Efficacy and safety of catheter ablation for atrial fibrillation in patients with history of cancer.

BACKGROUND: Though the incidence of atrial fibrillation (AF) is increased in patients with cancer, the effectiveness of catheter ablation (CA) for AF in patients with cancer is not well studied. METHODS: We conducted a retrospective cohort study of patients who underwent CA for AF. Patients with a history of cancer within 5-years prior to, or those with an exposure to anthracyclines and/or thoracic radiation at any time prior to the index ablation were compared to patients without a history of cancer who underwent AF ablation. The primary outcome was freedom from AF [with or without anti-arrhythmic drugs (AADs), or need for repeat CA at 12-months post-ablation]. Secondary endpoints included freedom from AF at 12 months post-ablation with AADs and without AADs. Safety endpoints included bleeding, pulmonary vein stenosis, stroke, and cardiac tamponade. Multivariable regression analysis was performed to identify independent risk predictors of the primary outcome. RESULTS: Among 502 patients included in the study, 251 (50%) had a history of cancer. Freedom from AF at 12 months did not differ between patients with and without cancer (83.3% vs 72.5%, p 0.28). The need for repeat ablation was also similar between groups (20.7% vs 27.5%, p 0.29). Multivariable regression analysis did not identify a history of cancer or cancer-related therapy as independent predictors of recurrent AF after ablation. There was no difference in safety endpoints between groups. CONCLUSION: CA is a safe and effective treatment for AF in patients with a history of cancer and those with exposure to potentially cardiotoxic therapy.

Prolactin Inhibition in Peripartum Cardiomyopathy: Systematic Review and Meta-analysis.

Heart failure (HF) is one of the leading causes of maternal mortality and morbidity in the United States. Peripartum cardiomyopathy (PPCM) constitutes up to 70% of all HF in pregnancy. Cardiac angiogenic imbalance caused by cleaved 16kDa prolactin has been hypothesized to contribute to the development of PPCM, fueling investigation of prolactin inhibitors for the management of PPCM. We conducted a systematic review and meta-analysis to assess the impact of prolactin inhibition on left ventricular (LV) function and mortality in patients with PPCM. We included English language articles from PubMed and EMBASE published upto March 2022. We pooled the mean difference (MD) for left ventricular ejection fraction (LVEF) at follow-up, odds ratio (OR) for LV recovery and risk ratio (RR) for all-cause mortality using random-effects meta-analysis. Among 548 studies screened, 10 studies (3 randomized control trials (RCTs), 2 retrospective and 5 prospective cohorts) were included in the systematic review. Patients in the Bromocriptine + standard guideline directed medical therapy (GDMT) group had higher LVEF% (pMD 12.56 (95% CI 5.84-19.28, I2=0%) from two cohorts and pMD 14.25 (95% CI 0.61-27.89, I2=88%) from two RCTs) at follow-up compared to standard GDMT alone group. Bromocriptine group also had higher odds of LV recovery (pOR 3.55 (95% CI 1.39-9.1, I2=62)). We did not find any difference in all-cause mortality between the groups. Our analysis demonstrates that the addition of Bromocriptine to standard GDMT was associated with a significant improvement in LVEF% and greater odds of LV recovery, without significant reduction in all-cause mortality.

Effect of Cocaine, Amphetamine, and Cannabis Use Disorders on 30-day Readmissions of Patients with Heart Failure.

There is limited evidence demonstrating whether cannabis, cocaine, amphetamine, or other stimulants use contributes to heart failure (HF) readmissions. We used the National Readmissions Database years 2016-2018 to identify patients with HF with and without substance use disorder (SUD) (defined as a composite of cannabis, cocaine, or other stimulant use disorders). The main outcome was to assess the risk of 30-day readmissions in HF patients with and without SUD. Of 978,217 HF hospitalizations that met the inclusion criteria, 34,717 (3.5%) had concomitant SUD. HF patients with SUD had significantly higher hazard for 30-day all-cause readmissions (adjusted hazard ratio [aHR] 1.16 [1.12-1.21]; P < 0.01) compared to HF patients without SUD. In conclusion, HF patients with SUD have an elevated risk of 30-day all-cause readmissions, mainly driven by cocaine and other stimulant disorders. Screening for substance use in hospitalized HF patients as well as timely referral for treatment are important to prevent HF readmissions.

