Venous thromboembolic outcomes in patients with lymphedema and lipedema: An analysis from the National Inpatient Sample.

BACKGROUND: Patients with lymphedema and lipedema share physical exam findings that may lead to misdiagnosis. Poor mobility is common in patients with obesity and patients with lymphedema and lipedema. This may constitute a risk factor for venous thromboembolism (VTE). Our objective was to evaluate the association of VTE in obese patients with lymphedema and lipedema. METHODS: The National Inpatient Sample (NIS) was searched from 2016 to 2020 to identify hospital admissions of obese female patients with lymphedema and lipedema. Patients were analyzed in the context of presence or absence of VTE while adjusting for complex cluster sampling techniques. Predictors of VTE were accessed by multivariable regression. RESULTS: Lymphedema was identified in 189,985 patients and lipedema in 50,645 patients. VTE was observed in 3.12% (n = 374,210) of patients with obesity. In patients with obesity, VTE was more common in patients with lymphedema than without (2.6% vs 1.6%; p < 0.01). Similarly, VTE was more common in patients with lipedema than without (0.6% vs 0.4%; p < 0.01). After multivariable logistic regression, VTE events in obese patients with lymphedema were higher versus without (OR 1.6; CI 1.08-2.43; p = 0.02). Similarly, VTE events were more common in obese patients with lipedema versus obese patients without lipedema (OR 1.20; CI 1.03-1.41; p = 0.02). CONCLUSIONS: In this hypothesis-generating study, lymphedema and lipedema show a positive association with VTE after adjusting for baseline patient characteristics such as obesity, which is a known independent risk factor for VTE. Mechanisms whereby lymphedema and lipedema are associated with VTE should be investigated.

Subclinical Leaflet Thrombosis After Balloon versus Self-Expandable Transcatheter Aortic Valve Implantation.

Hypoattenuated leaflet thickening (HALT) has been recognized as one of the complications after transcatheter aortic valve implantation and may promote structural valve degeneration and increase the risk of cerebrovascular events. The 2 main types of available transcatheter heart valves (THVs), the balloon-expandable (BE) and the self-expanding (SE), are interchangeably used in clinical practice despite substantial design differences. There is unclear evidence on whether these 2 different THV models are achieving similar or different rates of subclinical leaflet thrombosis/HALT. A systematic search of electronic databases was conducted to identify studies that reported the incidence of HALT between SE THVs and BE THVs. The Mantel-Haenszel method was used to calculate the 95% confidence interval and pooled risk ratio with a random-effects model. A total of 126 records were identified, of which 22 studies comprising 14,401 patients were included in our final analysis. Among 5,951 patients receiving SE THVs, 194 (3.2%) developed HALT, compared with 8,450 patients receiving BE THVs, of whom 484 (5.7%) developed HALT. There was a statistically significant decrease in the risk of developing HALT in patients receiving SE THVs compared with those receiving BE THVs (risk ratio 0.75, 95% confidence interval 0.59 to 0.95, I2 32%, p = 0.02). In conclusion, could potentially reduce the risk of HALT/subclinical leaflet thrombosis.

Outcomes Following Acute Coronary Syndrome in Patients With and Without Rheumatic Immune-Mediated Inflammatory Diseases.

Background Rheumatic immune mediated inflammatory diseases (IMIDs) are associated with high risk of acute coronary syndrome. The long-term prognosis of acute coronary syndrome in patients with rheumatic IMIDs is not well studied. Methods and Results We identified Medicare beneficiaries admitted with a primary diagnosis of myocardial infarction (MI) from 2014 to 2019. Outcomes of patients with MI and concomitant rheumatic IMIDs including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, dermatomyositis, or psoriasis were compared with propensity matched control patients without rheumatic IMIDs. One-to-three propensity-score matching was done for exact age, sex, race, ST-segment-elevation MI, and non-ST-segment-elevation MI variables and greedy approach on other comorbidities. The study primary outcome was all-cause mortality. The study cohort included 1 654 862 patients with 3.6% prevalence of rheumatic IMIDs, the most common of which was rheumatoid arthritis, followed by systemic lupus erythematosus. Patients with rheumatic IMIDs were younger, more likely to be women, and more likely to present with non-ST-segment-elevation MI. Patients with rheumatic IMIDs were less likely to undergo coronary angiography, percutaneous coronary intervention or coronary artery bypass grafting. After propensity-score matching, at median follow up of 24 months (interquartile range 9-45), the risk of mortality (adjusted hazard ratio [HR], 1.15 [95% CI, 1.14-1.17]), heart failure (HR, 1.12 [95% CI 1.09-1.14]), recurrent MI (HR, 1.08 [95% CI 1.06-1.11]), and coronary reintervention (HR, 1.06 [95% CI, 1.01-1.13]) (P<0.05 for all) was higher in patients with versus without rheumatic IMIDs. Conclusions Patients with MI and rheumatic IMIDs have higher risk of mortality, heart failure, recurrent MI, and need for coronary reintervention during follow-up compared with patients without rheumatic IMIDs.

