Ribosomal S6 kinase 4 (RSK4) tumor suppressor gene promoter methylation status in ovarian cancer.

BACKGROUND: Previously, we reported lower RSK4 mRNA and protein levels in malignant ovarian tumors compared to normal and benign ovarian tissues. Also, we observed a significant inverse correlation between the advanced ovarian cancer stages and RSK4 mRNA levels. We did not investigate the mechanisms involved in RSK4-reduced expression in ovarian cancer. Thus, this study investigates whether RSK4 promoter methylation in ovarian cancer tissues is responsible for its low expression. Additionally, the reactivation of RSK4 expression and its effect was studied in ovarian cancer cell lines. METHODS AND RESULTS: RSK4 promoter methylation percentage in malignant and benign ovarian tumors and normal ovary tissues was determined by combined bisulfite restriction analysis. The reactivation of RSK4 expression by decitabine treatment was studied in OVCAR3, SKOV3, TOV-112D, and TOV-21G cells by Western blotting. Cell proliferation was determined by XTT. A significantly high methylation percentage of the RSK4 promoter was observed among malignant and benign ovarian tumors but not in normal ovarian tissue. RSK4 promoter methylation was not associated with age, histological subtype, or stages of ovarian cancer. RSK4 promoter methylation correlates weakly but not significantly with RSK4 protein expression. No correlation was shown between RSK4 methylation and RSK4 mRNA expression. Decitabine induces RSK4 reactivation in all cell lines. However, cell proliferation was reduced only in TOV-112D cells. CONCLUSION: These data indicate that although RSK4 promoter methylation is increased in malignant ovarian tumors, this mechanism is unlikely to regulate its expression in ovarian cancer. RSK4 reactivation reduced cell proliferation only in the endometroid histological subtype.

Evaluation of genetic alterations in hereditary cancer susceptibility genes in the Ashkenazi Jewish women community of Mexico.

Background: Individuals of Ashkenazi Jewish ancestry have been identified as having higher prevalence of specific pathogenic variants associated with susceptibility to specific rare and chronic diseases. In Mexico, the prevalence and composition of rare cancer predisposing germline variants in Ashkenazi Jewish individuals has not been evaluated. Aim and methods: We aimed to evaluate the prevalence of pathogenic variants by massive parallel sequencing in a panel of 143 cancer-predisposing genes in 341 women from the Ashkenazi Jewish community of Mexico, who were contacted and invited to participate in the study through the ALMA Foundation for Cancer Reconstruction. Pre- and posttest genetic counseling was given and a questionnaire on personal, gyneco-obstetric, demographic and lifestyle variables was conducted. From peripheral blood DNA, the complete coding region, and splicing sites of a panel of 143 cancer susceptibility genes, including 21 clinically relevant genes, were sequenced. The Mexican founder mutation BRCA1 ex9-12del [NC_000017.10(NM_007294):c. (825+1-826-1)_(4,589+1-4,590-1)del] was also evaluated. Results: Among study participants (mean age ±standard deviation: 47 ± 14) 15% reported a personal history of cancer (50/341). Fourteen percent of participants (48/341) were carriers of pathogenic and likely pathogenic variants distributed among seven high-risk genes (APC, CHEK2, MSH2, BMPR1A, MEN1, MLH1, and MSH6), whereas 18.2% (62/341) had variants of uncertain clinical significance in genes associated with breast and ovarian cancer susceptibility (list of genes with VUS). Pathogenic and likely pathogenic variants in 16 susceptibility genes with ambiguous or non-well-established risk association for cancer were detected in 17.6% (60/341) of participants. Sixty four percent of participants reported current alcohol consumption compared with the 39 percent prevalence of alcohol consumption in Mexican women. None of the participants carried the recurrent Ashkenazi and Mexican founder mutations in BRCA1 or BRCA2, but 2% (7/341) had pathogenic Ashkenazi Jewish founder variants in BLM. Conclusion: Our findings show a diverse pathogenic variant composition among the recruited individuals of Ashkenazi Jewish ancestry in Mexico consistent with being a high-risk population for genetic diseases, which warrants further investigation to adequately assess the burden of hereditary breast cancer in this group and implement appropriate preventative programs.

