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Peripartum cardiomyopathy (PPCM) is an idiopathic form of pregnancy-induced heart failure associated with preeclampsia. Circulating factors in late pregnancy are thought to contribute to both diseases, suggesting a common underlying pathophysiological process. However, what drives this process remains unclear. Using serum proteomics, we identified the senescence-associated secretory phenotype (SASP), a marker of cellular senescence associated with biological aging, as the most highly up-regulated pathway in young women with PPCM or preeclampsia. Placentas from women with preeclampsia displayed multiple markers of amplified senescence and tissue aging, as well as overall increased gene expression of 28 circulating proteins that contributed to SASP pathway enrichment in serum samples from patients with preeclampsia or PPCM. The most highly expressed placental SASP factor, activin A, was associated with cardiac dysfunction or heart failure severity in women with preeclampsia or PPCM. In a murine model of PPCM induced by cardiomyocyte-specific deletion of the gene encoding peroxisome proliferator–activated receptor γ coactivator-1α, inhibiting activin A signaling in the early postpartum period with a monoclonal antibody to the activin type II receptor improved heart function. In addition, attenuating placental senescence with the senolytic compound fisetin in late pregnancy improved cardiac function in these animals. These findings link senescence biology to cardiac dysfunction in pregnancy and help to elucidate the pathogenesis underlying cardiovascular diseases of pregnancy. Editor's summary: Peripartum cardiomyopathy is a form of heart failure linked to preeclampsia. Roh et al. found that secreted proteins associated with senescence, a process linked to aging and cellular stress, were increased in sera from patients with peripartum cardiomyopathy or preeclampsia. Placentas from patients with preeclampsia also had elevated gene expression and tissue signatures of senescence. The most up-regulated senescence-associated secretory protein, activin A, was associated with worse heart function in human pregnancy cohorts that included patients with peripartum cardiomyopathy or preeclampsia. In a mouse model of peripartum cardiomyopathy with the peroxisome proliferator–activated receptor γ coactivator-1α gene deleted in cardiomyocytes, placentas also showed an amplified senescence phenotype. Treating these mice with the senolytic compound fisetin during mid to late pregnancy reduced placental senescence and improved heart function. Treatment with a monoclonal antibody directed against the activin type II receptor similarly improved heart function. These findings suggest that cardiovascular diseases of pregnancy could be targeted through reducing pathological cellular senescence in the placenta. —Brandon Berry [ABSTRACT FROM AUTHOR]

Objective: Airborne spread of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) remains a significant risk for healthcare workers. Understanding transmission of SARS‐CoV‐2 in the hospital could help minimize nosocomial infection. The objective of this pilot study was to measure aerosolization of SARS‐CoV‐2 in the hospital rooms of COVID‐19 patients. Methods: Two air samplers (Inspirotec) were placed 1 and 4 m away from adults with SARS‐CoV‐2 infection hospitalized at an urban, academic tertiary care center from June to October 2020. Airborne SARS‐CoV‐2 concentration was measured by quantitative reverse transcription polymerase chain reaction and analyzed by clinical parameters and patient demographics. Results: Thirteen patients with COVID‐19 (eight females [61.5%], median age: 57 years old, range 25–82) presented with shortness of breath (100%), cough (38.5%) and fever (15.4%). Respiratory therapy during air sampling varied: mechanical ventilation via endotracheal tube (n = 3), high flow nasal cannula (n = 4), nasal cannula (n = 4), respiratory helmet (n = 1), and room air (n = 1). SARS‐CoV‐2 RNA was identified in rooms of three out of three intubated patients compared with one out of 10 of the non‐intubated patients (p =.014). Airborne SARS‐CoV‐2 tended to decrease with distance (1 vs. 4 m) in rooms of intubated patients. Conclusions: Hospital rooms of intubated patients had higher levels of aerosolized SARS‐CoV‐2, consistent with increased aerosolization of virus in patients with severe disease or treatment with positive pressure ventilation through an endotracheal tube. While preliminary, these data have safety implications for health care workers and design of protective measures in the hospital. Level of Evidence: 2 [ABSTRACT FROM AUTHOR]

