ABSTRACT
Objective: The aim of the study was to identify predictors of heart-focused anxiety in patients with heart failure. A better understanding of such predictors may help in detecting the comorbidity underlying heart-focused anxiety and identifying patients who need psychological help. Methods: In order to account for multiple sources of heart-focused anxiety, we included psychological, lifestyle, and medical/laboratory predictors. The study involved 148 patients, of whom 74 had a leading diagnosis of worsening heart failure and were hospitalized during the COVID-19 epidemic. A second group of 74 patients suffering from cardiovascular diseases without a diagnosis of acute heart failure, were examined in various out-patient cardiology clinics. The sample consisted of 37.8% females and 62.2% males, with an average age of 63.35 years. The patients completed the Cardiac Anxiety Questionnaire, the Generalized Anxiety Disorder scale, the Patient Health Questionnaire, and the Intolerance of Uncertainty Scale. Results: Patients with heart failure with higher levels of depression and intolerance of uncertainty had higher overall levels of heart-focused anxiety, higher levels of fear about chest and heart sensations. Older patients with higher levels of depression had higher levels of activity avoidance, especially activities believed to elicit cardiac symptoms. Cardiac patients with higher level of anxiety and with anaemia as comorbidity had higher levels of heart-focused attention and monitoring of cardiac activity. Conclusion: In patients with heart failure, the presence of heart-focused anxiety significantly reduces the quality of life, leads to avoidant behaviours, and is associated with anxiety and depressive symptoms. These patients are more likely to seek medical help and specialist services, but the need for psychological help is very rarely recognized.
ABSTRACT
Background: Etavopivat, an investigational, once-daily, selective, activator of erythrocyte pyruvate kinase (PKR) increases PKR activity, resulting in decreased 2,3-DPG and increased ATP in red blood cells (RBCs) of healthy volunteers and patients (pts) with sickle cell disease (SCD).1,2 Aims: We report results of an open-label (OL) extension cohort from a Phase 1 study (NCT03815695) designed to characterize the safety and clinical activity of etavopivat at a maximal pharmacodynamic dose in pts with SCD. Methods: 15 pts were enrolled to receive etavopivat 400 mg once daily for 12 wks, followed by a 4-wk follow-up. Assessments included safety, pharmacokinetics, pharmacodynamics, RBC health parameters and systemic markers of SCD pathophysiology. Results: Of 15 pts (age 32.3 ±10.1 yr;HbSS/SC n=13/2), 14 completed 12-wks of treatment (tx);1 pt discontinued tx after ∼2 wks. Etavopivat 400 mg once daily was generally well tolerated. Adverse events (AEs) reported during tx and follow-up were commonly low grade (Gr) and consistent with pts' SCD. Gr1-2 AEs in >2 pts (n [%]) were sickle cell pain events (9 [60%]);headache (5 [33%]);and upper respiratory tract infection (3 [20%]). The Gr3-4 AE in >1 pt was sickle cell vaso-occlusion (VOC;4 [27%]). On-tx serious adverse events (SAEs;1 pt each) were Gr3 VOC post Gr3 COVID (not tx-related) and Gr3 left femoral deep vein thrombosis (possibly related, resulting in tx discontinuation as stated above). SAEs (1 pt each) during the 4-wk follow-up were Gr3 acute chest syndrome + Gr3 VOC, Gr3 non-cardiac chest pain and Gr3 syncope (all unrelated). Observed increases in ATP and decreases in 2,3-DPG were durable over 12 wks of etavopivat tx. Etavopivat tx normalized hemoglobin (Hb)S-oxygen affinity to that of HbA. Etavopivat tx over 12 wks improved overall sickle RBC health, demonstrated by a reduction in point of sickling as well as improved measures of deformability and hydration of sickle RBCs (all P<0.01;Figure). Etavopivat tx over 12 wks was associated with a sustained significant increase in Hb compared with baseline (BL;P<0.0001), with mean maximal increase of 1.5 (range 0.7-2.3) g/dL. Ontx increase in Hb >1g/dL was achieved in 11 (73%) pts, for whom the mean maximal Hb increase was 1.8 (1.2-2.3) g/dL. Absolute reticulocytes, indirect bilirubin and lactate dehydrogenase significantly decreased from BL and were sustained over the 12wk period (all P<0.05), indicative of increased RBC lifespan and decreased hemolysis. Several markers of disease activity significantly decreased from BL during daily etavopivat tx, including the inflammatory marker tumor necrosis factor-α , which decreased by 35% (P<0.001). Based on preliminary exploratory analysis with an aggregate duration of etavopivat exposure of 3.32 pt-yrs in the OL cohort, a decrease in the trend for VOC Hospitalizations was observed: annualized historical and on-tx VOC Hospitalization rates were 0.93 and 0.30, respectively;the 1 on-tx VOC Hospitalization was COVID-related. Summary/Conclusion: Etavopivat 400 mg once daily for up to 12 wks demonstrated a tolerable safety profile and showed improvements in various markers of RBC health in pts with SCD. Rapid and sustained increases in Hb were associated with decreases in reticulocyte counts and markers of hemolysis, supporting increased sickle RBC lifespan and improved anemia. Together, these results support further evaluation of etavopivat in the Phase 2/3 Hibiscus Study (NCT04624659) currently enrolling pts. (Figure Presented).
