1. health and fitness
2. disease

AUC Officers 2014-15
President
Jeffrey R. Bender, M.D.
Yale University School of Medicine
Vice President
C. Noel-Bairey-Merz M.D.
Cedars-Sinai Medical Center
Secretary-Treasurer
Ivor J. Benjamin, M.D.
The Medical College of Wisconsin
Councilors
Emelia J. Benjamin, M.D.
Boston University School of Medicine
Anne Curtis, M.D.
Buffalo General Hospital
Kim A. Eagle, M.D.
University of Michigan Health System
Robert Simari, M.D.
University of Kansas School of Medicine
PROGRAM
AND
ABSTRACTS
Association of University Cardiologists
Fifty-Fourth Annual Meeting
Carmel Valley Ranch
Carmel, California
January 21– 23, 2015
2015
2015 AUC Annual Meeting
Program
Thursday, January 22, 2015, cont.
Wednesday, January 21, 2015
2:00 PM – 5:00 PM
3:00 PM – 5:00 PM
6:00 PM – 8:00 PM
Council Meeting – Oak Room B
Emeritus Forum -Redwood CD
New Guidelines for the Prevention of
Cardiovascular Disease: Concept & Controversy
Sidney C. Smith, Jr., M.D., University of North
Carolina
Personalizing Medicine: Hype & Current Realty
Dan Roden, M.D., Vanderbilt University
Reception – Clubhouse
Thursday, January 22, 2015
8:00 – 9:00 AM
9:00 AM – 12:00 PM
9:00 – 9:45
1:05 – 1:35
An Evolving Understanding of Patients Presenting with
Non-ST Elevation Acute Coronary Syndromes (NSTE
ACS)
Robert A. Harrington, M.D., Professor of Medicine,
Stanford University
1:35 – 2:05
The Natriuretic Peptides and Cardiometabolic Health:
From Base Pairs to Bedside
Thomas J. Wang, M.D., Professor of Medicine
,Vanderbilt University Medical Center
2:05 – 2:35
Β- Aminoisobutyric Acid is an Exercise Myokine
Robert E. Gerszten, M.D., Professor of Medicine,
Massachusetts General Hospital
2:35 – 3:05
Moving Cardiovascular Risk Assessment Beyond a
Single Biomarker
L. Kristin Newby, M.D., Associate Professor of
Medicine, Duke University Medical Center
3:05 – 3:20
Break
3:20 – 3:50
The Heart Failure Epidemic: A Contemporary
Community Perspective
Veronique L. Roger, M.D., MPH Professor of Medicine
& Epidemiology, Mayo Clinic College of Medicine
3:50 – 4:20
Passive Myocardial Stiffness in Patients with Heart
Failure and a Preserved Ejection Fraction: Contributions
of Collagen and Titin
Michael R. Zile, M.D., Professor of Medicine, Medical
University of South Carolina & Department of Veterans
Affairs Medical Center
Continental Breakfast – Oak Room
The President’s Program - Redwood Room
THE 29th GEORGE BURCH MEMORIAL
LECTURE
Genes, Genomes and the Future of Medicine
Richard Lifton, M.D., Yale University School of
Medicine
9:45 – 10:30
FEATURED LECTURE
Cholesterol: A Guide for the Perplexed
Harlan Krumholz, M.D., Yale University School
of Medicine
10:30 – 11:00
Break – Oak Room
11:00 – 11:45
PRESIDENT’S LECTURE
Integrin-induced Effects on RNA Stability in
Angiogenesis and Neuroinflammation
Jeffrey Bender, M.D., Yale University School of
Medicine
11:45 – 12:00
Discussion
12:00 – 1:00
Lunch – Oak Room
1:00 – 5:00
First Scientific Session – Redwood Room
1:00 – 1:05
2015 AUC Annual Meeting
Program
Introduction of New Members in Attendance:
Keith Ferdinand
Robert Gerszten
Linda Gillam
Robert Harrington
L. Kristin Newby
Rita Redberg
Veronique Roger
Thomas Wang
2015 AUC Annual Meeting
Program
2015 AUC Annual Meeting
Program
Thursday, January 22, 2015, cont.