Preoperative Atrial Fibrillation and Cardiovascular Outcomes After Noncardiac Surgery.

BACKGROUND: The impact of pre-existing atrial fibrillation (AF) on outcomes after noncardiac surgery is not clear. OBJECTIVES: We aimed to study the impact of AF on the risk of adverse outcomes after noncardiac surgery in a nationwide cohort. METHODS: We identified Medicare beneficiaries admitted for noncardiac surgery from 2015 to 2019 and divided the study cohort into 2 groups: with and without AF. Noncardiac surgery was classified into vascular, thoracic, general, genitourinary, gynecological, orthopedics and neurosurgery, breast, head and neck, and transplant. We used propensity score matching on exact age, sex, race, urgency and type of surgery, revised cardiac risk index (RCRI) and CHA2DS2-VASc score, and tight caliper on other comorbidities. The study outcomes were 30-day mortality, stroke, myocardial infarction, and heart failure. We examined the incremental utility of AF in addition to RCRI to predict adverse events after noncardiac surgery. RESULTS: The study cohort included 8,635,758 patients who underwent noncardiac surgery (16.4% with AF). Patients with AF were older, more likely to be men, and had higher prevalence of comorbidities. After propensity score matching, AF was associated with higher risk of mortality (OR: 1.31; 95% CI: 1.30-1.32), heart failure (OR: 1.31; 95% CI: 1.30-1.33), and stroke (OR: 1.40; 95% CI: 1.37-1.43) and lower risk of myocardial infarction (OR: 0.81; 95% CI: 0.79-0.82). Results were consistent in subgroup analysis by sex, race, type of surgery, and all strata of RCRI and CHA2DS2-VASc score. AF improved the discriminative ability of RCRI (C-statistic 0.73 to 0.76). CONCLUSION: Pre-existing AF is independently associated with postoperative adverse outcomes after NCS.

Comparative Risk of Incident Coronary Heart Disease Across Chronic Inflammatory Diseases.

Background: Chronic inflammatory diseases (CIDs) are considered risk enhancing factors for coronary heart disease (CHD). However, sparse data exist regarding relative CHD risks across CIDs. Objective: Determine relative differences in CHD risk across multiple CIDs: psoriasis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), systemic sclerosis (SSc), and inflammatory bowel disease (IBD). Methods: The cohort included patients with CIDs and controls without CID in an urban medical system from 2000 to 2019. Patients with CIDs were frequency-matched with non-CID controls on demographics, hypertension, and diabetes. CHD was defined as myocardial infarction (MI), ischemic heart disease, and/or coronary revascularization based on validated administrative codes. Multivariable-adjusted Cox models were used to determine the risk of incident CHD and MI for each CID relative to non-CID controls. In secondary analyses, we compared CHD risk by disease severity within each CID. Results: Of 17,049 patients included for analysis, 619 had incident CHD (202 MI) over an average of 4.4 years of follow-up. The multivariable-adjusted risk of CHD was significantly higher for SLE [hazard ratio (HR) 1.9, 95% confidence interval (CI) 1.2, 3.2] and SSc (HR 2.1, 95% CI 1.2, 3.9). Patients with SLE also had a significantly higher risk of MI (HR 3.6, 95% CI 1.9, 6.8). When CIDs were categorized by markers of disease severity (C-reactive protein for all CIDs except HIV, for which CD4 T cell count was used), greater disease severity was associated with higher CHD risk across CIDs. Conclusions: Patients with SLE and SSc have a higher risk of CHD. CHD risk with HIV, RA, psoriasis, and IBD may only be elevated in those with greater disease severity. Clinicians should personalize CHD risk and treatment based on type and severity of CID.

