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Background: Hypertrophic cardiomyopathy (HCM) is commonly associated with mitral valve pathology. A large majority of patients with HCM have elongated anterior and posterior mitral leaflets. There remains debate regarding the necessity and role of concomitant mitral valve surgery at the time of septal myectomy. We aimed to describe the characteristics and share our surgical experiences with this specific group of patients. Methods: This retrospective single‐center study investigates adult patients with HCM, with or without elongated mitral valve leaflets (MVLs), who underwent elective septal myectomy with or without concomitant mitral valve intervention, between January 1, 2016, and June 30, 2020. Clinical data were obtained from institutional medical records as well as the Society of Thoracic Surgeons data registry. The clinical characteristics and in‐hospital surgical outcomes were compared between patients with an elongated MVL and those without. Results: In total, 379 patients underwent septal myectomy, and 22 patients with intrinsic mitral valve disease were excluded. In addition, 23 patients were excluded due to missing data. Of the remaining 334 patients, 131 (39.2%) had elongated MVL and concomitant MVL plication. Patients with elongated MVL had higher rates of preoperative mitral valve systolic anterior motion (SAM) (94.7% vs. 86.7%, p = 0.019) and higher preoperative provoked left ventricular outflow tract gradient (LVOTG) (134.5 mmHg versus 125.3 mmHg, p = 0.046). Post septal myectomy and mitral valve plication, they had lower rates of postoperative residual mitral regurgitation (3.8% vs. 12.8%, p = 0.006), comparable rates of residual SAM (28.2% vs. 31.5%, p = 0.524), postoperative provoked LVOTG (15.4 mmHg vs. 14.0 mmHg, p = 0.317), 30‐day major adverse cardiopulmonary events (2.3% vs. 3.9%, p = 0.409), and mortality (0% vs. 1.0%, p = 0.255). Conclusions: Elongated MVLs contribute more significantly to dynamic LVOT obstruction, as evidenced during provocative testing. Concomitant mitral valve intervention during septal myectomy can be performed safely and may provide an effective strategy to resolve SAM and stress‐induced LVOTG. [ABSTRACT FROM AUTHOR]

Purpose: Pericardiectomy has traditionally carried relatively high perioperative mortality and morbidity, with few published reports of intermediate- and long- term outcomes. We investigated our 15-year experience performing pericardiectomy at our institution.Methods: Retrospective study of all patients who underwent pericardiectomy at our institution between 2005 and 2019. Baseline demographics, intraoperative details, and postoperative outcomes including long-term survival were analyzed.Results: Sixty-three patients were included in the study. 66.7% of subjects underwent isolated pericardiectomy while 33.3% underwent pericardiectomy concomitantly with another cardiac surgical procedure. The most common indications for pericardiectomy were constrictive (79.4%) and hemorrhagic (9.5%) pericarditis. Preoperatively, 76.2% of patients were New York Heart Association class II and III, while postoperatively, 71.4% were class I and II. One-, three-, five-, and ten- year overall mortality was 9.5, 14.3, 20.6, and 25.4%, respectively. Overall pericarditis recurrence rate was 4.8%.Conclusion: Pericardiectomy carries relatively high overall mortality rates, which likely reflects underlying disease etiology and comorbidities. Patients with prior cardiac intervention, history of dialysis, and immunocompromised state are associated with worse outcomes. [ABSTRACT FROM AUTHOR]

The optimal time when surgery can be safely performed after stroke is unknown. The purpose of this study was to investigate how cardiac surgery timing after stroke impacts postoperative outcomes between 2011–2017 were reviewed. Variables were extracted from the institutional Society of Thoracic Surgeons database, statewide patient registry, and medical records. Subjects were classified based upon presence of endocarditis and further grouped by timing of preoperative stroke relative to cardiac surgery: Recent (stroke within two weeks before surgery), Intermediate (between two and six weeks before), and Remote (greater than six weeks before). Postoperative outcomes were compared amongst groups. 157 patients were included: 54 in endocarditis and 103 in non-endocarditis, with 47 in Recent, 26 in Intermediate, and 84 in Remote. 30-day mortality and postoperative stroke rate were similar across the three subgroups for both endocarditis and non-endocarditis. Of patients with postoperative stroke, mortality was 30% (95% CI 4.6–66). Timing of cardiac surgery after stroke occurrence does not seem to affect postoperative stroke or mortality. If postoperative stroke does occur, subsequent stroke-related mortality is high. [ABSTRACT FROM AUTHOR]