ABSTRACT
A decrease in patients accessing health care was documented during the first COVID-19 surge. We established a 24/7 cardiology telephone advice service during the first surge, this was provided by an experienced cardiology nurse based in a nurse-led cardiac assessment unit. Various options were available on the basis of the telephone consultation. We particularly wanted to see the outcomes of reassurance of patients (to see if the approach was safe) and the outcomes of patients who were directed to emergency departments (to see if this identified patients with significant cardiological and medical problems who may not otherwise have accessed healthcare). We reviewed the progress of the first 999 patients who used the telephonic service for which we had 90 day follow-up data. 141 patients were initially reassured by the nurse at the telephone call. Of these, 55 patients had no further engagement with healthcare providers in the subsequent 90 days. 7 were followed-up within the cardiac rehabilitation program that they were already participating in. 21 were referred to cardiology by their GP but all subsequently had normal assessment and/or investigation. 30 attended an emergency department of whom 22 were discharged directly from the ED;the other 8 patients were admitted to hospital which included 2 patients with non-cardiac chest pain and 2 with exacerbations of known heart failure. 28 patients recontacted the telephonic service during the 90 days and had subsequent face-to-face assessment. There was one death amongst the 141 patients, from a known malignancy. 161 patients were advised to attend an emergency department following telephonic evaluation of whom 50 did not attend. 84 patients were discharged home following assessment in the emergency department of whom 18 were discussed or referred to cardiology for outpatient assessment. 20 patients were admitted under cardiology (8 non-STEMI, 1 complete heart block, 1 profound bradycardia, 1 atrial fibrillation, 1 congestive cardiac failure, 1 critical aortic stenosis, 1 chemotherapy associated cardiotoxicity, 4 no significant cardiac issue found). Nine patients were admitted to non-cardiac wards. We believe that nurse-led telephonic triage can be effective in the management of patients in the community with established cardiac disease or with potential cardiac symptoms. We intend to further develop the service we established during the first surge of the COIVD-19 pandemic.
ABSTRACT
BACKGROUND: Radiological and pathological studies in severe COVID-19 pneumonia (SARS-CoV-2) have demonstrated extensive pulmonary immunovascular thrombosis and infarction. This study investigated whether these focal changes may present with chest pain mimicking pulmonary emoblism (PE) in ambulant patients. METHODS: CTPAs from outpatients presenting with chest pain to Leeds Teaching Hospital NHS Trust 1st March to 31 May 2020 (n = 146) and 2019 (n = 85) were compared. Regions of focal ground glass opacity (GGO), consolidation and/or atelectasis (parenchymal changes) were determined, and all scans were scored using British Society for Thoracic Imaging (BSTI) criteria for COVID-19, and the 2020 cohort was offered SARS-CoV-2 antibody testing. RESULTS: Baseline demographic and clinical data were similar between groups with absence of fever, normal lymphocytes and marginally elevated CRP and D-Dimer values. Evidence of COVID-19 or parenchymal changes was observed in 32.9% (48/146) of cases in 2020 compared to 16.5% (14/85) in 2019 (P = 0.007). 11/146 (7.5%) patients met BSTI criteria for COVID-19 in 2020 compared with 0/14 in 2019 (P = 0.008). 3/39 patients tested had detectable COVID-19 antibodies (2 with parenchymal changes and 1 with normal parenchyma) however 0/6 patients whose CTPA met BSTI criteria "likely/suspicious for COVID-19" and attended antibody testing were SARS-CoV-2 antibody positive. CONCLUSIONS: 32.8% ambulatory patients with suspected PE in 2020 had parenchymal changes with 7.5% diagnosed as COVID-19 infection by imaging criteria, despite the absence of other COVID-19 symptoms. These findings suggest that localized COVID-19 pneumonitis with immunothrombosis occurs distal to the bronchiolar arteriolar circulation, causing pleural irritation and chest pain without viraemia, accounting for the lack of fever and systemic symptoms.