4:20-4:50
4:50 PM
7:00 PM – 11:00 PM
10:00 – 10:30
Break
Cardiac Transplantation in Foreclosure
Lynne W. Stevenson, M.D., Professor of
Medicine, Brigham & Women’s Hospital
10:30 – 11:00
The Blood Pressure Effects of New Antidiabetic Drugs
Keith Ferdinand, M.D., Professor of Clinical Medicine,
Tulane University School of Medicine
Adjourn for the day
11:00 – 11:30
Cardiovascular Disease and Diabetes as Cause of
Death in a Semirural Black/White Population: The
Bogalusa Heart Study
Gerald S. Berenson, M.D., Emeritus Boyd Professor
Tulane University Health Sciences Center
11:30 – 12:00
Discordance Between Methods for Assessment of
Mitral Regurgitation Severity: What Can Ventricular
Remodeling Tell Us?
Linda Gillam, M.D., Professor of Medicine, Atlantic
Health System
RECEPTION AND DINNER (BLACK TIE)
7:00 – 8: 00
Reception - Oak Room
8:00 – 11:00
Dinner – Redwood Room
Friday, January 23, 2015
7:30 AM – 8:00 AM
Continental Breakfast – Oak Room
8:00 AM – 9:00 AM
Business Meeting – Redwood Room
Memorial Minutes
Election of New Members
Election of Officers
Other New Business
9:00 AM – 12:00 PM
Second Scientific Session – Redwood Room
9:00 – 9:30
Selective Reporting of High-Risk Cardiovascular
Device Trials
Rita F. Redberg, M.D., Professor of Medicine,
University of California San Francisco Medical
Center
9:30 – 10:00
Estimating Sympathetic Tone by Recording
Subcutaneous Nerve Activity in Ambulatory Dogs
Peng-Sheng Chen, M.D., Ph.D., Chair of Cardiology,
The Krannert Institute of Cardiology
Adjourn
2015 AUC Annual Meeting
ABSTRACTS
An Evolving Understanding of Patients Presenting with Non-ST Elevation
Acute Coronary Syndromes (NSTE ACS)
2015 AUC Annual Meeting
ABSTRACTS
The Natriuretic Peptides and Cardiometabolic Health: From Base Pairs to
Bedside
Robert A. Harrington, MD, Stanford University, Stanford, CA
Thomas J. Wang, MD, Vanderbilt University Medical Center
The acute coronary syndromes (ACS) remain a major public health problem with
more than 2 million hospital admissions for patients presenting with NSTE ACS
annually around the globe, including more than 1.2 million in the United States.
Much progress has been made in our understanding of these patients presenting
with ACS over the last twenty-five years. A critical piece of this knowledge advance
has been the formation and ongoing continuation of global academic collaborations
as a unifying force to drive the science, the clinical trials and the clinical practice
guidelines. Advances in the management of these patients has been accompanied
by a change in the disease terminology, moving from the static, and retrospective
diagnoses of unstable angina and non-q-wave infarction to the dynamic diagnosis of
ACS.
The heart serves a major endocrine function by producing a family of hormones
known as the natriuretic peptides (NPs). The classical actions of the NPs are
natriuresis,diuresis, and vasodilation. In the past decade, a large body of
experimental evidence has emerged that the NPs have metabolic actions as well,
including lipolysis, activation of brown fat, and enhanced thermogenesis.
Collectively, these data suggest that the NP axis could play a key role in
modulating susceptibility to cardiometabolic risk. Genetic and environmental
factors influence the heart’s ability to produce NPs at rest and with stress (for
instance, with salt loading). For instance, obese individuals have 20-40% lower
circulating NPs than lean individuals, despite having greater degrees of RAAS
activation, increased plasma volume, and hypertension (factors that should trigger
NP release). Reduced cardiac synthesis of NPs is observed in murine models of
weight gain and obesity, and may be mediated in part by altered insulin signaling.
