Fragmentation of the QRS Complex Is Associated with Right Ventricular Dilatation and Mortality in Critically Unwell Coronavirus Disease 2019 Patients.

BACKGROUND: QRS fragmentation (fQRS) is a depolarization disorder that can be detected on routine electrocardiography (ECG). Current evidence suggests that fQRS is a prognosticator of adverse cardiovascular events. This study aimed to assess the relationship between fQRS and all-cause mortality in critically unwell coronavirus disease 2019 (COVID-19) patients and to investigate the significance of associated abnormalities on echocardiography. METHODS: A retrospective cohort study of COVID-19 patients in a critical care setting was performed. Electrocardiography was performed on presentation to hospital, admission to the critical care unit, and at subsequent points according to clinical need. Transthoracic echocardiography was performed at clinical discretion to assess for structural and functional cardiac abnormalities. Primary outcome was in-hospital mortality and secondary outcome was the need for mechanical invasive ventilation. RESULTS: Totally, 212 consecutive patients were included of which 120 (57%) exhibited fQRS and inferior leads were involved in 88% of the patients. Overall, fQRS was a significant predictor of mortality [65% vs. 44% P =.003; multivariate odds ratio = 2.96, 95% confidence interval (CI): 1.42-6.40, P =.005] and inferior fQRS itself was a significant predictor of mortality (P =.03). There was no significant association between fQRS and the need for invasive mechanical ventilation. A total of 112 patients underwent echocardiography. There was a greater incidence of right ventricular (RV) dilatation in the fQRS group (16% vs. 2% respectively, P =.02) and pulmonary hypertension (33% vs. 14% respectively, P =.03) based on echocardiographic criteria. CONCLUSION: Our study demonstrates that fQRS is significantly associated with RV dilation, pulmonary hypertension, and mortality in critically unwell COVID-19 patients.

Polypharmacy and cumulative anticholinergic burden in older adults hospitalized with fall.

Introduction: Polypharmacy is a growing phenomenon associated with adverse effects in older adults. We assessed the potential confounding effects of cumulative anticholinergic burden (ACB) in patients who were hospitalized with falls. Methods: A noninterventional, prospective cohort study of unselected, acute admissions aged ≥ 65 years. Data were derived from electronic patient health records. Results were analyzed to determine the frequency of polypharmacy and degree of ACB and their relationship to falls risk. Primary outcomes were polypharmacy, defined as prescription of 5 or more regular oral medications, and ACB score. Key Results: Four hundred eleven (411) consecutive subjects were included, mean age 83.8 ± 8.0 years: 40.6% men. There were 38.4% patients who were admitted with falls. Incidence of polypharmacy was 80.8%, (88.0% and 76.3% among those admitted with and without fall, respectively). Incidence of ACB score of 0, 1, 2, ≥ 3 was 38.7%, 20.9%, 14.6%, and 25.8%, respectively. On multivariate analysis, age [odds ratio (OR) = 1.030, 95% CI:1.000 ~ 1.050, P = 0.049], ACB score (OR = 1.150, 95% CI:1.020 ~ 1.290, P = 0.025), polypharmacy (OR = 2.140, 95% CI:1.190 ~ 3.870, P = 0.012), but not Charlson Comorbidity Index (OR = 0.920, 95% CI:0.810 ~ 1.040, P = 0.172) were significantly associated with higher falls rate. Of patients admitted with falls, 29.8% had drug-related orthostatic hypotension, 24.7% had drug-related bradycardia, 37.3% were prescribed centrally acting drugs, and 12.0% were taking inappropriate hypoglycemic agents. Conclusion: Polypharmacy results in cumulative ACB and both are significantly associated with falls risk in older adults. The presence of polypharmacy and each unit rise in ACB score have a stronger effect of increasing falls risk compared to age and comorbidities.

Right heart thrombus in transit and peripherally inserted central catheters.

Right heart thrombus in transit or "free-floating right heart thrombus" is defined as thrombus(i) arising from the deep veins that embolises to the right atrium or right ventricle before reaching the pulmonary vasculature. It is almost always associated with pulmonary thromboembolism and is a medical emergency with reported mortality rates of over 40%. We present two cases of right heart thrombus in transit with pulmonary thromboembolism resulting from venous thrombosis associated with peripherally inserted central catheters that were managed with different approaches. The cases highlight that clinicians should have a low threshold to utilise imaging modalities such as computerised tomography and transthoracic echocardiography when there is an untoward change in physiological parameters among patients with peripherally inserted central catheters, particularly those with risk factors for peripherally inserted central catheter associated venous thrombosis. Furthermore, procedural optimisation surrounding peripherally inserted central catheters, such as insertion technique and choice of lumen size, is underscored.

Role of open access echocardiography in detection of cardiac structural and functional abnormalities.

