The Facts Karla M. Ku - The Methodist Hospital

Journal of THE METHodisT dEbakEy HEarT cEnTEr VoluME 2, nuMbEr 1, 2006 

Photo illustration of a graft 

A quarterly publication of 

The Methodist Hospital, Houston, TX 

Page 4 

Venous Thrombosis Trials at 

The Methodist Hospital in Houston 

James Muntz 

Page 8 

Cardiovascular Disease in 

Women: The Facts 

Karla M. Kurrelmeyer 

Page 13 

Surgery Versus Alcohol Septal 

Ablation for Hypertrophic Obstructive 

Cardiomyopathy: The Controversy 

William H. Spencer, III 

Page 18 

Obesity and Cardiovascular Disease: 

A Bad Relationship That Needs to 

Change 

Peter H. Jones 

Page 22 

Peroxisome Proliferator-Activated 

Receptors (PPAR): A Potential Strategy 

to Combat Lipotoxic Heart Disease 

Qi Tian, Philip M. Barger 

Page 25 

Combined Open and Stent Graft Repair 

of an Arch and Descending Thoracic 

Aortic Aneurysm: The Hybrid Procedure 

Michael J. Reardon, Wei Zhou, Jon-Cecil 

Walkes, Alan B. Lumsden

We Welcome your 

questions a nd comments 

inquiries and letters to the editor can be 

directed to jmdhc@tmh.tmc.edu. 

William l. Winters, Jr., Md 

Editor-in-chief 

Journal of the Methodist 

DeBakey Heart Center 

Journal of the 

me thodist deBake y 

he art center 

Volume 2, numBer 1 

William L. Winters, Jr., M.D. 

Editor-in-Chief 

Sheshe Giddens 

Managing Editor 

John K. Dietrich 

Assistant Editor 

Advisory Board: 

Christie Ballantyne, M.D. 

Stan Duchman, M.D. 

Raphael Espada, M.D. 

Robert Hust, M.D. 

Karla Kurrelmeyer, M.D. 

Mike Reardon, M.D. 

JMDHC provides an update from 

Methodist DeBakey Heart Center 

specialists about leading edge research, 

diagnosis and treatment. 

U.S.News & World Report ranks the 

Methodist DeBakey Heart Center’s 

cardiology, cardiothoracic and 

vascular surgery programs number 

16 in the nation. 

JMDHC is written for physicians and 

should be relied upon for medical 

education purposes only. It does 

not provide a complete overview of 

the topics covered and should not 

replace the independent judgment of 

a physician about the appropriateness 

or risks of a procedure or treatment 

for a given patient. 

© 2006 The Methodist Hospital 

Houston, Texas 

Methodist DeBakey 

Heart Center 

6565 Fannin 

Houston, Texas 77030 

Telephone: 713-DEBAKEY 

debakeyheartcenter.com

TO T E AC H I S TO L E A R N 

W i l l i a m L . W i n t e r s 

F r o m M e t h o d i s t D e B a k e y H e a r t C e n t e r a n d B a y l o r C o l l e g e o f M e d i c i n e , H o u s t o n , Te x a s 

How often have you heard someone 

say, “I learn more from preparing a 

lesson than my class will ever learn 

from listening to me deliver it”? It’s no 

secret that sharing personal experiences 

with others who have had similar experiences 

reinforces the message shared. 

Teaching and learning may be delivered 

in a variety of formats, especially in the 

field of medicine. 

I recently attended a superb conference 

structured around the discipline 

of echocardiography. As a disclaimer, I 

do admit to some bias toward echocardiography, 

having been seduced by the 

potential by-product of cardiac ultrasound 

some 40 years ago and then 

befriended by Drs. Inge Edler and 

Helmuth Hertz, whose fairly simple 

idea has blossomed into an extraordinary 

science. 

The message delivered at this conference 

was well prepared and presented. 

Some information was new, some old 

and revisited with new perspective, but 

when delivered expertly it is always 

worth hearing again. What has stuck 

with me after leaving that conference 

has been the message from the many 

case reports — including a brief clinical 

review and reports of the laboratory, 

ECG, X-ray and echocardiography 

findings — that were presented each 

morning. 

Echocardiography provided the 

opportunity to visualize the problem, 

discuss the pathophysiology, make 

differential diagnoses and highlight the 

important features. Each report was 

followed by a brief discussion directed 

by the case presenter and the moderator. 

The experience was absolutely spellbinding 

and guaranteed to have everyone 

awake and eager for the first lecturer. 

Upon my return, I came across an 

editorial by Dr. C. Richard Conti, 

editor-in-chief of Clinical Cardiology. 1 

For those of you who enjoy reading 

editorials, I believe his are among 

the most interesting and informative 

around. His topic is case-based teaching 

and learning. He and I are of an 

era when presentations of clinical cases 

by students to mentors, followed by 

brief discussions by all involved, was a 

major modus operandi for teaching clinical 

sciences. That put the onus on all 

parties to be prepared. Over the years, 

as the sheer volume and complexity of 

medical information has increased, not 

to mention the array of diagnostic capabilities 

and therapeutic options, it is my 

perception that didactic lectures are now 

the standard when planning educational 

programs — albeit with fascinating 

technical computer tricks to keep attention 

focused. 

In years past, medical grand rounds 

at The Methodist Hospital was a major 

weekly event where physicians vied for 

the opportunity to participate. Slide 

lectures were important, but the really 

entertaining and educational programs 

were those in which clinical cases were 

presented and discussed. I don’t believe 

that has occurred for the past 20 years. 

Roughly 35 years ago, in an attempt 

to stimulate an educational collegial 

spark among those interested in cardiovascular 

education, a small group of us 

from the American Heart Association’s 

Physicians’ Education Committee 

formed the Houston Society of 

Cardiology. The format required participation 

on a rotating basis of physicians 

interested in cardiovascular medicine. 

Physicians, students and trainees from 

each major hospital in the city, most 

of which were in the Texas Medical 

Center at that time, were all invited 

to participate. Attendance at those 

monthly meetings often exceeded 100 

individuals — far exceeding our expectations. 

Most presentations involved 

case reports, and it proved to be one 

of the most exciting and interesting 

educational enterprises I’ve ever been 

associated with. Prominent physicians 

joined in, among them cardiologists, 

cardiovascular surgeons, radiologists 

and pathologists. Rather than lectures, 

the cardiovascular surgeons presented 

fascinating surgical problems, the radiologists 

some unbelievable X-ray problems, 

and the pathologists those beguiling 

things we often overlooked as clinicians. 

On one occasion, Dr. Miguel Quiñones 

and I presented a town-meeting-type 

program around the discipline of echocardiography. 

We each stood at one side 

of a large screen and presented echocardiographic 

cases to each other with 

audience participation. It was a howling 

success, being entertaining as well as 

educational. 

Then a funny thing began to happen. 

After a number of years, respected guest 

lecturers began to appear in place of case 

reports. The requirement for program 

presentation by participating hospitals 

was dropped, and soon attendance at 

the meetings declined to the point where 

the American Heart Association lost 

interest and ultimately declined further 

support — ironic, given that the idea 

was originally conceived in the AHA 

Physicians’ Education Committee. I 

have always believed that a major culprit 

in the Houston Cardiology Society’s 

demise was the loss of local physician 

participation from the major hospital 

groups and the case-based teaching and 

discussion. 

As I read the editorial by Dr. Conti, 

I was reminded how echocardiography 

is the heart of cardiovascular imaging. 

Continued on page 28 

JMDHC | II (1) 2006 1

let te Rs to tHe e dItoR 

Send letters to the editor to 

William L. Winters, M.D., 

jmdhc@tmh.tmc.edu or mail 

a disk or CDROM and a print 

out to JMDHC, 8060 El Rio 

St., Houston, TX 77054. Letters 

discussing a recent JMDHC article 

should not exceed 600 words in 

length and limited to one figure 

or table and five references. They 

should be double-spaced and a 

word count should be provided. 

The names, academic degrees, and 

primary institutional affiliations of 

all authors as well as the address, 

telephone and fax numbers, and email 

address for the corresponding 

author must be included in the text 

of the letter in order to be considered 

for publication. Letters will be 

published at the discretion of the 

editor-in-chief and are subject to 

editing for style and space requirements. 

L E T T E R T O T H E E d I T O R 

Consultant Roles 

Dear Dr. Winters: 

I had occasion recently to read your 

essay on “Etiquette Guidelines for 

Consultants? Are There Any?” 

JMDHC 1(4) 2005. I enjoyed what 

you had to say. A colleague at the 

University of Miami Miller School of 

Medicine sent it to me after I sent him 

an expanded version of something he 

requested, which I prepared many years 

ago for GI fellows in training at UM. 

Having retired December 12, 2001, I 

had almost forgotten that I had. 

The teaching of important nontechnical 

(in the traditional sense) skills 

designed to improve doctor-doctor and 

doctor-patient communication, confidence, 

and trust should begin early in 

training. 

I hope you enjoy reading what I have 

prepared on the topic of becoming an 

effective consultant, whether performing 

a cognitive or technical service. 

Best wishes, 

Arvey I. Rogers, MD, FACP 

Professor Emeritus (Retired) 

Internal Medicine/Gastroenterology 

University of Miami Miller 

School of Medicine 

IntRoduCtIon 

• You will be asked frequently to 

provide assistance/expertise (consult) 

in the management of patients with 

suspected or established disorders of 

the digestive system. 

• The assistance may be of an urgent or 

elective nature. 

• The request for your expertise may 

come in written or verbal form. 

• You possess expertise which the 

consulting physician does not. 

• How you provide your expertise 

reflects on you specifically and the 

service you represent generally. 

• While there are many ways to func- 

tion at a high level as a consultant, a 

proposed set of guidelines follows: 

GuIdelInes 

1. Respond promptly to the consultation 

request. 

2. Communicate verbally with the 

consulting physician for several 

reasons: 

a. Establish a personal relationship. 

b. Assess the urgency of the consult. 

c. Determine the specific reason for 

the consult, i.e., To perform a procedure? 

To answer a question? To 

follow up on a consult provided 

previously by a colleague? 

d. Assess the level of knowledge of the 

consulting physician. 

e. Gather additional data to assist you 

in planning the consult, i.e., what is 

needed, in what setting, with what 

preparation, etc. 

f. Inform the consulting physician 

when you will be seeing the patient. 

3. Establish a consultant relationship 

with the patient, explaining 

your role; that you will be working 

closely with the patient’s primary 

physician who will be informed of 

your findings and recommendations; 

and that you will follow up as 

necessary. 

4. Provide answers and recommendations 

(verbally and in writing) 

expeditiously and be certain they are 

understood by the consulting physician. 

5. Teach with humility. 

6. Provide appropriate current or 

classic references (affix a copy of an 

article when appropriate). 

7. Be certain that the consulting physician 

wishes you to remain involved 

in the care of the patient; avoid 

assuming control or “taking over” 

the case. 

8. Write legibly! 

9. “Sign off” the case with the knowledge 

of the consulting physician. 

10. Be certain that your attending or 

responsible fellow (more senior to 

you) knows about the consult, your 

2 II (1) 2006 | JMDHC

ecommendations, and (when possible) 

actually reads what you have 

written. 

11. Follow up to learn the patient’s 

outcome! 

Pe RfoRmInG a PRoCeduRe — 

unIque GuIdelInes 

Many of the consultations you receive 

will be for the purpose performing 

a diagnostic/therapeutic procedure, 

urgently or electively. The following 

suggestions are offered to maximize 

your role as a consultant under these 

specific circumstances: 

1. If received “after hours,” assess the 

urgency of the request. 

2. Assess the level of urgency and 

whether or not to “come in” depend 

upon the level of knowledge/competency 

of the consulting physician, 

your assessment of same, and your 

assessment as well as to the level of 

anxiety experienced by the “consulting 

physician.” 

3. When in doubt, speak to the most 

senior member of the patient care 

team. 

4. When in doubt, meet the team at 

the bedside. 

5. In doing so, you accomplish the 

following: 

a. Make your own assessment of the 

situation 

b. Transmit knowledge and confidence 

to the patient and the team. 

c. Determine whether a procedure or 

needed or not and, if needed, when. 

d. You represent your department in 

the right light. 

6. Whenever a procedure is required, 

whether urgently or electively, and 

whether for diagnostic and/or therapeutic 

purposes, do the following: 

a. Be certain the consulting physician 

understands what you plan to do. 

b. Be certain s/he and the patient or 

a surrogate understand the limitations/risks 

of the procedure. 

c. Invite the consulting physician to be 

present at the procedure. 

7. Be certain that the consultant physi- 

JMDHC | II (1) 2006 

L E T T E R T O T H E E d I T O R 

cians (your colleagues) involved 

in performing the procedure are 

sufficiently skilled to handle the 

fundamentals as well as anticipated 

adverse occurrences. Involve your 

attending! 

