Interaction Between Risk Factors, Coronary Calcium, and CCTA Plaque Characteristics in Patients Age 18-45.

AIMS: The atherosclerotic profile and advanced plaque subtype burden in symptomatic patients ≤45 years old have not been established. This study aimed to assess the prevalence and predictors of coronary artery calcium (CAC), plaque subtypes, and plaque burden by coronary computed tomography angiography (CCTA) in symptomatic young patients. METHODS AND RESULTS: We included 907 symptomatic young patients (18-45 years) from Montefiore undergoing CCTA for chest pain evaluation. Prevalence and predictors of CAC, plaque subtypes, and burden were evaluated using semi-automated software. In the overall population (55% female and 44% Hispanic), 89% had CAC = 0. The likelihood of CAC or any plaque by CCTA increased with >3 risk factors (RF, OR 7.13 [2.14-23.7] and OR 10.26 [3.36-31.2], respectively). Any plaque by CCTA was present in 137 (15%); the strongest independent predictors were age ≥35 years (OR 3.62 [2.05-6.41]) and family history of premature CAD (FHx) (OR 2.76 [1.67-4.58]). Stenosis ≥50% was rare (1.8%), with 31% of those having CAC = 0. Significant non-calcified (NCP, 37.2%) and low-attenuation (LAP, 4.24%) plaque burdens were seen, even in those with non-obstructive stenosis. Among patients with CAC = 0, 5% had plaque, and the only predictor of exclusively non-calcified plaque was FHx (OR 2.29 [1.08-4.86]). CONCLUSIONS: In symptomatic young patients undergoing CCTA, the prevalence of CAC or any coronary atherosclerosis was not negligible, and the likelihood increased with RF burden. The presence of coronary stenosis ≥50% was rare and most often accompanied by CAC > 0 but there was a significant burden of NCP and LAP even within the non-obstructive group.

Elevated glycosylated hemoglobin levels are associated with severe acute kidney injury following coronary artery bypass surgery.

BACKGROUND: Diabetic patients are at increased risk of acute kidney injury (AKI) following surgery. The significance of uncontrolled diabetes on kidney function after coronary artery bypass grafting (CABG) remains controversial. Our aim was to study the association between pre-operative hemoglobin A1c (HbA1c) and severe cardiac surgery-associated AKI (CSA-AKI) following CABG. METHODS: A single-center, retrospective cohort study including patients who underwent isolated CABG from 2010 to 2018 was performed. Patients were grouped into pre-operative HbA1c of <6.5 %, 6.5-8.5 %, and ≥8.5 %. Postoperative serum creatinine levels were queried for up to 30 days, and the 30-day risk of severe AKI was compared among groups. Multivariable logistic regression was used to study factors associated with severe CSA-AKI and the association of severe CSA-AKI with postoperative outcomes. Cox regression was used to study the association between severe CSA-AKI and all-cause mortality from the time of surgery to the last follow-up or death. RESULTS: A total of 2424 patients met the inclusion criteria. Patients were primarily male (70.5 %), with a median age of 64 years (IQR 57-71). Median bypass and cross-clamp times were 95 (IQR 78-116) and 78 min (IQR 63-95). Severe CSA-AKI occurred within 30 days in 5.7 %, 6.7 %, and 9.1 % of patients with pre-op HbA1c of <6.5 %, 6.5-8.5 %, and ≥8.5 %, respectively. After adjusting for covariates, HbA1c >8.5 %, was independently associated with severe CSA-AKI 30 days after CABG (aOR 1.59, 95%CI 1.06-2.40). In addition, severe CSA-AKI was associated with increased 30- (aOR 15.83,95%CI 7.94-31.56) and 90- day mortality (aOR 9.54, 95%CI 5.46-16.67), prolonged length of stay (aOR 3.46,95%CI 2.41-4.96) and unplanned 30-day readmission (aOR 2.64, 95%CI 1.77-3.94). Lastly, severe CSA-AKI was associated with increased all-cause mortality (aHR 3.19, 95%CI 2.43-4.17). CONCLUSION: Elevated preoperative HbA1c (≥8.5 %) was independently associated with an increased 30-day risk of severe CSA-AKI, which is a consistent predictor of adverse outcomes after CABG. Delaying surgery to achieve optimal glycemic control in an elective setting may be reasonable.

Cardiometabolic predictors of high-risk CCTA phenotype in a diverse patient population.