Genetic data support the hypothesis that reduced NP production can interfere with
salt homeostasis and fat metabolism. Mice with NP deficiency have hypertension,
ventricular hypertrophy, and glucose intolerance. In humans, approximately 40% of
the inter-individual variability in circulating ANP and BNP is attributable to additive
genetic factors. A variant in the 3’ UTR of the NPPA gene (rs5068) is associated
with 50% higher levels of ANP in individuals on standardized diets, and a 10-15%
lower long-term risk of hypertension. We have shown that this effect is mediated
by a cardiac-expressed microRNA (miR-425) that modulates ANP production in an
allele-specific manner, with the minor allele conferring resistance to
downregulation by miR-425. These findings illustrate a novel mechanism for salt
homeostasis involving a microRNA. Given the tendency for obesity to inhibit NP
production, obese persons could be caught in a “vicious cycle,” whereby a
suppressed NP system impairs the ability to resist fat accumulation. Weight loss or
intensive lifestyle modification can, at least partially, reverse the low NP levels.
Pharmacologic interventions offer additional possibilities. For instance, preliminary
data suggest that augmenting cGMP with phosphodiesterase-5 inhibitors may
have favorable metabolic effects. Other agents that modulate NP/cGMP signaling,
in various phases of development and testing, could lead to novel approaches for
the treatment of individuals with cardiometabolic disease.
This shift in thinking about the acute presentation has provided some of the impetus
for the evolution of antithrombotic therapies, progressing from the use of aspirin and
unfractionated heparin to more sophisticated target directed-regiments of both
antiplatelets (glycoprotein IIb/IIIa inhibitors, P2Y12 inhibitors) and anticoagulants
(low molecular weight heparins, direct thrombin inhibitors, factor Xa inhibitors).
Critical insights into the optimal balance of ischemic protection while reducing
bleeding risk have been important, and ongoing, areas of clinical investigation. Risk
stratification initially, and importantly, focused on the 12-lead ECG but has evolved
to involve more detailed risk scores that incorporate patient characteristics, the ECG
and an increasing list of biomarkers to provide both prognostic and therapeutic
guidance at the point-of-care. Understanding how to integrate risk knowledge,
antithrombotic therapies and use of coronary angiography/revascularization has
been critical to continuing to improve outcomes among this group of patients.
While much focus of clinical investigation among the group of patients with NSTE
ACS, has been on the period of acute presentation given the heightened early risk
of death and other ischemic complications, the long-term follow-up studies has
made clear that much work needs to be done in attenuating the accumulating risk
over time.
2015 AUC Annual Meeting
ABSTRACTS
2015 AUC Annual Meeting
ABSTRACTS
Β-Aminoisobutyric Acid is an Exercise Myokine
Moving Cardiovascular Risk Assessment Beyond a Single Biomarker
Lee Roberts, Ponus Bostrom, John O’ Sullivan, Robert Schinzel, Gregory Lewis,
Andre Dejam, Youn-Kyoung Lee, Melinda J. Palma, Sondra Calhoun, Anastasia
Georgiadi, Ming-Juei Chen, Vasan Ramachandran, Martin Larson, Claude
Bouchard, Tuomo Rankinen, Amanda Souza, Clary Clish, Thomas Wang, Jennifer
Estall, Alexander Soukas, Chad Cowan, Bruce Spiegelman, Robert E. Gerszten,
Massachusetts General Hospital
Exercise is an effective intervention for both the prevention and treatment of obesity
and type 2 diabetes. Recent studies suggest that skeletal muscle integrates many
of the signals contributing to the salutary effects of exercise. The transcriptional coactivator peroxisome proliferator-activated receptor-gamma co-activator-1  (PGC1) regulates metabolic genes in skeletal muscle, and contributes substantially to
the response of muscle to exercise. Muscle specific PGC-1 transgenic expression
and exercise both increase the expression of thermogenic genes within white
adipose. How the PGC-1 mediated response to exercise in muscle conveys
signals to other tissues remains incompletely defined.
