Sex Differences in Thrombosis and Mortality in Patients Hospitalized for COVID-19.

Gender-specific differences in thrombosis have been reported in hospitalized patients with COVID-19. We sought to investigate the influence of age on the relation between gender and incident thrombosis or death in COVID-19. We identified consecutive adults aged ≥18 years hospitalized with COVID-19 from March 1, 2020, to April 17, 2020, at a large New York health system. In-hospital thrombosis and all-cause mortality were evaluated by gender and stratified by age group. Logistic regression models were generated to estimate the odds of thrombosis or death after multivariable adjustment. In 3,334 patients hospitalized with COVID-19, 61% were men. Death or thrombosis occurred in 34% of hospitalizations and was more common in men (36% vs 29% in women, p <0.001; adjusted odds ratio [aOR] 1.61, 95% confidence interval [CI] 1.36 to 1.91). When stratified by age, men had a higher incidence of death or thrombosis in younger patients (aged 18 to 54 years: 21% vs 9%, aOR 3.17, 95% CI 2.06 to 5.01; aged 55 to 74 years: 39% vs 28%, aOR 1.63, 95% CI 1.28 to 2.10), but not older patients (aged ≥75 years: 55% vs 48%; aOR 1.20, 95% CI 0.90 to 1.59) (interaction p value: 0.01). For the individual end points, men were at higher risk of thrombosis (19% vs 12%; aOR 1.65, 95% CI 1.33 to 2.05) and mortality (26% vs 23%; aOR 1.41, 95% CI 1.17 to 1.69) than women, and gender-specific differences were attenuated with older age. Associations between thrombosis and mortality were most striking in younger patients (aged 18 to 54 years, aOR 8.25; aged 55 to 74 years, aOR 2.38; aged >75 years, aOR 1.88; p for interaction <0.001) but did not differ by gender. In conclusion, the risk of thrombosis or death in COVID-19 is higher in men compared with women and is most apparent in younger age groups.

Cardiovascular Risk Factors and Perioperative Myocardial Infarction After Noncardiac Surgery.

BACKGROUND: Perioperative cardiovascular events are a leading cause of morbidity and mortality after noncardiac surgery. We propose a simplified method for perioperative risk stratification. METHODS: In a retrospective cohort study we identified patients who underwent noncardiac surgery between 2009 and 2015 in the US National Surgical Quality Improvement Program. Multivariable logistic regression models adjusted for age, sex, race, and surgery type were generated to estimate the effect of traditional cardiovascular risk factors (hypertension, diabetes mellitus, current smoking) on odds of perioperative myocardial infarction (MI). Time to event analysis was conducted using competing risk analysis, with MI as the outcome event and death as the competing risk. RESULTS: A total of 3,848,501 noncardiac surgeries were identified. Postoperative MI occurred in 0.37% of patients and 1.04% of patients died. The 30-day event rate of perioperative MI increased in a stepwise fashion with additional risk factors (0.42% for 1, 0.82% for 2, and 1.08% for 3; P for trend < 0.001) after accounting for the competing risk of death. Compared with those with no risk factors, patients with 1, 2, and 3 risk factors had increased odds of MI (adjusted odds ratio [aOR], 2.07 [95% confidence interval (CI), 1.96-2.19]; aOR, 3.63 [95% CI, 3.43-3.85]; and aOR, 5.54 [95% CI, 5.09-6.04], respectively). Perioperative MI was rare (0.10%) in patients without risk factors. CONCLUSIONS: Patients with cardiovascular risk factors are at increased risk of perioperative MI, those without risk factors are at low risk. Further evaluation is needed to determine the effect of a simplified risk score in the perioperative setting.

Diabetic Agents, From Metformin to SGLT2 Inhibitors and GLP1 Receptor Agonists: JACC Focus Seminar.

