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Certolizumab is a Fab fragment of a humanized monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha). Differing from the other TNF-alpha inhibitors due to the absence of Fc fragment and pegylation, it binds to both the soluble and transmembrane forms of TNF-alpha, creating a strong TNF-alpha blockage. Previously approved for psoriatic arthritis, certolizumab received another approval from FDA in 2018 for the treatment of moderate to severe chronic plaque psoriasis that does not respond to conventional systemic treatments or for which these treatments are contraindicated. Administered via subcutaneous injections, certolizumab also has a low-dose option for patients weighing less than 90 kg. Certolizumab is considered a safe biological drug that can be preferred during pregnancy and lactation.Copyright © 2022 by Turkish Society of Dermatology and Venereology.
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Objectives: COVID-19 infected over 150 million people and caused over 1 million deaths in the US. This study evaluates several variables thought to be associated with mortality risk in the COVID-19 population. Method(s): The IQVIA longitudinal medical and pharmacy claims databases identified 17,682,111 patients with a COVID-19 diagnosis between 4/1/2020-4/30/2022 from a population of >277 million patients in the US. Patients were linked to Veritas Data Research fact-of-death records (90% complete compared to CDC reporting) and confirmed deaths were flagged. Confirmed mortality rates (CMR) were evaluated by age group, socioeconomic status (SES) using the Area Deprivation Index (v2.0, University of Wisconsin, 2015), co-morbidities and COVID-specific (approved and unapproved) treatments. Result(s): Of the 563,744 patients (3.2%) identified as dead (3.67% in men, 2.85% in women overall), CMR was lowest in patients aged 0-17 (0.08%), highest in age 65-75 (5.92%) and >75 (16.40%). Patients in the lowest 40% of SES had CMR of 4.43% while in the highest 20% was 1.56%. Respiratory failure, pneumonia and sepsis were the most common acute diagnoses accompanying COVID-19 deaths in all SES. In patients with comorbid dementia or Alzheimer's disease, CMR were 21.62% and 23.40% respectively. Additionally, congestive heart failure (15.79%), atrial fibrillation (15.50%), chronic kidney disease (15.30%) and COPD (12.19%) were associated with high CMR. Among patients receiving approved therapies, casirivimab/imdevimab and remdesivir had CMR of 1.41% and 12.63% respectively, while for those receiving unapproved therapies, ivermectin and hydroxychloroquine had CMR of 2.54% and 2.45%. Conclusion(s): Compared to the 1.1% case-mortality rate (Johns Hopkins 2023) among US COVID-19 patients, we found CMR exceeded 3% among those with a medical claim for COVID-19. Advanced age, dementia, and cardio-renal disease were associated with mortality. Patients with the lowest SES had approximately 3 times the confirmed mortality rate compared to those in the highest SES group.Copyright © 2023
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182 Figure 1Cardiovascular events in COVID-19 Survivors by LGE Status[Figure omitted. See PDF] 182 Figure 2All-cause mortality in COVID-19 Survivors by LGE Status[Figure omitted. See PDF]Conflict of InterestNone
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Objective: Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. Method(s): From march 2020 to november 2021 we done 108 veno-venous ECMO therapies. 35 patients required implantation immediately in intensive care unit in place of call by mobile ECMO team. Depend from distance of call it was used medical ambulance, rescue helicopter or medical plane. Result(s): In the first analyzed period (March-December 2020), 90-day mortality was 41%. 8 (7.6%) patients were discharged from the Intensive Care Unit. The remaining 3 (4.2%) were discharged home. 7 patients (6.6%) had both lung transplants. 7 patients (6.6%) required conversion to VV-A ECMO therapy due to the development of acute heart failure. Conclusion(s): In the analyzed period of March-December 2020, the mortality was 41%. As a result, the lower effect of regression of consolidation and inflammatory lesions of lung tissue indicates that ECMO therapy remains the treatment method in high-risk patients as a bridge therapy to lung transplantation.