8. Discuss your findings and implications 

for management with the 

consulting physician. 

9. In a progress note, summarize your 

findings/recommendations/plans for 

follow-up. 

10. If biopsies are obtained or other 

tissue removed, accept responsibility 

for obtaining the results, discussing 

them and their implications for 

further management; write a brief 

note. 

11. Follow up to assess the patient’s 

outcome! 

e R R at u m 

In the Letter to the Editor, “Percutaneous Versus Surgical Treatment of 

Hypertrophic Obstructive Cardiomyopathy: the Pendulum Continues to 

Swing” by Tsung O. Cheng, M.D., published in the Journal of the Methodist 

DeBakey Heart Center 2005;1(4): 2 , the second sentence of the first paragraph 

should read “As Buergler and associates pointed out in their paper, since 

Sigwart’s original report of PTSMA in 1995, 4 several publications confirming 

the efficacy and safety of the procedure have appeared all around the world, 

including China. 5 ”

V E N O U S T H R O M B O S I S T R I A L S AT 

T H E M E T H O d I S T H O S P I TA L I N H O U S TO N 

J a m e s M u n t z 

F r o m M e t h o d i s t D e B a k e y H e a r t C e n t e r, H o u s t o n , Te x a s 

IntRoduCtIon 

Venous thromboembolism continues to be a significant problem in hospitalized patients. 1 according to Geerts et al., 

“the rationale for thromboprophylaxis is based on the high prevalence of venous thromboembolism among hospitalized 

patients, the clinically silent nature of the disease in the majority of patients, and the morbidity, costs and 

potential mortality associated with unprevented thrombi.” 2,3 approximately two million americans suffer from deep 

vein thrombosis (dVt) each year, 4 but because most of these clots are silent, the true incidence is actually unknown. 

In addition to the acute thrombotic event with its inherent morbidity and time missed from work, the late sequelae 

from even properly treated thrombi can present as venous stasis and leg ulcers. 

thromboembolic disease is responsible for approximately 200,000 deaths annually in the united states alone. 5 

the elderly are at highest risk, with a one-year mortality approaching 21%. 6 although excellent drugs are currently 

available to prevent and treat dVt, an investigation into new drugs with new targets and designer end points of anticoagulation 

seemed clinically relevant and timely. 

the following paper will discuss the different antithrombotic/anticoagulant agents that have been used in clinical 

trials at the methodist Hospital in Houston, texas. several of the trials have been successfully completed and 

featured in medical publications such as the New England Journal of Medicine and The Lancet. 

n e W a n t I t H R o m B o t I C 

s t R at e G I e s 

According to a review by Hirsh and 

Weitz, “anticoagulant strategies to block 

thrombogenesis have focused on inhibiting 

thrombin, preventing thrombin 

generation, or blocking the initiation 

of coagulation” (Figure 1). 7 The drugs 

studied at The Methodist Hospital will 

be discussed in chronological order, 

with the first new class of anticoagulant 

drugs being one of the Factor Xa inhibitors, 

pentasaccharide. 

f o n d a Pa R I n u X 

Fondaparinux is the first of a new class of 

antithrombotics: the synthetic inhibitors 

of Factor Xa (SIXa). Originally termed 

ORG31540/SR90107A, fondaparinux 

is a unique and novel pentasaccharide 

produced by total chemical synthesis 

and designed specifically to bind its 

target, the protein antithrombin, with 

very high affinity. Fondaparinux (trade 

name Arixtra) is obtained exclusively 

by chemical synthesis from basic building 

blocks synthesized from glucose, 

glucosamine and cellobiose. It has guar- 

anteed batch-to-batch consistency that 

eliminates the risk of contamination by 

pathogenic agents. 8 

Methodist physicians participated in 

the drug’s Phase II and Phase III trials, 

with ours being the largest enrolling site 

worldwide in the Phase II Pentathlon 

trial. Phase IIb studies, which included 

more than 900 patients undergoing 

total hip replacement surgery and 400 

undergoing knee replacement surgery, 

demonstrated statistically significant 

dose-dependent reductions in the risk 

of DVT with this agent. 9 

We also participated in a multi-center, 

double-blinded, dose-ranging Phase II 

study to determine optimal dosing in 

933 patients undergoing primary total 

hip replacement surgery. 10 Figures 2 and 

3 outline the efficacy and safety results 

from this trial. 11 Following this were 

four Phase III trials-randomizing more 

than 7,000 patients on five continentswhich 

demonstrated that once-daily 

fondaparinux in a 2.5 mg subcutaneous 

dose reduced the risk of overall 

DVT by 50% compared with the established 

standard of care (enoxaparin) in 

patients undergoing major orthopedic 

surgery. 12 These trials provided significant 

support of fondaparinux and were 

the basis of eventual FDA approval of 

the drug in orthopedic populations. 

X I m e l a G at R a n 

A prodrug of the active site-directed 

thrombin inhibitor melagatran, ximelagatran 

is absorbed from the small 

intestine and was the next drug to be 

studied in orthopedic populations at The 

Methodist Hospital. 13 Ximelagatran 

has a plasma half-life of three to four 

hours and was administered in a twicedaily 

dose. This drug was considered a 

savior in the anticoagulation world as it 

has no food or drug interactions and, 

due to its very predictable response, did 

not appear to require any anticoagulant 

monitoring. 

To evaluate the utility of this drug 

in North American orthopedic populations, 

we participated in the Platinum 

hip and knee trials. The Platinum 

Hip Trial randomized 1,557 patients 

with adequate venography undergoing 

total hip replacement to receive oral 

II (1) 2006 | JMDHC

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figure 1. Steps in blood coagulation. Initiation of coagulation is triggered by the factor 

VIIa/tissue factor complex (VIIa/TF), which activates factor IX (IX) and factor X (X). 

Activated factor IX (IXa) propagates coagulation by activating factor X in a reaction that 

utilizes activated factor VIII (VIIIa) as a cofactor. Activated factor X (Xa), with activated 

factor V (Va) as a cofactor, converts prothrombin (II) to thrombin (IIa). Thrombin then 

converts fibrinogen to fibrin. Tissue factor pathway inhibitor (TFPI) and nematode 

anticoagulant peptide (NAPc2) target VIIa/TF, whereas synthetic pentasaccharide and 

DX-9065a inactivate Xa. Hirudin, bivalirudin, argatroban, and H376/95 inactivate IIa. 

ximelagatran (24 mg twice daily) or 

enoxaparin (30 mg SQ twice daily) 

for seven to 12 days. 14 The results of 

the trial showed that enoxaparin was 

superior to ximelagatran when started 

postoperatively in the 24-mg, twicedaily 

dosage. Further trials altered the 

dosages of ximelagatran to 36 mg twice 

a day with an additional subcutaneous 

dose given on the day of surgery, which 

then demonstrated superiority over 

the enoxaparin regimen. 15 However, 

release of the drug in the U.S. market 

has been delayed due to FDA safety 

concerns regarding liver enzyme elevations 

that occurred in longer-term atrial 

fibrillation trials. 

I d R a Pa R I n u X 

A more highly sulfated derivative of 

fondaparinux, idraparinux is an inves- 

JMDHC | II (1) 2006 

sites of action of new anticoagulants 

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tigational drug with a half-life of 150 

hours. This promising and sophisticated 

new anticoagulant, to be studied 

in acute DVT and pulmonary embolism 

patients, was presented to us in 

the Van Gogh trials by Sanofi Aventis. 

In a Phase II trial performed elsewhere, 

idraparinux therapy was compared with 

warfarin therapy in 659 patients with 

acute proximal DVT. 16 After five to 

seven days of initial treatment with 

enoxaparin, patients were randomized 

to receive once-weekly subcutaneous 

doses of idraparinux (2.5, 5.0, 7.5 or 

10 mg.) or warfarin for 12 weeks. The 

primary end point, changes in compression 

ultrasound or new findings on 

perfusion lung scans, was similar in all 

of the idraparinux groups and no different 

in the warfarin group. 17 

Based on the above results and the 

fact that there was less bleeding in the 

lowest-dosage idraparinux group than 

in the warfarin group, the 2.5 mg, onceweekly 

dose of idraparinux was chosen 

for the Phase III trials. The Van Gogh 

DVT and pulmonary embolism trials 

are now completed, with the data to be 

reviewed and published. 

s o l u B l e 

t H R o m B o m o d u l I n 

The Methodist Hospital was next 

recruited by the Hamilton, Ontario 

group to participate in the soluble 

thrombomodulin trial. Figure 1 reveals 

where thrombomodulin affects propagation 

of thrombin. The initiation of 

coagulation is triggered by the tissue 

factor/factor VIIa complex that activates 

factor IX and factor X. Activated factor 

IX propagates coagulation by activating 

factor X in a reaction utilizing factor 

VIII as a cofactor. Activated protein C 

then blocks the propagation of coagulation 

by inactivating factors Va and 

VIIIa at the thrombin/thrombomodulin 

site. Protein C and thrombomodulin 

also target this step: According to Weitz 

et al., “soluble thrombomodulin binds 

thrombin and induces a conformational 

change in the active site of the enzyme 

that converts it into a potent activator of 

protein C.” 17 

In an open-label, dose-escalating 

study, soluble thrombomodulin positively 

affected coagulation abnormalities 

in patients with disseminated intravascular 

coagulation. 18 After these results 

were demonstrated, the Canadian group 

organized a Phase II dose-ranging study 

in patients undergoing elective total hip 

replacement surgery. 19 Patients were 

given thrombomodulin subcutaneously 

(0.3 or 0.45 mg/kg) two to four 

hours after surgery, and patients receiving 

the lower thrombomodulin dosage 

received another dose five days later. 

The primary end point, a composite 

of venographically detected and symptomatic 

venous thromboembolism, 

occurred in only 4.3% of those patients 

receiving the lower dose and in none 

of the 99 patients in the higher-dose

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figure 2. Efficacy results from fondaparinux Phase II dose-finding study in patients 

with total hip replacement. Data are expressed as percent of treated patients with 

venous thromboembolism. Enrollment in the 6 mg and 8 mg groups was discontinued 

early after an increase in bleeding incidence was noted. 

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figure 3. Safety results from fondaparinux Phase II dose-finding study in patients 

with total hip replacement. Data are expressed as percent of treated patients with 

major bleeding. Enrollment in the 6 and 8 mg groups was discontinued early because 

of this complication. 

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group. 17 Phase III trials will next be 

required to compare ART-123 (soluble 

thrombomodulin) to either enoxaparin 

or fondaparinux. 

C o n C l u s I o n 

Recently developed, highly selective, 

novel therapeutic agents such as those 

explored in our trials can optimize antithrombotic 

efficacy and improve the 

prevention of hemorrhagic complications. 

It is hoped that The Methodist 

Hospital’s participation in several landmark 

trials — with particular attention 

to patient care and safety — will lead 

to the development of new and possibly 

better anticoagulants that ultimately 

have a positive benefit for the future of 

medicine. 

R e f e R e n C e s 

1. Bergmann JF, Elkharrat D. Prevention of 

venous thromboembolic risk in non-surgical 

patients. Haemostasis. 1996;26 Suppl 

2:16-23. 

2. Geerts WH, Heit JA, Clagett GP, Pineo 

GF, Colwell CW, Anderson FA Jr, et al. 

Prevention of venous thromboembolism. 

Chest. 2001 Jan;119(1 Suppl):132S-175S. 

3. Prandoni P, Lensing AW, Cogo A, Cuppini 

S, Villalta S, Carta M, et al. The longterm 

clinical course of acute deep venous 

thrombosis. Ann Intern Med. 1996 Jul 

1;125(1):1-7. 

4. Hirsh J, Hoak J. Management of deep 

vein thrombosis and pulmonary embolism. 

A statement for health care professionals. 

Council on Thrombosis (in consultation with 

the Council on Cardiovascular Radiology), 

American Heart Association. Circulation. 

1996 Jun 15; 93(12):2212-45. 

5. Ferris EJ. George W. Holmes Lecture. 

Deep vein thrombosis and pulmonary 

embolism: correlative evaluation and therapeutic 

implications. Am J Roentgenol. 1992 

Dec;159(6):1149-55. 

6. Kniffin WD Jr, Baron JA, Barrett J, 

Birkmeyer JD, Anderson FA Jr. The epidemiology 

of diagnosed pulmonary embolism 

and deep vein thrombosis in the elderly. 

Arch Int Med. 1994 Apr 25;154(8):861-6. 

7. Weitz JI, Hirsh J. New anticoagulant drugs. 

Chest. 2001 Jan;119(1Suppl):95S-107S. 

6 II (1) 2006 | JMDHC 

��

8. Casu B. Structure and biological activity of 

heparin. Adv Carbohydr Chem Biochem. 