Study Objective: To identify risk factors for pediatric postoperative respiratory failure and develop a predictive model. Design: This retrospective case--control study utilized the US National Inpatient Sample (NIS) from 2012 to 2014. Significant predictors were selected, and the predicted probability of pediatric postoperative respiratory failure was calculated. Sensitivity, specificity, and accuracy were then calculated, and receiver--operator curves were drawn. Setting: National Inpatient Sample data sets from years 2012, 2013, and 2014 were used. Patients: Patients aged 17 and younger in the 2012, 2013, and 2014 NIS data sets. Interventions: Candidate predictors included demographic variables, type of surgical procedure, a modified pediatric comorbidity score, presence of substance abuse diagnosis, and presence/absence of kyphoscoliosis. Measurements: The primary outcome measure was the pediatric quality indicator (PDI 09), which is defined by the Agency for Healthcare Research Quality, and identifies pediatric patients with postoperative respiratory failure. Main Results: The incidence of pediatric postoperative respiratory failure in each year's data set varied from 1.31% in 2012 to 1.41% in 2014. Significant risk factors for the development of postoperative respiratory failure included abdominal surgery ([OR] = 1.92 in 2012 data set, 1.79 in 2013 data set), spine surgery (OR = 7.10 in 2012 data set, 6.41 in 2013 data set), and an elevated pediatric comorbidity score (score of 3 or greater: OR = 32.58 in 2012 data set, 22.74 in 2013 data set). A predictive model utilizing these risk factors achieved a C statistic of 0.82. Conclusions: Risk factors associated with postoperative respiratory failure in pediatric patients undergoing noncardiac surgery include type of surgery (abdominal and spine) and higher pediatric comorbidity scores. A prediction model based on the identified factors had good predictive ability. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the analytical and clinical performance of the Truvian Easy Check coronavirus disease 2019 (COVID-19) IgM/IgG anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody test.Serologic assays have become increasingly available for surveillance through the Food and Drug Administration emergency use authorization in the ongoing COVID-19 global pandemic. However, widespread application of serologic assays has been curbed by reports of faulty or inaccurate tests. Therefore, rapid COVID-19 antibody tests need to be thoroughly validated prior to their implementation.Methods: The Easy Check device was analytically evaluated and its performance was compared with the Roche Elecsys anti-SARS-CoV-2 antibody assay. The test was further characterized for cross-reactivity using sera obtained from patients infected by other viruses. Clinical performance was analyzed with polymerase chain reaction-confirmed samples and a 2015 prepandemic reference sample set.Results: The Easy Check device showed excellent analytical performance and compares well with the Roche Elecsys antibody assay, with an overall concordance of 98.6%. Clinical performance showed a sensitivity of 96.6%, a specificity of 98.2%, and an overall accuracy of 98.1%.Conclusions: The Easy Check device is a simple, reliable, and rapid test for detection of SARS-CoV-2 seropositivity, and its performance compares favorably against the automated Roche Elecsys antibody assay. [ABSTRACT FROM AUTHOR]

Many medications commonly used in the perioperative setting have well-known pharmacogenomic associations, and interindividual variability in responses can lead to decreased efficacy and/or adverse drug events (ADEs), resulting in devastating patient morbidity and mortality. Patient exclusion criteria include (i) patients who have undergone, or are being actively considered for, liver or kidney transplantation; (ii) patients with known active or prior leukemia; and (iii) patients who are unable to understand and give informed consent to participate. For both arms, all medications prescribed/administered will be tracked and patients will be monitored through the course of their perioperative care to determine the occurrence of pharmacogenomic-related drug toxicity and efficacy through medical record review. Each summary will employ our traffic light iconography - red "warning", yellow "caution", and green "favorable" lights - to provide physicians patient-specific recommendations of each drug-gene pair. [Extracted from the article]

Purpose: Our prospective, randomized clinical study aims to evaluate the utility of intraoperative transesophageal echocardiography (TEE) in patients undergoing radical cystectomy.Materials and Methods: Eighty patients were randomized to a standard of care group or the intervention group that received continuous intraoperative TEE. Data are presented as means ± standard deviations, median (25th percentile, 75th percentile), or numbers and percentages. Characteristics were compared between groups using independent sample t-tests, Wilcoxon-Mann-Whitney tests or Chi-square tests, as appropriate. All tests were two-sided and P < 0.05 was considered to indicate statistical significance.Results: Both groups had similar preoperative demographic characteristics. There was a significant difference between central line insertion with all insertions in the control group (15%, 6 vs. 0%, 0; P < 0.003). Of all the perioperative complications, 80% occurred in the control group versus 20% in the TEE group, with 21% of controls experiencing a cardiac or pulmonary complication compared to 5% in the TEE group (8 vs. 2, P < 0.04). The control group patients were more likely to have adverse cardiac complications than the TEE group (15%, 6 vs. 3%, 1; P < 0.040). Postoperative cardiac arrhythmia was observed only in the control group (13%, 5 vs. 0%, 0; P <.007). Prolonged intubation was only observed in the control group (10%, 4 vs. 0%, 0; P < 0.017).Conclusion: TEE can be a useful monitoring tool in patients undergoing radical cystectomy, limiting the use of central line insertion and potentially translating into earlier extubation and decreased postoperative cardiac morbidities. [ABSTRACT FROM AUTHOR]