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Introduction: Loop diuretics are the first-line treatment for volume overload in acute decompensation of congestive heart failure (AHF). Loop diuretic resistance is common due to pharmacologic tachyphylaxis. Therefore, thiazide and thiazide-like diuretics are often used as add-on therapy to combine two different pharmacologic mechanisms. This systemic review and meta-analysis aimed to synthesize the current evidence on the efficacy and safety of metolazone and other thiazide-like diuretics in AHF. Method(s): PRISMA guidelines were followed in conducting this systematic review. PubMed, Scopus, PubMed Central, and Embase databases were searched using relevant keywords for studies published before 5 Jan 2022. and title screening was performed, followed by full-text screening using the Covidence software. Data were extracted, and analysis was done using Cochrane Review Manager (RevMan v5.1). The results were reported in odds ratio and mean difference with 95% confidence intervals. Result(s): Out of 2999 studies identified by database search, eight studies met the inclusion criteria (2 RCTs and 6 cohort studies). Pooled analysis using a random-effects model showed no difference in mean difference among the metolazone group and control group for 24 hours total urine output (MD 69.32, 95% CI -638.29 to 776.94;n = 551;I2 = 84%), change in urine output in 24 hours (MD -284.09, 95% CI -583.99 to 15.81;n = 345;I2 = 0%), 48 hours total urine output (MD -465.62, 95% CI -1302.22 to 370.99;n = 242;I2 = 0%) and urine output at 72 hours (MD -13.24, 95% CI -90.88 to 64.40;n = 205;I2 = 0%). However, studies with furosemide only in the comparator arm, 24 hours of total urine outcome favored metolazone (MD 692.70, 95% CI 386.59 to 998.82;n = 334;I2 = 0%). There was no difference between the two groups in the rate of adverse events, loss of weight, mortality, or readmission rates. Conclusion(s): Metolazone therapy in diuretic resistant AHF may improves urine output and facilitates achieving a net negative balance. Thus, metolazone and thiazide-like diuretics can be used as add-on therapy in acute decompensation of heart failure, especially in diuretic resistance.Copyright © 2023 The Author(s)
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Coronavirus disease has many systemic disease symptoms and has severe consequences for the cardiovascular system. Objective. To assess the role of clinical and laboratory indicators in determining the risk of chronic heart failure (CHF) in COV-ID-19 survivors. Material and methods. In total, 151 patients treated in a monoinfectious hospital from 03.11.20 to 10.02.21 with a confirmed diagnosis of COVID-19 were retrospectively selected. Medical history and laboratory data were collected by reviewing electronic medical records. The data included age, gender, body mass index, smoking status, and comorbidities. The laboratory data included the results of hematology and blood chemistry, coagulation, and the levels of acute-phase proteins. The CHF occurrence was used as the study endpoint. Results and discussion. The study patients were divided into two groups depending on the presence of CHF: group 1 included 46 patients with CHF, and group 2 included 105 patients without CHF. The median age was 66.2 (50-92) years;91 (60.3%) were females. Laboratory tests, such as levels of the hs-C-reactive protein, lactate dehydrogenase, procalcitonin, creatinine, and bilirubin, were statistically significantly different in patients of the study groups, and the median values were higher in patients with CHF. Neutrophil-lymphocyte ratio (NLR) showed statistically significant differences between groups: in patients with CHF, the median was 4.97% compared to 3.62% (p=0.011) in those without CHF. The most significant predictors of an increased risk of CHF were age >=66 years (OR=8.038, p<0.001), procalcitonin level >=0.09 ng/mL (increased the CHF risk by 3.8 times, p<0.001), thrombocy-topenia <=220x109/L (p=0.010), an NLR ratio >=4.11% (p=0.010), and a history of chronic kidney disease (p=0.018). Conclusion. A model has been developed to determine the factors closely associated with the risk of chronic heart failure in CO-VID-19 survivors.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.