Introduction: Low-attenuation non-calcified plaque (LAP) burden and vascular inflammation by pericoronary adipose tissue (PCAT) measured from coronary CT angiography (CCTA) have shown to be predictors of cardiovascular outcomes. We aimed to investigate the relationships of cardiometabolic risk factors including lipoprotein(a) and epicardial adipose tissue (EAT) with CCTA high-risk imaging biomarkers, LAP and vascular inflammation. Methods: The patient population consisted of consecutive patients who underwent CCTA for stable chest pain and had a complete cardiometabolic panel including lipoprotein(a). Plaque, PCAT and EAT were measured from CT using semiautomated software. Elevated LAP burden and PCAT attenuation were defined as ≥4% and ≥70.5 HU, respectively. The primary clinical end-point was a composite of myocardial infarction, revascularization or cardiovascular death. Results: A total of 364 consecutive patients were included (median age 56 years, 64% female); the majority of patients were of Hispanic (60%), and the rest were of non-Hispanic Black (21%), non-Hispanic White (6%) and non-Hispanic Asian (4%) race/ethnicity. The prevalence of elevated LAP burden and PCAT attenuation was 31 and 18%, respectively, while only 8% had obstructive stenosis. There were significant differences in plaque characteristics among different racial/ethnic groups (p<0.001). Lipoprotein(a) correlated with LAP burden in Hispanic patients. Patients with elevated LAP were older, more likely to be have diabetes, hypertension, hyperlipidemia and smoke with higher CAC and EAT volume (all P<0.05). Patients with elevated LAP were more likely to develop the primary clinical outcome (p<0.001) but those with elevated PCAT were not (p=0.797). Conclusion: The prevalence of LAP and PCAT attenuation were 31 and 18%, respectively. Lipoprotein(a) levels correlated with LAP burden in Hispanic patients. Age, male sex, hypertension and hyperlipidemia increased the odds of elevated LAP, which showed prognostic significance.

Interplay Between Zero CAC, Quantitative Plaque Analysis, and Adverse Events in a Diverse Patient Cohort.

BACKGROUND: Coronary artery calcium scoring (CAC) has garnered attention in the diagnostic approach to chest pain patients. However, little is known about the interplay between zero CAC, sex, race, ethnicity, and quantitative coronary plaque analysis. METHODS: We conducted a retrospective analysis from our computed tomography registry of patients with stable angina without prior myocardial infarction or revascularization undergoing coronary computed tomography angiography at Montefiore Healthcare System. Follow-up end points collected included invasive angiography, type-1 myocardial infarction, coronary revascularization, cardiovascular and all-cause death. RESULTS: A total of 2249 patients were included (66% female). The median follow-up was 5.5 years. The median age of those without CAC was 52 years (interquartile range, 44-59) and 60 years (interquartile range, 53-68) in those with CAC. Most patients were Hispanic (58%), and the rest were non-Hispanic Black (28%), non-Hispanic White (10%), and non-Hispanic Asian (5%). The majority had CAC=0 (55%). The negative predictive value of CAC=0 was 92.8%, 99.9%, and 99.9% for any plaque, obstructive coronary artery stenosis, and the composite outcome of all-cause death, myocardial infarction, or coronary revascularization, respectively. Among patients without CAC (n=1237), 89 patients (7%) had evidence of plaque on their coronary computed tomography angiography with a median low-attenuation noncalcified plaque burden of 4% (2-7). There were no significant differences in the negative predictive value for CAC=0 by sex, race, or ethnicity. Patients with ≥2 risk factors had higher odds of having plaque with zero CAC. CONCLUSIONS: In summary, no sex, race, or ethnicity differences were demonstrated in the negative predictive value of a zero CAC; however, patients with ≥2 risk factors had a higher prevalence of plaque. A small percentage (7%) of symptomatic patients undergoing coronary computed tomography angiography with zero CAC had noncalcified coronary plaque, with the implication that caution is needed for downscaling of preventive treatment in patients with zero CAC, chest pain, and multiple risk factors.

Perioperative Cardiometabolic Targets and Coronary Artery Bypass Surgery Mortality in Patients With Diabetes.