Coronary artery bypass grafting after acute ST-elevation myocardial infarction.

OBJECTIVES: The study objectives were to describe the trends and outcomes of isolated coronary artery bypass grafting after ST-elevation myocardial infarction using a nationwide database. METHODS: We queried the 2002-2016 National Inpatient Sample database for hospitalized patients with ST-elevation myocardial infarction who underwent isolated coronary artery bypass grafting. We report temporal trends, predictors, and outcomes of coronary artery bypass grafting in the early (2002-2010) and recent (2011-2016) cohorts. RESULTS: Of 3,347,470 patients hospitalized for ST-elevation myocardial infarction, 7.7% underwent isolated coronary artery bypass grafting. The incidence of isolated coronary artery bypass grafting after ST-elevation myocardial infarction decreased over time (9.2% in 2002 vs 5.5% in 2016, Ptrend < .001), whereas perioperative crude in-hospital mortality did not change (5.1% in 2002 vs 4.2% in 2016, Ptrend = .66), coinciding with an increase in the burden of comorbidities. There was an increase in performing isolated coronary artery bypass grafting on hospitalization day 3 or more, as well as an increase in the use of mechanical support devices and precoronary artery bypass grafting percutaneous coronary intervention. In the early cohort, isolated coronary artery bypass grafting on days 1 and 2 was associated with higher in-hospital mortality. In the recent cohort, coronary artery bypass grafting on day 2 had similar in-hospital mortality compared with day 3 or more and lower rates of acute kidney injury, ischemic stroke, ventricular arrhythmia, and length of hospital stay. CONCLUSIONS: In this nationwide analysis, there has been a decline in the use of isolated coronary artery bypass grafting after ST-elevation myocardial infarction. Isolated coronary artery bypass grafting on day 1 was performed in sicker patients and was associated with higher in-hospital mortality than coronary artery bypass grafting performed on day 3 or more. In the recent cohort, isolated coronary artery bypass grafting on day 2 had similar in-hospital mortality compared with day 3 or more.

Evaluation of the Addition of Angiotensin II in Patients With Shock After Cardiac Surgery at a Veterans Affairs Medical Center.

BACKGROUND: Vasoplegic shock occurs in up to 37% of cardiac surgery patients. We investigated the use of angiotensin II for treating vasoplegic shock in these patients. OBJECTIVES: We assessed clinical outcomes and mortality in patients undergoing cardiac surgery at our center between March 1, 2018 and October 31, 2020 who developed vasoplegic shock, comparing those who received angiotensin II with those who did not. METHODS: This was a retrospective chart review. Response to angiotensin II was defined as increase in or maintenance of mean arterial pressure (MAP) and decrease in background vasopressor dosage. RESULTS: Angiotensin II was administered to 7 patients (postoperatively in 4 patients [57.1%]) with vasoplegic shock and baseline norepinephrine equivalent (NEE) of 0.49 ± 0.08 µg/kg/min; 12 patients with vasoplegic shock did not receive angiotensin II. Within 3 hours of angiotensin II administration, NEE decreased by 38.0 ± 33.1%. Angiotensin patients were more likely to newly require renal replacement therapy (66.7% vs 9.1%, P = 0.03) and had a longer, although not statistically significant, postoperative stay (23.1 vs 14.0 days, P = 0.16). Despite higher NEE requirements at baseline (0.49 vs 0.30, P = 0.03) and over the next 48 hours in the angiotensin group, no between-group differences in 7-day mortality (14.3% vs 0.0%, P = 0.37) or 30-day mortality (28.6% vs 8.3%, P = 0.52) were noted. CONCLUSION AND RELEVANCE: In patients who developed vasoplegic shock after cardiac surgery, angiotensin II administration allowed immediate dosage reductions of other vasopressors while maintaining MAP. Despite its small sample size, this study adds to the paucity of data in these patients and highlights future research needs.

Breast cancer prevention by short-term inhibition of TGFß signaling.