1985;43:51-134. 

9. Herbert JM, Petitou M, Lormeau JC, 

Cariou R, Necciari J, Magnani HN, et al. 

SR 90107A/Org 31540, a novel anti-factor 

Xa antithrombotic agent. Cardiovasc Drug 

Rev. 1997;15:1-26. 

10. Turpie AG, Gallus AS, Hoek JA. A 

synthetic pentasaccharide for the prevention 

of deep-vein thrombosis after total hip 

replacement. N Engl J Med. 2001 Mar 

1;344(9):619-25. 

11. Muntz JE. Fondaparinux for Prophylaxis. 

Techniques in Orthopaedics. 2004 

Dec;19(4):278-82. 

12. Turpie AG, Bauer KA, Eriksson BI, Lassen 

MR. Fondaparinux vs enoxaparin for the 

prevention of venous thromboembolism in 

major orthopedic surgery: a meta-analysis 

of 4 randomized double-blind studies. 

Arch Intern Med. 2002 Sep 9;162(16): 

1833-40. 

13. Gustafsson D, Nystrom J, Carlsson S, Bredberg 

U, Eriksson U, Gyzander E, et al. 

The direct thrombin inhibitor melagatran 

and its oral prodrug H 376/95: intestinal 

absorption properties, biochemical and 

pharmacodynamic effects. Throm Res. 2001 

Feb 1;101(3):171-81. 

14. Colwell CW, Berkowitz SD, Davidson BL, 

Lotke PA, Ginsberg JS, Lieberman JR, et 

al. Randomized, double-blind, comparison 

of ximelagatran, an oral direct thrombin 

inhibitor, and enoxaparin to prevent venous 

thromboembolism after total hip arthroplasty 

[abstract]. Blood. 2001;98:2952. 

15. Francis CW, Berkowitz SD, Comp PC, 

Lieberman JR, Ginsberg JS, Paiement G, 

et al. Comparison of ximelagatran with 

warfarin for the prevention of venous 

thromboembolism after total knee 

replacement. N Engl J Med. 2003 Oct 

30;349(18):1703-12. 

16. Büller HR, Cohen AT, Lensing AW, Prins 

MH, Monreal M, Schulman S, et al.; The 

PERSIST Investigators. A novel long-acting 

synthetic Xa inhibitor (SanOrg34006) to 

replace warfarin for secondary prevention in 

deep vein thrombosis: a Phase II evaluation. 

J Thromb Haemost. 2004 Jan;2:47-53. 

Erratum: J Thromb Haemost. 2004 

Mar;2(3):540. 

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17. Weitz JI, Hirsh J, Samama MM. New 

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Conference on Antithrombotic and Thrombolytic 

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Suppl):265S-286S. 

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and activated protein C in the 

treatment of disseminated intravascular 

coagulation. Thromb Haemost. 1999 

Aug;82(2):718-21. 

19. Kearon C, Comp P, Douketis J, Royds R, 

Yamada K, Gent M. Dose-response study 

of recombinant human soluble thrombomodulin 

(ART-123) in the prevention of 

venous thromboembolism after total hip 

replacement. J Thromb Haemost. 2005 

May;3(5):962-8.

C A R d I OVA S C U L A R d I S E A S E I N W O M E N : T H E FAC T S 

K a r l a M . K u r r e l m e y e r 


IntRoduCtIon 

Cardiovascular disease (CVd) is the leading cause of death in women. one of every 2.4 women will die of CVd, 

and it claims almost 500,000 female lives annually. 1 since women are more likely than men to have sudden death 

as their initial presenting symptom, early prevention measures are even more important in women to prevent this 

catastrophic outcome. 2 

Ironically, more than 50% of women who were surveyed did not know CVd was the leading killer of women, and 

only 5% identified heart disease as their greatest health problem. 3 this unawareness likely has contributed to the 

increase of cardiovascular deaths among women, whereas the number of cardiovascular deaths among men has 

slowly decreased since 1984. 4 

P R e V e n t I o n o f C V d 

I n W o m e n 

The risk factors for heart disease in 

women are similar to men, though 

the weighting differs. For example, 

smoking, hypertension, LDL cholesterol 

and family history increase risk 

in women as much as they do in men. 5 

Diabetes, however, is a stronger risk 

factor in women, as are elevated triglycerides 

and low HDL levels. 5,7 Diabetic 

women are five times more likely 

to develop CVD than non-diabetic 

women, whereas diabetic men are only 

two times more likely to develop CVD 

than non-diabetic men. 6 

Recommendation Class, 

by Risk level 

The most prevalent modifiable risk 

factor in American women is excess 

weight, and approximately 62% of 

American women are either overweight 

or obese. 8 Prospective data from the 

Nurses’ Health Study clearly demonstrates 

that the relative risk of death 

from CVD increases with body mass 

index (BMI – defined as weight in kilograms 

divided by the square of the 

height in meters) once the BMI exceeds 

19, the upper limit of normal; those 

with BMIs greater than 29, defined as 

obesity, are at greatest risk. 9 

The second most prevalent modifiable 

risk factor in women is elevated 

Guidelines outline best practices for treating CVd in women 

CVD treatment/prevention options for various risk levels 

High • Aspirin therapy 

• ACE inhibitor therapy 

• Glycemic control 

• Treatments for low/ 

intermediate risk 

Intermediate • BP control 

• Lipid control 

• Treatments for low risk 

Low/Optimal • Smoking cessation 

• Physical activity 

• Weight reduction 

table 1. Current ACC/AHA guidelines for treating CVD in women 

total and LDL cholesterol. 8 Diet and 

aerobic exercise have been shown to 

lower total and LDL cholesterol and 

raise HDL cholesterol in women if they 

are performed together, although either 

in isolation failed to reach statistical 

significance. 10 Unfortunately, the third 

most prevalent risk factor in women is 

physical inactivity. In 2002, 43% of 

American women reported that they 

were physically inactive. 8 The good 

news is their cholesterol abnormalities 

can be treated with medication. In the 

large statin trials, women responded 

similarly to drug therapy as men and 

benefited from a similar reduction in 

I IIa IIb III 

• depression 

evaluation and 

treatment 

• Omega-3 

fatty acid 

supplementation 

• Folic acid 


• Hormone therapy 

• Antioxidant 


• Aspirin therapy N/A • Hormone therapy 



N/A N/A • Aspirin therapy 

• Hormone therapy 



Source: Mosca et al. Circulation: 2/10/04. 

II (1) 2006 | JMDHC

major coronary events. 11 The bad news 

is they will not benefit from the myriad 

other effects of aerobic exercise. 

The current ACC/AHA guidelines 

for treating CVD in women are listed 

in Table 1. 38 Women have been stratified 

into four groups based on their risk 

for developing CVD: high risk means 

> 20% chance of developing CVD in 

10 years, intermediate risk means a 10- 

20% chance of developing CVD in 

10 years, and low/optimal risk means 

< 10% chance of developing CVD in 

10 years. For each group there are four 

different levels of recommendations: 

Class I describes interventions deemed 

safe and effective; Class IIa describes 

treatments favored by clinical evidence; 

Class IIb describes therapies for which 

evidence is less well established; and 

Class III describes interventions that are 

not useful and may be harmful. 38 Table 

2 demonstrates how to estimate 10-year 

risk for developing CVD in women. 39 

d I a G n o s I n G C o R o n a R Y 

a R t e R Y d I s e a s e I n 

W o m e n 

Diagnosing coronary artery disease 

(CAD) in women is difficult for several 

reasons. First, chest pain in women does 

not accurately predict the presence of 

CAD, making risk stratification based 

on this symptom alone practically 

useless. However, refining the diagnoses 

of chest pain into definite angina, 

probable angina, or nonspecific chest 

pain may improve the predictive value 

of symptoms. 18 Like men, nearly 90% 

of women with myocardial infarction 

(MI) in the Myocardial Infarction Trial 

and Intervention Project presented with 

chest pain. However, women with MI 

were also more likely than men to 

present with upper abdominal pain, 

dyspnea, nausea, and fatigue. 12-14 

Therefore, both chest pain and atypical 

symptoms of angina should be pursued 

in women based on the appropriate 

clinical context and the underlying 

probability of disease. Second, for a 

given age and risk factor profile, the 

prevalence of CAD in women when 

JMDHC | II (1) 2006 

compared to men is significantly less. 18 

Women develop CAD on average 10 

years later than men and therefore have 

frequently developed other diseases, 

which affect their ability to exercise. 17 

These factors decrease the accuracy of 

all available noninvasive tests, which 

may partially explain why women are 

less likely than men to be referred 

for diagnostic testing. 15,16 Some earlier 

studies demonstrated that women 

with positive test results are less likely 

to undergo coronary angiography 

and revascularization procedures and 

therefore are twice as likely as men 

to experience a cardiac event during 

follow-up. 19 However, these biases 

appear to be disappearing as physician 

awareness increases. 

The following gender-specific issues 

should be considered when choosing 

a noninvasive stress test to evaluate 

chest pain in women. The sensitivity 

and specificity of electrocardiography 

(ECG) stress testing is much lower 

in women than men. 20 This not only 

reflects the lower prevalence of CAD in 

women < 50 years old, higher prevalence 

of single-vessel disease in women 50-75 

years and lower exercise capacity of older 

women as previously stated, but also 

the ST-response used to evaluate ECG 

results is less accurate in women since 

it varies with the menstrual cycle and 

estrogen replacement therapy. Mitral 

valve prolapse, syndrome X, and coronary 

artery spasm are more prevalent in 

women and can cause an abnormal ST 

response in the absence of CAD. 21,22 

The sensitivity and specificity 

of pharmacologic or exercise testing 

is enhanced by adding imaging techniques. 

Myocardial perfusion imaging 

with gated SPECT has improved sensitivity 

over conventional treadmill 

testing, however breast tissue artifacts 

may lead to a false-positive test result 

(decreased specificity). 23,24 Breast tissue 

artifacts may be reduced and specificity 

increased with the use of newer highenergy 

agents such as technetium-99m 

sestamibi rather than thallium-201. 25 

Application of computerized breast 

attenuation correction algorithms may 

also lead to enhanced specificity. 

Likewise, echocardiography has 

improved sensitivity and specificity 

over conventional treadmill testing and 

is considered the most cost-effective 

approach to diagnosing CAD in 

women. 26 However, test accuracy is 

highly dependent on the image quality 

and the technician’s and interpreter’s 

skills. Inadequate imaging occurs in 

approximately 10% of cases secondary 

to obesity, severe lung disease, chest wall 

deformities and inexperience. Using 

newer techniques such as harmonic 

imaging and echocardiography contrast 

agents improves image quality. 27 

P R o G n o s I s a f t e R 

R e Va s C u l a R I Z at I o n 

Several studies have demonstrated a 

worse prognosis for women than men 

with ST elevation myocardial infarction, 

which may reflect increased 

severity of illness at presentation, 

increased age, more comorbidities in 

women when compared to men, and 

lower referral rates for coronary angiography 

and revascularization procedures. 

For example, the Framingham Study 

demonstrated that women were more 

likely than men to die in the hospital 

and within one year after infarction. 17 

The International Study of Infarct 

Survival (ISIS-1) examined the effects 

of atenolol post-MI and demonstrated 

greater one-week mortality for women 

compared with men. 36 ISIS-4 examined 

the effects of captopril after thrombolysis 

for acute MI and also suggested an 

increased short and long-term mortality 

in women. 35 Finally, the Global 

Utilization of Streptokinase and Tissue 

Plasminogen Activator for Occluded 

Arteries trial demonstrated higher 30day 

mortality in women and higher 

rates of intracerebral hemorrhage, possibly 

due to smaller body size and lack of 

thrombolytic dose adjustments. 33 

Meta-analysis of 10 randomized trials 

of primary angioplasty versus thrombolytic 

therapy demonstrated that primary 

angioplasty results in lower rates of

death and MI at 30 days in women 

presenting with acute ST elevation 

MI. 34 The CADILLAC trial examined 

the benefit of stent and abciximab in 

patients presenting within 12 hours of 

ST elevation MI and found a higher 

one-year mortality in women, possibly 

due to a longer time from symptom 

onset to percutaneous coronary inter- 

estimating the 10-Year Risk of CVd in Women 

Step 1. age 

Age, y 20-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 

Points -7 -3 0 3 6 8 10 12 14 16 

Point 

Total 

10-y 

Risk, % 

HdL, 

mg/dL 

TC, mg/dL 

Age, y 

20-39 

Step 2. total Cholesterol 

Age, y 

40-49 

Age, y 

50-59 

vention (PCI). Women who received 

a stent demonstrated no difference in 

mortality when compared to angioplasty 

alone, however they had less 

major adverse cardiac events at one 

year. 31 

The outcome of women and men 

with unstable angina and non-Q-wave 

MI (NQWMI) was found to be similar 

Age, y 

60-69 

< 160 0 0 0 0 0 

160-199 4 3 2 1 1 

200-239 8 6 4 2 1 

240-279 11 8 5 3 2 

> 280 13 10 7 4 2 

Age, y 

20-39 

Step 3. smoking status 

Age, y 

40-49 

Age, y 

50-59 

Age, y 

60-69 

Nonsmoker 0 0 0 0 0 

Smoker 9 7 4 2 1 

Age, y 

70-79 

Age, y 

70-79 

Step 4. Hdl Step 5. Blood Pressure 

> 60 50-59 40-49 < 40 

Systolic BP, 

mm Hg 

Untreated Treated 

Points -1 0 1 2 < 120 0 0 

Step 6. add up the Points 

120-149 1 3 

130-139 2 4 

140-159 3 5 

> 160 4 6 

< 9 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 > 25 

< 1 1 1 1 1 2 2 3 4 5 6 8 11 14 17 22 27 > 30 

table 2. Steps 1-6 demonstrate how to estimate the 10-year risk for CVD in women. 

in the Thrombolysis in Myocardial 

Ischemia (TIMI) IIIB Registry. 28 

TACTICS: TIMI 18 demonstrated 

that, like men, women with NQWMI 

receiving both aspirin and tirofiban 

benefited from early invasive treatment. 