There is a paucity of data describing the effect of time interval between diagnosis and surgery for Acute Type A Aortic Dissection. We describe our 8-year experience and investigate the impact of time interval between symptom onset, diagnosis and surgery on outcomes. Retrospective single-center study utilizing our Society of Thoracic Surgeons registry and patient records. Subjects were grouped by time interval between radiographic diagnosis and surgical treatment: Group A (0–4 h), Group B (4.1–8 h), Group C (8.1–12 h), and Group D (12.1 + h). Data were analyzed to identify factors associated with mortality and outcomes. 164 patients were included. Overall mortality was 21.3%. Group C had the greatest intervals between symptom onset to diagnosis to surgery, and also the highest mortality (66.7%). Preoperative tamponade, cardiac arrest, malperfusion, elevated creatinine, cardiopulmonary bypass time, and blood transfusions were associated with increased mortality, while distance of referring hospital was not. Time intervals between symptom onset, diagnosis and surgery have a significant effect on mortality. Surgery performed 8–12 h after diagnosis carries the highest mortality, which may be exacerbated by longer interval since symptom onset. Time-dependent effects should be considered when determining optimal strategy especially if inter-facility transfer is necessary. [ABSTRACT FROM AUTHOR]

Purpose: The effect of preoperative cardiac troponin level on outcomes after coronary artery bypass grafting (CABG) is unclear. We investigated the impact of preoperative cardiac troponin I (cTnI) level as well as the time interval between maximum cTnI and surgery on CABG outcomes.Methods: All patients who underwent isolated CABG at our institution between 2009 and 2016 and had preoperative cTnI level available were identified using our Society of Thoracic Surgeons registry. Receiver operating characteristic (ROC) analysis was performed to identify a cTnI threshold level. Subjects were divided into groups based on this value and outcomes compared.Results: A total of 608 patients were included. ROC analysis identified 5.74 µg/dL as the threshold value associated with worse postoperative outcomes. Patients with peak cTnI >5.74 µg/dL underwent CABG approximately 1 day later, had twice the risk of adverse postoperative events, and had 2.8 day longer postoperative length of stay than those with peak cTnI ≤5.74 µg/dL. cTnI level was not associated with mortality or 30-day readmission. Time interval between peak cTnI and surgery did not affect outcomes.Conclusion: Elevated preoperative cTnI level beyond a certain threshold value is associated with adverse postoperative outcomes but is not a marker for increased mortality. Time from peak cTnI does not affect postoperative outcomes or mortality and may not need to be considered when deciding timing of CABG. [ABSTRACT FROM AUTHOR]

Background: Postoperative critical care management is an integral part of cardiac surgery that contributes directly to clinical outcomes. In the United States there remains considerable variability in the critical care infrastructure for cardiac surgical programs. There is little published data investigating the impact of a dedicated cardiac surgical intensive care service.Methods: A retrospective study examining postoperative outcomes in cardiac surgical patients before and after the implementation of a dedicated cardiac surgical intensive care service at a single academic institution. An institutional Society of Thoracic Surgeons database was queried for study variables. Primary endpoints were the postoperative length of stay, intensive care unit length of stay, and mechanical ventilation time. Secondary endpoints included mortality, readmission rates, and postoperative complications. The effect on outcomes based on procedure type was also analyzed.Results: A total of 1703 patients were included in this study-914 in the control group (before dedicated intensive care service) and 789 in the study group (after dedicated intensive care service). Baseline demographics were similar between groups. Length of stay, mechanical ventilation hours, and renal failure rate were significantly reduced in the study group. Coronary artery bypass grafting patients observed the greatest improvement in outcomes.Conclusions: Implementation of a dedicated cardiac surgical intensive care service leads to significant improvements in clinical outcomes. The greatest benefit is seen in patients undergoing coronary artery bypass, the most common cardiac surgical operation in the United States. Thus, developing a cardiac surgical intensive care service may be a worthwhile initiative for any cardiac surgical program. [ABSTRACT FROM AUTHOR]