Effect of leaving against medical advice on 30-day infective endocarditis readmissions.

BACKGROUND: The burden of against medical advice (AMA) discharges on the readmission rate of infective endocarditis (IE) patients has been largely ignored. METHODS: We used the National Readmissions Database, years 2016 to 2019, to identify IE patients and categorized them into those who left AMA (IE AMA) and those who were discharged to home or skilled nursing facility (SNF)/other facility (IE non-AMA). The primary outcome was 30-day all-cause readmissions difference per AMA status. RESULTS: Of 26,481 patients with IE who met the inclusion criteria, 4,310 (16.3%) left the hospital AMA. IE AMA patients were younger (mean years; 43.7 vs 34.2; p < 0.01) and had a higher prevalence of injection drug use (IDU) (89.4% vs 45.2%; p < 0.01) but fewer comorbidities compared to IE non-AMA. In adjusted analyses, IE AMA had higher hazards for 30-day readmissions compared to IE non-AMA [hazards ratio (HR): 3.1 (2.9-3.5); p < 0.01]. CONCLUSION: IE AMA are at increased risk of 30-day readmissions and higher resource utilization at the time of readmission compared to IE non-AMA. Considering the high prevalence of IDU in IE AMA, the role of mental health to curb the burden of IE readmissions is an area of further research.

HDL cholesterol levels and susceptibility to COVID-19.

BACKGROUND: Host cell-membrane cholesterol, an important player in viral infections, is in constant interaction with serum high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C). Low serum lipid levels during hospital admission are associated with COVID-19 severity. However, the effect of antecedent serum lipid levels on SARS-CoV-2 infection risk has not been explored. METHODS: From our retrospective cohort from the Arkansas Clinical Data-Repository, we used log-binomial regression to assess the risk of SARS-CoV-2 infection among the trajectories of lipid levels during the 2 years antecedent to COVID-19 testing, identified using group-based-trajectory modelling. We used mixed-effects linear regression to assess the serum lipid level trends followed up to the time of, and 2-months following COVID-19 testing. FINDINGS: Among the 11001 individuals with a median age of 59 years (IQR 46-70), 1340 (12.2%) tested positive for COVID-19. The highest trajectory for antecedent serum HDL-C was associated with the lowest SARS-CoV-2 infection risk (RR 0.63, 95%CI 0.46-0.86). Antecedent serum LDL-C, total cholesterol (TC), and triglycerides (TG) were not independently associated with SARS-CoV-2 infection risk. In COVID-19 patients, serum HDL-C (-7.7, 95%CI -9.8 to -5.5 mg/dL), and LDL-C (-6.29, 95%CI -12.2 to -0.37 mg/dL), but not TG levels, decreased transiently at the time of testing. INTERPRETATION: Higher antecedent serum HDL-C, but not LDL-C, TC, or TG, levels were associated with a lower SARS-CoV-2 infection risk. Serum HDL-C, and LDL-C levels declined transiently at the time of infection. Further studies are needed to determine the potential role of lipid-modulating therapies in the prevention and management of COVID-19. FUNDING: Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1 TR003107.

Vegetarianism, microbiota, and cardiovascular health: looking back, and forward.