Given the intersection between diabetes mellitus and cardiovascular disease (CVD), pharmacologic agents used to treat type 2 diabetes mellitus must show cardiovascular safety. Comorbid conditions, including heart failure and chronic kidney disease, are increasingly prevalent in patients with diabetes; therefore, they also play a large role in drug safety. Although biguanides, sulfonylurea, glitazones, and dipeptidyl peptidase 4 inhibitors have variable effects on cardiovascular events, sodium glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists have consistently shown safety and reduction in cardiovascular events in patients with established CVD. These medications are becoming essential tools for cardioprotection for patients with diabetes and CVD. They may also have roles in primary prevention and renal protection. This paper will review the cardiovascular impact, adverse effects, and possible mechanisms of action of pharmacologic agents used to treat patients with type 2 diabetes.

Catheter-related right atrial thrombosis.

INTRODUCTION: Catheter-related right atrial thrombosis is an under-recognized complication of central venous catheter placement. We performed a retrospective review, characterizing clinical aspects of catheter-related right atrial thrombosis (CRAT). METHODS: To identify cases, a literature search was conducted in PubMed and additional items selected by review of related items and bibliography review. Key clinical data were extracted and analyzed both in total and as stratified by hemodialysis versus non-hemodialysis groups. RESULTS: A total of 68 catheter-related right atrial thrombosis events were reported in 63 patients (five recurrences, of which 4 involved catheter left in place following primary treatment). Median (interquartile range) time to CRAT diagnosis was longer among hemodialysis patients - 12 (4.0-24.0) weeks compared to 5.5 (1.8-16.1) weeks among non-hemodialysis patients. The most common presentations were asymptomatic in 16/68 (23.5%), fever/sepsis in 21/68 (30.9%), pulmonary embolism in 11/68 (16.2%), catheter dysfunction in 8/68 (11.8%), dyspnea in 8/68 (11.8%), and new murmur or valvular dysfunction in 8/68 (11.8%) patients. Primary treatment selection was anticoagulation in 33/68 (48.5%), surgical thrombectomy in 17/68 (25.0%), thrombolysis in 12/68 (17.6%), or no active therapy in 6/68 (8.8%) patients. Primary treatment failure for anticoagulation and thrombolysis was 27.3% and 33.3%, respectively. The most common rescue therapy was surgical thrombectomy, ultimately resulting in an overall rate of 26/62 (41.9%). Overall, per-patient mortality was 13/63 (20.6%). Intracardiac tip position - 27/34 (79.4%) - overshadowed thrombophilia - 16/63 (25.4%) - as a risk factor for CRAT. CONCLUSION: Catheter-related right atrial thrombosis is an underdiagnosed complication of central venous catheter placement. For the hemodialysis population, a fistula-first approach is advocated. While many instances were asymptomatic, the development of unexplained fever, dyspnea, catheter dysfunction, or new murmur should trigger a search for this complication.

Cardiovascular Risk Scores to Predict Perioperative Stroke in Noncardiac Surgery.

Background and Purpose- Perioperative stroke is associated with significant morbidity and mortality. Conventional cardiovascular risk scores have not been compared to predict acute stroke after noncardiac surgery. Methods- Patients undergoing noncardiac surgery between 2009 and 2010 were identified from the US National Surgical Quality Improvement Program (n=540 717). Patients were prospectively followed for 30 days postoperatively for the primary outcome of stroke. Established cardiovascular and perioperative risk scores (CHADS2, CHA2DS2-VASc, Revised Cardiac Risk Index, Mashour et al risk score, Myocardial Infarction or Cardiac Arrest risk score, and National Quality Improvement Project American College of Surgeons surgical risk calculator) were assessed to predict perioperative stroke. Results- Stroke occurred in the perioperative period of 1474 noncardiac surgeries (0.27%). Patients with perioperative stroke were older, more frequently male, had lower body mass index, and were more likely to have undergone vascular surgery or neurosurgery than patients without stroke (P<0.001 for each comparison). All risk prediction models were associated with increased risk of perioperative stroke (C statistic [AUC] range, 0.743-0.836). The Myocardial Infarction or Cardiac Arrest risk score (AUC, 0.833) and American College of Surgeons surgical risk calculator (AUC, 0.836) had the most favorable test characteristics and a greater ability to discriminate perioperative stroke when compared with Revised Cardiac Risk Index, CHADS2, CHA2DS2-VASc, and Mashour risk scores (P for comparison, <0.001; Delong). Risk scores did not provide consistent discriminative ability across surgery types and were least predictive in vascular surgery (AUC range, 0.588-0.672). Conclusions- The Myocardial Infarction or Cardiac Arrest risk score and American College of Surgeons surgical risk calculator surgical risk scores provide excellent risk discrimination for perioperative stroke in most patients undergoing noncardiac surgery. Stroke prediction was less optimal in patients undergoing vascular surgery.