Background Coronary artery bypass graft (CABG) surgery represents the preferred revascularization strategy for most patients with diabetes and multivessel disease. We aimed to evaluate the role of optimized, perioperative cardiometabolic targets on long-term survival in patients who underwent CABG. Methods and Results Single-institution retrospective study was conducted in patients with diabetes who underwent CABG between January 2010 and June 2018. Demographic, surgical, and cardiometabolic determinants were identified during the perioperative period. Clinical characteristics and longitudinal survival outcomes data were obtained. A total of 1534 patients with CABG were considered for analysis and 1273 met inclusion criteria. The mean age of patients was 63.3 years (95% CI, 62.7-63.8 years), and most were men (65%) and Hispanic or Latino (47%). Comorbidities included hypertension (95%) and dyslipidemia (88%). In total, 490 patients (52%) had a low-density lipoprotein cholesterol level >70 mg/dL. Furthermore, 390 patients (31%) had uncontrolled systolic blood pressure >130 mm Hg. Last, only 386 patients (29%) had a hemoglobin A1c level between 6% and 7%. At 5 years, 121 patients (10%) died. Failure to achieve goal systolic blood pressure was associated with all-cause (hazard ratio [HR], 1.573; 95% CI, 1.048-2.362 [P=0.029]) and cardiovascular (HR, 2.023; 95% CI, 1.196-3.422 [P=0.009]) mortality at 5 years post-CABG. In contrast, prescription of a statin during the perioperative interval demonstrated a protective effect for all-cause (HR, 0.484; 95% CI, 0.286-0.819 [P=0.007]) and cardiovascular (HR, 0.459; 95% CI, 0.229-0.920 [P=0.028]) mortality. There was no association between achievement of low-density lipoprotein cholesterol, triglycerides, non-high-density lipoprotein cholesterol, or hemoglobin A1c level goals and mortality risk at 5 years. Conclusions Among patients with diabetes, blood pressure control and statin therapy were the most important perioperative cardiometabolic survival determinants 5 years after CABG.

The COVID-19 Pandemic Did Not Affect Target Weight Loss 1 Year Post Bariatric Surgery.

BACKGROUND: Bariatric surgery is one of the most effective treatments for patients with severe and complex obesity. Lifestyle modifications in diet and exercise habits have long been important adjunct to the long-term success after bariatric surgery. The effect of the COVID-19 pandemic on the postoperative bariatric patient is not well understood. We sought to evaluate the impact the COVID-19 pandemic on postoperative weight loss at 1 year in a bariatric cohort. METHODS: All patients who underwent bariatric surgery from January 1, 2020, to March 12, 2020, were included. Patients who underwent bariatric surgery during the same period of the two preceding years (2018 and 2019) were included as control groups. Primary end point was %EBMIL at 1 year. A telephone survey was administered to all patients from 2020 to assess for their perception on the effects of the COVID-19 pandemic on weight loss. RESULTS: A total of 596 patients were included: 181 from 2020, 199 from 2019, and 216 from 2018. The response rate was 97% and 53.4% of patients reported that the lockdown affected their ability to lose weight. The %EBMIL at 1 year was 64.1%, 63.7%, and 68.1% for 2020, 2019, and 2018, respectively. There was no difference in weight loss at 1 year (p = 0.77) despite a decrease in exercise activity in those who had surgery just before the pandemic. CONCLUSION: There was no difference in target weight loss at 1 year in a cohort who underwent bariatric surgery before the pandemic.

Appendiceal adenocarcinoma found by surgery for acute appendicitis is associated with older age.

BACKGROUND: Appendectomy for acute appendicitis is the most common procedure performed emergently by general surgeons in the United States. The current management of acute appendicitis is increasingly controversial as non-operative management gains favor. Although rare, appendiceal neoplasms are often found as an incidental finding in the setting of appendectomy. Criteria and screening for appendiceal neoplasms are not standardized among surgical societies. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried for all patients who underwent appendectomy over a 9-year period (2010-2018). Over the same time period, patients who underwent appendectomy in two municipal hospitals in The Bronx, New York City, USA were reviewed. RESULTS: We found a 1.7% incidence of appendiceal neoplasms locally and a 0.53% incidence of appendiceal tumors in a national population sample. Both groups demonstrated an increased incidence of appendiceal carcinoma by age. This finding was most pronounced after the age of 40 in both local and national populations. In our study, the incidence of appendiceal tumors increased with each decade interval up to the age of 80 and peaked at 2.1% in patients between 70 and 79 years. CONCLUSIONS: Appendiceal adenocarcinomas were identified in patients with acute appendicitis that seem to be associated with increasing age. The presence of an appendiceal malignancy should be considered in the management of older patients with acute appendicitis before a decision to embark on non-operative therapy.

On-admission anemia predicts mortality in COVID-19 patients: A single center, retrospective cohort study.