Polymyxin B is used as a last treatment resort for multidrug‐resistant Gram‐negative bacterial infections. The objectives of this study were to examine the population pharmacokinetics of polymyxin B and investigate factor(s) influencing pharmacokinetic variability. Four serial blood samples each were collected from 35 adult patients at steady state. The concentrations of individual polymyxin B components were analyzed using a validated liquid chromatography / tandem mass spectrometry assay and combined to derive total concentrations. A maximum likelihood expectation maximization approach was used to fit the data. Various demographic variables were investigated as potential covariates for clearance and volume of distribution (Vd) using linear regression analysis. A one‐compartment model fit to the data satisfactorily (r2 = 0.96). The best‐fit mean ± SD for clearance and Vd were 2.5 ± 1.1 L/h and 34.3 ± 16.4 L, respectively. Creatinine clearance was found to be a statistically significant covariate of clearance, but the magnitude was deemed clinically insignificant. [ABSTRACT FROM AUTHOR]

Clinical trials often use a binary “fold increase” endpoint defined according to the ratio of interval-censored measurement at end-of-study to that at baseline. We propose a simple yet principled analytic approach based on the linear mixed-effects model for interval-censored data for the analysis of such paired measurements. Having estimated the model parameters, the risk ratio can be estimated by explicit composite estimand and the variance is estimated using the delta method. The estimation can be implemented using the existing procedures in popular statistical software. We use antibody data from the Chloroquine for Influenza Prevention Trial for illustration. [ABSTRACT FROM AUTHOR]

Heart failure is one of the fastest-growing epidemics worldwide in health care today. Although a wide variety of animal models exist to create chronic heart failure, there are few truly successful, reproducible models with ischemic dilation and mitral regurgitation. Six healthy sheep (36 ± 5 kg) underwent multiple, strategic coronary artery ligations on the left ventricle (LV). Six to eight ligations were performed transmurally on three of four segments of the LV: anterior, lateral, and posterior. Side branches of the left anterior descending and circumflex arteries were ligated to create multiple, patchy areas of myocardial infarction. Cardiac global and regional systolic function was assessed by echocardiography and cardiac magnetic resonance imaging (MRI). The extent, the characteristics, and the location of the myocardial infarction were qualitatively and quantitatively assessed by late gadolinium enhancement imaging. The overall mortality rate was 16.7% (1/6 animals). Animals who survived showed a significantly reduced ejection fraction (mean 60 ± 5% to 28 ± 7%; P < 0.05); additionally, two out of the remaining five (40%) animals developed mild to moderate mitral regurgitation quantified by cardiac MRI. Furthermore, each animal developed clinical signs of heart failure (tachycardia, dyspnea, and tachypnea) consistent with global, dilated cardiomyopathy noted on MRI. Creating and reproducing a model of global, ischemic cardiomyopathy with functional mitral regurgitation is an arduous task. We have developed a promising model of ischemic heart failure using multiple ligations, which mimics the sequelae of human cardiomyopathy. Our proposed model is highly effective, reproducible, and may be used for experimental research on heart failure (cardiac assist devices, heart transplant, etc.). [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV)-infected patients often take herbal medicines, which may interact with anti-retrovirals. American ginseng induces phase 2 and antioxidant enzymes in vitro and might increase the clearance of zidovudine and/or enhance antioxidant activity. Ten healthy volunteers received 300 mg of zidovudine orally before and after 2 weeks of treatment with a ginsen aside-enriched American ginseng extract 200 mg twice daily. This ginseng extract induced the phase 2 enzyme quinone reductase with an average concentration of doubling of enzyme activity of 190 µg/mL. Total ginsenoside content was 8.5 ± 0.5%. Pharmacokinetic profiles of zidovudine and oxidative stress marker concentrations were measured post-zidovudine dose. American ginseng does not significantly affect the formation clearance of zidovudine to its glucuronide (ratio post- to pre-American ginseng = 1.17; 90% confidence interval: 0.95-1.45; P = .21), total clearance (ratio = 0.97; 0.82-1.14; P = .70), or plasma zidovudine AUC0-8 (ratio = 1.03; 0.87-1.21; P = .77). Oxidative stress biomarkers are reduced post-American ginseng (F2-isoprostane ratio = 0.79; 0.72-0.86; P < .001; 8-hydroxy-deoxyguanosine ratio = 0.74; 0.59-0.92; P = .02). Two weeks of American ginseng does not alter zidovu dine pharmacokinetics but reduces oxidative stress markers. [ABSTRACT FROM AUTHOR]