Cancer prevention has a profound impact on cancer-associated mortality and morbidity. We previously identified TGFß signaling as a candidate regulator of mammary epithelial cells associated with breast cancer risk. Here, we show that short-term TGFBR inhibitor (TGFBRi) treatment of peripubertal ACI inbred and Sprague Dawley outbred rats induces lasting changes and prevents estrogen- and carcinogen-induced mammary tumors, respectively. We identify TGFBRi-responsive cell populations by single cell RNA-sequencing, including a unique epithelial subpopulation designated secretory basal cells (SBCs) with progenitor features. We detect SBCs in normal human breast tissues and find them to be associated with breast cancer risk. Interactome analysis identifies SBCs as the most interactive cell population and the main source of insulin-IGF signaling. Accordingly, inhibition of TGFBR and IGF1R decrease proliferation of organoid cultures. Our results reveal a critical role for TGFß in regulating mammary epithelial cells relevant to breast cancer and serve as a proof-of-principle cancer prevention strategy.

Hypervirulence and Multiresistance to Antibiotics in Klebsiella pneumoniae Strains Isolated from Patients with Hospital- and Community-Acquired Infections in a Mexican Medical Center.

Klebsiella pneumoniae is a pathogenic bacterium associated with different infectious diseases. This study aimed to establish the different association profiles of virulence genes related to the hypermucoviscous phenotype (HM), capsular serotypes, biofilm formation, and multidrug resistance in K. pneumoniae strains from patients with hospital- and community-acquired infections. K. pneumoniae virulence genes and capsular serotypes were identified by PCR, antibiotic susceptibility by the Kirby-Bauer method, HM by the string test, and biofilm formation by measurement in polystyrene microtiter plates. Of a total of 150 strains from patients with hospital- (n = 25) and community-acquired infections (n = 125), 53.3% (80/150) were HM-positive and 46.7% (70/150) were HM-negative. HM-positive (68/80) and HM-negative (67/70) strains were biofilm-forming. Moreover, 58.7% (47/80) HM-positive and 57.1% (40/70) HM-negative strains were multidrug-resistant. Among HM-positive, HM-negative, and serotypes K1 (25/150), K2 (48/150), and non-K1/K2 strains, (77/150) the frequently detected adhesion genes were fimH, mrkD, ycfM, and kpn; entB, irp2, irp1, and ybtS, for iron acquisition; and rmpA for protectins. The gene association pattern fimH/kpn/mrkD/ycfM/entB/irp1/irp2/ybtS/fyuA (18/150) was frequent among the strains. K. pneumoniae strains from patients with hospital- and community-acquired infections demonstrated a wide diversity of virulence gene profiles related to phenotype (hypermucoviscosity, multidrug resistance, and biofilm formation) and serotypes.

Decongestion Models and Metrics in Acute Heart Failure: ESCAPE Data in the Age of the Implantable Cardiac Pressure Monitor.

The United States Food and Drug Administration restricts the use of implantable cardiac pressure monitors to patients with New York Heart Association (NYHA) class III heart failure (HF). We investigated whether single-pressure monitoring could predict survival in HF patients as part of a model constructed using data from the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial. We validated survival models in 204 patients, using all-cause 180-day mortality. Two levels of model complexity were tested: 1) a simplified 1-pressure model based on pulmonary artery mean pressure ([PAM]1P) (information obtainable from an implanted intracardiac monitor alone), and 2) a pair of 5-variable risk score models based on right atrial pressure (RAP) + pulmonary capillary wedge pressure (PCWP) ([RAP+PCWP]5V) and on RAP + PAM ([RAP+PAM]5V). The more complex models used 5 dichotomous variables: a congestion index above a certain threshold value, baseline systolic blood pressure of <100 mmHg, baseline blood urea nitrogen level of ≥ 34 mg/dL, need for cardiopulmonary resuscitation or mechanical ventilation, and posttreatment NYHA class IV status. The congestion index was defined as posttreatment RAP+PCWP or posttreatment RAP+PAM, with congestion thresholds of 34 and 42 mmHg, respectively (median pulmonary catheter indwelling time, 1.9 d). The 5-variable models predicted survival with areas under the curve of 0.868 for the (RAP+PCWP)5V model and 0.827 for the (RAP+PAM)5V model, whereas the 1-pressure model predicted survival with an area under the curve of 0.718. We conclude that decongestion as determined by hemodynamic assessment predicts survival in HF patients and that it may be the final pathway for treatment benefit despite improvements in pharmacologic intervention since the ESCAPE trial.

Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Patients <60 Years of Age.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an alternative therapeutic modality to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS). In the current analysis, we compare the characteristics and outcomes of AVR procedures in patients <60 years of age. METHODS: We queried the Nationwide Readmissions Database for all AVR hospitalizations in patients 18-59 years of age between January 2012 and December 2017. We performed a propensity score matching analysis (1:1) and compared baseline characteristics, procedural complications, and outcomes between TAVR and SAVR patients. RESULTS: A total of 72,356 hospitalizations for AVR were identified in patients <60 years of age. Compared to their SAVR counterparts, TAVR patients were older (52.5 ± 7.6) vs. 48.8 ± 9.6, p < 0.001), more likely to be women (37.9% vs. 28.0%, p < 0.001), and have history of prior radiation (8.3% vs. 0.7%, p < 0.001). After propensity score matching, TAVR patients had lower procedural complications, but a similar mortality rate compared to SAVR patients (2.9% vs. 3.0%, p = 0.77). TAVR was associated with a shorter length of hospital stay [4 [2-9] vs. 6 [5-11], p < 0.001), but no significant difference in the 30-day readmission rate was noted (16.2% vs. 16.8%, p-value = 0.49). CONCLUSION: Our study demonstrates favorable short-term outcomes in younger patients undergoing TAVR, which improved over time. Further investigation of long-term outcomes in TAVR performed younger patients is warranted to draw a comprehensive picture of TAVR safety and efficacy in low-risk patients.

Insights into Immune Escape During Tumor Evolution and Response to Immunotherapy Using a Rat Model of Breast Cancer.

Animal models are critical for the preclinical validation of cancer immunotherapies. Unfortunately, mouse breast cancer models do not faithfully reproduce the molecular subtypes and immune environment of the human disease. In particular, there are no good murine models of estrogen receptor-positive (ER+) breast cancer, the predominant subtype in patients. Here, we show that Nitroso-N-methylurea-induced mammary tumors in outbred Sprague-Dawley rats recapitulate the heterogeneity for mutational profiles, ER expression, and immune evasive mechanisms observed in human breast cancer. We demonstrate the utility of this model for preclinical studies by dissecting mechanisms of response to immunotherapy using combination TGFBR inhibition and PD-L1 blockade. Short-term treatment of early-stage tumors induced durable responses. Gene expression profiling and spatial mapping classified tumors as inflammatory and noninflammatory, and identified IFNγ, T-cell receptor (TCR), and B-cell receptor (BCR) signaling, CD74/MHC II, and epithelium-interacting CD8+ T cells as markers of response, whereas the complement system, M2 macrophage phenotype, and translation in mitochondria were associated with resistance. We found that the expression of CD74 correlated with leukocyte fraction and TCR diversity in human breast cancer. We identified a subset of rat ER+ tumors marked by expression of antigen-processing genes that had an active immune environment and responded to treatment. A gene signature characteristic of these tumors predicted disease-free survival in patients with ER+ Luminal A breast cancer and overall survival in patients with metastatic breast cancer receiving anti-PD-L1 therapy. We demonstrate the usefulness of this preclinical model for immunotherapy and suggest examination to expand immunotherapy to a subset of patients with ER+ disease. See related Spotlight by Roussos Torres, p. 672.

Low left ventricular ejection fraction, complication rescue, and long-term survival after coronary artery bypass grafting.