29 Likewise, women and men 

have similar prognoses after successful 

high-risk PCI. EPIC, EPILOGUE and 

10 II (1) 2006 | JMDHC

EPISTENT demonstrated that the clinical 

benefit of abciximab in high-risk 

PCI is independent of gender, although 

women experience more minor bleeding. 

30 The Taxus-IV trial demonstrated 

that women benefit equally from the 

Taxus drug-eluting stent. 37 

The Coronary Artery Surgery Study 

demonstrated increased operative 

mortality for women, which may be 

secondary to differences in functional 

class, age, size of coronary arteries and 

greater likelihood of emergent surgery. 

However, coronary artery bypass surgery 

provides excellent relief of symptoms 

and comparable long-term survival in 

women. 18,32 


With respect to coronary artery disease, 

women are not “small men.” Differences 

in prevention, diagnosis, prognosis, 

and response to treatment have been 

identified. The reasons for these differences 

and the optimal management of 

coronary artery disease in women will 

hopefully be elucidated as more and 

more women are included in large, 

multicenter, randomized cardiovascular 

research trials. 


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17. Kannel WB, Sorlie P, McNamara PM. 

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18. Chaitman BR, Bourassa MG, Davis 

K, Rogers WJ, Tyras DH, Berger R, et 

al. Angiographic prevalence of high-risk 

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19. Shaw LJ, Miller DD, Romeis JC, Kargl D, 

Younis LT, Chaitman BR. Gender Differences 

in the Noninvasive Evaluation and 

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20. Gibbons RJ, Balady GJ, Bricker JT, Chaitman 

BR, Fletcher GF, Froelicher VF, et al. 

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of Cardiology/American Heart Association 

Task Force on Practice Guidelines (Committee 

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Available at: www.acc.org/clinical/guidelines/exercise/dirindex.htm. 

21. Barolsky SM, Gilbert CA, Faruqui A, 

Nutter DO, Schlant RC. Differences in 

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22. Rupp M, Grill HP, Granato JE. Acute 

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young: Gender specific etiologies and treatment. 

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23. Hung J, Chaitman BR, Lam J, Lesperance 

J, Dupras G, Fines P, et al. Noninvasive 

diagnostic test choices for the evaluation 

JMDHC | II (1) 2006 11

of coronary artery disease in women: a 

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24. Goodgold HM, Rehder JG, Samuels LD, 

Chaitman BR. Improved interpretation 

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1987 Nov;165(2):361-6. 

25. Taillefer R, DePuey EG, Udelson JE, Beller 

GA, Latour Y, Reeves F. Comparative 

Diagnostic Accuracy of TI-201 and Tc-99m 

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ECG-Gated SPECT) in Detecting Coronary 

Artery Disease in Women. J Am Coll 

Cardiol. 1997 Jan;29(1):69-77. 

26. Marwick TH, Anderson T, Williams MJ, 

Haluska B, Melin JA, Pashkow F, et al. 

Exercise echocardiography is an accurate 

and cost-efficient technique for detection 

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27. Cohen JL, Cheirif J, Segar DS, Gillam 

LD, Gottdiener JS, Hausnerova E, et al. 

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contrast agent. Results of a phase III 

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Sep;32(3):746-52. 

28. Hochman JS, McCabe CH, Stone PH, 

Becker RC, Cannon CP, DeFeo-Fraulini 

T, et al. Outcome and profile of women 

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Infarction. J Am Coll Cardiol. 1997 

Jul;30(1):141-8. 

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CP, et al. Benefit of an early invasive 

management strategy in women with 

acute coronary syndromes. JAMA. 2002 

Dec;288(24):3124-9. 

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Booth JE, Cabot C, et al. Clinical benefit 

of glycoprotein IIb/IIIa blockade with 

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the Prevention of Ischemic Complications. 

Evaluation in Percutaneous Transluminal 

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Y, Brodie BR, Cox DA, et al. Gender differences 

in outcomes after primary angioplasty 

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GT, Bhatnagar G, Heenan AL, et al. 

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Recently, the National Heart, Lung, and 

Blood Institute (NHLBI), the American 

Heart Association (AHA), the Sister to 

Sister: Everyone Has a Heart Foundation 

and the American College of Cardiology 

(ACC) have partnered to increase public 

awareness. The Red Dress — promoted 

by the NHLBI’s “The Heart Truth” 

campaign and the recognized 

symbol of heart disease awareness in 

women — cautions women to heed the 

threat of heart disease and take care 

of themselves. The AHA’s “Go Red for 

Women” campaign designated a National 

Wear Red Day to increase awareness 

and help stimulate donations for research 

and education. The Sister to Sister 

Foundation, dedicated to bringing free 

screening to women, designated February 

17 as National Woman’s Heart Day and 

offered free screenings and counseling in 

Dallas, Philadelphia, Miami, San Diego 

and Chicago. 

12 II (1) 2006 | JMDHC

S U R G E RY V E R S U S A L C O H O L S E P TA L A B L AT I O N F O R 

H Y P E R T R O P H I C O B S T R U C T I V E C A R d I O M YO PAT H Y: 

T H E C O N T R OV E R SY 

W i l l i a m H . S p e n c e r , I I I 

F r o m M e d i c a l U n i v e r s i t y o f S o u t h C a r o l i n a , C h a r l e s t o n , S o u t h C a r o l i n a 

I n t R o d u C t I o n 

Hypertrophic cardiomyopathy is a common genetic illness affecting approximately one in 500 of the general population. 

the disease may occur spontaneously or be inherited in an autosomal dominant pattern. 1 Initially, it was felt that 

most patients with this illness had severe symptoms of heart failure, angina and syncope and were at high risk for 

sudden death. However, population studies have revealed that many patients are asymptomatic and do not have the 

high risk of sudden death originally found in symptomatic patients referred to tertiary medical centers. 

Roughly one-third of those with hypertrophic cardiomyopathy have obstructed left ventricular outflow, and the 

severity of the obstruction is measured by the left ventricular outflow tract gradient. therapies that reduce the 

pressure gradient have been shown to improve symptoms and outcomes of patients with hypertrophic obstructive 

cardiomyopathy (HoCm). 2 many live with minimal symptoms while taking drugs such as beta blockers or calcium 

channel blockers. dual-chamber cardiac pacemakers, while originally thought to effectively reduce the left ventricular 

outflow tract gradient, have in reality had very limited applicability in treating HoCm. 1 for severely symptomatic 

patients, cardiac surgery has been a long-standing therapy. Recently, however, alcohol septal ablation (asa) has 

emerged as an alternative to surgery. 3 

s u R G e R Y V e R s u s a s a 

Ventricular septal myectomy is an 

established treatment for symptomatic 

HOCM, 4 and more than 2,000 

patients have received this surgery in the 

last 40 years. Long-term follow-up has 

revealed that surgery effectively reduces 

the left ventricular outflow tract gradient, 

improving symptoms and exercise 

tolerance. Refined surgical techniques 

have produced better outcomes, and a 

relatively low (1-2%) surgical mortality 

is possible in experienced centers. 

Recent reports show better long-term 

survival in patients with HOCM who 

undergo surgery. 4 

By contrast, ASA is a catheter-based 

procedure that instills pure alcohol into 

the hypertrophied ventricular septum via 

a septal perforator artery. 3 This results 

in a therapeutic myocardial infarction. 

The technique has been refined since 

its emergence a decade ago, and the 

procedural mortality even in the initial 

experience has been quite low. Ablation 

therapy has been shown to effectively 

lower the left ventricular outflow tract 

gradient and improve symptoms and 

exercise tolerance. 5 Longer-term followup 

of ASA shows that mortality from 

sudden cardiac death, which was originally 

feared to be high, actually is less 

than what might be expected in an 

untreated population of severely symptomatic 

patients. 5 Studies also show an 

improvement in left ventricular diastolic 

function and mitral regurgitation as 

well as long-term regression of left 

ventricular hypertrophy. 6 Unlike myectomy 

surgery, ASA can not be applied 

to all patients with HOCM. Those 

with abnormalities of the cardiac valves 

or papillary muscles must be treated 

with myectomy surgery combined with 

other techniques such as valve repair or 

replacement. 

t H e d e B at e o V e R a s a 

The advent of ASA as an alternate 

treatment for severely symptomatic 

HOCM patients has created controversy. 7 

Some say that the induced therapeutic 

myocardial infarction could result in 

an “arrhythmogenic scar.” Some also 

claim that this “arrhythmogenic scar” 

will result in an increased incidence of 

sudden death, ventricular dysfunction 

and/or heart failure during long-term 

follow-up. Because large numbers of 

patients have undergone ASA worldwide, 

many believe that the indications for 

therapy in terms of disease severity 

and symptoms have been lowered 

considerably below those for surgery. 

Finally, there have been reports that 

short-term results with ASA are inferior 

to surgery because they produced less 

gradient reduction and more mitral 

regurgitation on follow-up, and that a 

number of ASA-treated patients have 

required a second procedure because 

results from the first were inadequate. 

s t u d Y R e s u lt s f R o m t H e 

m e t H o d I s t H o s P I ta l 

Several studies comparing the results 

of ASA and surgical myectomy have 

been published, and all have been non 

randomized, uncontrolled and observational. 

The results of ASA performed 

at The Methodist Hospital in Houston, 

JMDHC | II (1) 2006 1

Texas were compared with those of 

myectomy surgery performed at the 

Mayo Clinic in Rochester, Minnesota. 8 

Both techniques produced a similar 

reduction in left ventricular outflow 

tract gradient and improvement in 

patient symptomatology, and both 

resulted in similar statistically significant 

improvement in exercise tolerance 

as measured by a treadmill exercise test. 

There was no procedural mortality in 

either group. However, the incidence of 

complete heart block requiring a pacemaker 

was considerably higher in the 

ASA group because this was an early 

cohort, whereas the incidence of postoperative 

atrial fibrillation and aortic 

regurgitation was higher in the surgery 

group. 

Several other non randomized 

studies of both procedures found 

similar results in terms of reductions of 

the left ventricular outflow tract gradient 

and improved symptoms. These 

studies also have shown some relatively 

minor benefits favoring surgery versus 

ASA. 9,10 While there have been calls for 

a randomized trial of these two therapies, 

such a study appears to be unlikely 

due to: 1) the ethical and moral issues 

involved in randomizing patients to 

open-heart surgery, 2) the low volume 

of patients available at any one site, and 

3) the lack of sites having comparable 

expertise in both therapies to make a 

valid comparison. 


Both ventricular septal myectomy 

surgery and ASA have proven to 

be effective therapies for treating 

symptomatic patients with hypertrophic 

obstructive cardiomyopathy, although 

further delineation of the roles of both 

procedures is needed. In the future, 

longer-term results of ASA will clarify 

its effect on the long-term outcome 

of patients with HOCM. Because of 

the perceived simplicity of the catheter 

technique, however, there is a danger 

that ASA will be widely used by 

operators with minimal experience 

and in practices that lack broad-based 

institutional support in terms of treating 

hypertrophic cardiomyopathy. 

For now, it is recommended that 

both ASA and myectomy surgery 

be limited to tertiary centers 

with relatively high volumes and 

expertise in treating hypertrophic 

cardiomyopathy — including the 

clinical, genetic, electrophysiologic 

and echocardiographic aspects of the 

disease. 