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Objectives: COVID-19 had an impact on health care, including diagnostics. Early diagnosis of MM is a critical factor for prognosis. We examined the impact of COVID-19 on incidence of NDMM patients and on characteristics in NDMM patients in US and in Germany. Method(s): 44,164 NDMM patients were identified in TriNetX federated network across 55 healthcare organizations in US between January 2018 and December 2021. A bivariate analysis examined changes in patient characteristics in two cohorts before (Cohort 1;n=25513) and after (Cohort 2;n=18.651) the start of the COVID-19 pandemic in March 2020. 4172 NDMM patients were identified in the German database in a sample of across >100 healthcare organizations in the same time period. Similarly, bivariate analysis examined changes in patient characteristics before (Cohort 1;n=2252) and after (Cohort 2;n=1920) the start of pandemic. Result(s): Analysis of US data showed a significant decrease in incidence of NDMM. Bivariate analysis revealed that NDMM patients in Cohort 2 have a significantly higher risk profile compared with patients in Cohort 1, higher incidence of renal failure (13.5% v. 15.43%), heart failure (10.3% v 11.26%), bone lesions (12.6% v. 13.05%) and anemia (26.8% v. 29.75%). The German data indicated an increased risk profile in Cohort 2, with higher reporting of renal impairment (12.3% v. 15.5%) and cardiac impairment (8.3% v. 10.9%). The higher risk profile was reflected in a significant increase of all SLiM-CRAB criteria, notably hypercalcemia (24.1 % v. 36.9%), bone marrow plasma cell infiltration (28.1% v. 36.8%) and free light chain involvement (27.3% v. 41.3%). Conclusion(s): The results provide real-world evidence of a change in risk profile for patients with NDMM during COVID-19. This higher risk profile is observed in both the US and Germany, and may negatively impact outcomes such as progression-free and five-year overall survival.Copyright © 2023
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Bruton tyrosine kinase inhibitors (BTKis) were approved for use at the end of 2013 and have since been used for indications including chronic lymphocytic leukaemia (CLL), Waldenstrom's macroglobulinaemia and mantle cell lymphoma. The use of BTKis has increased significantly in the UK since they achieved NICE (National Institute for Health and Care Excellence) approval for frontline treatment of CLL in 2021. However, they are associated with significant adverse cardiovascular events. In September 2021 the British Journal of Haematology published good practice guidelines for the management of cardiovascular complications of BTKis. Our aim was to see whether these guidelines had been adhered to for patients taking BTKis. Method(s): Data was collected for all patients being prescribed BTKis (ibrutinib and acalabrutinib) in the South Tees NHS Trust in July 2022. Patients' medical records were used to assess whether their management adhered to the good practice guidelines. Data was collated for 67 patients in total. Result(s): The data showed that although all patients were consented for the risk of atrial fibrillation only 6% were consented for hypertension and only 1.5% for ventricular arrhythmias and sudden cardiac death. The guidelines recommend a baseline ECG (electrocardiogram) on commencement of treatment;however, only 7% had this completed and 0% had the minimum monitoring recommendation of 6-monthly ECGs. Thirty patients (45%) had an indication for a baseline echocardiogram;however, only one had this completed. For patients reporting symptoms of syncope, dizziness or palpitations only 50% had an ECG completed. Three patients developed worsening heart failure. The recommendations suggest referral to a cardio-oncologist;however, due to lack of availability of this service the referrals were instead made to the usual cardiologist. Conclusion(s): Although there was a lack of compliance with guideline recommendations, it should be considered that most usual checks were affected by COVID-19 outbreaks and a drop in face-to- face clinics, which were replaced by phone clinics and home delivery of medications. However, the premade consent forms for BTKis need to be updated to include consent for ventricular arrhythmias and sudden cardiac death. There also needs to be routine procedures in place to ensure that regular blood pressure testing and ECG monitoring occurs and that there is prompt recognition of cardiovascular complications. Action and implementation: To ensure improved compliance with these guidelines we plan to update our consent forms and create a proforma for clinic use to ensure that clinicians are aware of the various monitoring criteria required.
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Background: Catheter ablation is a cornerstone treatment for symptomatic atrial fibrillation (AF) with major improvements in safety over time. However, rates of adverse events with use of current techniques in a contemporary quality-focused network remain undefined. Objective(s): Across a large, real-world sample, we sought to describe (1) rates of major, adverse events associated with catheter ablation of AF and (2) patient-level factors associated with complications. Method(s): Utilizing the REAL-AF collaboration, a registry of contemporary AF ablation procedures with granular patient, procedural and follow-up data comprised of cases from over 50 operators across academic and non-academic sites, we evaluated all patients undergoing their first ablation procedure from January 2018 - June 2022. Risk-adjusted analyses were conducted to evaluate the