OBJECTIVES: We investigated the impact of anemia based on admission hemoglobin (Hb) level as a prognostic risk factor for severe outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: A single-center, retrospective cohort study was conducted from a random sample of 733 adult patients (age ≥ 18 years) obtained from a total of 4356 laboratory confirmed SARS-CoV-2 cases who presented to the Emergency Department of Montefiore Medical Center between March-June 2020. The primary outcome was a composite endpoint of in-hospital severe outcomes of COVID-19. A secondary outcome was in-hospital all-cause mortality. RESULTS: Among the 733 patients included in our final analysis, 438 patients (59.8%) presented with anemia. 105 patients (14.3%) had mild, and 333 patients (45.5%) had moderate-severe anemia. Overall, 437 patients (59.6%) had a composite endpoint of severe outcomes. On-admission anemia was an independent risk factor for all-cause mortality, (Odds Ratio 1.52, 95% CI [1.01-2.30], p = 0.046) but not for composite severe outcomes. However, moderate-severe anemia (Hb < 11 g/dL) on admission was independently associated with both severe outcomes (OR1.53, 95% CI [1.05-2.23], p = 0.028) and mortality (OR 1.67, 95% CI [1.09-2.56], p = 0.019) during hospitalization. CONCLUSION: Anemia on admission was independently associated with increased odds of all-cause mortality in patients hospitalized with COVID-19. Furthermore, moderate-severe anemia (Hb <11 g/dL) was an independent risk factor for severe COVID-19 outcomes. Moving forward, COVID-19 patient management and risk stratification may benefit from addressing anemia on admission.

De Novo Renal Failure and Clinical Outcomes of Patients With Critical Coronavirus Disease 2019.

OBJECTIVES: To describe the characteristics and outcomes associated with concomitant renal and respiratory failure in patients with critical coronavirus disease 2019. DESIGN, SETTING, AND PATIENTS: This is a case series of patients from a U.S. healthcare system in New York City. All adult patients (≥ 18 yr) admitted to the hospital with positive coronavirus disease 2019 testing between March 10, 2020, and March 31, 2020, who required mechanical ventilatory support were included. Patients who remained hospitalized were followed through May 1, 2020. INTERVENTIONS: Renal replacement therapy included at least one session of dialysis, continued venovenous hemofiltration, or peritoneal dialysis. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics, laboratory markers, 30-day in-hospital outcomes, ventilator days, and survival to discharge were included. Multivariate predictors for mortality and need for renal replacement therapy were identified. A total of 330 patients were included in this analysis and were most commonly greater than or equal to 70 years (40%), male (61%), Black or African American (41%), and Hispanic or Latino (38%). Renal replacement therapy was required in 101 patients (29%), most commonly among Blacks or African Americans (50%). Elevated d-dimer, C-reactive protein, and procalcitonin were associated with renal replacement therapy, compared with the nondialysis cohort. Overall, 243 patients (74%) died and 56 (17%) were discharged from the hospital, of which 9 (3%) required renal replacement therapy. Male sex (odds ratio, 2.0; 1.1-3.5; p = 0.020), Black race (odds ratio, 1.8; 1.0-3.1; p = 0.453), and history of hypertension (odds ratio, 2.7; 1.3-5.4; p = 0.005) were predictors for requiring renal replacement therapy. Risk factors for in-hospital mortality included age greater than or equal to 60 years (odds ratio, 6.2; 3.0-13.0; p < 0.0001), male sex (odds ratio, 3.0; 1.4-6.4; p = 0.004), and body mass index greater than or equal to 30 kg/m2 (odds ratio, 2.1; 1.0-4.4; p = 0.039). Concomitant renal failure in critical coronavirus disease 2019 was not a significant predictor of death (odds ratio, 2.3; 0.98-5.5; p = 0.057). CONCLUSIONS: This case series concludes that respiratory failure conveys significant mortality risk in patients with coronavirus disease 2019 and that survival with concomitant renal failure is rare.

Mechanical Circulatory Support: a Comprehensive Review With a Focus on Women.

PURPOSE OF THE REVIEW: The purpose of this review is to analyze the evidence for use of mechanical circulatory support (MCS) with a focus on women, namely, intra-aortic balloon pump (IABP), Impella, ventricular assist devices (VAD), and extracorporeal membrane oxygenation (ECMO). RECENT FINDINGS: There is paucity of data examining management options for cardiogenic shock (CS) in women specifically. In published data, although only a minority of MCS recipients (33%) were women, there is a trend toward even lower use in women relative to men over time. Women presenting with CS tend to have a higher risk profile including older age, greater comorbidities, higher Society of Cardiothoracic Surgery (STS) mortality scores, more hypotension and index vasopressor requirements, and longer duration of CS. Overall, women receiving mechanical support suffer increased bleeding and vascular complications and have higher 30-day readmission rates. The incidence of cardiogenic shock (CS) has been rising at a higher rate in women compared to men. Women in CS tend to present with an overall higher risk profile including older age, greater burden of medical comorbidities, more hypotension and index vasopressor requirements, higher STS mortality scores, and more out-of-hospital cardiac arrest. After adjusting for comorbidities and traditional cardiovascular risk factors, mortality remained higher in younger women compared to men of similar age. In spite of these facts, evidence points to the underutilization of support devices in eligible female patients. Higher complication rates, such as vascular complications requiring surgery and bleeding requiring transfusion, may be deterring factors that limit the use of MCS and hinderoperator confidence and experience with devices in women. This suggests that future research should address the sex disparities in outcomes of contemporary MCS practices.