PURPOSE: To evaluate the prevalence and incidence of significant structural heart disease in targeted patients with cardiac symptoms referred by general practitioners (GPs) using open access echocardiography, without prior clinical evaluation by a cardiologist. DESIGN: Data were derived from 488 subjects who underwent transthoracic echocardiography between January and April 2018. Patients were referred directly by GPs in East Berkshire, South England, through an online platform. Echocardiography was performed within 4-6 weeks of referral and all reports were assessed by a consultant cardiologist with expedited follow-up facilitated pro re nata. Results were analysed to determine the frequency of detection of structural abnormalities, particularly of the left ventricle and cardiac valves. RESULTS: Echocardiography was prospectively performed in consecutive subjects (50% male, mean (±SD) age 68.5±22 years; 50% female; mean (±SD) 64.6 (±19.1)). At least one abnormality likely to change management was found in 133 (27.3%) of all open access echocardiograms. Clinical heart failure with left ventricular systolic dysfunction (LVSD) and diastolic dysfunction was confirmed in 46 (9%) and 69 (14%), respectively. Of the 46 patients with LVSD, 33 were new diagnoses. Significant cardiac valve disease was found in 42 (8.6%) patients. 12 of these had known valvular disease or previous valvular surgery, and 30 were new diagnoses. CONCLUSION: Major structural and functional cardiac abnormalities are common in late middle-aged patients who present to GPs with cardiac symptoms and signs. Reported, unrestricted open access echocardiography enables early detection of significant cardiac pathology and timely intervention may improve cardiovascular outcomes.

Recurrent Nonbacterial Thrombotic Endocarditis and Primary Antiphospholipid Antibody Syndrome.

In 2015, a 37-year-old man was referred for evaluation of hypertension and was found to have a mobile structure on the posterior mitral valve leaflet on echocardiography. Laboratory investigations yielded a diagnosis of primary antiphospholipid antibody syndrome (APLS). He underwent excision of the lesion and mitral valve repair. Histology confirmed the diagnosis of nonbacterial thrombotic endocarditis (NBTE). The patient was anticoagulated with warfarin up until 2018, which was substituted for rivaroxaban because of an erratic international normalised ratio. Serial echocardiography up to 2020 was unremarkable. In 2021, he presented with breathlessness and peripheral oedema. Echocardiography demonstrated large vegetation on both mitral valve leaflets. At the operation, vegetations were also evident on the left and noncoronary cusps of the aortic valve and he underwent mechanical aortic and mitral valve replacement. Histology confirmed NBTE. The case is unusual and highlights recurrent NBTE requiring re-do valve surgery.

Recent insights into crosstalk between genetic parasites and their host genome.

The bulk of higher order organismal genomes is comprised of transposable element (TE) copies, i.e. genetic parasites. The host-parasite relation is multi-faceted, varying across genomic region (genic versus intergenic), life-cycle stages, tissue-type and of course in health versus pathological state. The reach of functional genomics though, in investigating genotype-to-phenotype relations, has been limited when TEs are involved. The aim of this review is to highlight recent progress made in understanding how TE origin biochemical activity interacts with the central dogma stages of the host genome. Such interaction can also bring about modulation of the immune context and this could have important repercussions in disease state where immunity has a role to play. Thus, the review is to instigate ideas and action points around identifying evolutionary adaptations that the host genome and the genetic parasite have evolved and why they could be relevant.

Vitamin D in the news: A call for clear public health messaging during Covid-19.

Background: The public are increasingly reliant on the internet and media to access healthcare related information during the Covid-19 pandemic. Vitamin D is essential for musculoskeletal and immune health, with daily supplementation advised by public health bodies. Several studies assessing a possible link between vitamin D and Covid-19 severity have arrived at conflicting results and news articles have been rapidly disseminating such research to the public. There has been little focus on studying the quality of information available. Aim: To identify if online search interest in vitamin D increased with pandemic burden and analyse the accuracy of public health messaging relating to vitamin D in online news articles. Methods: Online search interest data for vitamin D was correlated with pandemic burden, defined as the number of Covid-19 deaths. Online news articles discussing vitamin D and Covid-19 were analysed using qualitative coding. Results: Online search interest for vitamin D increased as pandemic burden increased (p < 0.0001, Spearman's rank). Of the 72 articles identified, most (50%) offered a mixed opinion on the benefit of vitamin D in Covid-19. From articles making a recommendation for vitamin D supplementation, 23% of articles gave mixed messaging or advised against supplementation. 16% of articles recommended a dose which exceeded the safe limit of 4000 IU/day, risking toxicity. Conclusion: A significant number of articles provided mixed messaging or incorrectly advised supratherapeutic doses. This study highlights an opportunity for public health bodies to utilise the increased interest in vitamin D during the pandemic to raise awareness with accurate information.

Role of open access echocardiography in detection of cardiac structural and functional abnormalities.