We employed a metabolic profiling approach to examine metabolites secreted from
myocytes with forced expression of PGC-1, and identified β-aminoisobutyric acid
(BAIBA) as a novel small molecule myokine. BAIBA increases the expression of
brown adipocyte-specific genes in white adipose tissue and fatty acid β-oxidation in
hepatocytes both in vitro and in vivo through a PPARα mediated mechanism,
induces a brown adipose-like phenotype in human pluripotent stem cells, and
improves glucose homeostasis in mice. In humans, plasma BAIBA concentrations
are increased with exercise and inversely associated with metabolic risk factors in
population based cohorts such as the Framingham Heart Study. BAIBA may thus
contribute to exercise-induced protection from metabolic diseases.
L. Kristen Newby, MD, MHS, Duke University Medical Center
Hundreds of reports of protein biomarker associations with cardiovascular
outcomes appear in the peer reviewed literature each year, but often in isolation of
other putative biomarkers and with limited consideration of clinical predictors of
outcome. As a first step to understanding the relative importance of the biomarkers
in published observations, we assayed 53 of these putative protein biomarkers that
had at least modest literature-reported association with outcomes (HR >1.50) in 550
individuals with suspected coronary disease in the MURDOCK Horizon 1
Cardiovascular Disease Study. Using a modern statistical approach (penalized
regression using the Elastic Net) to perform coefficient estimation and variable
selection simultaneously across potentially collinear variables (proteins sharing the
same biological “pathway”) as well as unrelated biomarkers and detailed clinical
characterization, we generated smaller panels of biomarkers that were
independently associated with outcomes. For example, this method identified a set
of 6 biomarkers (ICAM-1, MMP-3, NT-proBNP, IL-6, sCD40L, and IGFBP2) and 5
clinical variables (age, red-cell distribution width, diabetes mellitus, hemoglobin, and
New York Heart Association class) that were strongly associated with death or
myocardial infarction during a median 2.5 years of follow up. While this reflects an
important step forward, these methods and results only scratch the surface of what
is needed and soon may be possible to bring the promise of “stratified medicine” to
fruition. Although genetic, protein, metabolite, and transcriptomic biomarkers have
been associated with cardiovascular risk, their contributions that may reflect
multiple intersecting pathways or read outs on the same pathway may not be
considered in the context of systems biology, and most frequently assessment of
disease state and risk is static, failing to incorporate the influence of temporal
changes in biology or the interactions of the macro- and micro-environment or
individual behavior with biology over time. Longitudinal population registries and
biorepositories, advances in molecular platform technology, and access to
electronic health records combined with evolution in computing, informatics, and
statistical capabilities promise to enable temporal characterization of health and
disease not only by gross phenotypic observation but according to underlying
molecular mechanism and influence of social determinants, and in turn enable
development of targeted therapeutic interventions and disease prevention
strategies at the individual and population levels.
2015 AUC Annual Meeting
ABSTRACTS
The Heart Failure Epidemic: A Contemporary Community Perspective
2015 AUC Annual Meeting
ABSTRACTS
Passive Myocardial Stiffness in Patients with Heart Failure and a
Preserved Ejection Fraction: Contributions of Collagen and Titin
Veronique L. Roger, MD,MPH, Mayo Clinic College of Medicine
Designated at the turn of the century as a new epidemic of cardiovascular disease,
heart failure (HF) constitutes a staggering clinical and public health problem,
associated with significant mortality, morbidity, and healthcare expenditures,
particularly problematic in an aging population. Epidemiologic data indicate that the
incidence of HF has in fact remained stable over the past two decades and that the
burden of HF is related to recurrent hospitalizations among a growing number of
persons living with HF.
HF symptoms reflect is a heterogeneous clinical syndrome, which can present with
preserved or reduced ejection fraction. The case mix of HF has changed markedly
over time with a growing proportion of cases presenting with preserved ejection
fraction. It is increasingly recognized that HF with preserved ejection fraction is itself
a heterogeneous condition and its mechanistic underpinnings have yet to be fully
delineated. Indeed, numerous factors have been envisioned involving the heart and
other organs and a complex cross talk with coexisting chronic conditions.
Importantly, there is no specific treatment for HF with preserved EF and its
outcomes, death and hospitalizations, are similar to those of HF with reduced EF.
While important progress has been made in improving the survival of patients living
with HF, hospitalizations remain frequent and a substantial number of
hospitalizations are not related to HF.