1. Maron BJ, McKenna W, Danielson GK, 

Kappenberger LJ, Kuhn HJ, Seidman CE, 

et al. American College of Cardiology/ 

European Society of Cardiology clinical 

expert consensus document on hypertrophic 

cardiomyopathy. A report of the American 

College of Cardiology Foundation Task Force 

on Clinical Expert Consensus Documents 

and the European Society of Cardiology 

Committee for Practice Guidelines. J Am 

Coll Cardiol. 2003 Nov;42(9):1687-713. 

2. Maron MS, Olivotto I, Betocchi S, Casey 

SA, Lesser JR, Losi MA, et al. Effect 

of left ventricular outflow tract obstruction 

on clinical outcome in hypertrophic 

cardiomyopathy. N Engl J Med. 2003 

Jan;348(4):295-303. 

3. Sigwart U. Non-surgical myocardial 

reduction for hypertrophic 

obstructive cardiomyopathy. Lancet. 1995 

Jul;346(8969):211-4. 

4. Ommen SR, Maron BJ, Olivotto I, Maron 

MS, Cecchi F, Betocchi S, et al. Longterm 

effects of surgical septal myectomy on 

survival in patients with obstructive hypertrophic 

cardiomyopathy. J Am Coll Cardiol. 

2005;46(3):470-6. 

5. Fernandes VL, Nagueh SF, Wang W, Roberts 

R, Spencer WH 3rd. A prospective followup 

of alcohol septal ablation for symptomatic 

hypertrophic obstructive cardiomyopathy— 

the Baylor experience (1996-2002). Clin 

Cardiol. 2005 Mar;28(3):124-30. 

6. Mazur W, Nagueh SF, Lakkis NM, 

Middleton KJ, Killip D, Roberts R, et al. 

Regression of left ventricular hypertrophy 

after non-surgical septal reduction therapy 

for hypertrophic obstructive cardiomyopathy. 

Circulation. 2001;103:1492-6. 

7. Maron BJ, Surgery for Hypertrophic Obstruc- 

tive Cardiomyopathy: Alive and Quite Well. 

Circulation. 2005;111:2016-18. 

8. Nagueh SF, Ommen SR, Lakkis NM, Killip 

D, Zoghbi WA Schaff HV, et al. Comparison 

of ethanol septal reduction therapy with 

surgical myectomy for the treatment of 

hypertrophic obstructive cardiomyopathy. J 

Am Coll Cardiol. 2001;38:1701-6. 

9. Qin JX, Shiota T, Lever HM, Kapadia 

SR, Sitges M, Rubin DN, et al. Outcome 

of patients with hypertrophic obstructive 

cardiomyopathy after percutaneous transluminal 

septal myocardial ablation and septal 

myectomy surgery. J Am Coll Cardiol. 2001 

Dec;38(7):1994-2000. 

10. Firoozi S, Elliott PM, Sharma S, Murday 

A, Brecker SJ, Hamid MS, et al. Septal 

myotomy-myectomy and transcoronary septal 

alcohol ablation in hypertrophic obstructive 

cardiomyopathy. A comparison of clinical, 

haemodynamic and exercise outcomes. Eur 

Heart J. 2002 Oct;23(20):1617-24. 

1 II (1) 2006 | JMDHC

How often is a new academic department born? 

Rarely. Would such an event create a ripple of interest? 

Absolutely. Is the department likely to survive and 

thrive? That depends primarily on the new chairman 

and available resources…which brings me to the reason 

for this essay. 

As part of its strategic plan, The Methodist Hospital 

administration in a bold stroke has created its own 

department of Cardiology — 

separate from the department of 

Medicine, where it resides in most 

instances. A national search was 

dutifully conducted for a chairman 

with the vision and courage to raise 

such a department to prominence 

from scratch. (And, I daresay, 

someone with thick skin and a 

sated ego, which seem to me to be 

prerequisites for a fledgling department 

chairman.) Such an individual 

was found “in house” in the person 

of dr. Miguel A. Quiñones, who 

has worked as a cardiologist at 

Methodist since his return from mili- 

d E B A k E Y H E A R T C E N T E R U P d A T E 

P O R T R A I T O F A C H A I R M A N 

by echocardiographic techniques. In addition to 

his educator activities as professor of medicine at 

Baylor, dr. Quiñones has been central to various 

educational programs at the American College of 

Cardiology (ACC), where he chaired the Learning 

Center Committee and still serves on the Strategic 

Education directions Committee. In 2004 he was 

elected to the ACC Board of Trustees. He has 

participated on committees related 

to education and cardiac imaging 

for the American Heart Association 

Council of Clinical Cardiology, has 

served on the board of the American 

Society of Echocardiography (ASE) 

in addition to a variety of ASE 

educational writing committees, and 

his professional activities have led to 

appointments on many cardiovascular 

journal editorial boards. 

Closer to home, dr. Quiñones has 

served as the director of Continuing 

Medical Education at Baylor and 

as acting chairman of Baylor’s 

division of Cardiology. He presided 

tary service in 1977. 

His background seems ideal for 

Dr. Miguel A. Quiñones 

as medical director of the Methodist 

deBakey Heart Center and as the 

the challenge. A native of Puerto Rico, dr. Quiñones center’s interim chief. In September 2005 he assumed 

graduated from the University of Puerto Rico School of the chair of Methodist’s department of Cardiology. 

Medicine with an Alpha Omega Alpha award. A summer He is blessed with a loving and supportive family and 

clerkship at Columbia University Hospital in New York for years has had the respect and admiration of his 

City led to a position in their internal medicine resi- colleagues. The thickness of his skin remains to be 

dency program. In 1971 he came under the influence seen, but when asked how he would like the success 

of dr. J.k. Alexander at the VA hospital here in Houston of his chairmanship to be judged in years to come, 

during his cardiology fellowship training at Baylor 

his response was one from a sated ego: “I want 

College of Medicine. dr. Alexander became his primary the department to be recognized for its individual 

mentor during his cardiology training, shaping his 

members — not its chairman.” 

education while instilling the seeds of inquiry and scien- As for resources to manage and develop a new 

tific research. In 1975, dr. Quiñones went on to serve academic department, the hospital — with its new 

as chief of cardiology at the Moncrief Army Hospital in affiliate partner, Weill Medical College of Cornell 

Fort Jackson, South Carolina. 

University — has already provided a strong founda- 

Returning to Houston and Baylor in 1977, dr. 

tion and the promise of continued support. Methodist 

Quiñones joined The Methodist Hospital staff as 

is in a strong financial position to address its strategic 

director of the echocardiography laboratory, which plan for patient care, research and education, and the 

had been established in 1969. This marked the begin- new department of Cardiology, with its rich heritage 

ning of a long, illustrious research career in the field in the cardiovascular field, will be a major player in 

of echocardiography — complementing his growth those plans. The Journal of the Methodist deBakey 

as an educator, mentor to many young physicians 

Heart Center wishes dr. Quiñones Godspeed in his 

and superb clinician. His CV is replete with seminal quest. 

publications addressing cardiac function defined 

— William L. Winters, Jr., M.D., Editor-in-Chief 

JMDHC | II (1) 2006 1


C O N T I N U I N G M E d I C A L E d U C AT I O N 

VulneRaBle Plaque summIt 2006 

methodist deBakey Heart Center 

saturday, June 10, 2006 

8 a.m. – 3 p.m. 

the Houstonian Hotel 

Houston, texas 

Is there a way to detect a heart attack before it 

happens? Researchers across the globe are hoping so, 

and they’re looking at vulnerable plaque for possible 

answers. Vulnerable plaque — the culprit lesion 

responsible for most heart attacks — is one of the most 

pressing and debated topics in cardiology, and MdHC 

is illuminating the debate by hosting the first Vulnerable 

Plaque Summit. 

directed by MdHC cardiologists Juan F. Granada 

and Albert E. Raizner, the summit brings together the 

country’s top researchers, clinicians and thought 

leaders to present the most up-to-date information in 

the field of vulnerable plaque research. With more than 

20 consecutive presentations, this fast-paced, information-packed 

program will address key issues from all 

perspectives, including the benefits and risks of early 

detection in asymptomatic patients and plenty of firsthand 

experience in detection technologies and 

therapies. 

Scientists and clinicians will share their research, 

experiences and theories on the correlation between 

vulnerable plaque and future coronary events, 

identifying at-risk patients, invasive identification and 

characterization of non-obstructive lesions, the role of 

blood cells in assessing risk, the role of systemic and 

local interventional therapies, and the future of 

vulnerable plaque research. 

The goal, says Granada, is to present the most 

current data from the “cream of the crop” in vulnerable 

plaque research. 

“Most meetings are biased, with like-minded people 

in the same field presenting corroborating information,” 

Granada explains. “This summit is designed to 

assemble experts from different universities, industries 

and specialties so that all facets of the topic are 

represented, even opposing views. This first meeting is 

intentionally broad to present an overview, whereas 

future meetings will focus on those areas that have 

seen the most advances in vulnerable plaque research.” 

Granada, Raizner and fellow MdHC investigator 

Greg kaluza are developing an animal model that 

simulates human vulnerable plaque, with the ultimate 

goal of understanding how, why and — most 

importantly — when a heart attack occurs. 

This program will be jointly sponsored by Weill 

Medical College of Cornell University and Methodist 

deBakey Heart Center. 

faculty 

• John Ambrose • Marco Costa 

• Zahi A Fayad • Antonio M. Gotto, Jr. 

• Juan F. Granada • Greg kaluza 

• Neal kleiman • Martin B. Leon 

• Eli Lev • Mohammed Madjid 

• James Muller • Harry Phillips 

• Albert Raizner • Robert Schwartz 

• Guillermo Tearney • Renu Virmani 

• Ron Waksman • James Willerson 

• Marvin Woodall 

To register for this activity, please call 

713-441-4CME (4263). 

16 II (1) 2006 | JMDHC

mdHC ReseaRCH at aCC sCIentIfIC 

sessIons 2006 

Research and expertise from Methodist deBakey 

Heart Center (MdHC) cardiologists was highlighted 

in more than 25 talks at the 2006 American College 

of Cardiology (ACC) Scientific Sessions in Atlanta in 

March. 

Topics ranged from advanced cardiac diagnostic 

imaging to novel therapies for heart failure to new 

treatments for conditions such as arterial stenosis, 

atrial fibrillation and valvular heart disease, among 

others. 

“This conference was an exceptional forum to share 

new ideas in research with our peers across the nation 

and around the world,” said Miguel A. Quiñones, M.d., 

chair of the department of cardiology at The Methodist 

Hospital and medical director of the Methodist deBakey 

Heart Center. “The spirit of collaboration, ingenuity 

and excellence is central as we prepare our research 

for presentation at the American College of Cardiology 

Scientific Sessions.” 


M d H C R E S E A R C H 

Four sessions at the prestigious conference were cochaired 

by MdHC cardiologists, dr. William Zoghbi, 

medical director of the echocardiography laboratory 

at Methodist, dr. Guillermo Torre-Amione, medical 

director of the heart transplant service at Methodist, 

dr. Neal kleiman, medical director of the cardiac 

catheterization laboratory at Methodist, and dr. John 

Mahmarian, medical director of nuclear cardiology at 

Methodist. 

MdHC researchers and cardiologists collaborate with 

The Methodist Hospital Research Institute in pioneering 

research in areas such as advanced heart failure/ 

transplant, atherosclerosis, preventative cardiology, 

cardiovascular sciences, cardiovascular surgery, 

echocardiography, genetics, proteomics, interventional 

cardiology, nuclear cardiology and vascular surgery. 

Presentations given by MdHC physicians at this year’s 

ACC represent six primary areas of research: advanced 

heart failure, ischemic heart disease, arrhythmia 

therapy, valvular heart disease, vascular disease and 

atherosclerosis, and metabolic syndrome and diabetes. 

o n G o I n G C l I n I C a l 

t R a I l s 

The Methodist deBakey Heart 

Center is dedicated to improving 

clinical outcomes through evidence 

based-based medicine. Visit 

www.debakeyheartcenter.com 

to access information regarding 

ongoing clinical trails related to 

cardiovascular disease. 

