David H. Adams

Predictors of atrial fibrillation after coronary artery surgery. Current trends and impact on hospital resources.

BACKGROUND Atrial fibrillation (AF) after coronary artery bypass surgery (CABG) is the most common sustained arrhythmia. Its pathophysiology is unclear, and its prevention and management remain suboptimal. The aim of this prospective study was to determine the current incidence of AF, identify its clinical predictors, and examine its impact on resource utilization. METHODS AND RESULTS Over a 12-month period ending July 31, 1994, a CABG procedure was performed on 570 consecutive patients (age range, 32 to 87 years; median age, 67 years; 232 [41%] were > or = 70 years; 175 [31%] were women; 173 [30%] were diabetics; 364 [65%] required nonelective surgery; 86 [15%] had had a prior CABG; and 86 [15%] had had prior percutaneous transluminal coronary angioplasty). AF occurred in 189 patients (33%). The median age for patients with AF was 71 years compared with 66 for patients without (P = .0001). Multivariate logistic regression analysis (odds ratio, +/- 95% CI, P value) was used to identify the following independent predictors of postoperative AF: increasing age (age 70 to 80 years [OR = 2; CI, 1.3 to 3; P = .002], age > 80 years [OR = 3; CI, 1.6 to 5.8; P = .0007]), male gender (OR = 1.7; CI, 1.1 to 2.7; P = .01), hypertension (OR = 1.6; CI, 1.0 to 2.3; P = .03), need for an intraoperative intraaortic balloon pump (OR = 3.5; CI, 1.2 to 10.9; P = .03), postoperative pneumonia (OR = 3.9; CI, 1.3 to 11.5; P = .01), ventilation for > 24 hours (OR = 2; CI, 1.3 to 3.2; P = .003), and return to the intensive care unit (OR = 3.2; CI, 1.1 to 8.8; P = .03). The mean length of hospital stay after surgery was 15.3 +/- 28.6 days for patients with AF compared with 9.3 +/- 19.6 days for patients without AF (P = .001). The adjusted length of hospital stay attributable to AF was 4.9 days, corresponding to > or =

EAE/ASE recommendations for image acquisition and display using three-dimensional echocardiography.

10 055 in hospital charges. CONCLUSIONS AF remains the most common complication after CABG and consequently is a drain on hospital resources. Concerted efforts to reduce the incidence of AF and the associated increased length of stay would result in substantial cost saving and decrease patient morbidity.

Transcatheter aortic valve replacement using a self-expanding bioprosthesis in patients with severe aortic stenosis at extreme risk for surgery

Roberto M. Lang, MD, FASE*‡, Luigi P. Badano, MD, FESC†‡, Wendy Tsang, MD*, David H. Adams, MD*, Eustachio Agricola, MD†, Thomas Buck, MD, FESC†, Francesco F. Faletra, MD†, Andreas Franke, MD, FESC†, Judy Hung, MD, FASE*, Leopoldo Pérez de Isla, MD, PhD, FESC†, Otto Kamp, MD, PhD, FESC†, Jaroslaw D. Kasprzak, MD, FESC†, Patrizio Lancellotti, MD, PhD, FESC†, Thomas H. Marwick, MBBS, PhD*, Marti L. McCulloch, RDCS, FASE*, Mark J. Monaghan, PhD, FESC†, Petros Nihoyannopoulos, MD, FESC†, Natesa G. Pandian, MD*, Patricia A. Pellikka, MD, FASE*, Mauro Pepi, MD, FESC†, David A. Roberson, MD, FASE*, Stanton K. Shernan, MD, FASE*, Girish S. Shirali, MBBS, FASE*, Lissa Sugeng, MD*, Folkert J. Ten Cate, MD†, Mani A. Vannan, MBBS, FASE*, Jose Luis Zamorano, MD, FESC, FASE†, and William A. Zoghbi, MD, FASE*