OBJECTIVES: To evaluate the association between low left ventricular ejection fraction (LVEF), complication rescue, and long-term survival after isolated coronary artery bypass grafting. METHODS: National cohort study of patients who underwent isolated coronary artery bypass grafting (2000-2016) using Veterans Affairs Surgical Quality Improvement Program data. Left ventricular ejection fraction was categorized as ≥35% (n = 55,877), 25%-34% (n = 3893), or <25% (n = 1707). Patients were also categorized as having had no complications, 1 complication, or more than 1 complication. The association between LVEF, complication rescue, and risk of death was evaluated with multivariable Cox regression. RESULTS: Among 61,477 patients, 6586 (10.7%) had a perioperative complication and 2056 (3.3%) had multiple complications. Relative to LVEF ≥35%, decreasing ejection fraction was associated with greater odds of complications (25%-34%, odds ratio, 1.30 [1.18-1.42]; <25%, odds ratio, 1.65 [1.43-1.92]). There was a dose-response relationship between decreasing LVEF and overall risk of death (≥35% [ref]; 25%-35%, hazard ratio, 1.46 [1.37-1.55]; <25%, hazard ratio, 1.68 [1.58-1.79]). Among patients who were rescued from complications, there were decreases in 10-year survival, regardless of LVEF. Among those rescued after multiple complications, LVEF was no longer associated with risk of death. CONCLUSIONS: While decreasing LVEF is associated with post-coronary artery bypass grafting complications, patients rescued from complications have worse long-term survival, regardless of left ventricular function. Prevention and timely treatment of complications should remain a focus of quality improvement initiatives, and future work is needed to mitigate their long-term detrimental impact on survival.

Left Ventricle Mass Regression After Surgical or Transcatheter Aortic Valve Replacement in Veterans.

BACKGROUND: Differences in left ventricular mass regression (LVMR) between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) have not been studied. We present clinical and echocardiographic data from veterans who underwent TAVR and SAVR, evaluating the degree of LVMR and its association with survival. METHODS: We retrospectively reviewed TAVR (n = 194) and SAVR (n = 365) procedures performed in veterans from 2011 to 2019. After 1:1 propensity matching, we evaluated mortality and secondary outcomes. Echocardiographic data (median follow-up 957 days, interquartile range 483-1652 days) were used to evaluate LVMR, its association with survival, and predictors of LVMR. RESULTS: There was no difference between SAVR and TAVR patients in mortality (for up to 8 years), stroke at 30 days, myocardial infarction, renal failure, prolonged ventilation, reoperation, or structural valve deterioration. SAVR patients (67.3% [101 of 150]) were more likely to have LVMR than TAVR patients (55.7% [44 of 79], P = .11). The magnitude of LVMR was greater for the SAVR patients (median, -23.3%) than for the TAVR patients (median, -17.8%, P = .062). SAVR patients with LVMR had a survival advantage over SAVR patients without LVMR (P = .016). However, LVMR was not associated with greater survival in TAVR patients (P = .248). CONCLUSIONS: SAVR patients were more likely to have LVMR and had a greater magnitude of LVMR than TAVR patients. LVMR was associated with better survival in SAVR patients, but not in TAVR patients.

Demographic Landscape of Cardiothoracic Surgeons and Residents at United States Training Programs.

BACKGROUND: Recruiting and promoting women and racial/ethnic minorities could help enhance diversity and inclusion in the academic cardiothoracic (CT) surgery workforce. However, the demographics of trainees and faculty at US training programs have not yet been studied. METHODS: Traditional, integrated (I-6), and fast-track (4+3) programs listed in the Accreditation Council for Graduate Medical Education (ACGME) public database were analyzed. Demographics of trainees and surgeons, including gender, race/ethnicity, subspecialty, and academic appointment (if applicable), were obtained from ACGME Data Resource Books, institutional websites, and public profiles. Chi-square and Cochran-Armitage trend tests were performed. RESULTS: In July 2020, 78 institutions had at least 1 CT surgery training program; 40 (51%) had only a traditional program, 20 (26%) traditional and I-6, 6 (8%) all 3 types of program, and 4 (5%) only I-6. The proportion of female trainees increased significantly from 2011 to 2019 (19% vs 24%, P < .001), with female I-6 trainees outnumbering female traditional trainees since 2018. Significant increases by race/ethnicity were observed overall and by program type, notably for Asian and Hispanic individuals in I-6 programs and Black individuals in traditional programs. Finally, of the 1175 CT surgeons identified, 633 (54%) were adult cardiac surgeons, 360 (37%) assistant professors, 116 (10%) women, and 33 (3%) Black. CONCLUSIONS: The demographic landscape of CT surgery trainees and faculty across multiple training pathways reflects increasing representation by gender and race/ethnicity. However, we must continue to work toward equitable representation in the workforce to benefit the diverse patients we treat.

High Virulence and Multidrug Resistance of Escherichia coli Isolated in Periodontal Disease.