Background: Despite showing a prognostic value in general surgical patients, preoperative asymptomatic elevated white blood cell (WBC) count is not considered a risk factor for cardiac surgery. Whereas there is sporadic evidence of its value as a preoperative risk marker, it has not been looked at methodically as a specific index of outcome during cardiac surgery. Using a national database we sought to determine the relationship between preoperative WBC count and postoperative outcome in cardiac surgical patients. Methods: Cardiac surgeries were extracted from the 2007–2013 American College of Surgeons National Surgical Quality Improvement Program database. Leukocytosis was defined by a preoperative WBC count greater than 11,000 cells/μL. A univariate analysis compared the incidence of adverse outcomes for patients with and without leukocytosis. A multivariate logistic regression model was constructed in order to test whether leukocytosis was an independent predictor of morbidity and mortality. Results: Out of a total of 10,979 cardiac surgery patients 863 (7.8%) had preoperative leukocytosis. On univariate analysis, patients with leukocytosis experienced greater incidences of 30-day mortality, wound complications, and medical complications. Wound complications included surgical site infection as well as wound dehiscence. The medical complications included all other non-surgical causes of increased morbidity and infection leading to urinary tract infection, pneumonia, ventilator dependence, sepsis and septic shock. After stepwise model adjustment, leukocytosis was a strong predictor of medical complications (OR 1.22, 95% CI: 1.09–1.36, p = 0.002) with c-statistic of 0.667. However, after stepwise model adjustment leukocytosis was not a significant predictor of 30-day mortality and wound complications. Conclusion: Preoperative leukocytosis is associated with adverse postoperative outcome after cardiac surgery and is an independent predictor of infection-related postoperative complications. [ABSTRACT FROM AUTHOR]

Objective: To study the association between cardiac function measured by myocardial performance index (MPI), blood pressures and angiogenic factors measured at the time of echocardiography in patients with and without hypertensive disorders of pregnancy (HDP).Methods: We prospectively studied 189 pregnant women and evaluated whether changes in cardiac function observed on echocardiography were correlated with higher blood pressures and whether higher blood pressures were associated with antiangiogenic proteins (soluble fms-like tyrosine kinase, sFlt1; soluble endoglin, sEng). Comprehensive echocardiograms, including measurement of MPI, were performed on all patients. sFlt1 and sEng levels were measured using enzyme-linked immunosorbent assay.Results: Overall, 189 patients were divided into tertiles based on mean arterial pressure (MAP). The MPI was worst in tertile 3 (0.50 ± 0.15) compared to tertile 1 (0.42 ± 0.10), p = 0.0004. sFlt1 (pg/ml) and sEng (ng/ml) were highest in tertile 3 compared to tertile 1: 15055.37 vs. 1623.01 and 33.06 vs. 8.15, respectively, with p-value <0.001. In crude multivariate regression analysis, MAP was positively correlated with MPI (r = 0.32, p < 0.001), GLS (r = 0.54, p < 0.001), sFlt1 (r = 0.60, p < 0.001) and sEng (r = 0.61, p < 0.001). After adjustment for confounders, these relationships persisted between MAP and MPI (r = 0.31, p = 0.0003), GLS (r = 0.46, p < 0.001), sFlt1 (r = 0.56, p < 0.001) and sEng (r = 0.58, p < 0.001).Conclusion: Mean arterial pressure correlates with worsening cardiac function as measured by MPI and serum levels of angiogenic factors. Further studies are needed to evaluate whether a reduction in blood pressure will reverse changes in MPI or reduce levels of angiogenic proteins seen among women with HDP. [ABSTRACT FROM AUTHOR]