The gut microbiota and host health: a new clinical frontier

OBJECTIVES This study sought to evaluate the safety and efficacy of the CoreValve transcatheter heart valve (THV) for the treatment of severe aortic stenosis in patients at extreme risk for surgery. BACKGROUND Untreated severe aortic stenosis is a progressive disease with a poor prognosis. Transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis is a potentially effective therapy. METHODS We performed a prospective, multicenter, nonrandomized investigation evaluating the safety and efficacy of self-expanding TAVR in patients with symptomatic severe aortic stenosis with prohibitive risks for surgery. The primary endpoint was a composite of all-cause mortality or major stroke at 12 months, which was compared with a pre-specified objective performance goal (OPG). RESULTS A total of 41 sites in the United States recruited 506 patients, of whom 489 underwent attempted treatment with the CoreValve THV. The rate of all-cause mortality or major stroke at 12 months was 26.0% (upper 2-sided 95% confidence bound: 29.9%) versus 43.0% with the OPG (p < 0.0001). Individual 30-day and 12-month events included all-cause mortality (8.4% and 24.3%, respectively) and major stroke (2.3% and 4.3%, respectively). Procedural events at 30 days included life-threatening/disabling bleeding (12.7%), major vascular complications (8.2%), and need for permanent pacemaker placement (21.6%). The frequency of moderate or severe paravalvular aortic regurgitation was lower 12 months after self-expanding TAVR (4.2%) than at discharge (10.7%; p = 0.004 for paired analysis). CONCLUSIONS TAVR with a self-expanding bioprosthesis was safe and effective in patients with symptomatic severe aortic stenosis at prohibitive risk for surgical valve replacement. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902).

Minimally invasive cardiac valve surgery improves patient satisfaction while reducing costs of cardiac valve replacement and repair.

Over the last 10–15 years, our understanding of the composition and functions of the human gut microbiota has increased exponentially. To a large extent, this has been due to new ‘omic’ technologies that have facilitated large-scale analysis of the genetic and metabolic profile of this microbial community, revealing it to be comparable in influence to a new organ in the body and offering the possibility of a new route for therapeutic intervention. Moreover, it might be more accurate to think of it like an immune system: a collection of cells that work in unison with the host and that can promote health but sometimes initiate disease. This review gives an update on the current knowledge in the area of gut disorders, in particular metabolic syndrome and obesity-related disease, liver disease, IBD and colorectal cancer. The potential of manipulating the gut microbiota in these disorders is assessed, with an examination of the latest and most relevant evidence relating to antibiotics, probiotics, prebiotics, polyphenols and faecal microbiota transplantation.

Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell–mediated liver damage

OBJECTIVE This study compares the quality of valve replacement and repair performed through minimally invasive incisions as compared to the standard operation for aortic and mitral valve replacement. SUMMARY BACKGROUND DATA With the advent of minimally invasive laparoscopic approaches to orthopedic surgery, urology, general surgery, and thoracic surgery, it now is apparent that standard cardiac valve operations can be performed through very small incisions with similar approaches. METHODS Eighty-four patients underwent minimally invasive aortic (n = 41) and minimally invasive mitral valve repair and replacement (n = 43) between July 1996 and April 1997. Demographics, procedures, operative techniques, and postoperative morbidity and mortality were calculated, and a subset of the first 50 patients was compared to a 50-patient cohort who underwent the same operation through a conventional median sternotomy. Demographics, postoperative morbidity and mortality, patient satisfaction, and charges were compared. RESULTS Of the 84 patients, there were 2 operative mortalities both in class IV aortic patients from multisystem organ failure. There was no operative mortality in the patients undergoing mitral valve replacement or repair. The operations were carried out with the same accuracy and attention to detail as with the conventional operation. There was minimal postoperative bleeding, cerebral vascular accidents, or other major morbidity. Groin cannulation complications primarily were related to atherosclerotic femoral arteries. A comparison of the minimally invasive to the conventional group, although operative time and ischemia time was higher in minimally invasive group, the requirement for erythrocytes was significantly less, patient satisfaction was significantly greater, and charges were approximately 20% less than those in the conventional group. CONCLUSIONS Minimally invasive aortic and mitral valve surgery in patients without coronary disease can be done safely and accurately through small incisions. Patient satisfaction is up, return to normality is higher, and requirement for postrehabilitation services is less. In addition, the charges are approximately 20% less. These results serve as a paradigm for the future in terms of valve surgery in the managed care environment.

Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties.

Hepatitis B virus (HBV) causes chronic infection in more than 350 million people worldwide. It replicates in hepatocytes but is non-cytopathic; liver damage is thought to be immune mediated. Here, we investigated the role of innate immune responses in mediating liver damage in patients with chronic HBV infection. Longitudinal analysis revealed a temporal correlation between flares of liver inflammation and fluctuations in interleukin (IL)-8, interferon (IFN)-α, and natural killer (NK) cell expression of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) directly ex vivo. A cross-sectional study confirmed these findings in patients with HBV-related liver inflammation compared with healthy carriers. Activated, TRAIL-expressing NK cells were further enriched in the liver of patients with chronic HBV infection, while their hepatocytes expressed increased levels of a TRAIL death–inducing receptor. IFN-α concentrations found in patients were capable of activating NK cells to induce TRAIL-mediated hepatocyte apoptosis in vitro. The pathogenic potential of this pathway could be further enhanced by the ability of the IFN-α/IL-8 combination to dysregulate the balance of death-inducing and regulatory TRAIL receptors expressed on hepatocytes. We conclude that NK cells may contribute to liver inflammation by TRAIL-mediated death of hepatocytes and demonstrate that this non-antigen–specific mechanism can be switched on by cytokines produced during active HBV infection.

