Karl T. Weber, MD
Karl T. Weber is the Neuton Stern Professor of Cardiovascular Medicine and Director of the Division of Cardiovascular Diseases at the University of Tennessee Health Science Center. His academic career, which has spanned more than 30 years, has led to over 600 publications in the scientific literature. His continuous federally funded research now spans 40 years.
Beginning in the early 1970s, Dr. Weber’s research focused on myocardial mechanics and energetics. Instantaneous force-velocity-length relationships were identified and applied to understanding the behavior of the failing heart, its consumption of oxygen, and its aerobic limit. During this time, he also pioneered the use of breath-by-breath respiratory gas exchange, termed cardiopulmonary exercise testing, to determine the anaerobic threshold and its utility in predicting the impairment in oxygen delivery (or cardiac reserve) in patients with chronic cardiac and circulatory failure of diverse causality and severity.
In ensuing decades, he continued his research on the failing heart, but broadened its scope from a contractile element to the in-series and in-parallel elastic elements represented by the heart’s fibrillar collagen matrix. His work would pioneer an understanding of the presence and importance of cardiac fibrosis in leading to abnormal myocardial stiffness and would identify the role of neurohormonal activation in regulating such adverse structural remodeling of myocardium by fibrous tissue. In particular, effector hormones of the renin-angiotensin-aldosterone system were identified as integral to such remodeling. His research with an aldosterone receptor antagonist in preventing fibrosis would prove an important element to the design of recently completed international clinical trials (RALES and EPHESUS), where the efficacy of such an antagonist was demonstrated in patients with systolic heart failure. Moreover, he would broaden our understanding of the importance of aldosterone to the pathophysiologic origins of the congestive heart failure (CHF) syndrome and which was underscored by the positive outcomes observed in these large clinical trials.
In the new millennium, Dr. Weber’s research would address the pathogenic origins of myocardial fibrosis. This work has led to an even broader perspective of CHF, one extending beyond the cardiocentric perspective to address the systemic illness that accompanies it. This proinflammatory phenotype features: oxi-/nitrosative stress; an immunostimulatory state with activated lymphocytes and monocytes; and a catabolic state with wasting of lean tissue, fat and bone. The role of aldosteronism in contributing to this phenotype is addressed in rats and has identified the appearance of secondary hyperparathyroidism in what can be considered a neurohormonal-immune interface gone awry. The potential for recovery from this phenotype is also under investigation. This new paradigm is now being translated to investigator-initiated, hypothesis-driven, clinical research studies in human CHF. Studies in African-Americans with heart failure, hospitalized at the Regional Medical Center in Memphis, have identified secondary hyperparathyroidism as a covariant of CHF, together with hypovitaminosis D and deficiencies of several micronutrients that include zinc and selenium.
The current direction of Dr. Weber’s research is directed at identifying components of a mitochondriocentric pathway to cardiomyocyte necrosis and subsequent reparative fibrosis. This includes: the role played by calcium overloading of the subsarcolemmal population of cardiac mitochondria; the induction of oxidative stress in these organelles which overwhelms endogenous antioxidant defenses provided largely by Zn2+- and Se2+-based metalloenzymes; and the opening of the mitochondria’s inner membrane permeability transition pore. Mitochondria-targeted interventions which may serve as cardioprotective strategies are under investigation.
The Division of Cardiovascular Diseases at the University of Tennessee Health Science Center has a tripartite mission: to mentor; to discover; and to serve. Its training program in cardiovascular medicine is accredited by the Residency Review Committee (RRC) of the American College of Graduate Medical Education and accordingly its curriculum contains all recommended components for clinical training and research.
The Division is composed of 18 full-time faculty, each of whom is dedicated to the education of its 14 trainees. Inpatient and outpatient activities are provided at three sites: Shelby County’s Regional Medical Center (or MED); the Veterans Administration Medical Center; and the Methodist University Hospital. Accordingly, trainees interact with diverse patient populations. Each health care site has an Emergency Room, Coronary Care and Telemetry Units, inpatient and outpatient services, and noninvasive and invasive laboratories.
Objectives of the Training Program
The Division is dedicated to training individuals who have completed their residency in internal medicine at an accredited program. Fellowship program objectives: to train competent, confident, and compassionate clinical cardiologists who will come to understand the practice of cardiovascular medicine in the context of its underlying pathophysiologic basis. In so doing, its trainees will come to use a maturity in judgment that will enable them to individualize management strategies for each of their patients and to place in perspective the results of large clinical trials.
Unique Aspects of the Educational Program
Daily conferences are provided to promote self-motivated learning. These sessions include: a Monday conference on graphics (e.g., ECG-related, echocardiography, hemodynamics); a core curriculum of fundamental topics on Tuesday; a journal club, a pro-and-con debate, or a review of ongoing research on Wednesday; on Thursday a morbidity and mortality conference; and on Friday, a joint conference with members of the Division of Cardiothoracic Surgery or a case-of-the-month presentation.
Fellows, together with a faculty mentor, are responsible for presenting all but the Tuesday core curriculum. In preparing for these conferences, fellows learn to: pose a question relevant to one of their patients; research the relevant scientific literature; address the problem selected; field questions from their peers; and to reach a conclusion. These sessions are also intended to provide trainees with an appreciation of self-motivated learning and promote personal enrichment through a lifetime of learning.
Cardiology Grand Rounds are held monthly on Tuesday evening and feature an intramural or invited senior clinician or basic scientist, who also meets with trainees during his/her visit.
The Division’s Annual Research Day is held in late January and features presentations by fellows, residents and medical students who worked with faculty on a basic or clinical research study. A copy of the 2012 program can be found here .
The Division offers opportunities in both the basic sciences and patient-based clinical research. The foundation of this program is investigator-initiated, hypothesis-driven research conducted in a mode of discovery. A bedside-to-bench and bench-to-bedside approach forms the underpinning to its translational research program.
A listing of several recent publications relevant to basic and applied research in heart failure appears on our Research page.
Whether viewed in-series or in-parallel, cellular or subcellular, searching for new frontiers beyond current wisdom is the philosophical underpinning of the Division’s Research Program.
Karl T. Weber, MD
Neuton Stern Professor of Cardiovascular Medicine
Director, Division of Cardiovascular Diseases