Left Atrial Dilation and Risk of One-Year Readmission after Embolic Stroke of Undetermined Source.

BACKGROUND: Structural left atrial and ventricular abnormalities on the electrocardiogram (ECG) and transthoracic echocardiogram (TTE) at the time of ischemic stroke have been associated with morbidity and mortality. Yet, the prognostic impact of the same in embolic stroke of undetermined source (ESUS), a relevant subtype of ischemic stroke with a unique pathophysiology, has not been well studied to date. Our aim was to assess the predictive impact of left atrio-ventricular ECG and TTE abnormalities on one-year hospital readmission after ESUS from an ongoing single center prospective stroke registry in the U.S. METHODS: We identified 369 ESUS patients who had at least 1 year of complete follow-up between 2013 and 2018. We examined the association of abnormal left atrio-ventricular findings on ECG and TTE, as well as basic demographic and clinical characteristics, measured at index admission with time to 1-year hospital readmission using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards regression. RESULTS: Recurrent ischemic stroke and cardiovascular causes constituted 60% of all readmissions. Patients with left atrial dilation on TTE were more likely to readmitted within 1 year (HR 1.51; 95% CI, 1.04-2.21). Bundle branch block, pathologic Q-wave, and troponin elevation curves diverged, but were not significantly associated with readmission (log-rank p=0.34, p=0.08, p=0.42, respectively). CONCLUSIONS: Following ESUS, left atrial dilation on TTE was associated with 1-year overall hospital readmission, of which cardiovascular and cerebrovascular ischemic events, and heart failure were a notable proportion. Our data support ongoing studies of atrial cardiopathy in ESUS patients.

Differential Associations of Chronic Inflammatory Diseases With Incident Heart Failure.

OBJECTIVES: The purpose of this study was to compare the risks of incident heart failure (HF) among a variety of chronic inflammatory diseases (CIDs) and to determine whether risks varied by severity of inflammation within each CID. BACKGROUND: Individuals with CIDs are at elevated risk for cardiovascular diseases, but data are limited regarding risk for HF. METHODS: An electronic health records database from a large urban medical system was examined, comparing individuals with CIDs with frequency-matched controls without CIDs, all of whom were receiving regular outpatient care. Rates of incident HF were determined by using the Kaplan-Meier method and subsequently used multivariate-adjusted proportional hazards models to compare HF risks for each CID. Exploratory analyses determined HF risks by proxy measurement of CID severity. RESULTS: Of 37,636 patients (n = 18,278 patients with CIDs; and n = 19,358 controls without CIDs) there were 960 incident HF cases over a median of 3.6 years. Risks for incident HF were significantly or borderline significantly elevated for patients with systemic sclerosis (hazard ratio [HR]: 7.26; 95% confidence interval [CI]: 5.72 to 9.21; p < 0.01), systemic lupus erythematosus (HR: 3.15; 95% CI: 2.41 to 4.11; p < 0.01), rheumatoid arthritis (HR: 1.39; 95% CI: 1.13 to 1.71; p < 0.01), and human immunodeficiency virus (HR: 1.28; 95% CI: 0.99 to 1.66; p = 0.06). There was no association between psoriasis or inflammatory bowel disease and incident HF, although patients with those CIDs with higher levels of C-reactive protein had higher risks for HF than controls. CONCLUSIONS: Systemic sclerosis and systemic lupus erythematosus were associated with the highest risks of HF, followed by rheumatoid arthritis and HIV. Measurements of inflammation were associated with HF risk across different CIDs.

Ankle-brachial index and incident heart failure with reduced versus preserved ejection fraction: The Multi-Ethnic Study of Atherosclerosis.