Degenerative mitral valve regurgitation: best practice revolution

CD8+ T lymphocytes play a key role in host defense, in particular against important persistent viruses, although the critical functional properties of such cells in tissue are not fully defined. We have previously observed that CD8+ T cells specific for tissue-localized viruses such as hepatitis C virus express high levels of the C-type lectin CD161. To explore the significance of this, we examined CD8+CD161+ T cells in healthy donors and those with hepatitis C virus and defined a population of CD8+ T cells with distinct homing and functional properties. These cells express high levels of CD161 and a pattern of molecules consistent with type 17 differentiation, including cytokines (e.g., IL-17, IL-22), transcription factors (e.g., retinoic acid-related orphan receptor γ-t, P = 6 × 10−9; RUNX2, P = 0.004), cytokine receptors (e.g., IL-23R, P = 2 × 10−7; IL-18 receptor, P = 4 × 10−6), and chemokine receptors (e.g., CCR6, P = 3 × 10−8; CXCR6, P = 3 × 10−7; CCR2, P = 4 × 10−7). CD161+CD8+ T cells were markedly enriched in tissue samples and coexpressed IL-17 with high levels of IFN-γ and/or IL-22. The levels of polyfunctional cells in tissue was most marked in those with mild disease (P = 0.0006). These data define a T cell lineage that is present already in cord blood and represents as many as one in six circulating CD8+ T cells in normal humans and a substantial fraction of tissue-infiltrating CD8+ T cells in chronic inflammation. Such cells play a role in the pathogenesis of chronic hepatitis and arthritis and potentially in other infectious and inflammatory diseases of man.

Hepatic Endothelial CCL25 Mediates the Recruitment of CCR9+ Gut-homing Lymphocytes to the Liver in Primary Sclerosing Cholangitis

Degenerative mitral valve disease often leads to leaflet prolapse due to chordal elongation or rupture, and resulting in mitral valve regurgitation. Guideline referral for surgical intervention centres primarily on symptoms and ventricular dysfunction. The recommended treatment for degenerative mitral valve disease is mitral valve reconstruction, as opposed to valve replacement with a bioprosthetic or mechanical valve, because valve repair is associated with improved event free survival. Recent studies have documented a significant number of patients are not referred in a timely fashion according to established guidelines, and when they are subjected to surgery, an alarming number of patients continue to undergo mitral valve replacement. The debate around appropriate timing of intervention for asymptomatic severe mitral valve regurgitation has put additional emphasis on targeted surgeon referral and the need to ensure a very high rate of mitral valve repair, particularly in the non-elderly population. Current clinical practice remains suboptimal for many patients, and this review explores the need for a ‘best practice revolution’ in the field of degenerative mitral valve regurgitation.

Aberrant homing of mucosal T cells and extra-intestinal manifestations of inflammatory bowel disease.

Primary sclerosing cholangitis (PSC), a chronic inflammatory liver disease characterized by progressive bile duct destruction, develops as an extra-intestinal complication of inflammatory bowel disease (IBD) (Chapman, R.W. 1991. Gut. 32:1433–1435). However, the liver and bowel inflammation are rarely concomitant, and PSC can develop in patients whose colons have been removed previously. We hypothesized that PSC is mediated by long-lived memory T cells originally activated in the gut, but able to mediate extra-intestinal inflammation in the absence of active IBD (Grant, A.J., P.F. Lalor, M. Salmi, S. Jalkanen, and D.H. Adams. 2002. Lancet. 359:150–157). In support of this, we show that liver-infiltrating lymphocytes in PSC include mucosal T cells recruited to the liver by aberrant expression of the gut-specific chemokine CCL25 that activates α4β7 binding to mucosal addressin cell adhesion molecule 1 on the hepatic endothelium. This is the first demonstration in humans that T cells activated in the gut can be recruited to an extra-intestinal site of disease and provides a paradigm to explain the pathogenesis of extra-intestinal complications of IBD.