JMDHC | II (1) 2006 1

O B E S I T Y A N d C A R d I OVA S C U L A R d I S E A S E : 

A B A d R E L AT I O N S H I P T H AT N E E d S TO C H A N G E 

P e t e r H . J o n e s 


IntRoduCtIon 

obesity is strongly associated with an increased risk of cardiovascular disease, and conventional wisdom reasons 

that reducing weight would favorably reduce that risk. 1 an abundance of evidence associates excess adipose tissue, 

particularly in the visceral compartment, with insulin resistance, a risk for developing diabetes, increased blood 

pressure and lipoprotein disorders (low high-density lipoprotein, cholesterol and high triglycerides). there also is 

evidence that short-term weight loss can improve insulin sensitivity, reduce blood pressure and improve lipoprotein 

levels. 2 unfortunately, there are no long-term randomized clinical trials that demonstrate a reduction in cardiovascular 

endpoints with sustained weight loss. an obvious explanation is the lack of effective methods to induce and sustain 

weight loss over many years in most people. 

the complex biologic and genetic relationship of hunger and energy balance is finally receiving much-needed 

scientific attention, and new research is focusing on lifestyle habits, such as the composition of food intake and 

exercise, and drugs that modulate hunger/satiety and energy expenditure. even so, the dramatic global rise in obesity 

threatens the progress thus far in reducing cardiovascular disease (CVd) risk factors. this article examines the 

epidemic of obesity, its effect on traditional CVd risk factors and the effect of weight loss on controlling CVd risk. 

o B e s I t Y a n d 

C a R d I o Va s C u l a R d I s e a s e 

Observational studies have established 

that the risk of total and cardiovascular 

mortality increases progressively as 

the body mass index (BMI) rises over 

25 kg/m 2 . Over the past decade, the 

prevalence of obesity has increased 

to where more than 30% of U.S. 

adults have a BMI >30 kg/m 2 . 3 The 

prevalence is influenced by age, gender 

and ethnicity, with a graded increase 

as one ages and a higher prevalence in 

women and Hispanics. 

Obesity influences numerous disease 

states that impact longevity and quality 

of life, such as type 2 diabetes, hypertension, 

coronary heart disease (CHD), 

stroke, obstructive sleep apnea, nonalcoholic 

fatty liver disease, osteoarthritis 

and cancer. Recent analysis from the 

National Health and Nutrition 

Examination Survey (NHANES) I, II 

and III that followed patients from 

1971 to 1994 show that Caucasian men 

and women at age 20 with a BMI >45 

have 8-13 years of lost life compared to 

similar-aged subjects with a BMI of 24. 4 

Likewise, African-American men and 

women with a BMI >45 at age 20 have 

5-20 years of lost life. 

This increase in obesity prevalence 

has not escaped our children, and this 

alarming trend is threatening their 

life expectancy. 5 The cause is probably 

not the result of genetic alterations. 

Although genetics play a major role in 

one’s propensity for obesity, the change 

in lifestyle habits — larger portion sizes, 

readily available high-calorie foods, 

sedentary lifestyle — over the past few 

decades has been a major contributor. 6 

The health benefits of weight loss have 

been confined to various low-caloric 

diets that produced at least a 5-10% 

reduction in body weight, which in turn 

showed significant reductions in systolic 

and diastolic blood pressure, glucose, 

LDL cholesterol and triglycerides and 

increases in HDL cholesterol. A recent 

meta-analysis of clinical outcomes 

from bariatric surgery has confirmed 

the impressive improvement in obesityrelated 

comorbidities with substantial 

weight loss. 7 With an average loss of 

60% of excess weight following surgery, 

77% of type 2 diabetics had normal 

glucoses, 70% of dyslipidemic patients 

improved, 62% of hypertensives had 

resolution, and 86% of obstructive 

sleep apnea subjects resolved their 

symptoms. Although there have been 

no hypocaloric diet or anorectic drug 

randomized clinical trials performed to 

evaluate hard cardiovascular endpoints, 

it is presumed that the improvement 

in surrogate cardiovascular risk factors 

(blood pressure, glucose control, 

lipoproteins) with short-term weight loss 

would translate to long-term benefits. 

With this in mind, the National Heart 

Lung and Blood Institute (NHLBI) 

recommends that weight-loss treatment 

be offered to patients with a BMI >30 or 

between 27-29.9 with two or more risk 

factors for vascular disease, one of which 

can be high waist circumference. 8 The 

goal of a weight-loss treatment should 

be 10% of baseline weight within six 

months followed by a maintenance 

program and further weight loss if 

feasible. The NIH classification of 

overweight and obese — with the risk 

for type 2 diabetes, hypertension and 

1 II (1) 2006 | JMDHC

cardiovascular disease associated with 

waist circumference — is shown in 

Table 1. 

o B e s I t Y a n d I n s u l I n 

R e s I s ta n C e 

As the prevalence of obesity has risen 

over the last decade, so too has the 

incidence of type 2 diabetes. The vast 

majority of these cases are insulin 

resistant, meaning that the liver, 

skeletal muscle and adipose tissue are 

less responsive to insulin-medicated 

actions such as glucose uptake and 

lipogenesis. Although the exact cause of 

insulin resistance is not known, adipose 

tissue, particularly in the visceral 

location, is thought to play a permissive 

role. Adipocytes are known to secrete 

many products that can negatively 

affect insulin action — products such 

as nonesterified fatty acids (NEFA), 

tumor necrosis factor (TNF-A), resistin, 

interleukin-6e — and they fail to release 

a beneficial hormone, adiponectin. 9 

The compensatory hyperinsulinemia 

of insulin resistance, combined with 

increased free fatty acids, leads to hepatic 

steatosis and hepatic overproduction 

of triglycerides as well as increased 

renal sodium absorption that can 

result in hypertension. The clustering 

of these clinical findings has been 

termed the “metabolic syndrome” and 

has been defined by several consensus 

organizations. The National Cholesterol 

Education Program Adult Treatment 

Panel (ATP) III requires three out 

of five for a diagnosis of metabolic 

syndrome (Table 2). 10 To highlight the 

importance of abdominal obesity, the 

International Diabetes Federation now 

uses increased waist circumference plus 

two of several other criteria to define 

metabolic syndrome. 11 At least 25% 

of the U.S. adult population meets the 

ATP III metabolic syndrome criteria, 

and this increases with age and in 

certain ethnic groups. 12 Recent studies 

confirm that individuals with or without 

CHD who have metabolic syndrome 

are at increased risk of cardiovascular 

disease. 13,14 

Risk for type 2 diabetes, Hypertension and CVd 

table 1. Classification of overweight and obesity 

Research has shown that people with 

metabolic syndrome who lose weight 

(approximately 7% of baseline) and 

exercise regularly (at least 150 minutes/ 

week) reduce the progression of diabetes 

by 41%. 15 

It appears clear that central or 

abdominal obesity is not only a culprit 

in causing insulin resistance but 

that reducing weight can reverse the 

components of metabolic syndrome. 

t H e e f f e C t s o f 

W e I G H t l o s s 

The Methodist Hospital Wellness 

Services has provided a rapid weight- 

loss program for patients with BMI 

>30 for the past decade. It uses a very 

low-calorie (VLCD, 800 calories), lowcarbohydrate, 

liquid protein plan that 

results in consistent weight loss of 2-5 

pounds/week. Research conducted at 

the Methodist DeBakey Heart Center 

found this drastic caloric deficit diet to 

improve the components of metabolic 

syndrome within weeks, well before the 

patients lose substantial weight (Table 

3). 16 Accompanying the reduction in 

glucose, triglycerides and blood pressure 

was a lowering of plasma insulin and 

an improvement in the homeostatic 

model assessment of insulin resistance. 

JMDHC | II (1) 2006 1 

BmI 

obesity 

Class 

Waist Circumference 

normal High 

Overweight 25.0-29.9 Increased High 

Obesity 30.0 -34.9 I High Very High 

35.0-39.9 II Very High Very High 

Extreme >40 III Extremely High Extremely High 

High waist circumference: men >40 inches; women >35 inches 

National Institutes of Health. Obes Res. 1998;6(suppl 2):51S. 1998;6(suppl 2):51S–209S. 

atP III Criteria for the metabolic syndrome; 

diagnose with any 3 of the following: 

Risk factor defining level 

Abdominal Obesity 

(waist circumference) 

Men >102 cm (>40 inches) 

Women >88 cm (>35 inches) 

Triglycerides >150mg/dL 

HdL-C 

Men 85 mm Hg 

Fasting Glucose >110 mg/dL (>100 mg/dL) 

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486. 

table 2. ATP III criteria for the metabolic syndrome

Based on previous assumptions that 

certain peptides are central to causing 

insulin resistance, we measured serum 

levels in metabolic syndrome patients 

on the liquid protein diet and found no 

reduction in TNF-A or NEFA nor an 

increase in adiponectin in the first four 

weeks (Table 4). 17 These results suggest 

that while there are strong correlations 

between the peptides/hormones 

produced by adipocytes and insulin 

resistance, the observed improvement 

in glucose tolerance is not dependent 

on correcting them nor on losing 

substantial fat mass. Continued work 

from our group on fat obtained from 

subjects before and after 4-6 weeks of 

VLCD participation has focused on 

the genetic expression of an array of 

important steps in energy metabolism. 

Preliminary results suggest a marked 

suppression of stearoyl coenzyme A 

desaturase 1 (SCD1), which would 

cause fat to be shunted from storage to 

energy metabolism. 18 It is possible that 

the early benefit on insulin sensitivity 

from marked caloric restriction is 

through suppression of SCD1 rather 

than increases in adiponectin, and that 

sustained improvement in metabolic 

syndrome components are from the 

increase in adiponectin that occurs with 

substantial weight loss. 


As obesity approaches epidemic status 

in the United States, there are important 

implications on cardiovascular disease 

risk. The American Heart Association 

has addressed the issue in a conference 

symposium and states that weight 

loss and increased physical activity 

are the cornerstones for preventing 

obesity-related CHD risk factors. 2 

Recent studies with rapid weight-loss 

diets suggest that early improvements 

in insulin resistance and components 

of metabolic syndrome are mediated 

through mechanisms that regulate 

energy metabolism, and that long-term 

maintenance of insulin sensitivity is 

probably controlled by reduced visceral 

fat and improved adipose tissue function 

Variable Initial 4 Weeks P value 

Weight 261 244 6.5% < 0.001 

BMI 40.7 38.2 < 0.001 

Systolic BP 140 mm Hg 129 mm Hg < 0.001 

diastolic BP 85 mm Hg 75 mm Hg < 0.001 

Glucose 115 98 15% < 0.001 

Triglycerides 232 137 40% < 0.001 

Cholesterol 208 171 18% < 0.001 

table 3. Weight loss and the metabolic syndrome at 4 weeks 

through release of adiponectin. 


1. Sowers JR. Obesity as a cardiovascular risk 

factor. Am J Med. 2003;115(Suppl 8A): 

S37-41. 

2. Klein S, Burke LE, Bray GA, Blair S, 

Allison DB, Pi-Sunyer X, et al. Clinical 

implications of obesity with specific 

focus on cardiovascular disease: A statement 

for professionals from the American 

Heart Association Council on Nutrition, 

Physical activity and Metabolism. 

Circulation. 2004;110:2952-2967. 

Diab. Met. Obes. 2002;4:407 

Variable Before after P value 

BMI 39 36 < 0.001 

Weight 257 239 < 0.001 

SBP 135 129 0.01 

dBP 85 80 < 0.001 

Glucose 108 92 0.01 

TG 280 127 < 0.001 

HdL-C 44 41 < 0.001 

LdL-C 118 98 0.001 

NEFA 0.5 0.6 NS 

hs-CRP 5.0 4.3 0.02 

Insulin 168 59 < 0.001 

HOMA-IR 7.7 2.3 < 0.001 

Leptin 2964 1727 < 0.001 

Adiponectin 7.5 7.1 NS 

TNF-a 3.3 3.3 NS 

table 4. VLCD effects in metabolic syndrome at 4 weeks 

3. Hedley AA, Ogden CL, Johnson CL, Carroll 

MD, Curtin LR, Flegal KM. Prevalence of 

overweight and obesity among US children, 

adolescents and adults, 1999-2002. JAMA. 

2004;291:2847-2850. 

4. Fontaine KR, Redden DT, Wang C, Westfall 

AO, Allison DB. Years of life lost due to 

obesity. JAMA. 2003:289:187-193. 

5. Osharsky SJ, Passaro DJ, Hershow RC, 

Layden J, Carnes BA, Brody J, et al. A 

potential decline in life expectancy in the 

United States in the 21st century. N Engl J 

Med. 2005;352:1138-1145. 

6. Manson JE, Skerrett PJ, Greenland P, 

20 II (1) 2006 | JMDHC

Van Itallie TB. The escalating pandemics 

of obesity and sedentary lifestyle. Arch 

Intern Med. 2004;164:249-258. 

7. Buchwald H, Avido Y, Braunwald E, 

Jensen MD, Pories W, Fahrbach K, et al. 

Bariatric surgery; A systematic review and 

meta-analysis. JAMA. 2004;292:1724- 

1737. 

8. National Institutes of Health. Clinical 

guidelines on the Identification, Evaluation 

and Treatment of Overweight and Obesity 

in Adults—The Evidence Report. Obes Res. 