relationship between patient factors and complications. Result(s): Among 3144 patients (age 66.1 +/- 11.0 years, 42% female, 67.1% paroxysmal, 32.9% persistent) who underwent AF ablation, procedure-related complications (n =77) were identified in 65 patients (2.1%) with multiple complications occurring in 9 patients (0.2%). Most complications (n=70, 93.5%) occurred in the peri-procedural (within 30 days) period and 6.5% (n=5) after 30 days, the latter of which all represented vascular injuries (Figure). Major complications (18 of 72 peri-procedural complications, 25.0%) are defined, detailed, and associated data reported in the Figure. Unadjusted (16.0% without CHF vs. 33.3% with CHF, p = 0.045) and risk-adjusted (OR 2.8, 95% CI 1.03-7.60, p=0.045) analyses indicated history of CHF was associated with a composite outcome of major complications. Analyses of independent complications showed those who suffered from peri-procedural stroke (n=3) were of significantly greater age (77.3 +/- 5.5 years vs. 66.1 +/- 10.9 years, p=0.035). Risk-adjusted analyses showed history of vascular disease (OR 2.9, 95% CI 1.02-8.20, p=0.045) was associated with vascular injury (n=18). From 0-695 days post-procedure, 31 deaths occurred (unknown cause: 17, COVID-19 related: 4, heart failure: 2, cardiac arrest: 2). Conclusion(s): Major complications represent rare events among those undergoing AF ablation in current practice. Risk-adjusted analyses suggest a history of CHF is associated with major complications. Similarly, older age and a history of vascular disease are associated with stroke and vascular complications, respectively. [Formula presented]Copyright © 2023
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Introduction: The Covid-19 pandemic has led to an uncomfortable and often recurrent situation in foot care services in the UK which frequently manifests in the older, White British, overweight, lone male population who often are manual workers. Result(s): These patients are unaware of local or national health promotion campaigns (e.g. iDEAL group's ACT NOW campaign, Diabetes UK's Putting Feet First) so have little awareness and education regarding potential foot problems. They are not aware of 5-to drive, eat 5 portions of fruit and vegetables a day, check your feet every day or walk 10,000 steps initiatives. They do not access public health materials and do not follow social media platforms, magazines, or newspapers. Therefore when they present in clinic, often after an emergency appointment with their GP, or an attendance at A&E, they present with significant soft tissue damage or systemic infection, frequently catastrophic tissue loss and serious co-morbidity (often in the form of renal or cardiac failure). Many require immediate hospital admission, intra-venous antibiotics, surgical debridement, vascular intervention and/or amputation. Unfortunately for some early mortality (often from an overwhelming cardio-vascular event) is the reality before they get as far as a major amputation. Discussion(s): Patients with more long-term conditions have increased risk of missing GP appointments (after controlling for number of appointments made) and are at increased risk of all-cause mortality, with those with long-term mental-health conditions who miss >2 appointments per year having >8x risk of all-cause mortality compared with those similar diagnoses who missed no appointments (McQueenie et al. 2019).
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151 Figure 1Day after discharge from hospitalDid you feel well today?Please write yes or no.Weight, kg123456789101112131415161718192021222324252627282930 151 Table 1Baseline characteristicsBaseline characteristicsStandard Follow-UpN=9Intensive Follow-UpN=17Age (years)78 [69,81]74 [65,82]Gender [number of females (%)] 2 (22%)7 (41%)Rockwood Frailty Score (2 weeks pre admission) 3 [3,5]5 [3,5]Left Ventricular Systolic Function (%)Preserved 34%Mildly impaired 11%Moderately impaired 33%Severely impaired 22%Preserved 35%Mildly impaired 12%Moderately impaired 18%Severely impaired 35%NTproBNP ng/L4772 [2883,4859]9 88 [4333,14876]eGFR on discharge, ml/min/1.73m246 [35,63]51 [30,82]Comorbidity Number (in addition to HF)3 [2,4]5 [3,6]SBP, mmHg108 [106,111]110 [103,120]Number of people known COVID positive (%)0%6%Descriptive statistics are expressed as Median [IQR] or N (%).Abbreviations: eGFR: Estimated Glomerular Filtration Rate, HF: Heart failure, IQR: Inter-Quartile Range, NTproBNP: N-terminal prohormone of brain natriuretic peptide, SBP: Systolic Blood Pressure. 151 Table 2Effectiveness of intensive follow-upStandard Follow-UpIntensive Follow-UpDays alive and well out of hospital12 [8,25]22 [15,28]Days with weight recorded27 [14,30]27 [7,30]ACEi, ARB, or entresto (%)6 (67%)14 (82%)Beta-Blocker (%)8 (89%)16 (94%)% max. dose of Beta-Blocker 44 [25,53]50 [34,100]MRA%5 (56%)9 (53%)Dose of MRA, mg25 [25,25]25 [25, 25]SGLT2 inhibitor (on Dapaglifozin or empaglifozin) (%)5 (56%)14 (82%)Total number of Disease Modifying Agents (max 4)3 [2,4]3 [3,4]Descriptive statistics are expressed as Median [IQR] or N (%).Abbreviations: ACEi: Angiotensin Converting Enzyme Inhibitor, ARB: Angiotensin Receptor Blocker, IQR: Inter-Quartile Range, MRA: Mineralocorticoid receptor antagonist, SGLT2 inhibitors: Sodium-glucose cotransporter-2 inhibitors.Conflict of InterestNone