Objective: Cardiogenic shock (CS) may occur during pregnancy and dramatically worsen peripartum outcomes.Methods: We analyzed the National Inpatient Sample from 2002 to 2013 to describe the incidence of, risk factors for and outcomes of CS during pregnancy.Results: Of the 53,794,192 hospitalizations analyzed, 2044 were complicated by CS. The mortality rate in peripartum women with CS was 18.81% versus 0.02% without. It occurs more often during postpartum (58.83%) as compared with delivery (23.47%) or antepartum (17.70%) hospitalizations. Factors associated with CS -related death included cardiac arrest, renal failure, and sepsis.Conclusions: CS during pregnancy occurs more commonly in the postpartum period and is associated with a high mortality. [ABSTRACT FROM AUTHOR]

Background: In sepsis, tachycardia may indicate low preload, adrenergic stimulation, or both. Adrenergic overstimulation is associated with septic cardiomyopathy. We sought to determine whether tachycardia was associated with left ventricular longitudinal strain, a measure of cardiac dysfunction. We hypothesized an association would primarily exist in patients with high preload. Methods: We prospectively observed septic patients admitted to three study ICUs, who underwent early transthoracic echocardiography. We measured longitudinal strain using speckle tracking echocardiography and estimated preload status with an echocardiographic surrogate ( E/ e′). We assessed correlation between strain and heart rate in patients with low preload ( E/ e′ < 8), intermediate preload ( E/ e′ 8-14), and high preload ( E/ e′ > 14), adjusting for disease severity and vasopressor dependence. Results: We studied 452 patients, of whom 298 had both measurable strain and preload. Abnormal strain (defined as >−17%) was present in 54%. Patients with abnormal strain had higher heart rates (100 vs. 93 beat/min, p = 0.001). After adjusting for vasopressor dependence, disease severity, and cardiac preload, we observed an association between heart rate and longitudinal strain ( β = 0.05, p = 0.003). This association persisted among patients with high preload ( β = 0.07, p = 0.016) and in patients with shock ( β = 0.07, p = 0.01), but was absent in patients with low or intermediate preload and those not in shock. Conclusions: Tachycardia is associated with abnormal left ventricular strain in septic patients with high preload. This association was not apparent in patients with low or intermediate preload. [ABSTRACT FROM AUTHOR]

Background: Septic shock is a common and often devastating syndrome marked by severe cardiovascular dysfunction commonly managed with vasopressors. Whether markers of heart rate complexity before vasopressor up-titration could be used to predict success of the up-titration is not known. Methods: We studied patients with septic shock requiring vasopressor, newly admitted to the intensive care unit. We measured the complexity of heart rate variability (using the ratio of fractal exponents from detrended fluctuation analysis) in the 5 min before all vasopressor up-titrations in the first 24 h of an intensive care unit (ICU) admission. A successful up-titration was defined as one that did not require further up-titration (or decrease in mean arterial pressure) for 60 min. Results: We studied 95 patients with septic shock, with a median APACHE II of 27 (IQR: 20-37). The median number of up-titrations, normalized to 24 h, was 12.2 (IQR: 8-17) with a maximum of 49. Of the up-titrations, the median proportion of successful interventions was 0.28 (IQR: 0.12-0.42). The median of mean arterial pressure (MAP) at the time of a vasopressor up-titration was 66 mmHg; the average infusion rate of norepinephrine at the time of an up-titration was 0.11 mcg/kg/min. The ratio of fractal exponents was not associated with successful up-titration on univariate or multivariate regression. On exploratory secondary analyses, however, the long-term fractal exponent was associated (p = 0.003) with success of up-titration. Independent of heart rate variability, MAP was associated (p < 0.001) with success of vasopressor up-titration, while neither Sequential Organ Failure Assessment (SOFA) nor Acute Physiology and Chronic Health Evaluation II (APACHE II) score was associated with vasopressor titration. Conclusions: Only a third of vasopressor up-titrations were successful among patients with septic shock. MAP and the long-term fractal exponent were associated with success of up-titration. These two, complementary variables may be important to the development of rational vasopressor titration protocols. [ABSTRACT FROM AUTHOR]