Cardiovascular diseases (CVDs) are the leading cause of death globally, with over 17.9 million attributed deaths in 2019. Unhealthy diet is an often-overlooked major modifiable risk factor for CVD. Global Burden of Disease (GBD) estimates suggest that unhealthy diets account for nearly 26% of all deaths, of which 84% were attributed to CVD. Plant-based diets (PBDs), which are a diverse group of dietary patterns focused on plant produce, with flexibility for varying levels of vegetarianism, have been suggested to decrease the incidence of various cardiovascular and cardiometabolic diseases. In this review, we aim to delve into the spectrum of PBDs, revisit objective definitions and classifications, and compare them with standard non-vegetarian diets. We examine plausible mechanisms underlying the cardiovascular benefits of PBDs with a particular focus on the dietary manipulation of gut microbiota-host interaction and its effect on energy metabolism, and local and systemic inflammation. In addition, we explore the evidence on the impact of PBDs on CVD, examine the challenges and limitations associated with dietary intervention studies, and devise strategies to draw valid conclusions. Dietary interventions, such as PBDs are one of the most powerful, attainable, cost-effective tools for health and environmental protection at the population level. We conclude with a clear appreciation for PBDs in environmental sustainability, climate change, and animal welfare.

Scurvy in the Modern World: Extinct or Not?

Scurvy is a nutritional disorder caused by vitamin C deficiency. It was a notorious disease in the ancient world, especially among the sailors, and is of rare occurrence in contemporary, developed countries due to increased access and advancement in nutrition services. Scurvy primarily affects the skin and soft tissue, presenting with a myriad of clinical manifestations ranging from musculoskeletal to bleeding-related complaints and even sudden death in later stages. In this article, we present the case of an elderly female with scurvy-related weakness and gait instability leading to mechanical falls, easy bruising, fatigue, and petechial rash. She had improvement in her constitutional symptoms after the initiation of vitamin C supplements. This case reinforces the need to consider scurvy as one of the differentials for petechial rash and easy bruising apart from bleeding diathesis and vasculitis in the contemporary world, especially in at-risk populations.

Association of Lipid Levels With COVID-19 Infection, Disease Severity and Mortality: A Systematic Review and Meta-Analysis.

Background: Coronavirus disease 2019 (COVID-19) ranges from asymptomatic infection to severe illness. Cholesterol in the host cell plasma membrane plays an important role in the SARS-CoV-2 virus entry into cells. Serum lipids, especially low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), are in constant interaction with the lipid rafts in the host cell membranes and can modify the interaction of virus with host cells and the resultant disease severity. Recent studies on serum lipid levels and COVID-19 disease severity lack consistency. Objectives: Our systematic review and meta-analysis compared the serum levels of total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG) between (1) COVID-19 patients vs. healthy controls; (2) severe vs. non-severe COVID-19 disease; (3) deceased vs. surviving COVID-19 patients. Methods: PRISMA guidelines were followed. We included peer-reviewed articles on observational (case-control and cohort) studies from PubMed and Embase published from the database inception until September 1, 2021. We used random-effects meta-analysis for pooled mean-differences (pMD) in lipid levels (mg/dL) for the above groups. Results: Among 441 articles identified, 29 articles (26 retrospective and 3 prospective cohorts), with an aggregate of 256,721 participants, were included. COVID-19 patients had lower TC (pMD-14.9, 95%CI-21.6 to -8.3) and HDL-C (pMD-6.9, 95%CI -10.2 to -3.7) levels (mg/dL). Severe COVID-19 patients had lower TC (pMD-10.4, 95%CI -18.7 to -2.2), LDL-C (pMD-4.4, 95%CI -8.4 to -0.42), and HDL-C (pMD-4.4, 95%CI -6.9 to -1.8) at admission compared to patients with non-severe disease. Deceased patients had lower TC (pMD-14.9, 95%CI -21.6 to -8.3), LDL-C (pMD-10.6, 95%CI -16.5 to -4.6) and HDL-C (pMD-2.5, 95%CI -3.9 to -1.0) at admission. TG levels did not differ based on COVID-19 severity or mortality. No publication bias was noted. Conclusion: We demonstrated lower lipid levels in patients with COVID-19 infection and an association with disease severity and mortality. Their potential role in COVID-19 pathogenesis and their utility as prognostic factors require further investigation.