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Introduction: Variants in PPP1R13L are associated with severe childhood-onset cardiomyopathy resulting in rapid progression to death or cardiac transplantation. PPP1R13L is proposed to encode a protein that limits the transcriptional activity of the NFkappaB pathway leading to elevated IL-1, IL-6, and TNF-alpha production in murine models. Optimal medical management for PPP1R13L-related cardiomyopathy is unknown. Here we report usage of a targeted anti-IL-1 immuno-modulatory therapy resulting in cardiac stabilization in a pediatric patient with congenital cardiomyopathy secondary to PPP1R13L variants. Case Report: A 4-year-old boy presented acutely with fever in the setting of persistent abdominal pain, vomiting, fatigue, and decreased appetite for two months following a mild COVID-19 related illness. Echocardiogram revealed severely depressed biventricular systolic function with an ejection fraction of 30%. Due to acute decompensated heart failure symptoms with hemodynamic instability, he was intubated and placed on continuous inotropic infusions with aggressive diuresis. Cardiac MRI demonstrated extensive subepicardial to near transmural fibrosis by late gadolinium enhancement in right and left ventricles. An implantable cardioverter-defibrillator (ICD) was placed due to frequent runs of polymorphic non-sustained ventricular tachycardia. Testing for viral pathogens was positive for rhino/enterovirus. Initial genetic testing was non-diagnostic (82-gene cardiomyopathy panel) but given the patient's significant presentation whole genome sequencing was pursued that showed two separate PPP1R13L variants in trans (c.2167A>C,p.T723P and c.2179_2183del,p. G727Hfs*25, NM_006663.4). Patient serum cytokine testing revealed elevations in IL-10 (4.7 pg/mL) and IL-1beta (20.9 pg/mL). Given the patient's tenuous circumstances and concern for continued progression of his cardiac disease, a trial of IL-1 inhibition via anakinra dosed at 3 mg/kg or 45 mg daily was initiated following hospital discharge. With approximately 6 months of therapy, the patient's cardiac function is stable with normalization of IL-10 and IL-1beta serum levels. Notably, the ventricular arrhythmia decreased after initiation of anakinra with no ICD shocks given. Therapy overall has been well tolerated without infectious concerns. Conclusion(s): In patients with PPP1R13L-related cardiomyopathy, immuno-modulatory therapies should be considered in an attempt to slow cardiac disease progression.Copyright © 2023 Elsevier Inc.
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Aim. To determine the prevalence and show the features of the development of newly diagnosed heart failure (HF) in patients with dyspnea after a coronavirus disease 2019 (COVID-19). Material and methods. This clinical prospective observational study was conducted during 2020-2022. The study consecutively included 368 outpatients with shortness of breath, who applied to the clinic. Depending on the presence of prior COVID-19, the patients were divided into 2 groups: the first group consisted of 205 patients with shortness of breath after COVID-19, the second group - 163 patients without prior COVID-19. All patients underwent a clinical examination within 3 days after presentation with an assessment of outpatient records and other medical documents for the differential diagnosis of dyspnea. The severity of dyspnea was determined using the Modified Medical Research Council Dyspnoea Scale (mMRC). The diagnosis of HF was verified in accordance with the 2020 Russian Society of Cardiology guidelines and in some cases reclassified in accordance with the 2021European Society of Cardiology guidelines. For further analysis, 2 subgroups of patients with HF were identified depending on the presence and absence of prior COVID-19. The subgroup analysis excluded patients with acute heart failure, acute illness, and conditions requiring hospitalization and/or intensive care. Results. Among 368 patients who presented to the clinic with dyspnea during 2020-2022, 205 patients (55,7%) had COVID-19. The average period of treatment after COVID-19 was 3,5 [1,5;22,4] months. Patients after COVID-19 applied earlier after the onset of dyspnea, which is associated with higher mMRC score. The prevalence of HF among patients with shortness of breath after COVID-19 was significantly higher than in patients without this pathology in history, and amounted to 19,0% vs 9,8% (p=0,021). Prior COVID-19 increased the relative risk (RR) of HF in patients with shortness of breath by 1,7 times. RR for HF in systolic blood pressure >140 mm Hg increased by 1,9 times, while in diastolic blood pressure >90 mm Hg - by 1,9 times, with the development of a hypertensive crisis - by 28%, with a heart rate >80 bpm at rest - by 1,4 times, with the development of type 2 diabetes - by 31%, in the presence of pulmonary fibrosis - by 2,3 times. Patients with shortness of breath after COVID-19 had more severe HF, both according to clinical tests and according to the blood concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP), mainly with the preserved ejection fraction (EF) with a higher prevalence of left atrial (LA) enlargement in combination with a decrease in right ventricular (RV) systolic function and its dilatation. In patients after COVID-19 in the presence of chronic kidney disease, the RR for HF increased by 4,5 times;in the presence of C-reactive protein >4 mg/l - by 1,6 times. Conclusion. Every fifth patient with shortness of breath 3,5 months after COVID-19 had more severe HF, both according to clinical tests and according to blood NT-proBNP concentration, mainly with preserved EF with a higher prevalence of LA increase in combination with a decrease in RV systolic function and its dilatation. The risk of HF is interrelated with the female sex and multiple comorbidities.Copyright © 2023, Silicea-Poligraf. All rights reserved.