Periodontal disease is caused by different gram-negative anaerobic bacteria; however, Escherichia coli has also been isolated from periodontitis and its role in periodontitis is less known. This study aimed to determine the variability in virulence genotype, antibiotic resistance phenotype, biofilm formation, phylogroups, and serotypes in different emerging periodontal strains of Escherichia coli, isolated from patients with periodontal disease and healthy controls. E. coli, virulence genes, and phylogroups, were identified by PCR, antibiotic susceptibility by the Kirby-Bauer method, biofilm formation was quantified using polystyrene microtiter plates, and serotypes were determined by serotyping. Although E. coli was not detected in the controls (n = 70), it was isolated in 14.7% (100/678) of the patients. Most of the strains (n = 81/100) were multidrug-resistance. The most frequent adhesion genes among the strains were fimH and iha, toxin genes were usp and hlyA, iron-acquisition genes were fyuA and irp2, and protectin genes were ompT, and KpsMT. Phylogroup B2 and serotype O25:H4 were the most predominant among the strains. These findings suggest that E. coli may be involved in periodontal disease due to its high virulence, multidrug-resistance, and a wide distribution of phylogroups and serotypes.

Cis-Acting Factors Causing Secondary Epimutations: Impact on the Risk for Cancer and Other Diseases.

Epigenetics affects gene expression and contributes to disease development by alterations known as epimutations. Hypermethylation that results in transcriptional silencing of tumor suppressor genes has been described in patients with hereditary cancers and without pathogenic variants in the coding region of cancer susceptibility genes. Although somatic promoter hypermethylation of these genes can occur in later stages of the carcinogenic process, constitutional methylation can be a crucial event during the first steps of tumorigenesis, accelerating tumor development. Primary epimutations originate independently of changes in the DNA sequence, while secondary epimutations are a consequence of a mutation in a cis or trans-acting factor. Secondary epimutations have a genetic basis in cis of the promoter regions of genes involved in familial cancers. This highlights epimutations as a novel carcinogenic mechanism whose contribution to human diseases is underestimated by the scarcity of the variants described. In this review, we provide an overview of secondary epimutations and present evidence of their impact on cancer. We propose the necessity for genetic screening of loci associated with secondary epimutations in familial cancer as part of prevention programs to improve molecular diagnosis, secondary prevention, and reduce the mortality of these diseases.

The Evolution of Clinically Aggressive Triple-Negative Breast Cancer Shows a Large Mutational Diversity and Early Metastasis to Lymph Nodes.

In triple-negative breast cancer (TNBC), only 30% of patients treated with neoadjuvant chemotherapy achieve a pathological complete response after treatment and more than 90% die due to metastasis formation. The diverse clinical responses and metastatic developments are attributed to extensive intrapatient genetic heterogeneity and tumor evolution acting on this neoplasm. In this work, we aimed to evaluate genomic alterations and tumor evolution in TNBC patients with aggressive disease. We sequenced the whole exome of 16 lesions from four patients who did not respond to therapy, and took several follow-up samples, including samples from tumors before and after treatment, as well as from the lymph nodes and skin metastases. We found substantial intrapatient genetic heterogeneity, with a variable tumor mutational composition. Early truncal events were MCL1 amplifications. Metastatic lesions had deletions in RB1 and PTEN, along with TERT, AKT2, and CCNE1 amplifications. Mutational signatures 06 and 12 were mainly detected in skin metastases and lymph nodes. According to phylogenetic analysis, the lymph node metastases occurred at an early stage of TNBC development. Finally, each patient had three to eight candidate driving mutations for targeted treatments. This study delves into the genomic complexity and the phylogenetic and evolutionary development of aggressive TNBC, supporting early metastatic development, and identifies specific genetic alterations associated with a response to targeted therapies.

