Multimodality Cardiac Imaging, Cardiac Symptoms, and Clinical Outcomes in Patients Who Recovered from Mild COVID-19.

Background Many patients have persistent cardiac symptoms after mild COVID-19. However, studies assessing the relationship between symptoms and cardiac imaging are limited. Purpose To assess the relationship between multi-modality cardiac imaging parameters, symptoms, and clinical outcomes in patients recovered from mild COVID-19 compared to COVID-19 negative controls. Materials and Methods Patients who underwent PCR testing for SARS-CoV-2 between August 2020 and January 2022 were invited to participate in this prospective, single-center study. Participants underwent cardiac MRI, echocardiography, and assessment of cardiac symptoms at 3-6 months after SARS-CoV-2 testing. Cardiac symptoms and outcomes were also evaluated at 12-18 months. Statistical analysis included Fisher's exact test and logistic regression. Results This study included 122 participants who recovered from COVID-19 ([COVID+] mean age, 42 years ± 13 [SD]; 73 females) and 22 COVID-19 negative controls (mean age, 46 years ± 16 [SD]; 13 females). At 3-6 months, 20% (24/122) and 44% (54/122) of COVID+ participants had at least one abnormality on echocardiography and cardiac MRI, respectively, which did not differ compared to controls (23% [5/22]; P = .77 and 41% [9/22]; P = .82, respectively). However, COVID+ participants more frequently reported cardiac symptoms at 3-6 months compared to controls (48% [58/122] vs. 23% [4/22]; P = .04). An increase in native T1 (10 ms) was associated with increased odds of cardiac symptoms at 3-6 months (OR, 1.09 [95% CI: 1.00, 1.19]; P = .046) and 12-18 months (OR, 1.14 [95% CI: 1.01, 1.28]; P = .028). No major adverse cardiac events occurred during follow-up. Conclusion Patients recovered from mild COVID-19 reported increased cardiac symptoms 3-6 months after diagnosis compared to controls, but the prevalence of abnormalities on echocardiography and cardiac MRI did not differ between groups. Elevated native T1 was associated with cardiac symptoms 3-6 months and 12-18 months after mild COVID-19.

Statins to prevent early cardiac dysfunction in cancer patients at increased cardiotoxicity risk receiving anthracyclines.

BACKGROUND AND AIMS: Anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD). We aimed to assess whether statins prevent decline in left ventricular ejection fraction (LVEF) in anthracycline-treated patients at increased risk for CTRCD. METHODS: In this multicenter double-blinded, placebo-controlled trial, patients with cancer at increased risk of anthracycline-related CTRCD (per ASCO guidelines) were randomly assigned to atorvastatin 40 mg or placebo once-daily. Cardiovascular magnetic resonance (CMR) imaging was performed before and within 4 weeks after anthracyclines. Blood biomarkers were measured at every cycle. The primary outcome was post-anthracycline LVEF, adjusted for baseline. CTRCD was defined as a fall in LVEF by >10% to <53%. Secondary endpoints included left ventricular (LV) volumes, CTRCD, CMR tissue characterization, high sensitivity troponin I (hsTnI), and B-type natriuretic peptide (BNP). RESULTS: We randomized 112 patients (56.9 ± 13.6 years, 87 female, and 73 with breast cancer): 54 to atorvastatin and 58 to placebo. Post-anthracycline CMR was performed 22 (13-27) days from last anthracycline dose. Post-anthracycline LVEF did not differ between the atorvastatin and placebo groups (57.3 ± 5.8% and 55.9 ± 7.4%, respectively) when adjusted for baseline LVEF (P = 0.34). There were no significant between-group differences in post-anthracycline LV end-diastolic (P = 0.20) or end-systolic volume (P = 0.12), CMR myocardial edema and/or fibrosis (P = 0.06-0.47), or peak hsTnI (P ≥ 0.99) and BNP (P = 0.23). CTRCD incidence was similar (4% versus 4%, P ≥ 0.99). There was no difference in adverse events. CONCLUSIONS: In patients at increased risk of CTRCD, primary prevention with atorvastatin during anthracycline therapy did not ameliorate early LVEF decline, LV remodeling, CTRCD, change in serum cardiac biomarkers, or CMR myocardial tissue changes. TRIAL REGISTRATION: NCT03186404.

Efficacy and safety of erythropoietin and iron therapy to reduce red blood cell transfusion in surgical patients: a systematic review and meta-analysis.

PURPOSE: Iron restricted anemia is prevalent in surgical patients and is associated with an increased risk of allogeneic red blood cell (RBC) transfusion and adverse events. Treatment of anemia includes oral and intravenous iron and erythropoiesis stimulating agents (ESAs). More recent studies have focused on the use of intravenous iron as the primary approach to treating anemia. Nevertheless, the optimal treatment strategy for anemia remains to be established. Our primary objective was to evaluate the efficacy and safety of ESA and iron therapy relative to iron therapy alone in reducing RBC transfusion in surgical patients. SOURCE: We searched the Cochrane Library, MEDLINE, EMBASE, and ClinicalTrials.gov from inception to May 2018. We included randomized-controlled trials in which adult surgical patients received an ESA and iron, vs iron alone, prior to cardiac and non-cardiac surgery. Our primary outcome was RBC transfusion rate. Secondary outcomes included hemoglobin concentration (post-treatment and postoperatively), number of RBC units transfused, mortality, stroke, myocardial infarction (MI), renal dysfunction, pulmonary embolism (PE), and deep vein thrombosis (DVT). PRINCIPAL FINDINGS: In total, 25 studies (4,719 participants) were included. Erythropoiesis stimulating agents and iron therapy reduced RBC transfusion relative to iron therapy (relative risk [RR] 0.57; 95% confidence interval [CI], 0.46 to 0.71) without any change in mortality (RR 1.31; 95% CI, 0.80 to 2.16), stroke (RR 1.91; 95% CI, 0.63 to 5.76), MI (RR 1.12; 95% CI, 0.50 to 2.50), renal dysfunction (RR 0.96; 95% CI, 0.72 to 1.26), PE (RR 0.92; 95% CI, 0.15 to 5.83), or DVT (RR 1.48; 95% CI, 0.95 to 2.31). CONCLUSION: Administration of ESA and iron therapy reduced the risk for RBC transfusion compared with iron therapy alone in patients undergoing cardiac and non-cardiac surgery. Nevertheless, publication bias and heterogeneity reduces the confidence of the finding. Although the analysis was probably under-powered for some outcomes, no difference in the incidence of serious adverse events was observed with ESA and iron compared with iron alone. Further large prospective trials are required to confirm these findings.