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The medical documentation (n = 146912) introduced into the system "Regional fragment of the unified state information system in the field of healthcare” of Saint Petersburg for 2019–2021 was analyzed. To evaluate the mortality of patients due to heart failure, all deceased patients from 2019 to 2021 in Saint Petersburg (n = 192133) were taken as a basis, and based on a thorough study of medical documentation, patients who died from cardiovascular diseases and because of heart failure were singled out separately. The total mortality from all causes in Saint Petersburg in 2019 was 53025 people;in 2020, 66468 people;and in 2021, 72640 people. The analysis of mortality due to cardiovascular diseases from 2019 to 2021 showed an upward trend of 20.1% over the 3-year period of data analysis. When analyzing the prevalence of heart failure among deceased patients, an increase of 129.4% was noted over this period. The obtained results of the prevalence, mortality, and mortality of patients due to heart failure on the example of a megalopolis are the most relevant at the current time;they indicate a steady increase in the number of patients suffering from heart failure with an increase in the burden on the city's healthcare system. Simultaneously, there is insufficient continuity in the provision of medical care to patients suffering from heart failure, which is because of not only a shortage of medical personnel at all stages of medical care but also insufficient compliance of patients who either do not want to be treated or cannot continue treatment. Moreover, a significant disconnect was found in the continuity of medical care at the stages of pre-hospital and hospital treatment, as well as further outpatient follow-up of patients suffering from heart failure in the metropolis. All this leads to a significant increase in the mortality and mortality of patients suffering from heart failure, despite all the existing modern effective drug therapies. It appears critical to create a unified register platform for recording patients with heart failure, which will allow for a more accurate understanding of epidemiological aspects, the solution of which will improve the quality of medical care, identify the need for the crucial medicines, and reduce mortality, and mortality rates due to heart failure. All rights reserved © Eco-Vector, 2022.
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IntroductionHeart Failure (HF) carries significant mortality and morbidity, especially due to comorbidities such as Atrial Fibrillation (AF). Previous work illustrates that mitochondrial dysfunction underpins the pathophysiology of both HF and AF, including decreased Adenosine TriPhosphate (ATP) production, Ca2+ mishandling, oxidative stress and elevated apoptosis. In addition to these problems, recent work suggests the Mitochondrial Permeability Transition Pore (MPTP) in ventricular cardiomyocytes may become sensitised to Ca2+ during HF, leading to increased apoptosis. Nevertheless, the role of mitochondrial dysfunction has not been investigated in the atria. In this study, we investigated the role of Ca2+ sensitivity of the MPTP and mitochondrial aerobic capacity in atrial muscle of the failing heart.MethodsRight atrial appendage and right ventricular free wall were dissected from 15 sheep representing an ovine model of tachycardia-induced HF. The tissue was subsequently homogenized and differentially centrifuged, yielding isolated mitochondria. Respiratory function was measured using a respirometer, with the electron transport system (ETS) selectively probed through addition of various substrates stimulating differing ETS complexes. A Calcium Retention Capacity (CRC) assay determined MPTP Ca2+ sensitivity, which involved Ca2+ titrations onto isolated mitochondria containing a Ca2+-sensitive fluorescent dye. An increase in fluorescence marked MPTP opening.ResultsAerobic capacity was not affected by HF, but an increase in ventricular leak respiration was statistically significant (p=0.0140). HF reduced atrial mitochondrial efficiency by 68% (p=0.0063) but did not affect maximal mitochondrial respiration. There was no significant effect of HF or tissue-type on MPTP Ca2+ sensitivity and mitochondrial Ca2+ buffering capacity.ConclusionOur data suggests HF affects atrial and ventricular mitochondrial respiratory function asymmetrically, with HF affecting atrial mitochondrial efficiency and ventricular leak respiration. The COVID-19 pandemic hindered this research project;however, it provides rationale on the unequal effect of HF on mitochondrial function across the atria and ventricle. Future research should therefore consider incorporating atrial samples when assessing potential HF therapies.Conflict of InterestNil
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Background: Non-communicable diseases (NCDs) are rising in low middle income countries (LMICs) mainly driven by cardiometabolic disease (cardiovascular disease, diabetes, and hypertension). Aim(s): To develop a model of care, based on the chronic care model and collaborative care model, to improve care, outcomes and risk factor control for adults with cardio metabolic disease in LMICs in the Covid-19 era. This will contribute to the sustainable development goals of promoting good health, well-being and reducing inequalities. Method(s): Using an iterative consultative approach with healthcare workers, clients, and community leaders in Kenya, Ghana and Mozambique, we developed a model of care, which includes core features from chronic care models: self-management support;decision support;clinical information systems;delivery system design;and community linkages. Result(s): We produced a culturally adapted self-management education programme, a training package for educators delivering the programme, as well as a training package for community and healthcare professional leaders to increase awareness and self-care for cardiometabolic disease. Given the lack of a robust health information system, we are offering a global registry to provide real world data on patient management and quality of care for people with type 2 diabetes, hypertension, heart failure and chronic kidney disease. Conclusion(s): This intervention will be tested in a mixed-methods single-arm feasibility study in five sites across three African countries: Kenya, Ghana, Mozambique.