Long-Term Outcomes of Veteran Patients After Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become a mainstay treatment for severe aortic stenosis and is increasingly used for veterans, producing excellent short-term outcomes. There is a paucity of long-term outcome data after TAVR in the veteran population. METHODS: We examined consecutive patients who underwent TAVR at a single Veterans Affairs medical center through 2019. Baseline characteristics, echocardiographic and angiographic variables, and clinical outcomes were abstracted. All-cause mortality was the primary outcome of interest. Factors associated with all-cause mortality and cardiac-specific mortality, including the presence of significant non-revascularized coronary artery disease (CAD), were assessed with multivariable regression and competing-risk analyses. RESULTS: The 189 consecutive patients enrolled (mean age, 76.6 ± 8.4 years) had a median Society of Thoracic Surgeons (STS) score of 6.0 (interquartile range [IQR], 4.0-8.5). After a maximum follow-up of 7.5 years, 71 (37.6%) deaths occurred, of which 76% had a cardiac cause. Median overall survival was 3.55 years (95% confidence interval [CI], 3.21-5.30); significant graded differences were observed across STS risk subgroups (P<.001). After multivariable adjustment, CAD was significantly associated with cardiac mortality (hazard ratio [HR], 2.6; 95% CI, 1.3-5.3) and all-cause mortality (HR, 2.2; 95% CI, 1.1-4.3). Other independent variables associated with all-cause mortality included age (P=.01), baseline creatinine (P<.01), and chronic obstructive pulmonary disease (P=.03). Baseline ejection fraction (P=.04), age (P<.01), creatinine (P=.02), and vascular disease (P=.04) were independently associated with cardiac-specific mortality. CONCLUSION: Long-term survival of veterans after TAVR is comparable to that of their non-veteran counterparts. Significant CAD, along with age and select comorbidities, was associated with poorer survival.

Parámetros ecocardiográficos relacionados a hipertensión arterial pulmonar en pacientes con leucemia mieloide crónica en tratamiento con dasatinib / Echocardiographic parameters related to pulmonary arterial hypertension in patients with chronic myeloid leukemia under dasatinib treatment

Introducción: La leucemia mieloide crónica (LMC) es un desorden clonal de células madre hematopoyéticas, predomina en el género masculino entre 55 y 65 años. El ecocardiograma transtorácico (ECOTT) para detección temprana de hipertensión arterial pulmonar (HAP) permite hacer modificaciones al tratamiento con dasatinib. Ojetivos: Determinar los parámetros ecocardiográficos y la probabilidad ecocardiográfica para HAP en pacientes con LMC tratados con dasatinib. Métodos: Estudio de correlación, transversal, retrospectivo, unicéntrico; se incluyeron pacientes con LMC tratados con dasatinib. Se utilizó correlación de Spearman y Pearson. Resultados: Se analizaron 16 pacientes, edad promedio 53,5 años; 62,5% hombres, 37,5% mujeres. La dosis de dasatinib fue 50 mg/día en 18,7%, y 100 mg/día en 81,2%, presión media de la arteria pulmonar (mPAP) 26,3 mmHg, velocidad máxima de regurgitación tricuspídea (VmxRT) media 2,9 m/s, presión sistólica de arteria pulmonar (PSAP) media 41 mmHg. El 56,2% presentó disfunción diastólica del ventrículo derecho (DDVD). Se categorizaron 43% en baja probabilidad para HAP, 18,7% intermedia y 37,5% en alta. Relación entre mPAP y VmxRT con p=0,012. Relación entre mPAP y función diastólica del ventrículo derecho (FDVD), con p=0,002. Relación entre probabilidad para HAP y mPAP, con p=0,008. Conclusión: Los parámetros ecocardiográficos mPAP, VmxRT, PSAP, DDVD son útilesy la probabilidad ecocardiográfica para HAP deben realizarse de forma temprana y como seguimiento, ya que se encontró relación positiva con la presencia de HAP, la cual no es dependiente del tiempo de tratamiento ni de la dosis de dasatinib.