PURPOSE: To evaluate the prevalence and incidence of significant structural heart disease in targeted patients with cardiac symptoms referred by general practitioners (GPs) using open access echocardiography, without prior clinical evaluation by a cardiologist. DESIGN: Data were derived from 488 subjects who underwent transthoracic echocardiography between January and April 2018. Patients were referred directly by GPs in East Berkshire, South England, through an online platform. Echocardiography was performed within 4-6 weeks of referral and all reports were assessed by a consultant cardiologist with expedited follow-up facilitated pro re nata. Results were analysed to determine the frequency of detection of structural abnormalities, particularly of the left ventricle and cardiac valves. RESULTS: Echocardiography was prospectively performed in consecutive subjects (50% male, mean (±SD) age 68.5±22 years; 50% female; mean (±SD) 64.6 (±19.1)). At least one abnormality likely to change management was found in 133 (27.3%) of all open access echocardiograms. Clinical heart failure with left ventricular systolic dysfunction (LVSD) and diastolic dysfunction was confirmed in 46 (9%) and 69 (14%), respectively. Of the 46 patients with LVSD, 33 were new diagnoses. Significant cardiac valve disease was found in 42 (8.6%) patients. 12 of these had known valvular disease or previous valvular surgery, and 30 were new diagnoses. CONCLUSION: Major structural and functional cardiac abnormalities are common in late middle-aged patients who present to GPs with cardiac symptoms and signs. Reported, unrestricted open access echocardiography enables early detection of significant cardiac pathology and timely intervention may improve cardiovascular outcomes.

Drug-related bradycardia precipitating hospital admission in older adults: an ongoing problem.

BACKGROUND: Drug-related bradycardia (DRB) is a common clinical conundrum and can result in multiple hospital admissions as a result of the increased prescription of rate-limiting medications that can predispose to presyncopal or syncopal episodes. AIM: To evaluate the incidence of DRB in elderly hospital inpatients. METHODS: We conducted a retrospective analysis of all patients admitted to our acute medical unit between November 2018 and February 2019 and identified patients over the age of 70 with more than one diurnal bradycardic episode during their admission. We extracted patient demographics, presenting complaint, admission 12-lead ECG and medications from the hospital electronic database. RESULTS: We screened 2312 adults and identified 100 patients over the age of 70 years with two or more episodes of diurnal bradycardia during their hospital admission. This constituted 4.32% of total admissions. Beta blockers were the most commonly prescribed rate-limiting medication (n=54, 87.1%), of which bisoprolol was the most frequently prescribed (n=41) and sinus bradycardia was the most commonly identified rhythm disturbance in our cohort of patients (n=41, 41%). Syncope was the most common presenting symptom and occurred in 23 patients, 14 (60.9%) of which were diagnosed with a DRB. Atrial fibrillation was more common in those with DRB compared with those with bradycardia not caused by medications (35.5% vs 10.5%, p=0.006), and atrial fibrillation was a significant predictor of DRB (OR=10.2, 95% CI 3.3 to 31.6, p<0.001). CONCLUSION: Bradycardia is a significant cause of hospital admissions in older adults and can be avoided with pharmacovigilance. Caution should be exercised when initiating or changing the dose of rate-limiting agents in these patients; while those with atrial fibrillation should undergo regular review of their heart rate followed by appropriate medication dose adjustments.

Dexamethasone treatment may mitigate adverse effects of vitamin D deficiency in hospitalized Covid-19 patients.

AIMS: We have previously demonstrated that vitamin D deficiency might be associated with worse outcomes in hospitalized Covid-19 patients. The aim of our study was to explore this relationship with dexamethasone therapy. METHODS: We prospectively studied two cohorts of hospitalized Covid-19 patients between March and April and between September and December 2020 (n = 192). Patients were tested for serum 25-hydroxyvitamin D (25-OH-D) levels during admission. The first cohort not treated with dexamethasone (n = 107) was divided into vitamin D deficient (25-OH-D ≤ 30 nmol/L) (n = 47) and replete subgroups (25-OH-D > 30 nmol/L) (n = 60). The second cohort treated with dexamethasone (n = 85) was similarly divided into deficient (25-OH-D ≤ 30 nmol/L) (n = 27) and replete subgroups (25-OH-D > 30 nmol/L) (n = 58). Primary outcome was in-hospital mortality and secondary outcomes were elevation in markers of cytokine storm and ventilatory requirement. RESULTS: No mortality difference was identified between cohorts and subgroups. The "no dexamethasone" cohort 25-OH-D deplete subgroup recorded significantly higher peak D-Dimer levels (1874 vs. 1233 µgFEU/L) (p = 0.0309), CRP (177 vs. 107.5) (p = 0.0055), and ventilatory support requirement (25.5% vs. 6.67%) (p = 0.007) compared to the replete subgroup. Among the 25-OH-D deplete subgroup higher peak neutrophil counts, peak CRP, peak LDH, peak ferritin, and lower trough lymphocyte counts were observed, without statistical significance. In the "dexamethasone" cohort, there was no apparent association between 25-OH-D deficiency and markers of cytokine storm or ventilatory requirement. CONCLUSION: Vitamin D deficiency is associated with elevated markers of cytokine storm and higher ventilatory requirements in hospitalized Covid-19 patients. Dexamethasone treatment appears to mitigate adverse effects of vitamin D deficiency.