To prevent hospitalizations, a comprehensive characterization of their determinants
is imperative and must integrate the impact of multimorbidity related to coexisting
conditions. New models of patient-centered care that draw on community-based
resources to support HF patients with complex coexisting conditions hold the
promise to alter the course of the burden of hospitalizations in HF.
Michael R. Zile, MD, C. Baicu, J. Ikonomidis, R. Stroud, P. Nietert, A.
Bradshaw, R. Slater, B. Palmer, P. Van Buren, M. Meyer, M. Redfield, D. Bull,
H. Granzier, M. LeWinter, Medical University of South Carolina
Medical University of South Carolina & Department of Veterans Affairs Medical
Center, Charleston, SC, University of Arizona, Tucson, AZ, University of Vermont,
Burlington, VT, Mayo Clinic, Rochester, MN, University of Utah Health Sciences
Center, Salt Lake City, UT.
Background: The purpose of this study was to determine whether patients with
heart failure and a preserved ejection fraction (HFpEF) have an increase in
passive myocardial stiffness and the extent to which discovered changes are
dependent on changes in extracellular matrix fibrillar collagen and/or
cardiomyocyte titin.
Methods and Results: Seventy patients undergoing coronary artery bypass grafting
underwent an echocardiogram, plasma biomarker determination, and intraoperative left ventricular (LV) epicardial anterior wall biopsy. Patients were divided
into 3 groups: referent control (n=17, no hypertension or diabetes), hypertension
(HTN) without(-) HFpEF (n=31), and HTN with (+)HFpEF (n=22). One or more of
the following studies were performed on the biopsies: passive stiffness
measurements to determine total, collagen-dependent and titin-dependent
stiffness (differential extraction assay), collagen assays (biochemistry or histology),
or titin isoform and phosphorylation assays. Compared with controls, patients with
HTN(-)HFpEF had no change in LV end diastolic pressure (LVEDP), myocardial
passive stiffness, collagen, or titin phosphorylation but had an increase in
biomarkers of inflammation (CRP, sST2, TIMP-1). Compared with both control and
HTN(-)HFpEF, patients with HTN(+)HFpEF had increased LVEDP, left atrial
volume, NT-proBNP, total, collagen-dependent and titin-dependent stiffness,
insoluble collagen, increased titin phosphorylation on PEVK S26, reduced
phosphorylation on N2B S469, and increased biomarkers of inflammation.
Conclusions: Hypertension in the absence of HFpEF, did not alter passive
myocardial stiffness. Patients with HTN(+)HFpEF had a significant increase in
passive myocardial stiffness; collagen-dependent and titin-dependent stiffness
were increased. These data suggest that the development of HFpEF is
dependent on changes in both collagen and titin homeostasis.
2015 AUC Annual Meeting
ABSTRACTS
Cardiac Transplantation in Foreclosure
Lynne W. Stevenson, MD, Brigham & Women’s Hospital
Current estimates of about 150,000 potentially eligible patients contrast with the donor
supply of about 2,200 hearts annually. After listing, the highest of 3 priority levels, Status
IA, requires ongoing support with high dose inotropic therapy, extracorporeal support, or a
life-threatening complication of an implanted VAD. Although this priority assumed death
would otherwise be imminent within a few days, the average waiting time at IA ranges is
currently over 6 months in the worst regions. The proportion of recipients supported by
VAD prior to transplant is about 40% nationwide, but almost 100% in regions with longer
waiting times, where ideal candidates for transplantation must undergo obligatory VAD
surgery first, after which over 30% will become ineligible for transplantation. The most
troubling ethical aspect of the current lifeboat dilemma is the inequity of access; patients
with sufficient resources now move across the country with their families for 6-12 months
to undergo transplantation with short waiting times in the regions where donor hearts are
more plentiful.
Focus on risk scores for revision of the priority system diverts attention from the
fundamental insolvency of the waiting list. In addition to 4,000 patients already waiting
for hearts, about 30% more patients are listed each year than actually undergo
transplantation. While laudable efforts continue to encourage organ donation and
improve donor preservation, the most consistent response to the donor- recipient
disparity is to take greater risks with marginal donors. Regardless of these efforts, we
cannot continue to make more promises than we can keep. The list must return to an
equilibrium at which the number of added patients matches the number of patients
removed.