Higher Serum Cholesterol Levels Are Associated With Reduced Systemic Inflammation and Mortality During Tuberculosis Treatment Independent of Body Mass Index.

Background: Lipids play a central role in the pathogenesis of tuberculosis (TB). The effect of serum lipid levels on TB treatment (ATT) outcomes and their association with serum inflammatory markers have not yet been characterized. Methods: Our retrospective cohort study on drug-susceptible TB patients, at the National Taiwan University Hospital, assessed the association of baseline serum lipid levels such as low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC) and triglycerides (TG) with all-cause and infection-related mortality during first 9 months of ATT and baseline inflammatory markers namely C-reactive protein (CRP), total leukocyte count (WBC), and neutrophil-lymphocyte ratio (NL ratio). Results: Among 514 patients, 129 (26.6%) died due to any-cause and 72 (14.0%) died of infection. Multivariable Cox-regression showed a lower adjusted hazard ratio (aHR) of all-cause mortality in the 3rd tertiles of HDL (aHR 0.17, 95% CI 0.07-0.44) and TC (aHR 0.30, 95% CI 0.14-0.65), and lower infection-related mortality in the 3rd tertile of HDL (aHR 0.30, 95% CI 0.14-0.65) and TC (aHR 0.30, 95% CI 0.14-0.65) compared to the 1st tertile. The 3rd tertiles of LDL and TG showed no association in multivariable analysis. Similarly, 3rd tertiles of HDL and TC had lower levels of baseline inflammatory markers such as CRP, WBC, and NL ratio using linear regression analysis. Body mass index (BMI) did not show evidence of confounding or effect modification. Conclusions: Higher baseline serum cholesterol levels were associated with lower hazards of all-cause and infection-related mortality and lower levels of inflammatory markers in TB patients. BMI did not modify or confound this association.

Effect of Diabetes Mellitus on 30 and 90-Day Readmissions of Patients With Heart Failure.

The prevalence of diabetes mellitus (DM) in hospitalized heart failure (HF) patients is increasing over time. However, the effect of DM on short-term readmissions for HF is not well established. We investigated the effects of DM on readmissions of HF patients. All adult hospitalizations with a primary diagnosis of HF were identified in the National Readmission Database (NRD) for 2018 and were categorized into those with and without a secondary diagnosis of DM. The primary outcome was to assess risk difference in 30 and 90-day all-cause readmissions. Multivariate Cox survival analysis and multivariate Cox regression were performed to estimate the readmission risk difference in HF patients with and without DM. Of 925,637 HF hospitalizations that met the inclusion criteria, 441,295 (47.6%) had concomitant DM. Diabetics hospitalized for HF had higher prevalence of obesity (37.3% vs 19.5%), kidney disease (58.4% vs 29.2%) and coronary disease (61.1% vs 51.0%), compared to HF hospitalizations without DM. In adjusted analyses, DM was associated with higher hazards for all-cause [hazards ratio (HR), 30 days: 1.04 (1.02-1.06); 90 days: 1.07 (1.05-1.09)], HF [HR, 30 days: 1.05 (1.02-1.07); 90 days: 1.08 (1.05-1.10)] and myocardial infarction (MI) [HR, 30 days: 1.26 (1.12-1.41); 90 days: 1.38 (1.25-1.52)] readmissions. In conclusion, in patients with HF-related hospitalizations, the presence of DM was associated with a higher risk of 30 and 90-day all-cause, HF and MI readmissions.

The association of atherosclerotic cardiovascular disease and statin use with inflammation and treatment outcomes in tuberculosis.