Concurrent use of natural health products (NHPs) with antiretroviral drugs (ARVs) is widespread among human immunodeficiency virus-infected patients. This article reviews the clinical pharmacokinetic and pharmacodynamic interactions between NHPs and ARVs. Many NHPs are complex mixtures and are likely to contain organic compounds that may induce and/or inhibit drug metabolizing enzymes and drug transporters. Although the weight of evidence for the effects of certain NHPs varies and many studies of these products lack scientific rigor, it has been observed that St. John's wort clearly induces cytochrome P450 3A4 and P-glycoprotein and reduces protease inhibitor and nonnucleoside reverse-transcriptase inhibitor concentrations, thereby increasing the likelihood of therapeutic failure. Limited clinical research suggests that intake of garlic and vitamin C results in reductions in ARV concentrations. The intake of milk thistle, Echinacea species, and goldenseal inhibits cytochrome P450 enzymes in vitro and may increase ARV concentrations, but by clinically unimportant amounts. Intake of fish oil reduces ARV-induced hypertriglyceridemia without significantly affecting lopinavir concentrations. Before recommending the use of NHPs as adjuncts to ARV use, studies should first exclude significant pharmacokinetic interactions and ensure that ARV efficacy is maintained. [ABSTRACT FROM AUTHOR]

Current approaches to stratify the risk for disease progression in thoracic aortic aneurysm (TAA) lack precision, which hinders clinical decision making. Connective tissue phenotyping of children with TAA previously identified the association between skin striae and increased rate of aortic dilation. The objective of this study was to analyze associations between connective tissue abnormalities and clinical endpoints in adults with aortopathy. Participants with TAA or aortic dissection (TAD) and trileaflet aortic valve were enrolled from 2016 to 2019 in the setting of cardiothoracic surgical care. Data were ascertained by structured interviews with participants. The mean age among 241 cases was 61 ± 13 years. Eighty (33%) had history of TAD. While most participants lacked a formal syndromic diagnosis clinically, connective tissue abnormalities were identified in 113 (47%). This included 20% with abdominal hernia and 13% with skin striae in atypical location. In multivariate analysis, striae and hypertension were significantly associated with TAD. Striae were associated with younger age of TAD or prophylactic aortic surgery. Striae were more frequent in TAD cases than age- and sex-matched controls. Thus, systemic features of connective tissue dysfunction were prevalent in adults with aortopathy. The emerging nexus between striae and aortopathy severity creates opportunities for clinical stratification and basic research. [ABSTRACT FROM AUTHOR]

Polymyxin B is the last line of defense in treating multidrug-resistant gram-negative bacterial infections. Dosing of polymyxin B is currently based on total body weight, and a substantial intersubject variability has been reported. We evaluated the performance of different population pharmacokinetic models to predict polymyxin B exposures observed in individual patients. In a prospective observational study, standard dosing (mean 2.5 mg/kg daily) was administered in 13 adult patients. Serial blood samples were obtained at steady state, and plasma polymyxin B concentrations were determined by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The best-fit estimates of clearance and daily doses were used to derive the observed area under the curve (AUC) in concentration–time profiles. For comparison, 5 different population pharmacokinetic models of polymyxin B were conditioned using patient-specific dosing and demographic (if applicable) variables to predict polymyxin B AUC of the same patient. The predictive performance of the models was assessed by the coefficient of correlation, bias, and precision. The correlations between observed and predicted AUC in all 5 models examined were poor (r2 < 0.2). Nonetheless, the models were reasonable in capturing AUC variability in the patient population. Therapeutic drug monitoring currently remains the only viable approach to individualized dosing. [ABSTRACT FROM AUTHOR]