If we reduced new listings by 20-25%, within 5 years the list could reach a steady state at
less than 1,000, and a majority of patients listed would be again able to undergo
transplantation within a year. It would not be necessary for patients to undergo additional
surgery for ventricular assist devices except when needed urgently to sustain organ
function and the success of transplantation. How could the list be trimmed? Many contraindications for transplantation have been stretched since approval for reimbursement in
1984, such as diabetes, renal dysfunction, substance abuse or non-compliance, obesity
and advanced age. Regardless of which criteria are selected for revision, it will be
necessary to reach national consensus. Like disarmament, constraint will not be effective
if optional, as patients will shop among centers for a favorable decision. The transplant
community bears responsibility for failing to support both realistic expectations and a
robust portfolio of alternative care programs when neither transplantation nor mechanical
support are good options. There have always been many more people rejected for
transplantation than accepted. It is vital that the medical community align to say "no" to a
few more in order to ensure that all available hearts are distributed equitably and ethically
for the greatest benefit.
2015 AUC Annual Meeting
ABSTRACTS
Selective Reporting of High-Risk Cardiovascular Device Trials
Chang L, Dhruva S, Chu J, Bero L, and Redberg RF.
Objective: To compare clinical trial characteristics and safety and effectiveness
results reported in FDA documents for recently approved high-risk cardiovascular
devices with the trial characteristics and results reported in peer-reviewed
publications.
Design and Setting: A search of the publicly available FDA database was
performed for all cardiovascular devices receiving premarket approval between Jan
1, 2000 and December 31, 2010. For each study listed in the premarket approval
documents, a Medline search was conducted to obtain the corresponding
publication.
Main Outcome Measures: Clinical trial characteristics, primary endpoints, and
safety and efficacy results were compared between the FDA documents and their
corresponding publications.
Results: There were 106 cardiovascular devices that received premarket approval
between January 1, 2000 and December 31, 2010. FDA premarket approval
documents for these devices contained a total of 177 studies of which 86 (49%)
were published as of January 1, 2013. The mean time from FDA approval to
publication was 6.5 months (range -4.8 to 7.5 years). Enrollment number differed
for 22 (26%) of the studies compared. Of 152 primary endpoints identified in the
FDA documents, three (2%) were labeled as secondary, 43 (28%) were unlabeled,
and 15 (10%) were not found in the corresponding publications. Among the primary
results, 69 (45%) were identical, 35 (23%) were similar, 17 (11%) were substantially
different, and 31 (20%) could not be compared.
Conclusions: Many clinical trials for FDA-approved high-risk cardiovascular
devices remain unpublished. Even when published, the study population, primary
endpoints, and results can differ substantially from data submitted to the FDA.
2015 AUC Annual Meeting
ABSTRACTS
Estimating Sympathetic Tone by Recording Subcutaneous Nerve Activity in
Ambulatory Dogs
Peng-Sheng Chen, MD, The Krannert Institute of Cardiology and Division of
Cardiology, Department of Medicine, Indiana University School of Medicine
Background. The skin of the canine upper thorax is extensively innervated by
sympathetic nerves from the stellate ganglion. We hypothesize that it is possible to
record sympathetic nerve activity from the subcutaneous tissues of the skin, and
that the subcutaneous nerve activity (SCNA) can be used to estimate the stellate
ganglion nerve activity (SGNA).