Objective: The mechanisms leading to worse outcomes in African-American (AA) women with preeclampsia/eclampsia remain unclear. Our objective was to identify racial differences in maternal comorbidities, peripartum characteristics, and maternal and fetal outcomes.Methods/results: When compared to white women with preeclampsia/eclampsia, AA women had an increased unadjusted risk of inpatient maternal mortality (OR 3.70, 95% CI: 2.19-6.24). After adjustment for covariates, in-hospital mortality for AA women remained higher than that for white women (OR 2.85, 95% CI: 1.38-5.53), while the adjusted risk of death among Hispanic women did not differ from that for white women. We also found an increased risk of intrauterine fetal death (IUFD) among AA women. When compared to white women with preeclampsia, AA women had an increased unadjusted odds of IUFD (OR 2.78, 95% CI: 2.49-3.11), which remained significant after adjustment for covariates (adjusted OR 2.45, 95% CI: 2.14-2.82). In contrast, IUFD among Hispanic women did not differ from that for white women after adjusting for covariates.Conclusions and Relevance: Our data suggest that African-American women are more likely to have risk factors for preeclampsia and more likely to suffer an adverse outcome during peripartum care. Future research should examine whether controlling co-morbidities and other risk factors will help to alleviate racial disparities in outcomes in this cohort of women. [ABSTRACT FROM AUTHOR]

Background: Maternal cardiopulmonary arrest is a rare but often fatal emergency. The authors used a modified Delphi method to create a checklist of tasks for practitioners.Methods: Within each round, experts ranked tasks on a scale from zero through five. Consensus was defineda priorias 80% exact agreement.Results: Three rounds were required to achieve consensus resulting in a checklist of 45 tasks. Round One results revealed five tasks, Round Two included 25 tasks, and Round Three resulted in 29 tasks with 80% exact agreement.Conclusions: The modified Delphi method resulted in a weighted scoring system that can be used to objectively assess team performance. [ABSTRACT FROM AUTHOR]

Importance: The association between hospital volume and inpatient mortality for severe sepsis is unclear. Objective: To assess the effect of severe sepsis case volume and inpatient mortality. Design Setting and Participants: Retrospective cohort study from 646,988 patient discharges with severe sepsis from 3,487 hospitals in the Nationwide Inpatient Sample from 2002 to 2011. Exposures: The exposure of interest was the mean yearly sepsis case volume per hospital divided into tertiles. Main Outcomes and Measures: Inpatient mortality. Results: Compared with the highest tertile of severe sepsis volume (>60 cases per year), the odds ratio for inpatient mortality among persons admitted to hospitals in the lowest tertile (≤10 severe sepsis cases per year) was 1.188 (95% CI: 1.074–1.315), while the odds ratio was 1.090 (95% CI: 1.031–1.152) for patients admitted to hospitals in the middle tertile. Similarly, improved survival was seen across the tertiles with an adjusted inpatient mortality incidence of 35.81 (95% CI: 33.64–38.03) for hospitals with the lowest volume of severe sepsis cases and a drop to 32.07 (95% CI: 31.51–32.64) for hospitals with the highest volume. Conclusions and Relevance: We demonstrate an association between a higher severe sepsis case volume and decreased mortality. The need for a systems-based approach for improved outcomes may require a high volume of severely septic patients. [ABSTRACT FROM AUTHOR]

Mediators of cardiac injury in preeclampsia are not well understood. Preeclamptic women have decreased cardiac global longitudinal strain (GLS), a sensitive measure of systolic function that indicates fibrosis and tissue injury. GLS is worse in preeclampsia compared to gestational hypertension, despite comparable blood pressure, suggesting that placental factors may be involved. We previously showed that Activin A, a pro-fibrotic factor produced in excess by the placenta in preeclampsia, predicts impaired GLS postpartum. Here, we hypothesized that chronic excess levels of Activin A during pregnancy induces cardiac dysfunction. Rats were assigned to sham or activin A infusion (1.25–6 µg/day) on a gestational day (GD) 14 (n = 6–10/group). All animals underwent blood pressure measurement and comprehensive echocardiography followed by euthanasia and the collection of tissue samples on GD 19. Increased circulating activin A (sham: 0.59 ± 0.05 ng/mL, 6 µg/day: 2.8 ± 0.41 ng/mL, p < 0.01) was associated with impaired GLS (Sham: −22.1 ± 0.8%, 6 µg/day: −14.7 ± 1.14%, p < 0.01). Activin A infusion (6 µg/day) increased beta-myosin heavy chain expression in heart tissue, indicating cardiac injury. In summary, our findings indicate that increasing levels of activin A during pregnancy induces cardiac dysfunction and supports the concept that activin A may serve as a possible mediator of PE-induced cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1?, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1?. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM. [ABSTRACT FROM AUTHOR]

. (J Card Surg 2011;26:177-180) [ABSTRACT FROM AUTHOR]