1998 Sept; 6 (Suppl 2):S51-209. 

9. Ruan H, Lodish HF. Regulation of insulin 

sensitivity by adipose tissue-derived hormones 

and inflammatory fytokines. Curr Opin 

Lipidol. 2004 Jun; 15(3):297-302. 

10. Expert Panel on Detection, Evaluation 

and Treatment of High Blood Cholesterol 

in Adults. Executive summary of the third 

report of the National Cholesterol Education 

Program (NCEP) expert panel on detection, 

evaluation and treatment of high blood 

cholesterol in adults (Adult Treatment 

Panel III). JAMA. 2001;285:2486-2497. 

11. International Diabetes Federation [homepage 

on the Internet]. Belgium; c2003 

[updated 2005 Apr 14; accessed 2005 Jul]. 

The IDF consensus worldwide definition 

of the metabolic syndrome. Available from 

www.idf.org. 

12. Ford ES, Giles WH, Dietz WH. Prevalence 

of the metabolic syndrome among US 

adults: Findings from the third National 

Health and Nutrition Examination Survey. 

JAMA. 2002;287:356-359. 

13. Lakka HM, Laaksonen DE, Lakka TA, 

Niskanen LK, Kumpusalo E, Tuomilehto J, 

et al. The metabolic syndrome and total and 

cardiovascular disease mortality in middleaged 

men. JAMA. 2002;288:2709-2716. 

14. Levantesi G, Macchia A, Marfisi RM, 

Franzosi MG, Maggioni AP, Nicolosi GL, 

et al. Metabolic syndrome and risk of cardiovascular 

events after myocardial infarction. 

J Am Coll Cardiol. 2005; 46(2):277-283. 

15. Orchard TJ, Temprosa M, Goldberg R, 

Haffner S, Ratner R, Marcovina S, Fowler 

S, for the Diabetes Prevention Program 

Research Group (2005). The effect of 

metformin and intense lifestyle intervention 

on the metabolic syndrome: The Diabetes 

Prevention Program Randomized Trial. 

Ann Intern Med. 2005;142:611-619. 

16. Case CC, Jones PH, Nelson K, O’Brian 

Smith E, Ballantyne CM. Impact of weight 

loss on the metabolic syndrome. Diab 

Obesity Metab. 2002;4:407-414. 

17. Xydakis AM, Case CC, Jones PH, 

Hoogeveen RC, Liu M-Y, Smith EO, et al. 

Adiponectin, inflammation, and the expression 

of the metabolic syndrome in obese 

individuals: the impact of rapid weight loss 

through caloric restriction. J Clin Endocrinol 

Metab. 2004;89(6):2697-2703. 

18. Cohen P, Friedman JM. Leptin and 

the control of metabolism: role for stearoyl-CoA 

desaturase 1 (SCD-1). J Nutr. 

2004;134(Suppl):S2455-2463. 

JMDHC | II (1) 2006 21

P E R OX I S O M E P R O L I F E R ATO R - AC T I VAT E d 

R E C E P TO R S ( P PA R ) : A P OT E N T I A L S T R AT E GY TO 

C O M B AT L I P OTOX I C H E A R T d I S E A S E 

Q i T i a n , P h i l i p M . B a r g e r 

F r o m W i n t e r s C e n t e r f o r H e a r t F a i l u r e R e s e a r c h , B a y l o r C o l l e g e o f M e d i c i n e 

a n d Te x a s H e a r t I n s t i t u t e , S t L u k e’s E p i s c o p a l H o s p i t a l , H o u s t o n , Te x a s 

IntRoduCtIon 

obesity has been increasing dramatically in developed countries, which portends a higher incidence of cardiovascular 

risk factors such as insulin resistance, type 2 diabetes and hypertension. accumulating evidence shows that 

the occurrence of heart disease in obesity is associated with the systemic dysregulation of lipid metabolism and not 

necessarily with hypertension and coronary artery disease. the impaired lipid metabolism may lead to cardiac lipid 

accumulation or “lipotoxic heart disease.” 1 this is also encountered in diabetic cardiomyopathy and in late stages of 

heart failure when global cardiac energy production is impaired. the accumulation of excess lipids has been known to 

cause cell dysfunction and/or cell death in non-adipose tissues such as the pancreas, although it is unknown whether 

a direct link between lipid accumulation and cell death occurs in the heart. nevertheless, prevention or antagonism of 

cardiac lipid accumulation may serve as an adjunctive therapy for a variety of heart disorders that are accompanied 

by metabolic derangement. 

m e C H a n I s m s o f 

l I P o t o X I C H e a R t d I s e a s e 

Normally, fatty acid (FA) supply is 

tightly coupled to need in non-adipose 

cells, leaving little or no unoxidized FAs 

in these cells. In pathological states such 

as obesity or overnutrition, circulating 

FA levels increase and thus oversupply 

FAs to non-adipose cells. After entering 

cells, FAs are esterified to fatty acyl- 

CoAs and then transported across the 

mitochondrial membrane to undergo 

b-oxidation, producing acetyl CoA that 

enters the tricarboxylic acid cycle and 

yields ATP. If FA overload is imposed 

and/or FA utilization is suppressed or 

impaired, the fatty acyl-CoAs can accumulate 

in the cytoplasm. These excess 

fatty acyl-CoAs will be diverted to 

synthesize triglycerides (TG), which 

are relatively inert and keep fatty acyl- 

CoAs away from pathways leading to 

apoptosis. When the content of intracellular 

fatty acyl-CoAs exceeds the 

TG storage capacity, which is limited 

in cardiac myocytes, fatty acyl-CoAs 

enter nonoxidative pathways such as 

ceramide synthesis. Ceramide has long 

been implicated in FA-induced apoptosis 

in non-adipose cells and could 

predictably result in loss of cardiac function. 

The accumulated acyl-CoAs also 

disrupt the insulin-signaling cascade 

that normally causes movement of 

glucose transporter 4 to the cell surface, 

resulting in impaired glucose uptake 

and cellular insulin resistance. The fates 

of fatty acyl-CoAs in cardiomyocytes 

are summarized in Figure 1. 

K e Y R o l e o f P Pa R s 

I n C a R d I a C l I P I d 

m e ta B o l I s m 

It has been well established that FA 

metabolism is transcriptionally 

regulated by peroxisome proliferatoractivated 

receptors (PPARs), members 

of the ligand-activated nuclear 

receptor superfamily. 2 PPAR isoforms 

heterodimerize with the retinoid- 

X receptor (RXR) for binding to a 

conserved specific DNA sequence in 

the promoters of PPAR target genes 

and then activate transcription. To 

date, three PPAR isoforms — a, b/δ 

and γ have been identified with 

specific tissue distribution; PPARa 

and b/δ are abundantly expressed in 

cardiac myocytes. Activation of PPAR 

transcriptional complexes occurs via 

binding of ligands, including both 

naturally occurring long-chain FAs 

and synthetic compounds such as the 

fibrate class of hypolipidemic drugs. 

In the heart, activation of PPARa and 

b/δ increases the expression of genes 

involved in cellular FA uptake as well 

as mitochondrial and peroxisomal boxidation, 

3 thus creating a positive 

feedback loop to handle the normal 

flow of intracellular FAs. 

The important role of PPARa and 

b/δ in cardiac physiology has been illustrated 

in genetically engineered mice. 

Heart-restricted PPARb/δ knockout 

mice exhibit a considerable reduction 

of FA oxidative capacity and undergo 

progressive accumulation of neutral 

lipids in the heart. 4 Similarly, systemic 

PPARa knockout mice have lower 

constitutive cardiac expression of FA 

oxidative enzymes and exhibit agedependent 

histological abnormalities 

such as contraction band necrosis and 

myocardial fibrosis when compared 

with wild-type controls. 5 In the fasting 

state, stored triglycerides in adipose 

tissue are hydrolyzed to release FAs that 

are taken up by the liver, heart or other 

tissues to yield ATP. However, this 

22 II (1) 2006 | JMDHC

fasting-induced increase of FA utilization 

is completely abolished in PPARa 

knockout mice and is accompanied 

by myocardial lipid accumulation. 6 

Whether PPARγ plays a physiologic 

role in the heart is still a matter for 

debate, but PPARγ activity in skeletal 

muscle and adipose tissue may impact 

the function of myocardial PPARa and 

b/δ through the effects of reducing 

circulating FA levels. 

I n V o lV e m e n t o f P Pa R s I n 

C a R d I a C l I P o t o X I C I t Y 

As shown in Figure 1, cardiac lipotoxicity 

is thought to result from two 

different situations: oversupply of FA 

to the heart or impairment of FA utilization. 

The first situation is frequently 

encountered in obesity, hyperlipidemia, 

high-fat diet and diabetes mellitus, 

while impaired FA utilization is mainly 

seen in aging, hypertrophied or failing 

hearts. Through proton magnetic 

resonance spectroscopy, Petersen et 

al. showed that the elderly exhibit 

increased fat accumulation in muscle 

due to reduced mitochondrial oxidative 

activity. 7 Moreover, healthy, young, 

lean but insulin-resistant offspring of 

patients with type 2 diabetes have 80% 

higher intramyocellular lipid content 

when compared to insulin-sensitive 

controls. These studies beg the question 

as to whether the incidence of 

lipotoxic disease involves an impaired 

PPAR regulatory pathway due to its 

critical role in lipid metabolism. Indeed, 

evidence shows that down-regulation of 

FA oxidative enzymes and their transcription 

factor, PPARa, is the main 

reason for intracellular lipid accumulation 

in hearts from obese rats and results 

in marked apoptosis and contractile 

dysfunction. 8,9 During cardiac hypertrophy 

and heart failure, reduced FA 

oxidation (FAO) rates result in lipid 

accumulation. This metabolic derangement 

is mediated, at least in part, 

through the down-regulation of the 

PPARa signaling pathway as the expression 

of PPARa, RXRa, and the PPAR 

interacting protein PGC-1 is reduced 

�� 

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figure 1. Schematic mechanisms of lipotoxic heart disease. In the normal state, most 

fatty acids (FAs) that are imported to the heart enter the mitochondrial b-oxidation 

pathway. Oversupply of fatty acids or impaired fatty acid oxidative capacity leads 

to the accumulation of fatty acyl-CoAs in cardiac myocytes. A surplus of nonesterified 

FAs may increase the expression of FA oxidative enzymes (represented by gold 

stars) and thus normalize the intracellular FA level by serving as PPAR agonists. 

Surplus fatty acyl-CoAs can also be used to synthesize triglycerides. When the 

surplus intracellular FAs exceed the limit of these compensatory mechanisms, they 

will enter nonoxidative pathways such as ceramide synthesis and may contribute to 

lipotoxicity (indicated by red lines). Therefore, reducing the supply of long-chain FAs 

may keep the content of intracellular acyl-CoAs within the limits of oxidative capacity 

(A). Alternatively, increasing FA oxidation will divert the accumulated acyl-CoAs from 

nonoxidative pathways (B) and thus ameliorate lipotoxicity. 

Abbreviations: ACO=acyl-CoA oxidase; ACS=acyl-CoA synthetase; CPT I=carnitine 

palmitoyltransferase I; FATP=fatty acid transportation protein; FAT/CD36=fatty acid 

translocase CD36; PPAR=peroxisome proliferator-activated receptors; RXR=retinoid-X 

receptor; TCA cycle=tricarboxylic acid cycle; TG=triglycerides. 

to fetal levels during cardiac hypertrophy. 

10 Collectively, disturbance of the 

normal PPAR signaling pathway is a 

hallmark signature for lipotoxic heart 

disease. Although the role of PPARb/ 

δ and γ in lipotoxic heart disease has 

not been completely investigated, their 

importance in FA metabolism presumes 

that both also play key roles in the 

pathogenesis or treatment of cardiac 

lipotoxicity. 

u s e o f P Pa R a G o n I s t s I n 

C a R d I a C l I P o t o X I C I t Y 

Figure 1 suggests there are two potential 

strategies to prevent or ameliorate 

cardiac lipotoxicity: reduce the supply 

of FAs to the heart and/or improve 

FAO in the heart. PPAR agonists 

might be ideal candidates to combat 

cardiac lipotoxicity by either increasing 

myocardial FAO capacity or reducing 

plasma FAs available to the heart through 

their actions in the liver, muscle and 

adipose tissue. In Zucker diabetic fatty 

rats, treatment with the PPARγ agonist, 

troglitazone, lowers myocardial TG and 

prevents apoptosis of cardiomyocytes 

and loss of cardiac function. 9 In other 

experimental models, administration of 

JMDHC | II (1) 2006 2 

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PPARa agonists diminishes myocardial 

TG accumulation, inhibits production 

of inflammatory factors such as tumor 

necrosis factor, attenuates cardiac 

fibrosis and improves cardiac function. 11 

Theoretically, PPARa activation could 

also induce the expression of FA 

importing proteins and thus increase FA 

uptake from the circulation. Therefore, 

the question of whether PPARa agonists 

induce or normalize an imbalance 

between the uptake and utilization of 

FAs requires further investigation. 

