percentile of the upper reference limit. The incidence of all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE, including cardiovascular death, admission for acute or chronic coronary syndrome, hospitalization for heart failure, and stroke/transient ischemic attack) at follow-up were the primary outcomes. Arrhythmias, inflammatory heart diseases, and/or thrombotic disorders were analyzed as well. Results: Among the 701 COVID-19 survivors (mean age 66.4 ± 14.4 years, 40.2% female), myocardial injury occurred in 75 (10.7%) patients. At a median follow-up of 270 days (IQR 165, 380), all-cause mortality (21.3% vs. 6.1%, p < 0.001), MACCE (25.3% vs. 4.5%, p < 0.001), arrhythmias (9.3% vs. 5.0%, p = 0.034), and inflammatory heart disease (8.0% vs. 1.1%, p < 0.001) were more frequent in patients with myocardial injury compared to those without. At multivariate analysis, myocardial injury (HR 1.95 [95% CI:1.05-3.61]), age (HR 1.09 [95% CI:1.06-1.12]), and chronic kidney disease (HR 2.63 [95% CI:1.33-5.21]) were independent predictors of death. Myocardial injury (HR 3.92 [95% CI:2.07-7.42]), age (HR 1.05 [95% CI:1.02-1.08]), and diabetes (HR 2.35 [95% CI:1.25-4.43]) were independent predictors of MACCE. Conclusion: In COVID-19 survivors, myocardial injury during the hospital stay portends a higher risk of mortality and cardiovascular sequelae and could be considered for the risk stratification of COVID-19 sequelae in patients who are successfully discharged.

Impaired clinical outcome and increased postoperative complications in COVID-19 patients undergoing cardiopulmonary bypass

Objective Previous studies reported unfavorable results in COVID-19 patients who underwent cardiac surgery. Complications most frequently observed were respiratory failure and higher incidence of thromboembolic events. We present our single-center experience in patients with perioperative diagnosis of COVID-19 infection undergoing cardiac surgery with extracorporeal circulation. Methods In this observational matched case-control (propensity match 1:2) study, we collected data of patients undergoing open heart cardiac surgery from January 2020 to May 2021, having positive perioperative diagnosis of COVID-19 infection confirmed by polymerase Chain Reaction-PCR (study group). Patients were compared with 56 corresponding controls (control group) who matched for age, sex, body mass index (BMI) and Euro-Score II. Results In the study period 1060 patients underwent cardiac surgery with cardiopulmonary bypass (CPB). Among them, 28 consecutive patients, aged 70.1±9.3 years, had perioperative diagnosis of COVID-19 infection. Four (14%) patients underwent emergency surgery for type-A aortic dissection, 2 (7%) patients died in the Intensive Care Unit for severe respiratory failure, shock and multiple organ failure. Significant bleeding complications occurred in 14 (50%) patients in the study group (vs 6% in the control group, p=<0.05). In the study group, 11 (39%) patients required early surgical reexploration for bleeding, 5 presented cardiac tamponade, 5 (18%) underwent multiple surgical revisions for recurrent bleeding. Three (11%) patients required late chest drainage of a massive sero-hemorrhagic pleural effusion, 1 (4%) presented late postoperative intracranial hemorrhage. Fourteen (50%) patients had severe thrombocytopenia (vs 9% in the control group, p=<0.05). In the study group blood components transfusion and procoagulant drugs administration increased (79% and 78% vs 18% and 11% in the control group, respectively, p=<0.05). In the study group 6 (21%) patients presented postoperative acute renal failure (2% in the control group, p=<0.05), 7 (25%) acute respiratory failure (p=<0.05) requiring prolonged postoperative orotracheal intubation. Sternal dehiscence was observed in 4 (14%) patients in the study group (vs 4% in the control group, p=< 0.05). Complications significantly influenced hospital stay length (20 ± 3.1 vs 8.1 ± 3.9 days, p=< 0.05). In the multivariable logistic regression model the SARS-CoV-2 infection and renal failure were independent factors associated with severe postoperative complications (p=<0.01). Conclusions Clinical outcome of open heart cardiac surgery patients with perioperative COVID-19 infection appears significantly impaired in terms of mortality and postoperative complications. CPB-related inflammatory reaction could likely exacerbate the deleterious effect of COVID-19 on the respiratory and renal systems, as well as on the coagulation pathways. Early and late hemorrhagic complications were very frequent with significantly increased surgical reexplorations for bleeding, a higher incidence of severe thrombocytopenia, of blood components transfusion and procoagulant drugs administration. The increased surgical risk should suggest a cautious attitude in indicating open heart surgery in patients with perioperative COVID-19 infection and surgery should be limited to not postponable or to urgent cases.

Bleeding Complications in Patients With Perioperative COVID-19 Infection Undergoing Cardiac Surgery: A Single-Center Matched Case-Control Study.

