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THE ROLE OF SURGERY IN HEART FAILURE - PART 6 pdf

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A matrix metalloproteinase induction/activation system exists in the human left ventricular myocardium and is upregulated in heart failure.. Time-dependent changes in matrix metalloprote

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collagen content Am J Surg 2000;180(6):498–501

[discussion: 501–2]

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respira-tion in failing human hearts J Am Coll Cardiol

2000;36(6):1897–902

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De-creased expression of tumor necrosis factor-alpha in

failing human myocardium after mechanical

circu-latory support: a potential mechanism for cardiac

recovery Circulation 1999;100(11):1189–93

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Myo-cyte recovery after mechanical circulatory support

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1998;97(23):2316–22

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Struc-tural and left ventricular histologic changes after

implantable LVAD insertion Ann Thorac Surg

1995;59(3):609–13

[110] Birks EJ, Latif N, Bowles C Measurement of

cyto-kine levels and activation of the apoptotic pathway

in patients requiring left ventricular assist device

(LVAD): implication for timing of implantation

Circulation 1999;99:2565–70

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Mechanisms of extracellular matrix remodeling in

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[114] Maisch B Ventricular remodeling Cardiology

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[115] Maisch B Extracellular matrix and cardiac

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exists in the human left ventricular myocardium

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Remodeling of human myocardial collagen in idio-pathic dilated cardiomyopathy: role of metallopro-teinases and pyridinoline cross links Am J Pathol 1996;148:1639–48

[121] Spinale FG, Coker ML, Thomas CV, et al Time-dependent changes in matrix metalloproteinase ac-tivity and expression during the progression of con-gestive heart failure: relation to ventricular and myocyte function Circ Res 1998;82:482–95 [122] Spinale FG, Coker ML, Krombach RS, et al Ma-trix metalloproteinase inhibition during developing congestive heart failure: effects on left ventricular geometry and function Circ Res 1999;85:364–76 [123] Ries C, Petrides PE Cytokine regulation of matrix metalloproteinase activity and regulatory dysfunc-tion in disease Biol Chem 1995;376:345–55 [124] Chancey AL, Brower GL, Peterson JT, et al Effects

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Patients Who Have Dilated Cardiomyopathy

Must Have a Trial of Bridge to Recovery:

The Case Against That Proposition

Philip A Poole-Wilson, MD, FRCP, FMedSci * National Heart & Lung Institute, Imperial College London, London, UK

Propositions containing the word ‘‘must’’ are

usually mistaken and this proposition is no

exception.

In the last few years the management of patients

who have severe heart failure has increased in

complexity, requiring greater skills and finer

judg-ment from the physician and surgeon New drugs

have emerged, the expertise of physicians in using

these drugs has improved, the indications for

cardiac transplantation have changed, new surgical

techniques have developed, and effective left

ven-tricular assist devices (LVADs) have become

avail-able The newer LVADs are an engineering

triumph but raise critical issues regarding how

and when they should be used This problem has

been exacerbated by the decline in the number of

patients undergoing transplantation, by the dearth

of donor hearts, and possibly by a growing public

aversion to cardiac transplantation.

Indications for the use of left ventricular

assist devices

The availability on the market of many devices

to assist the pumping function of the heart has

resulted in a new vocabulary This has led to

a surplus of confusion, even misunderstanding,

extending from the characteristics and phenotypes

of patients and the indications for the use of

LVADs to the appropriate assessment of benefit,

if any.

The phrase ‘‘bridge to recovery’’ is used to encapsulate the idea that doctors can identify patients who have reversible cardiac dysfunction and who only require transient support of the circulation before spontaneous functional recov-ery of the heart in situ Established clinical entities

in which this can occur include acute myocarditis, Takotsubo syndrome, acute alcohol ingestion, and depression of cardiac function by toxins or drugs The phrase might also include patients who have cardiogenic shock attributable to a second group

of patients who have myocardial infarction in whom the likely outcome may be transformed In recent years several authors have possibly identi-fied a third group in which a sizable proportion of patients presenting with severe heart failure of idiopathic origin and with large hearts (dilated cardiomyopathy) do recover spontaneously These authors have argued that such patients should receive a device pending a decision as to whether to proceed to transplantation The extent

to which this claim is correct is unknown largely because many of these patients may in reality belong to the other two groups of patients The phrases ‘‘destination treatment’’ or ‘‘life-time therapy’’ are used to describe the intention at the moment of insertion of the device: that it should remain in place for the life of the patient and that there is no intention to proceed to transplantation The first such device inserted with this intention was reported in 2000 [1] Since then many patients around the world have re-ceived devices of different designs, although the efficacy remains somewhat uncertain [2,3]