Potential biomarkers of tissue hypoxia during acute hemodilutional anemia in cardiac surgery: A prospective study to assess tissue hypoxia as a mechanism of organ injury.

PURPOSE: Hemodilutional anemia is associated with acute kidney injury (AKI) and mortality in patients undergoing cardiac surgery by mechanisms that may include tissue hypoxia. Our hypothesis was to assess if changes in the potential hypoxic biomarkers, including methemoglobin and erythropoietin, correlated with a decrease in hemoglobin (Hb) concentration following hemodilution on cardiopulmonary bypass (CPB). METHODS: Arterial blood samples were taken from patients (n = 64) undergoing heart surgery and CPB at baseline, during CPB, following CPB, and in the intensive care unit (ICU). Potential hypoxic biomarkers were measured, including methemoglobin, plasma Hb, and erythropoietin. Data were analyzed by repeated measures one-way analysis of variance on ranks and linear regression. RESULTS: Hemoglobin levels decreased following CPB and methemoglobin increased in the ICU (P < 0.001 for both). No correlation was observed between the change in Hb and methemoglobin (P = 0.23). By contrast, reduced Hb on CPB correlated with increased lactate, reduced pH, and increased erythropoietin levels following CPB (P ≤ 0.004 for all). Increased plasma Hb (P < 0.001) also correlated with plasma erythropoietin levels (P < 0.001). CONCLUSION: These data support the hypothesis that erythropoietin rather than methemoglobin is a potential biomarker of anemia-induced tissue hypoxia. The observed relationships between decreased Hb during CPB and the increase in lactate, reduced pH, and increase in erythropoietin levels suggest that early changes in plasma erythropoietin may be a pragmatic early biomarker of anemia-induced renal hypoxia. Further study is required to determine if anemia-induced increases in erythropoietin may predict AKI in patients undergoing cardiac surgery. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01883713). Registered 21 June 2013.

Experimental assessment of oxygen homeostasis during acute hemodilution: the integrated role of hemoglobin concentration and blood pressure.

BACKGROUND: Low hemoglobin concentration (Hb) and low mean arterial blood pressure (MAP) impact outcomes in critically ill patients. We utilized an experimental model of "normotensive" vs. "hypotensive" acute hemodilutional anemia to test whether optimal tissue perfusion is dependent on both Hb and MAP during acute blood loss and fluid resuscitation, and to assess the value of direct measurements of the partial pressure of oxygen in tissue (PtO2). METHODS: Twenty-nine anesthetized rats underwent 40% isovolemic hemodilution (1:1) (or sham-hemodilution control, n = 4) with either hydroxyethyl starch (HES) (n = 14, normotensive anemia) or saline (n = 11, hypotensive anemia) to reach a target Hb value near 70 g/L. The partial pressure of oxygen in the brain and skeletal muscle tissue (PtO2) were measured by phosphorescence quenching of oxygen using G4 Oxyphor. Mean arterial pressure (MAP), heart rate, temperature, arterial and venous co-oximetry, blood gases, and lactate were assessed at baseline and for 60 min after hemodilution. Cardiac output (CO) was measured at baseline and immediately after hemodilution. Data were analyzed by repeated measures two-way ANOVA. RESULTS: Following "normotensive" hemodilution with HES, Hb was reduced to 66 ± 6 g/L, CO increased (p < 0.05), and MAP was maintained. These conditions resulted in a reduction in brain PtO2 (22.1 ± 5.6 mmHg to 17.5 ± 4.4 mmHg, p < 0.05), unchanged muscle PO2, and an increase in venous oxygen extraction. Following "hypotensive" hemodilution with saline, Hb was reduced to 79 ± 5 g/L and both CO and MAP were decreased (P < 0.05). These conditions resulted in a more severe reduction in brain PtO2 (23.2 ± 8.2 to 10.7 ± 3.6 mmHg (p < 0.05), a reduction in muscle PtO2 (44.5 ± 11.0 to 19.9 ± 12.4 mmHg, p < 0.05), a further increase in venous oxygen extraction, and a threefold increase in systemic lactate levels (p < 0.05). CONCLUSIONS: Acute normotensive anemia (HES hemodilution) was associated with a subtle decrease in brain tissue PtO2 without clear evidence of global tissue hypoperfusion. By contrast, acute hypotensive anemia (saline hemodilution) resulted in a profound decrease in both brain and muscle tissue PtO2 and evidence of inadequate global perfusion (lactic acidosis). These data emphasize the importance of maintaining CO and MAP to ensure adequacy of vital organ oxygen delivery during acute anemia. Improved methods of assessing PtO2 may provide an earlier warning signal of vital organ hypoperfusion.