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IntroductionRecent results from the IRONMAN trial add to previous data and demonstrate that correction of iron deficiency in patients with heart failure, with high dose IV iron can improve quality of life, and reduce the risk of heart failure hospitalisation (by around 25% in meta-analysis). Yet there are theoretical risks that IV iron administration may increase the risk from bacterial infection. A meta-analysis in 2021 (across many clinical indications) suggested an excess risk of infections with IV iron but noted most trials did not pre-specify infection as an end point, with risk of reporting bias. To answer this important question hospitalisation for infection or death due to infection were pre-specified safety endpoints in IRONMAN.MethodsIRONMAN was a prospective, randomised open-label, blinded endpoint (PROBE) event-driven trial of IV ferric derisomaltose (FDI) and usual care versus usual care alone in patients with heart failure (LVEF ≤45% ) and iron deficiency (ferritin <100 µg/L and/or TSAT <20%, provided ferritin ≤400 µg/L). Patients were enrolled if they had a current or recent hospitalisation for heart failure or elevated natriuretic peptide plasma concentration. Every four months, IV iron was administered if either ferritin was <100 µg/L or TSAT was <25% (provided ferritin ≤400 µg/L). All hospitalisations and deaths were adjudicated blindly. Given that a large part of the trial was conducted during the COVID-19 pandemic, we also evaluated COVID-19 related SAEs.Results1137 patients (26.4% women) with median (IQR) age 73 (63 to 79) years were recruited by the Ironman Study Group between Aug 2016 and Oct 2021 across 70 UK sites. Median (IQR) follow-up was 2·7 (1·8 to 3·6) years. 97% of patients consented to record linkage to national databases of deaths and hospital discharge summaries, thereby ensuring investigators were aware of all potential events. There were a similar number of hospitalisations due to infection for those assigned to ferric derisomaltose (175) and usual care (213) (p = 0.16) and infection related death (34 and 28, respectively, p = 0.43). When considering first events of hospitalisation for infection or infection death there were 120 (21.1%) events for those randomised to IV FDI and 146 (25.7%) for the usual care arm (figure). There were fewer patients with COVID related SAEs in those randomised to IV FDI (12) as compared with usual care (30), HR (95% CI) 0.40 (0.20, 0.78). p=0.007. For deaths attributed to COVID-19, 4 were seen in the IV FDI arm and 8 in the usual care arm: HR 0.51 (0.15, 1.68) p=0.27.ConclusionsThere was no excess risk of infection related hospitalisation or death in patients receiving IV ferric derisomaltose. Fewer COVID-19 related SAEs were seen in patients receiving IV FDI. Given that iron plays an important role in the T and B cell response to vaccination, further analysis needs to be done in this area.Conflict of InterestHonorarium for education from Pharmocosmos
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Background: Atrial fibrillation (AF) is the most common arrhythmia in the United States. Concomitant Covid-19 infection and the outcomes of AF are unknown. Objective(s): The study's goals were to analyze the outcomes of AF during the Covid-19 pandemic. Method(s): We conducted a retrospective cohort study based on the 2020 National Inpatient Sample (NIS) of Adults (>18 years) hospitalized for AF as the primary admitting diagnosis based on the ICD-10 codes and stratified these groups into concomitant covid-19 infection vs. non-covid-19 infection. All-cause mortality was our primary outcome, while the rate of ICU admission, length of stay, hospital charges were our secondary outcomes. Temporal trends were assessed using logistic regression. Result(s): In 2020, there were 1,994,985 admissions for atrial fibrillation, out of whom 104,495 (5.3%) had concomitant Covid-19. In the 104,495 AF admissions with covid-19, the mean age was 75y and 56.8% were males. Our