There are no reports to date of deteriorating 

cardiac function in humans 

treated with fibrates — synthetic 

PPARa agonists — despite widespread 

use to treat hyperlipidemia in patients 

with known cardiac disease, suggesting 

that PPARa agonists may provide a net 

benefit to the cardiovascular system. 


PPARs transcriptionally regulate 

every aspect of fatty acid metabolism. 

Therefore, development of efficient 

and targeted PPAR agonists may serve 

as a novel strategy to combat heart 

disease complicated by myocyte lipid 

imbalance. 


1. Unger RH. Lipotoxic diseases. Annu Rev 

Med. 2002;53:319-36. 

2. Barger PM, Kelly DP. PPAR signaling 

in the control of cardiac energy metabolism. 

Trends Cardiovasc Med. 2000 

Aug;10(6):238-45. 

3. Tian Q, Barger PM. Do PPARs play a role 

in cardiac hypertrophy and heart failure? 

Drug Discovery Today: Disease Mechanism. 

2005;2(1):109-14. 

4. Cheng L, Ding G, Qin Q, Huang Y, Lewis 

W, He N, et al. Cardiomyocyte-restricted 

peroxisome proliferator-activated receptordelta 

deletion perturbs myocardial fatty acid 

oxidation and leads to cardiomyopathy. Nat 

Med. 2004 Nov;10(11):1245-50. 

5. Watanabe K, Fujii H, Takahashi T, 

Kodama M, Aizawa Y, Ohta Y, et al. 

Constitutive regulation of cardiac fatty 

acid metabolism through peroxisome proliferator-activated 

receptor alpha associated 

with age-dependent cardiac toxicity. J Biol 

Chem. 2000 Jul;275(29):22293-9. 

6. Leone TC, Weinheimer CJ, Kelly DP. A 

critical role for the peroxisome proliferatoractivated 

receptor alpha (PPARalpha) in 

the cellular fasting response: the PPARalpha-null 

mouse as a model of fatty acid 

oxidation disorders. Proc Natl Acad Sci U 

S A. 1999 Jun;96(13):7473-8. 

7. Petersen KF, Dufour S, Befroy D, Garcia 

R, Shulman GI. Impaired mitochondrial 

activity in the insulin-resistant offspring of 

patients with type 2 diabetes. N Engl J Med. 

2004 Feb;350(7):664-71. 

8. Young ME, Guthrie PH, Razeghi P, 

Leighton B, Abbasi S, Patil S, et al. 

Impaired long-chain fatty acid oxidation 

and contractile dysfunction in the 

obese Zucker rat heart. Diabetes. 2002 

Aug;51(8):2587-95. 

9. Zhou YT, Grayburn P, Karim A, Shimabukuro 

M, Higa M, Baetens D, et al. 

Lipotoxic heart disease in obese rats: implications 

for human obesity. Proc Natl Acad 

Sci U S A. 2000 Feb;97(4):1784-9. 

10. Sack MN, Disch DL, Rockman HA, Kelly 

DP. A role for Sp and nuclear receptor transcription 

factors in a cardiac hypertrophic 

growth program. Proc Natl Acad Sci USA. 

1997 Jun;94(12):6438-43. 

11. Aasum E, Belke DD, Severson DL, 

Riemersma RA, Cooper M, Andreassen M, 

et al. Cardiac function and metabolism in 

type 2 diabetic mice after treatment with 

BM 17.0744, a novel PPAR-alpha activator. 

Am J Physiol Heart Circ Physiol. 2002 

Sept;283(3):H949-57. 

2 II (1) 2006 | JMDHC

C O M B I N E d O P E N A N d S T E N T G R A F T R E PA I R O F A N A R C H 

A N d d E S C E N d I N G T H O R AC I C AO R T I C A N E U RYS M : 

T H E H Y B R I d P R O C E d U R E 

M i c h a e l J . R e a r d o n , W e i Z h o u , J o n - C e c i l W a l k e s , A l a n B . L u m s d e n 


IntRoduCtIon 

surgeons at the methodist Hospital and the methodist deBakey Heart Center have a long history of contributions 

to the treatment of thoracic aortic aneurysms. In the 1950s, dr. michael e. deBakey pioneered the use of artificial 

grafts for aortic replacement and drs. deBakey and denton Cooley introduced the use of cardiopulmonary bypass 

to repair aneurysms of the ascending aorta and aortic arch. dr. stanley Crawford then introduced surgical repair of 

the descending and thoracoabdominal aneurysm. Half a century later, the methodist deBakey Heart Center has now 

performed more descending and thoracoabdominal aortic aneurysm repairs than any other institution in the world. 

despite these advances, treatment of aneurysms involving both the ascending aorta/aortic arch segment and the 

descending thoracic aorta have continued to pose a formidable surgical challenge: aortic arch repair traditionally 

requires circulatory arrest and profound hypothermia via median sternotomy followed by a later descending thoracic 

aorta repair through a left thoracotomy. 

Recently, a patient who had undergone previous ascending thoracic aortic aneurysm repair for dissection 

presented with a large arch and descending thoracic aortic aneurysm and a high risk of standard surgical repair. a 

unique, minimally-invasive hybrid approach of open and stent graft repair with aortic arch debranching was successfully 

employed, again advancing the field of thoracic aortic surgery at the methodist deBakey Heart Center. 

C a s e H I s t o R Y 

Mr. TF is an 81-year-old male with a 

history of previous graft replacement 

of his ascending thoracic aorta for 

dissection in 1996. His current medical 

history included hypertension, COPD 

with a 120-pack-year history of smoking, 

history of a CVA and parkinsonism. 

He presented with chest and back 

pain and a chest X-ray showing a wide 

mediastinum (Figure 1). Arteriography 

evaluation revealed a large aneurysm 

beginning at his distal ascending aortic 

graft and extending through his aortic 

arch into the distal descending thoracic 

aorta (Figure 2). Evaluation by the 

consulting medical services placed 

his risk of standard surgical repair at 

30-50%. Further, the patient refused 

consideration of a standard open, twostage 

repair because of prior difficulty 

in recovering from his initial dissection 

surgery. 

A hybrid procedure of minimallyinvasive 

debranching of the aortic arch 

and stent graft repair of the arch and 

C L I N C I A L B R I E F 

figure 1. Chest X-ray showing wide mediastinum 

JMDHC | II (1) 2006 2

figure 2. Arteriogram showing arch and 

descending aortic aneurysm 

descending thoracic aortic aneurysm 

was offered as a therapeutic approach. 

t R a d I t I o n a l t e C H n I q u e 

The ascending aorta and aortic arch 

are typically approached via median 

sternotomy, and the descending 

thoracic aorta and thoracoabdominal 

aorta are approached through a left 

thoracotomy. Aneurysms involving 

both of these segments typically require 

figure 3. Surgical incisions 

figure 4. Left subclavian embolization 

a two-stage surgical approach. In 

addition, surgical repair of the aortic 

arch is usually performed under deep 

hypothermia with circulatory arrest 

for neurologic protection. Standard 

repair of these problems represents 

a formidable undertaking even in 

relatively healthy patients. Furthermore, 

in most series, about 50% of patients 

who undergo Stage 1 refuse to undergo 

the second-stage surgical repair because 

of difficulties they encountered in 

recovering from their initial surgery. 

Since our patient had multiple medical 

comorbidities, the risk would be very 

large. Our challenge was to design a 

one-stage, minimally-invasive approach 

acceptable to the patient. Surgical 

planning would include provisions 

for debranching and subsequent 

revascularization of the aortic arch, 

provision of adequate “landing zones” 

or zones of attachment proximally and 

distally for the stent grafts, and access 

for introducing the stent grafts. 

s u R G I C a l t e C H n I q u e 

Extra anatomic reconstruction 

of the aortic arch and debranching 

or disconnection of the arch vessels 

was provided via small right anterior 

thoracotomy, left and right neck 

incisions for carotid artery access, and 

left supraclavicular incision for left 

subclavian artery access (Figure 3). A 

small right fourth interspace anterior 

thoracotomy allowed exposure of the 

previous graft and dissection of a 

proximal portion of that graft. A sidebiting 

clamp was placed on the graft, 

and a 14 mm Dacron graft was sewn 

into the side of his old ascending aortic 

graft. 

Previously, this graft had a 10 mm 

graft sewn into its side, forming an 

“L” going superiorly where it came off 

the ascending graft. The 14 mm graft 

allowed access to the ascending aorta, 

and the 10 mm graft was brought up 

through the thoracic outlet and anastomosed 

in the side into the right carotid 

artery. An 8 mm Dacron graft was 

then taken from this graft at the level 

of the carotid over to the left carotid 

artery, passing in a “U” fashion below 

the sternal notch. Another 8 mm graft 

was then taken from the graft to the left 

carotid artery and anastomosed end to 

side into the left subclavian artery. 

The innominate artery was ligated 

and divided as was the left carotid 

artery, disconnecting these two vessels 

from the aortic arch. The left subclavian 

artery then had coils placed proximally, 

occluding the takeoff left subclavian 

26 II (1) 2006 | JMDHC

figure 5. Graft deployment figure 6. Final graft placement 

artery at its origin but allowing retrograde 

flow from our bypass grafts into 

the left vertebral artery (Figure 4). This 

resulted in an extra anatomic bypass of 

the aortic arch with disconnection of all 

the arch vessels. By placing the 14 mm 

graft low on the ascending graft, there 

was approximately 7 cm of ascending 

graft distal to this that could be used 

as a proximal landing zone for our stent 

graft. Anatomically, the patient’s aneurysm 

stopped at the distal descending 

figure 7. End result 

aorta, leaving a 5 cm segment proximal 

to the celiac axis appropriate for a distal 

landing zone. 

The 14 mm graft was then brought 

through a second, small stab incision 

in the right anterior chest through the 

eighth interspace. This allowed the angle 

of the graft approaching the ascending 

graft to be somewhat parallel. The 

introduction system for the stent graft 

was then placed through the 14 mm 

graft, and stents were deployed start- 

ing with an overlap at the preexisting 

ascending graft and extending down to 

the distal aorta (Figure 5). Completion 

of an aortogram shows exclusion of the 

entire arch and descending aneurysm 

with good revascularization of the arch 

vessels (Figure 6). 

R e C o V e R Y 

The patient recovered from this 

procedure without neurologic sequelae 

and with good cardiac function. His 

wounds healed very quickly, and he 

experienced little impairment of activity 

because of his minimally-invasive 

incisions (Figure 7). 


Aneurysms that involve both the arch 

and descending aorta can be approached 

in a one-stage hybrid procedure with 

debranching of the aortic arch and 

stent graft repair of the aneurysms. We 

believe this provides a simpler approach 

for our patients, with less risk and 

enhanced recovery. 

JMDHC | II (1) 2006 2

Continued from page 1 

(You are free to take issue — if you 

dare.) There is no better technique 

to complement and augment the 

cardiovascular physical diagnosis. 

It provides a wonderful unifying 

discipline upon which to conduct casebased 

educational programs. It is safe, 

noninvasive and relatively inexpensive. 

It epitomizes the old adage, “A picture 

is worth a thousand words.” If it 

becomes sufficiently compact, it may 

one day become an extension of the 

stethoscope. 

What I hope for most is 

that the various applications of 

echocardiography will provide a 

foundation to return to more casebased 

teaching by virtue of its ability 

to define structure and function of the 

heart and blood vessels, something no 

other discipline has been able to do. If 

that should happen, then the fun and 

usefulness of a vanishing art (the art 

of auscultation) may be resurrected 

by combining the auditory and visual 

senses at the bedside. 


1. Conti, CR. Case-based teaching and 

learning. Clin Cardiol. 2006;29:1-2. 

2 II (1) 2006 | JMDHC

6565 Fannin 

Houston, Texas 77030 

713-DeBakey 

www.debakeyheartcenter.com 

A B o u t t H e M e t H o D i s t 

D e B A k e y H e A r t C e n t e r 

The Methodist debakey Heart center 

continues the groundbreaking work begun 

by famed heart care pioneer, dr. Michael E. 

debakey and his associates, who developed 

many of today’s life-saving techniques, tools 

and procedures at The Methodist Hospital. 

located in Houston, Texas, the Methodist 

debakey Heart center combines research, 

prevention, diagnostic care, surgery and 

rehabilitation services in a coordinated 

multi-disciplinary program with one focus: 

delivering compassionate, effective care and 

treatment to patients suffering from heart 

disease. 

nonprofit 

organization 

u.s. Postage 

Paid 

houston, tX 

Permit no. 6311

The Facts Karla M. Ku - The Methodist Hospital

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