Tuberculosis (TB) and atherosclerotic cardiovascular disease (ASCVD) have a close epidemiological and pathogenetic overlap. Thus, it becomes essential to understand the relationship between ASCVD and TB outcomes. From our retrospective cohort on drug-susceptible TB patients at the National Taiwan University Hospital, we assessed the association of pre-existing ASCVD (coronary artery disease (CAD) and atherothrombotic stroke (ATS)) with 9-month all-cause and infection-related mortality and the extent of mediation by systemic inflammatory markers. We determined the effect of pre-existing ASCVD on 2-month sputum microbiological status. Among ASCVD patients, we assessed the association of statin use on mortality. Nine-month all-cause mortality was higher in CAD patients with prior acute myocardial infarction (CAD+AMI+) (adjusted HR 2.01, 95%CI 1.38-3.00) and ATS patients (aHR 2.79, 95%CI 1.92-4.07) and similarly, for infection-related mortality was higher in CAD+AMI+ (aHR 1.95, 95%CI 1.17-3.24) and ATS (aHR 2.04, 95%CI 1.19-3.46) after adjusting for confounding factors. Pre-existing CAD (AMI- or AMI+) or ATS did not change sputum culture conversion or sputum smear AFB positivity at 2 months. The CAD+AMI+ group had significantly higher levels of CRP at TB diagnosis in the multivariable linear regression analysis (Adjusted B(SE) 1.24(0.62)). CRP mediated 66% (P = 0.048) and 25% (P = 0.033) of the association all-cause mortality with CAD+AMI- and CAD+AMI+, respectively. In summary, patients with ASCVD have higher hazards of 9-month all-cause and infection-related mortality, with elevated serum inflammation mediating one to three-quarters of this association when adjusted for confounders. Statin use was associated with lower all-cause mortality among patients with ASCVD.

Role of Platelets in Chronic Kidney Disease.

Platelet-dependent mechanisms for excessive clotting and bleeding in CKD remain undefined. Moreover, platelets' contribution to inflammation, and specifically to CKD, are equally elusive. To date, descriptions of changes in the functional properties of circulating platelets during CKD have provided confusing interpretations. Experimental approaches that can advance our understanding of platelet dysfunction in CKD are needed, and studies that provide mechanistic insights into the dynamic relationships between thrombosis, bleeding, and inflammation associated with CKD will be essential to improve clinical management and outcomes for this vulnerable population. This article summarizes existing literature characterizing platelets in CKD and identifies areas that need further investigation.

Male Sex Is Associated With Worse Microbiological and Clinical Outcomes Following Tuberculosis Treatment: A Retrospective Cohort Study, a Systematic Review of the Literature, and Meta-analysis.

BACKGROUND: Although the incidence of tuberculosis is higher in men than in women, the relationship of sex with tuberculosis treatment outcomes has not been adequately studied. METHODS: We performed a retrospective cohort study and a systematic review and meta-analysis of observational studies during the last 10 years to assess sex differences in clinical and microbiological outcomes in tuberculosis. RESULTS: In our cohort of 2894 Taiwanese patients with drug-susceptible pulmonary tuberculosis (1975 male and 919 female), male patients had higher adjusted hazards of 9-month mortality due to all causes (hazard ratio, 1.43 [95% confidence interval (CI), 1.03-1.98]) and infections (1.70 [1.09-2.64]) and higher adjusted odds of 2-month sputum culture positivity (odds ratio [OR], 1.56 [95% CI, 1.05-2.33]) compared with female patients. Smear positivity at 2 months did not differ significantly (OR, 1.27 [95% CI, .71-2.27]) between the sexes. Among 7896 articles retrieved, 398 were included in our systematic review describing a total of 3 957 216 patients. The odds of all-cause mortality were higher in men than in women in the pooled unadjusted (OR, 1.26 [95% CI, 1.19-1.34]) and adjusted (1.31 [1.18-1.45]) analyses. Men had higher pooled odds of sputum culture (OR, 1.44 [95% CI, 1.14-1.81]) and sputum smear (1.58 [1.41-1.77]) positivity, both at the end of the intensive phase and on completion of treatment. CONCLUSIONS: Our retrospective cohort showed that male patients with tuberculosis have higher 9-month all-cause and infection-related mortality, with higher 2-month sputum culture positivity after adjustment for confounding factors. In our meta-analysis, male patients showed higher all-cause and tuberculosis-related mortality and higher sputum culture and smear positivity rates during and after tuberculosis treatment.