OBJECTIVE: Previous studies reported a poor outcome in patients with coronavirus 2019 (COVID-19) undergoing cardiac surgery. Complications most frequently described were respiratory failure, renal failure, and thromboembolic events. In their recent experience, the authors observed a very high incidence of bleeding complications. The purpose of the study was to investigate a possible significant correlation between perioperative COVID-19 infection and hemorrhagic complications compared to non-COVID-19 patients. DESIGN: Single-center, observational, retrospective, matched case-control (1:2) study involving patients who underwent open-heart cardiac surgery from February 2020 and March 2021 with positive perioperative diagnosis of COVID-19 infection, matched with patients without COVID-19 infection. SETTING: Cardiac surgery unit and intensive care unit of a university tertiary center in a metropolitan area. PARTICIPANTS: In the study period, 773 patients underwent cardiac surgery on cardiopulmonary bypass (CPB). Among them, 23 consecutive patients had perioperative diagnosis of COVID-19 infection (study group). These patients were compared with 46 corresponding controls (control group) that matched for age, sex, body mass index, and Society of Thoracic Surgeons score. INTERVENTIONS: Open-heart cardiac surgery on CPB. MEASUREMENTS AND MAIN RESULTS: In the study group, 2 patients (9%) died in the intensive care unit from severe respiratory failure, shock, and multiple organ failure. In the study group, patients showed a significantly higher incidence of bleeding complications (48% v 2%, p = 0.0001) and cases of surgical reexploration for bleeding (35% v 2%, p = 0.0001), a higher incidence of severe postoperative thrombocytopenia (39% v 6%, p = 0.0007), and a higher need of blood components transfusions (74% v 30%, p = 0.0006). Chest tubes blood loss and surgical hemostasis time were markedly prolonged (p = 0.02 and p = 0.003, respectively). CONCLUSIONS: A worrisome increased risk of early and late bleeding complications in COVID-19 patients was observed, and it should be considered when assessing the operative risk. CPB-related inflammatory reaction could exacerbate the deleterious effect of COVID-19 on the coagulation system and likely deviate it toward a hemorrhagic pattern.

Incidence and Predictors of Thrombotic Complications in 4742 Patients with COVID-19 or Other Acute Infectious Respiratory Diseases: A Propensity Score-Matched Study.

BACKGROUND: A prothrombotic state, attributable to excessive inflammation, cytokine storm, hypoxia, and immobilization, is a feature of SARS-CoV-2 infection. Up to 30% of patients with severe COVID-19 remain at high risk of thromboembolic events despite anticoagulant administration, with adverse impact on in-hospital prognosis. METHODS: We retrospectively studied 4742 patients with acute infectious respiratory disease (AIRD); 2579 were diagnosed to have COVID-19 and treated with heparin, whereas 2163 had other causes of AIRD. We compared the incidence and predictors of total, arterial, and venous thrombosis, both in the whole population and in a propensity score-matched subpopulation of 3036 patients (1518 in each group). RESULTS: 271 thrombotic events occurred in the whole population: 121 (4.7%) in the COVID-19 group and 150 (6.9%) in the no-COVID-19 group (p < 0.001). No differences in the incidence of total (p = 0.11), arterial (p = 0.26), and venous (p = 0.38) thrombosis were found between the two groups after adjustment for confounding clinical variables and in the propensity score-matched subpopulation. Likewise, there were no significant differences in bleeding rates between the two groups. Clinical predictors of arterial thrombosis included age (p = 0.006), diabetes mellitus (p = 0.034), peripheral artery disease (p < 0.001), and previous stroke (p < 0.001), whereas history of solid cancer (p < 0.001) and previous deep vein thrombosis (p = 0.007) were associated with higher incidence of venous thrombosis. CONCLUSIONS: Hospitalized patients with COVID-19 treated with heparin do not seem to show significant differences in the cumulative incidence of thromboembolic events as well as in the incidence of arterial and venous thrombosis separately, compared with AIRD patients with different etiological diagnosis.

Evidence for Biological Age Acceleration and Telomere Shortening in COVID-19 Survivors.

The SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokine release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called persistent post-COVID-19 syndrome (PPCS) is a common finding. In COVID-19 survivors, PPCS presents one or more symptoms: fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. In this study, a cohort of 117 COVID-19 survivors (post-COVID-19) and 144 non-infected volunteers (COVID-19-free) was analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. The results show a consistent biological age increase in the post-COVID-19 population, determining a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality) compared with 3.68 ± 8.17 years for the COVID-19-free population (p < 0.0001). A significant telomere shortening parallels this finding in the post-COVID-19 cohort compared with COVID-19-free subjects (p < 0.0001). Additionally, ACE2 expression was decreased in post-COVID-19 patients, compared with the COVID-19-free population, while DPP-4 did not change. In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID-19 condition, particularly in younger patients (< 60 years).

Stay Home! Stay Safe! First Post-Discharge Cardiologic Evaluation of Low-Risk-Low-BNP Heart Failure Patients in COVID-19 Era.