This study investigated the relationship between ankle-brachial index (ABI) and risk for heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). ABI has previously been associated with mortality, cardiovascular disease (CVD), and overall HF but the relationship between ABI and risk of HF stratified by EF has not been well characterized. We analyzed data from 6553 participants (53% female; mean age 62 ± 10 years) enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) who were free of known clinical CVD/HF at baseline (2000-2002) and had baseline ABI measured. Participants were classified as low (≤ 0.90), borderline-low (0.91-1.00), normal (1.01-1.40), and high (> 1.40) ABI. Incident hospitalized HF was determined over a median follow-up of 14 years; we classified HF events (n = 321) as HFrEF with EF < 50% (n = 155, 54%) or HFpEF with EF ⩾ 50% (n = 133, 46%). Low ABI was associated with incident HFrEF (hazard ratio (HR): 2.02, 95% CI 1.19-3.40, p = 0.01) and had no significant association with HFpEF (HR: 0.67, 95% CI 0.30-1.48, p = 0.32). Borderline-low and high ABI were not significantly associated with HFrEF or HFpEF. Cubic spline analyses showed association with both low and high ABI for HFrEF and high ABI for HFpEF. A 1 SD lower ABI (for ABI < 1.1) was associated with incident HFrEF in multivariable analysis (HR: 1.27, 95% CI 1.05-1.54) but was not significant after additionally adjusting for interim myocardial infarction (HR: 1.21, 95% CI 0.99-1.48). Low ABI was associated with higher risk for incident HFrEF but not HFpEF in persons free of known CVD. Future studies of a larger size are needed for high ABI analyses.

Heart rate is an independent predictor of all-cause mortality in individuals with type 2 diabetes: The diabetes heart study.

AIM: To assess the association of resting heart rate with all-cause and cardiovascular disease (CVD) mortality in the Diabetes Heart Study (DHS). METHODS: Out of a total of 1443 participants recruited into the DHS, 1315 participants with type 2 diabetes who were free of atrial fibrillation and supraventricular tachycardia during the baseline exam were included in this analysis. Heart rate was collected from baseline resting electrocardiogram and mortality (all-cause and CVD) was obtained from state and national death registry. Kaplan-Meier (K-M) and Cox proportional hazard analyses were used to assess the association. RESULTS: The mean age, body mass index (BMI) and systolic blood pressure (SBP) of the cohort were 61.4 ± 9.2 years, 32.0 ± 6.6 kg/m2, and 139.4 ± 19.4 mmHg respectively. Fifty-six percent were females, 85% were whites, 15% were blacks, 18% were smokers. The mean ± SD heart rate was 69.8 (11.9) beats per minute (bpm). After a median follow-up time of 8.5 years (maximum follow-up time is 14.0 years), 258 participants were deceased. In K-M analysis, participants with heart rate above the median had a significantly higher event rate compared with those below the median (log-rank P = 0.0223). A one standard deviation increase in heart rate was associated with all-cause mortality in unadjusted (hazard ratio 1.16, 95%CI: 1.03-1.31) and adjusted (hazard ratio 1.20, 95%CI: 1.05-1.37) models. Similar results were obtained with CVD mortality as the outcome of interest. CONCLUSION: Heart rate is an independent predictor of all-cause mortality in this population with type 2 diabetes. In this study, a 1-SD increase in heart rate was associated with a 20% increase in risk suggesting that additional prognostic information may be gleaned from this ubiquitously collected vital sign.

The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.

The inoculum effect (IE) refers to the decreasing efficacy of an antibiotic with increasing bacterial density. It represents a unique strategy of antibiotic tolerance and it can complicate design of effective antibiotic treatment of bacterial infections. To gain insight into this phenomenon, we have analyzed responses of a lab strain of Escherichia coli to antibiotics that target the ribosome. We show that the IE can be explained by bistable inhibition of bacterial growth. A critical requirement for this bistability is sufficiently fast degradation of ribosomes, which can result from antibiotic-induced heat-shock response. Furthermore, antibiotics that elicit the IE can lead to 'band-pass' response of bacterial growth to periodic antibiotic treatment: the treatment efficacy drastically diminishes at intermediate frequencies of treatment. Our proposed mechanism for the IE may be generally applicable to other bacterial species treated with antibiotics targeting the ribosomes.