Factors associated with disease severity and mortality among patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID-19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19. METHODS: We searched PubMed, Embase and WHO database for English language articles from inception until May 8, 2020. We included Observational studies with direct comparison of clinical characteristics between a) patients who died and those who survived or b) patients with severe disease and those without severe disease. Data extraction and quality assessment were performed by two authors independently. RESULTS: Among 15680 articles from the literature search, 109 articles were included in the analysis. The risk of mortality was higher in patients with increasing age, male gender (RR 1.45, 95%CI 1.23-1.71), dyspnea (RR 2.55, 95%CI 1.88-2.46), diabetes (RR 1.59, 95%CI 1.41-1.78), hypertension (RR 1.90, 95%CI 1.69-2.15). Congestive heart failure (OR 4.76, 95%CI 1.34-16.97), hilar lymphadenopathy (OR 8.34, 95%CI 2.57-27.08), bilateral lung involvement (OR 4.86, 95%CI 3.19-7.39) and reticular pattern (OR 5.54, 95%CI 1.24-24.67) were associated with severe disease. Clinically relevant cut-offs for leukocytosis(>10.0 x109/L), lymphopenia(< 1.1 x109/L), elevated C-reactive protein(>100mg/L), LDH(>250U/L) and D-dimer(>1mg/L) had higher odds of severe disease and greater risk of mortality. CONCLUSION: Knowledge of the factors associated of disease severity and mortality identified in our study may assist in clinical decision-making and critical-care resource allocation for patients with COVID-19.

Outcomes of COVID-19 in Patients With a History of Cancer and Comorbid Cardiovascular Disease.

BACKGROUND: Cancer and cardiovascular disease (CVD) are independently associated with adverse outcomes in patients with COVID-19. However, outcomes in patients with COVID-19 with both cancer and comorbid CVD are unknown. METHODS: This retrospective study included 2,476 patients who tested positive for SARS-CoV-2 at 4 Massachusetts hospitals between March 11 and May 21, 2020. Patients were stratified by a history of either cancer (n=195) or CVD (n=414) and subsequently by the presence of both cancer and CVD (n=82). We compared outcomes between patients with and without cancer and patients with both cancer and CVD compared with patients with either condition alone. The primary endpoint was COVID-19-associated severe disease, defined as a composite of the need for mechanical ventilation, shock, or death. Secondary endpoints included death, shock, need for mechanical ventilation, need for supplemental oxygen, arrhythmia, venous thromboembolism, encephalopathy, abnormal troponin level, and length of stay. RESULTS: Multivariable analysis identified cancer as an independent predictor of COVID-19-associated severe disease among all infected patients. Patients with cancer were more likely to develop COVID-19-associated severe disease than were those without cancer (hazard ratio [HR], 2.02; 95% CI, 1.53-2.68; P<.001). Furthermore, patients with both cancer and CVD had a higher likelihood of COVID-19-associated severe disease compared with those with either cancer (HR, 1.86; 95% CI, 1.11-3.10; P=.02) or CVD (HR, 1.79; 95% CI, 1.21-2.66; P=.004) alone. Patients died more frequently if they had both cancer and CVD compared with either cancer (35% vs 17%; P=.004) or CVD (35% vs 21%; P=.009) alone. Arrhythmias and encephalopathy were also more frequent in patients with both cancer and CVD compared with those with cancer alone. CONCLUSIONS: Patients with a history of both cancer and CVD are at significantly higher risk of experiencing COVID-19-associated adverse outcomes. Aggressive public health measures are needed to mitigate the risks of COVID-19 infection in this vulnerable patient population.