* National Heart & Lung Institute, Imperial College

London, Dovehouse Street, London SW3 6LY, United

Kingdom

E-mail address:p.poole-wilson@imperial.ac.uk

1551-7136/07/$ - see front matterÓ 2007 Elsevier Inc All rights reserved

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Cardiac Transplantation: Any Role Left?

Martin Cadeiras, MD, Manuel Prinz von Bayern, PhD,

Mario C Deng, MD, FACC, FESC *

College of Physicians and Surgeons, Columbia University, New York, NY, USA

Heart transplantation was introduced as

a breakthrough therapy that dramatically

pro-longed life in individually selected patients

thought to be near death Unlike most other

ther-apeutic modalities, the survival benefit of cardiac

transplantation compared with conventional

treatment in advanced heart failure has never

been tested in a prospective randomized trial,

probably because the benefit of cardiac

transplan-tation compared with conventional therapy

usu-ally was assumed clinicusu-ally evident The early

experience at Stanford University Medical Center

between January 1968 and August 1976

demon-strated overall 1- and 2-year survival rates of

52% and 43%, respectively, and a 90% return

to functional class I New York Heart Association

(NYHA) functional status among transplant

sur-vivors, most of them returning to their preillness

activities In this initial series, 95% of the patients

selected for transplantation for whom donors did

not become available were dead 6 months after

evaluation These data suggested that cardiac

transplantation probably not only prolonged

sur-vival, but could also return carefully selected

re-cipients to active lives [1] In 1993, the 24th

Bethesda Conference on Cardiac Transplantation

recommended heart transplantation as the gold

standard therapy in selected patients who had re-fractory advanced heart failure [2] Ten years later, according to the established Registry of the International Society for Heart and Lung Transplantation, more than 3000 new transplant patients were being reported to the database each year accounting for a total of 71,040 heart transplants since it started in 1982 [3] The early observations of the Stanford group may not apply today, because major changes on the understand-ing and refinement of the therapeutic orchestra available for patients in the advanced phase of heart failure have occurred, specifically with the introduction of highly specialized heart failure units and comprehensive multidisciplinary teams; new pharmacologic compounds, including angio-tensin-converting enzyme (ACE) inhibitors, an-giotensin-receptor blockers, spironolactone and beta-blockers; novel devices, including trichamber pacemakers, defibrillators, and mechanical circu-latory support devices; and improved outcomes with high-risk cardiac surgical procedures Impor-tant improvements in the evaluation of heart transplant patients were achieved after the intro-duction of functional capacity evaluation by mea-suring oxygen consumption [4] and subsequently

a multivariate model to identify patients at highest risk of death The heart failure survival score was derived from a prospective cohort and indepen-dently validated allowing to dissect the referred population into three groups with low-, medium-,

or high-risk profile [5] Using this tool, a highly pro-vocative national cohort study suggested that heart transplantation may not confer a survival benefit during the first year posttransplantation for pa-tients having low- or medium-risk profiles [6,7] These findings were supported by subsequent re-ports using United Network for Organ Sharing

This work was supported at least in part by Grant

N HL 077096-01 from the National Institute of Health

(MPB, MCD) and by research Funds, Columbia

University, Division of Cardiology (MC)

* Corresponding author Department of Medicine,

Division of Cardiology, College of Physicians &

Sur-geons, Columbia University, 622 West 168th Street,

PH12 STEM Room 134, New York NY 10032

E-mail address:md785@columbia.edu

(M.C Deng)

1551-7136/07/$ - see front matterÓ 2007 Elsevier Inc All rights reserved

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