Introduction: The use of dasatinib in patients with CML has improved life expectancy and follow-up with transthoracic echocardiography (ECOTT) for early detection of PAH allows modifications to the treatment. Objectives: To determine the echocardiographic parameters and echocardiographic probability for PAH in patients with CML treated with dasatinib. Methods: Correlation, cross-sectional, retrospective, single-center study; patients with CML treated with dasatinib were included. Spearman and Pearson correlation was used. Results: 16 patients were analyzed, mean age 53.5 years; 62.5% men, 37.5% women. The dasatinib dose was 50 mg / day in 18.7%, and 100 mg / day in 81.2%, mean pulmonary arterial pressure (mPAP) 26.3 mmHg, mean maximum tricuspid regurgitation velocity (VmxRT) 2.9 m / s, mean pulmonary artery systolic pressure (PSAP) 41 mmHg. 56.2% had right ventricular diastolic dysfunction (RVDD). 43% were categorized as low probability for PAH, 18.7% intermediate, and 37.5% as high. Relationship between PAPm and VmxRT with p = 0.012. Relationship between mPAP and RV diastolic function, with p = 0.002. Relationship between probability for PAH and mPAP, with p = 0.008. Conclusions: The echocardiographic parameters PAPm, VmxRT, PSAP, DDVD and echocardiographic probability for PAH are useful and necessary for the diagnosis of PAH. The determination of all these parameters should be carried out early and as a follow-up, since a considerable positive relationship was found for each one with the presence of PAH, which is not dependent on the treatment time or the dose of dasatinib.

Temporal Trends and Outcomes of Elective Thoracic Aortic Repair and Acute Aortic Syndromes in Bicuspid Aortic Valves: Insights from a National Database.

INTRODUCTION: There is paucity of data on the outcomes of hospitalization for bicuspid aortic valve (BAV)-related aortopathies. METHODS: We queried the NIS database (2012-2016) for hospitalizations for elective thoracic aortic repair or acute aortic syndrome (AAS) among those with BAV versus trileaflet aortic valve (TAV). RESULTS: Our analysis yielded 38,010 hospitalizations for elective aortic repair, of whom 34.4% had BAV, as well as 81,875 hospitalizations for thoracic AAS, of whom 1.1% had BAV. Hospitalizations for BAV were younger and had fewer comorbidities compared with their TAV counterparts. The number of hospitalizations for BAV during the observational period was unchanged. After propensity matching, elective aortic repair for BAV was associated with lower mortality (0.5% versus 1.7%, odds ratio = 0.28; 95% CI 1.5-0.50, p < 0.001), use of mechanical circulatory support, acute stroke, and shorter length of hospital stay compared with TAV. After propensity matching, AAS among those with BAV had a greater incidence of bleeding events, blood transfusion, cardiac tamponade, ventricular arrhythmias, and a longer length of hospital stay compared with TAV. Among those with BAV, predictors of lower mortality if undergoing elective aortic repair included larger hospitals and teaching hospitals. Predictors of higher mortality in patients with AAS included heart failure, chronic kidney disease, and coronary artery disease. CONCLUSION: Data from a national database showed no change in the number of hospitalizations for BAV-related aortopathy, with relatively lower incidence of AAS. Compared with TAV, elective aortic repair for BAV is associated with lower mortality, while BAV-related AAS is associated with higher in-hospital complications.

Single-Dose del Nido Cardioplegia Compared With Standard Cardioplegia During Coronary Artery Bypass Grafting at a Veterans Affairs Hospital.

Del Nido cardioplegic solution (DNC), used chiefly in pediatric patients, rapidly induces prolonged cardiac arrest during cardiac surgery. To determine whether surgical outcomes after coronary artery bypass grafting in a United States military veteran population differed when DNC was used instead of our standard Plegisol cardioplegia, we retrospectively reviewed 155 consecutive operations performed from July 2016 through June 2017. Del Nido cardioplegia was used to induce cardiac arrest in 70 patients, and Plegisol in 85. Compared with the Plegisol group, the DNC group had a shorter mean cardiopulmonary bypass time (96.8 vs 117 min; P <0.01) and aortic cross-clamp time (63.9 vs 71.7 min; P=0.02). On multiple linear regression, DNC use and number of bypasses performed were predictors of cardiopulmonary bypass time. The groups were similar in median number of bypasses performed, median time to extubation, intensive care unit stay, and total postoperative stay; however, the DNC group had a shorter mean operating room time (285.8 vs 364.5 min; P <0.01). Del Nido cardioplegia, number of bypasses, cardiopulmonary bypass time, and red blood cell transfusion were predictors of operating room time. Outcomes in the groups were similar for 30- and 180-day death, stroke, renal failure, ventilation time >48 hours, atrial fibrillation, tracheostomy, reintubation, and mechanical circulatory support. We conclude that single-dose DNC is safe, effective, and cost-effective for achieving cardiac arrest in U.S. veteran populations.