BACKGROUND: The COVID-19 pandemic has had a deep impact on periodic outpatient evaluations. The aim of this study was to evaluate the impact of low brain natriuretic peptide (BNP) values in predicting adverse events in heart failure (HF) patients in order to evaluate implications for safe delay of outpatient visits. METHODS: This was a retrospective study. One-thousand patients (mean age: 72 ± 10 years, 561 women) with HF and BNP values <250 pg/mL at discharge were included. A 6-month follow-up was performed. The primary endpoint was a combination of deaths and readmissions for HF within 6-month after discharge. RESULTS: At 6-month follow-up, 104 events (10.4%) were recorded (65 HF readmissions and 39 all-cause deaths). Univariate Cox analysis identified as significant predictors of outcome were age (p < 0.001, hazard ratio [HR] = 1.044), creatinine (p = 0.001, HR = 1.411), and BNP (p < 0.001, HR = 1.010). Multivariate Cox regression confirmed that BNP (p < 0.001, HR = 1.009), creatinine (p = 0.016, HR = 1.247), and age (p = 0.013, HR = 1.027) were independent predictors of events in HF patients with BNP values <250 pg/mL at discharge. Patients with BNP values >100 pg/mL and creatinine >1.0 mg/dL showed increased events rates (from 4.3% to 19.0%) as compared to those with lower values (p < 0.000, HR = 4.014). CONCLUSIONS: Low pre-discharge BNP levels were associated with low rates of cardiovascular events in HF patients, independently of the frequency of follow-up.

Telemedicine for adult congenital heart disease patients during the first wave of COVID-19 era: a single center experience.

AIM: To summarize our experience on the implementation of a telemedicine service dedicated to adult congenital heart disease (ACHD) patients during the lockdown for the first wave of Coronavirus disease 2019 (COVID-19). METHODS: This is a prospective study enrolling all ACHD patients who answered a questionnaire dedicated telematic cardiovascular examination. RESULTS: A total of 289 patients were enrolled, 133 (47%) were male, 25 (9%) were affected by a genetic syndrome. The median age was 38 (29-51) years, whereas the median time interval between the last visit and the telematic follow-up was 9.5 (7.5-11.5) months. Overall, 35 patients (12%) reported a worsening of fatigue in daily life activity, 17 (6%) experienced chest pain, 42 (15%) had presyncope and 2 (1%) syncope; in addition, 28 patients (10%) presented peripheral edema and 14 (5%) were orthopneic. A total of 116 (40%) patients reported palpitations and 12 had at least one episode of atrial fibrillation and underwent successful electrical (8) or pharmacological (4) cardioversion. One patient was admitted to the emergency department for uncontrolled arterial hypertension, five for chest pain, and one for heart failure. Two patients presented fever but both had negative COVID-19 nasal swab. CONCLUSION: During the COVID-19 pandemic, the use of telemedicine dramatically increased and here we report a positive experience in ACHD patients. The postpandemic role of telemedicine will depend on permanent regulatory solutions and this early study might encourage a more systematic telematic approach for ACHD patients.

Cardiac surgery practice during the COVID-19 outbreak: a multicentre national survey.

OBJECTIVES: Healthcare systems worldwide have been overburdened by the coronavirus disease 2019 (COVID-19) outbreak. Accordingly, hospitals had to implement strategies to profoundly reshape both non-COVID-19 medical care and surgical activities. Knowledge about the impact of the COVID-19 pandemic on cardiac surgery practice is pivotal. The goal of the present study was to describe the changes in cardiac surgery practices during the health emergency at the national level. METHODS: A 26-question web-enabled survey including all adult cardiac surgery units in Italy was conducted to assess how their clinical practice changed during the national lockdown. Data were compared to data from the corresponding period in 2019. RESULTS: All but 2 centres (94.9%) adopted specific protocols to screen patients and personnel. A significant reduction in the number of dedicated cardiac intensive care unit beds (-35.4%) and operating rooms (-29.2%), along with healthcare personnel reallocation to COVID departments (nurses -15.4%, anaesthesiologists -7.7%), was noted. Overall adult cardiac surgery volumes were dramatically reduced (1734 procedures vs 3447; P < 0.001), with a significant drop in elective procedures [580 (33.4%) vs 2420 (70.2%)]. CONCLUSIONS: This national survey found major changes in cardiac surgery practice as a response to the COVID-19 pandemic. This experience should lead to the development of permanent systems-based plans to face possible future pandemics. These data may effectively help policy decision-making in prioritizing healthcare resource reallocation during the ongoing pandemic and once the healthcare emergency is over.

A nontrivial differential diagnosis in COVID-19 pandemic: a case report and literary review of amiodarone-induced interstitial pneumonia.

Amiodarone is a drug commonly used to treat and prevent cardiac arrhythmias, but it is often associated with several adverse effects, the most serious of which is pulmonary toxicity. A 79-year-old man presented with respiratory failure due to interstitial pneumonia during the COVID-19 pandemic. The viral etiology was nevertheless excluded by repeated nasopharyngeal swabs and serological tests and the final diagnosis was amiodarone-induced organizing pneumonia. The clinical and computed tomography findings improved after amiodarone interruption and steroid therapy. Even during a pandemic, differential diagnosis should always be considered and pulmonary toxicity has to be taken into account in any patient taking amiodarone and who has new respiratory symptoms.

Weathering the Cytokine Storm in COVID-19: Therapeutic Implications.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis. SUMMARY: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients' clinical outcomes and prognosis. Key Messages: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19.