Methods and Results: In the first study, we implanted radiotransmitters in normal
ambulatory dogs to record left SGNA, left thoracic vagal nerve activity (VNA) and
left thoracic SCNA. There was a significant positive correlation between integrated
SGNA (iSGNA) and integrated SCNA (iSCNA) in 7 ambulatory dogs, with
correlation coefficient of 0.70 (95% confidence interval, CI, 0.61 to 0.84, p < 0.05 for
each dog). Tachycardia episodes (heart rate exceeding 150 bpm for ≥ 3 s), were
invariably preceded by SGNA and SCNA. There was circadian variation of both
SCNA and SGNA. Video monitoring in additional 3 dogs showed that movement
was not a cause of high frequency SCNA. The right SGNA correlated strongly with
right SCNA and heart rate in 2 anesthetized dogs after apamin injection into the
right stellate ganglion. In a second study, we implanted radio transmitters to
continuously monitor left stellate ganglion and subcutaneous electrical activities in 7
ambulatory dogs with myocardial infarction, complete heart block and nerve growth
factor infusion to the left stellate ganglion. SCNA preceded a ventricular tachycardia
(VT), ventricular fibrillation (VF), frequent bigeminy or couplets and premature
ventricular contractions within 15 s in 70%, 59% and 61% of arrhythmias,
respectively. Similar incidence of 75%, 69% and 62% was noted for SGNA. The
Pearson’s correlation coefficient for integrated SCNA and SGNA was 0.73±0.18
(p<0.0001 for all dogs, n=5). Both SCNA and SGNA exhibited circadian variation.
Conclusions: SCNA recorded by bipolar subcutaneous electrodes can be used to
estimate the sympathetic tone and predict susceptibility to VT and VF in a canine
model of ventricular arrhythmia and sudden cardiac death.
2015 AUC Annual Meeting
ABSTRACTS
The Blood Pressure Effects of New Antidiabetic Drugs
Keith Ferdinand MD, Professor of Clinical Medicine, Tulane University School of
Medicine
More than 70% persons with diabetes mellitus(DM ) have hypertension (HTN) or
take antihypertensive medications; and coexisting HTN and DM is associated with:
,
doubling stroke or cardiovascular (CV) disease risk 5- to 6-fold X risk for end stage
),
renal disease(ESRD increased peripheral vascular disease and lower extremity
amputations and retinopathy The mechanism(s) of action and associated blood
pressure (BP) effects of new antidiabetic drugs, sodium glucose co-transporter
(SGLT) inhibitors and glucagon-like peptide–1 (GLP-1) agonists, are described. The
SGLT2 inhibitors, the newest antidiabetic medication class approved, block the
reabsorption of glucose in the kidney; the chronic osmotic diuresis may reduce BP.
There are reductions in clinic SBP up to 5mmHg described in trials with
dapagliflozin and canagliflozin. A new study will use the better technique of
ambulatory blood pressure monitor (ABPM) to study the effects of empagliflozin, the
most recently approved agent, in African Americans, who have a higher risk for DM,
HTN and CV disease. Assessment of both glucose and BP lowering effects of
empagliflozin in hypertensive African American patients with type 2 DM could
provide clinically highly relevant, new information for the use of empagliflozin.
The injectable GLP-1 agonists lower glucose by direct interaction with GLP-1
receptors on specific tissues and may lower BP. A recent large, randomized,
placebo-controlled, international trial (N=755), with ambulatory blood pressure
monitor (ABPM) has been published. The once-weekly GLP-1 receptor agonist,
dulaglutide doses (0.75 mg and 1.5mg) shown to be noninferior to placebo on
mean 24-hr SBP and DBP. Moreover, dulaglutide 1.5 mg shown to significantly
reduce mean 24-hour SBP approximately 2 to 3 mm Hg. The clinical significance of
the reduction in SBP and small HR increase with dulaglutide is not known. The
potential mechanism(s) of action and outcome significance of these BP/HR effects
findings are not known.
2015 AUC Annual Meeting
ABSTRACTS
Cardiovascular Disease and Diabetes as Cause of Death in a Semirural
Black/White Population: The Bogalusa Heart Study
Gerald S. Berenson, MD, Sathanur R. Srinivasan, PhD, Rupert Barshop, MPH,
Camilio Fernandez, MD, MSC; Ji-Hua Xu, MD; Wei Chen, MD, PhD. Tulane
University Health Sciences Center, New Orleans, LA
Tulane University Health Sciences Center. New Orleans, LA
The Bogalusa Heart Study (BHS) has been ongoing over the past 4 decades. Its
primary mission and most critical observation is that cardiovascular (CV) diseases,
hypertension and diabetes are the major causes of death with evidences of risk
factors related to these causes begin in childhood. Some 566 deaths have now
occurred from all causes, including: traumatic, motor vehicle accidents, homicides
and suicides. Cardiovascular events as an apparent cause begin to appear in the
4th decade of life. Some 156 have cardiac events and 40 cases have died from
myocardial infarction based on local obituaries, coroner records and death
certificates and personal information by BHS staff. Comparative risk factor data from
their last observation and in those with myocardial infarction, 4 to 35 years ago to
earlier levels in childhood show differences from the overall general population.