results, image 1, showed AF with and without concomitant Covid-19 had similar rates of comorbid conditions including HTN, DM, OSA, CAD. HFrEF, and ESRD. AF patients with Covid-19 infection had a lower prevalence of smoking (31.83% vs. 39.4%, p<.001) and alcohol use (2% vs. 4.2%, p<.001). AF patients from both groups had similar rates of stroke (1.6% vs. 1.0%, p<.001). New AF patients with concomitant Covid-19 had worsening in-hospital outcomes such as shock (12.8% vs. 3.7%, p<.001), admission to the ICU (18.1% vs. 6.4%, p<0.001), higher all-cause mortality (21.8% vs. 3.9%, p<0.001), a longer length of stay (9.96 days vs 6.08 days, p<.001), and total hospital costs ($114,387 vs. $85,830, p<.0001). The incidence of AF catheter ablation on initial hospital admission for AF Covid-19 was lower compared to the AF non-covid-19 patients (.08% vs. 1.39%, p<.001). Conclusion(s): In 2020, Covid-19 infection was an independent predictor of higher all-cause mortality, length of stay, and costs in patients admitted for atrial fibrillation. In addition, these patients were less likely to get catheter ablation on hospital admission. [Formula presented]Copyright © 2023
ABSTRACT
Narrowed arteries block the blood flow to the heart muscle and other parts of the body, which can cause chest pain. Coronary arteries disease (CAD) can weaken the heart muscle causing heart failure, in which the heart cannot pump blood. A person with underlying diseases is more prone to get highly affected by COVID-19 because of the decreased immunity. Cardiovascular disease and coronary heart disease have been associated with worsened outcomes of COVID-19 patients. Thus, detecting CAD at a proper stage is crucial to avoid any further serious issues. This paper is an empirical analysis to predict stable angina for CAD using Histogram gradient boosting (HGB) and Adaboost (ADB) classifier algorithm and compared the performance with traditional Naïve Bayes (NB) algorithm. © 2023 IEEE.
ABSTRACT
Objectives: To describe demographic characteristics, comorbidities, and exacerbations in a cohort of patients with COPD in Chile. Method(s): Retrospective cohort study using INTEGRAMEDICA (a network of ambulatory medical centers) electronic medical records of patients with COPD aged >=40 years at index with data available one year before (baseline) and after (follow-up) index. Index date was fixed at 28-Feb-2019 to avoid including data from the COVID-19 pandemic. Moderate and severe exacerbations were defined as prescription of systemic corticosteroid/antibiotics and emergency visit/hospitalization, respectively. Result(s): In total, 19,000 patients were included. In the baseline period, 86% (n=16,400) had no moderate or severe exacerbations (NMSE), 13% (n=2,503) had only moderate exacerbations (OME) and <1% (n=96) had >=1 severe exacerbation (SEV). Mean age/proportion of females was: 64 years/60% (total cohort), 65 years/59% (NMSE), 61 years/67% (OME) and 73 years/62% (SEV). The four most frequent comorbidities were: hypertension (total: 17.6%;NMSE: 16.2%;OME: 26.0%;SEV: 24.0%), asthma (total: 8.9%;NMSE: 7.8%;OME: 15.3%;SEV: 17.7%), diabetes type 1/2 (total: 6.3%;NMSE: 5.9%;OME: 9.1%;SEV: 7.3%) and congestive heart failure (total: 3.2%;NMSE: 3.2%;OME: 2.9%;SEV: 4.2%). The proportion of patients with >=1 moderate/severe exacerbation during follow-up was 14% (total), 10% (NMSE), 38% (OME) and 35% (SEV). The severe exacerbation rate was 2.00 per 1,000 person-years in the overall population and increased based on exacerbation history (NMSE: 0.91;OME: 1.60;SEV: 197.92) Conclusion(s): Preliminary results indicate that severe exacerbations were more frequent in patients with a history of SEV compared with patients with a history of OME or NMSE. In addition, comorbidities were more frequent in patients with a history of exacerbation. To improve patient health outcomes, strategies with a multisectoral approach should be prioritized as COPD can coexist with, and be aggravated by, other chronic comorbidities. Funding(s):GSK [209968].Copyright © 2023