Peripheral vascular disease risk in diabetic individuals without coronary heart disease.

BACKGROUND AND AIMS: Diabetes mellitus is a coronary heart disease (CHD) risk-equivalent for the outcome of peripheral vascular disease. The impact of diabetes with comorbid risk factors on the outcome of peripheral vascular disease remains unexplored. METHODS: We performed a cross-sectional analysis of participants in Lifeline Vascular Screening Inc. age 40-90 who were screened for peripheral vascular disease, defined as lower extremity peripheral artery disease (PAD, ABI <0.9) and/or carotid artery stenosis (CAS, internal CAS ≥50%). CHD was defined as prior myocardial infarction or revascularization. Risk factors included hypertension, hyperlipidemia, smoking, obesity, sedentary lifestyle and family history of cardiovascular disease. RESULTS: Among 3,517,804 participants, PAD and CAS was identified in 4.4% and 3.7%, respectively. Diabetes was identified in 376,528 participants, 324,680 (86%) of whom did not have CHD. Among diabetic participants without CHD, prevalence of PAD increased with 1-2 (4.3%), 3-4 (7.3%), and ≥5 (12.0%) comorbid risk factors (p trend < 0.0001). The pattern was similar for CAS (3.7%, 6.2%, 8.8%, p trend < 0.0001). Compared to participants without diabetes, those with diabetes and 1-2, 3-4 and ≥5 risk factors had increasing odds of PAD and CAS after adjustment for age, sex and race/ethnicity (1.0, 95% CI 0.98-1.06; 1.8, 95% CI 1.8-1.89; 3.5, 95% CI 3.43-3.64, respectively, p trend < 0.0001). By comparison, in nondiabetic participants, CHD increased odds of PAD and CAS by 2-fold (2.06, 95% CI 2.02-2.1; 2.19, 95% CI 2.15-2.23 respectively). CONCLUSIONS: Diabetes, particularly with comorbid risk factors, confers increased odds of PAD and CAS, even in the absence of CHD. Counseling regarding screening and prevention for peripheral vascular disease among individuals with diabetes and multiple risk factors may be useful.

Influence of Diabetes on Trends in Perioperative Cardiovascular Events.

OBJECTIVE: Patients undergoing noncardiac surgery frequently have diabetes mellitus (DM) and an elevated risk of cardiovascular disease. It is unknown whether temporal declines in the frequency of perioperative major adverse cardiovascular and cerebrovascular events (MACCEs) apply to patients with DM. RESEARCH DESIGN AND METHODS: Patients ≥45 years of age who underwent noncardiac surgery from January 2004 to December 2013 were identified using the U.S. National Inpatient Sample. DM was identified using ICD-9 diagnosis codes. Perioperative MACCEs (in-hospital all-cause mortality, acute myocardial infarction, or acute ischemic stroke) by DM status were evaluated over time. RESULTS: The final study sample consisted of 10,581,621 hospitalizations for major noncardiac surgery; DM was present in ∼23% of surgeries and increased over time (P for trend <0.001). Patients with DM experienced MACCEs in 3.3% of surgeries vs. 2.8% of surgeries for patients without DM (P < 0.001). From 2004 to 2013, the odds of perioperative MACCEs after multivariable adjustment increased by 6% (95% CI 2-9) for DM patients, compared with an 8% decrease (95% CI -10 to -6) for patients without DM (P for interaction <0.001). Trends for individual end points were all less favorable for patients with DM versus those without DM. CONCLUSIONS: In an analysis of >10.5 million noncardiac surgeries from a large U.S. hospital admission database, perioperative MACCEs were more common among patients with DM versus those without DM. Perioperative MACCEs increased over time and individual end points were all less favorable for patients with DM. Our findings suggest that a substantial unmet need exists for strategies to reduce the risk of perioperative cardiovascular events among patients with DM.