Trends of risk factor differences are noted but because of small numbers of subjects
with MI the childhood values for prediction are not statistically significant. The
average age of death from MI is shown in the attached table.
It is apparent that deaths from CV disease and type II diabetes mellitus are
prominent and occur at a young age. These observations provide a reason to begin
primordial prevention in early life.
2015 AUC Annual Meeting
ABSTRACTS
Discordance Between Methods for Assessment of Mitral Regurgitation
Severity: What Can Ventricular Remodeling Tell Us?
Linda Gillam, MD, Atlantic Health System
Background: Recent guidelines supporting prophylactic surgery in asymptomatic patients
with primary mitral regurgitation (MR) who are free of left ventricular systolic dysfunction and
other triggers for intervention (atrial fibrillation, pulmonary hypertension) mandate an accurate
reproducible assessment of MR severity. Since the surgery is associated with risks of death,
stroke and the possibility of unsuccessful repair, it is important that intervention be limited to
those whose regurgitation is severe. While magnetic resonance imaging (MRI) provides robust
methods for assessing valvular regurgitation, the assessment of MR severity is frequently
based on echocardiography alone. While the American Society of Echocardiography
recommends an integrated approach, its guidelines provide no guidance as to weighting of
what may be discordant measures and emphasize parameters that reflect color Doppler jet
characteristics assessed at a single point in systole. Prior studies have reported variable
agreement between MRI and echocardiographic estimates of MR severity but have been
limited by the absence of a reliable independent gold standard, the limitations of angiographic
grading being well appreciated. The degree of left ventricular remodeling following mitral valve
surgery may provide such a reference standard.
Methods: In a series of prospective multicenter studies, MR severity has been assessed
using both echocardiography (2D and 3D) and MRI. Echocardiographic methods include vena
contracta, PISA determined effective regurgitant orifice area, regurgitant volume, regurgitant
fraction, jet area as well as the assessment of pulmonary venous and peak antegrade mitral
flow velocities. MRI derived indices are regurgitant volume and regurgitant fraction as well as
left ventricular volumes. Clinical variables including symptom status, exercise performance
and BNP are also captured. In patients, undergoing isolated mitral valve surgery, an
additional MRI is performed 5-7 months following surgery to reassess LV volumes. Primary
analyses have focused on the reproducibility of the methods, concordance of
echocardiographic and MRI grading of MR and the ability of MR quantitation to predict postsurgical LV remodeling.
Initial results (in press): In the initial cohort of 103 pts with MR (82% primary, 18%
functional), 38 of whom underwent mitral surgery and 26 of whom had post-surgical MRI,
agreement between MRI and integrated 2D echocardiographic estimates of MR severity was
modest (r = 0.6, p <0.0001) with poorer correlation in the subset sent for surgery (r = 0.4,
p=0.01) and with echo tending to overestimate MR severity as judged by MRI. There was a
strong correlation between post surgical LV remodeling and MR severity as assessed by MRI
(r = 0.85, p<0.0001), and no correlation between post surgical LV remodeling and MR severity
as assessed by 2D echocardiography (r = 0.32, p=0.1).
Conclusions: MRI may be superior to 2D echo for the assessment of MR severity and may
be important in confirming the presence of severe MR in patients being considered for
surgery, particularly in the absence of symptoms.
Ongoing studies: Additional studies are underway incorporating clinical outcomes, subgroup
analyses based on MR etiology, and evaluating echo-MRI correlation for 3D echo approaches
as well as individual 2D echo approaches.
AUC Upcoming Meetings
UPCOMING MEETINGS

January 13-15, 2016
Renaissance Vinoy, St. Petersburg, Florida

January 18-20, 2017
Royal Palms Resort & Spa, Phoenix, Arizona