Unusual recurrence of breast cancer in a BRCA-variant patient after fat grafting.

The oncologic safety of fat grafting procedures remains well-characterized in the recent literature; however, we recommend exercising vigilance when evaluating BRCA-positive and other patients at higher oncologic risk after reconstruction and fat grafting, whose cancer recurrence diagnosis may pose significant clinical challenges.

Methylene blue attenuates traumatic brain injury-associated neuroinflammation and acute depressive-like behavior in mice.

Traumatic brain injury (TBI) is associated with cerebral edema, blood brain barrier breakdown, and neuroinflammation that contribute to the degree of injury severity and functional recovery. Unfortunately, there are no effective proactive treatments for limiting immediate or long-term consequences of TBI. Therefore, the objective of this study was to determine the efficacy of methylene blue (MB), an antioxidant agent, in reducing inflammation and behavioral complications associated with a diffuse brain injury. Here we show that immediate MB infusion (intravenous; 15-30 minutes after TBI) reduced cerebral edema, attenuated microglial activation and reduced neuroinflammation, and improved behavioral recovery after midline fluid percussion injury in mice. Specifically, TBI-associated edema and inflammatory gene expression in the hippocampus were significantly reduced by MB at 1 d post injury. Moreover, MB intervention attenuated TBI-induced inflammatory gene expression (interleukin [IL]-1ß, tumor necrosis factor α) in enriched microglia/macrophages 1 d post injury. Cell culture experiments with lipopolysaccharide-activated BV2 microglia confirmed that MB treatment directly reduced IL-1ß and increased IL-10 messenger ribonucleic acid in microglia. Last, functional recovery and depressive-like behavior were assessed up to one week after TBI. MB intervention did not prevent TBI-induced reductions in body weight or motor coordination 1-7 d post injury. Nonetheless, MB attenuated the development of acute depressive-like behavior at 7 d post injury. Taken together, immediate intervention with MB was effective in reducing neuroinflammation and improving behavioral recovery after diffuse brain injury. Thus, MB intervention may reduce life-threatening complications of TBI, including edema and neuroinflammation, and protect against the development of neuropsychiatric complications.

Indoleamine 2,3-dioxygenase inhibition attenuates lipopolysaccharide induced persistent microglial activation and depressive-like complications in fractalkine receptor (CX(3)CR1)-deficient mice.

An impaired ability to regulate the activation of microglia by fractalkine (CX3CL1) leads to persistent neuroinflammation and behavioral alterations following lipopolysaccharide (LPS) challenge. While these responses are usually transient, LPS injection caused prolonged depressive-like behavior in fractalkine receptor deficient mice (CX3CR1(-/-)) that was associated with exaggerated microglial activation and induction of the tryptophan (TRP) degrading enzyme indoleamine 2,3-dioxygenase (IDO). IDO activation and subsequent generation of neuroactive kynurenine metabolites may have a pivotal role in the development of depression. Therefore, the purpose of this study was to determine the extent to which LPS-induced depressive-like behavior in CX3CR1(-/-) mice was dependent on IDO activation. CX3CR1(-/-) mice were implanted prior to LPS challenge with a slow release pellet of 1-methyl-tryptophan (1-MT), a competitive inhibitor of IDO. Here we show that the depressive-like behavior evident in CX3CR1(-/-) mice 72 h after LPS injection was abrogated by inhibition of IDO. LPS also decreased body weight and locomotor activity in CX3CR1(-/-) mice, but these effects were independent of 1-MT. Consistent with the increased metabolism of TRP by IDO, the ratio of 3-hydroxykynurenine (3-HK) to TRP was increased in the brain 72 h after LPS. Increased serotonin (5-HT) turnover was also evident in the brain. The LPS-associated increases in both 3-HK:TRP and 5-HIAA:5-HT ratios were prevented by the inhibition of IDO. Last, IDO blockade attenuated microglial activation in the prefrontal cortex and hippocampus 72 h after LPS. Collectively these data indicate that LPS-induced IDO activation contributes to persistent microglial activation and depressive-like behavior in CX3CR1(-/-) mice.