Cell mediated immunity plays a vital role in defense against influenza infection in humans. Less is known about the role of vaccine-induced cell mediated immunity and the cytokine responses elicited. We measured CD4+ and CD8+ T-cell reactivity in human subjects following vaccination with licensed trivalent influenza vaccine and a novel virus-like particle based vaccine. We detected influenza-specific CD4+ T-cell responses following vaccination with the licensed trivalent influenza vaccine and found that these correlated with antibody measurements. Administration of the novel virus-like particle based vaccine elicited influenza-specific CD4+ and CD8+ T-cell responses and the induction of the cytokines IFN-γ, IL-17A, IL17F, IL-5, IL-13, IL-9, IL-10 and IL-21. Pre-existing cytokine responses influenced the profile of the cytokine response elicited by vaccination. In a subset of individuals the VLP vaccine changed pre-vaccination production of type 2 cytokines such as IL-5 and IL-13 to a post-vaccination type 1 cytokine signature characterized by IFN-γ. A transcriptional signature to vaccination was found to correlate with antibody titer, IFN-γ production by T-cells and expression of a putative RNA helicase, DDX17, on the surface of immune cells. [ABSTRACT FROM AUTHOR]

An abstract of the paper "Characterization of Peri-infarct Zone by Cardiac Magnetic Resonance: Validation Compared to Ex-vivo Imaging and Post-mortem Histology ," by Lawrence S. Lee and colleagues, from the 2011 SCMR/Euro CMR Joint Scientific Sessions, held in Nice, France, from February 3-6, 2011, is presented.

The article discusses a study on the inter-ethnic difference in the central nervous system (CNS) toxicity caused by the use of efavirenz. The study performs genome wide genotyping with the Illumina 1M and the Affymetrix 6.0 microarrays in healthy volunteers from the three major ethnic groups in Singapore, the Chinese, Malays, and Indians. It reveals a significant ethnic differences in CYP2B6 516 G>T mutations in the nation.

Ventricular assist device (VAD) support in patients with a prosthetic heart valve had previously been considered a relative contraindication due to an increased risk of thromboembolic complications. We report our clinical experience of VAD implantation in patients with prosthetic heart valves, including both mechanical and bioprosthetic valves. The clinical records of 133 consecutive patients who underwent VAD implantation at a single institution from January 2002 through June 2009 were retrospectively reviewed. Six of these patients had a prosthetic valve in place at the time of device implantation. Patient demographics, operative characteristics, and postoperative complications were reviewed. Of the six patients, four were male. The mean age was 57.8 years (range 35-66 years). The various prosthetic cardiac valves included a mechanical aortic valve ( n = 2), a bioprosthetic aortic valve ( n = 3), and a mechanical mitral valve ( n = 1). The indications for VAD support included bridge to transplantation ( n = 2), bridge to recovery ( n = 1), and postcardiotomy ventricular failure ( n = 3). Three patients underwent left ventricular assist device placement and three received a right ventricular assist device. Postoperatively, standard anticoagulation management began with a heparin infusion (if possible) followed by oral anticoagulation. The 30-day mortality was 50% (3/6). The mean duration of support among survivors was 194.3 days (range 7-369 days) compared with 16.0 days (range 4-29 days) for nonsurvivors. Of the three survivors, two were successfully bridged to heart transplantation and one recovered native ventricular function. Among the three nonsurvivors, acute renal failure developed in each case, and two developed heparin-induced thrombocytopenia. This study suggests that VAD placement in patients with a prosthethic heart valve, either mechanical or bioprosthetic, appears to be a reasonable option. [ABSTRACT FROM AUTHOR]