Acquired Coagulopathy and Hemorrhage Secondary to Subcutaneous Heparin Prophylaxis.

Unfractionated heparin and low-molecular-weight heparins are commonly used as thromboprophylaxis for hospitalized patients. Though generally considered safe at prophylactic doses, cases of catastrophic hemorrhage have been reported. The proposed mechanism involves bioaccumulation of heparin through saturation of the rapid-elimination pathway in its metabolism. We present an unusual case of an average-weight man with metastatic melanoma who suffered hemorrhage with syncope and end-organ damage while on prophylactic three times daily unfractionated heparin. Coagulation studies were consistent with heparin toxicity. Despite administration of protamine, the clearance of heparin was remarkably delayed, as demonstrated by serial coagulation studies. We review the suspected risk factors for heparin bioaccumulation and the emerging understanding of this unusual adverse event involving a nearly ubiquitous medication.

Environmental drivers of the spatiotemporal dynamics of respiratory syncytial virus in the United States.

Epidemics of respiratory syncytial virus (RSV) are known to occur in wintertime in temperate countries including the United States, but there is a limited understanding of the importance of climatic drivers in determining the seasonality of RSV. In the United States, RSV activity is highly spatially structured, with seasonal peaks beginning in Florida in November through December and ending in the upper Midwest in February-March, and prolonged disease activity in the southeastern US. Using data on both age-specific hospitalizations and laboratory reports of RSV in the US, and employing a combination of statistical and mechanistic epidemic modeling, we examined the association between environmental variables and state-specific measures of RSV seasonality. Temperature, vapor pressure, precipitation, and potential evapotranspiration (PET) were significantly associated with the timing of RSV activity across states in univariate exploratory analyses. The amplitude and timing of seasonality in the transmission rate was significantly correlated with seasonal fluctuations in PET, and negatively correlated with mean vapor pressure, minimum temperature, and precipitation. States with low mean vapor pressure and the largest seasonal variation in PET tended to experience biennial patterns of RSV activity, with alternating years of "early-big" and "late-small" epidemics. Our model for the transmission dynamics of RSV was able to replicate these biennial transitions at higher amplitudes of seasonality in the transmission rate. This successfully connects environmental drivers to the epidemic dynamics of RSV; however, it does not fully explain why RSV activity begins in Florida, one of the warmest states, when RSV is a winter-seasonal pathogen. Understanding and predicting the seasonality of RSV is essential in determining the optimal timing of immunoprophylaxis.

Effects of a multimodality blood conservation schema toward improvement of intraoperative hemoglobin levels and off-pump transfusions in coronary artery bypass graft surgery.

BACKGROUND: Cardiothoracic surgery places significant demands on blood bank resources. Measures aimed at reducing intraoperative hemodilution were initiated as part of a blood conservation program. STUDY DESIGN AND METHODS: We initiated a series of measures aimed at reducing hemodilution volume: 1) reduction of intravenous fluid (IVF) volume, 2) reduction of circuit size, and 3) use of autologous priming techniques. All sources and volumes of IVF were obtained from the medical record. Intraoperative hematocrit (Hct) measurements were performed at the following intervals: first in operating room (OR), lowest on-pump, last on-pump, after protamine reversal, and immediately before discharge from OR. Red blood cell (RBC) transfusions were recorded. Intraoperative IVF, Hct levels, and transfusions were analyzed by cardiopulmonary bypass phase (prepump, on-pump, and off-pump), comparing preimplementation and postimplementation periods. RESULTS: Total intraoperative IVF volume was reduced by 973.7 mL (95% confidence interval, 671.6-1275.9 mL; p < 0.001) leading to a mean on-pump Hct improvement of more than 2% (p < 0.004). This contributed to a reduction in off-pump RBC transfusions by 20.6% (p = 0.014). A significant degree of heterogeneity in transfusion practice was noted between anesthesiologists. CONCLUSIONS: Blood conservation efforts in cardiac surgery should include efforts aimed at reducing hemodilution. Potential improvements are blunted by variation in transfusion practice.