Terapia de resincronizacion cardiaca


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Terapia de resincronizacion cardiaca

  1. 1. 1093The physiological underpinning for cardiac resynchroni-zation therapy (CRT) began with Carl Wiggers in 1925.He showed that when contraction of the heart was induced bydirect cardiac electric stimulation, the early phase of contrac-tion of the heart was slowed and myocardial tension developedmore gradually.1Wiggers explained these findings by differ-ences in the order of excitation of the ventricle. Subsequentstudies by a number of investigators highlighted the fact thata left bundle-branch block conduction pattern was associatedwith dyssynchronous contraction that exacerbated left ven-tricular systolic dysfunction. Few people appreciate the factthat Dr Morton Mower, who was involved in the developmentof the implantable cardioverter defibrillator,2,3also developedthe patent for cardiac resynchronization therapy in 19904thatwas assigned to CPI/Guidant and subsequently licensed toMedtronic.In 1994, Cazeau et al5reported 1 patient with widened QRSand advanced heart failure who achieved dramatic improve-ment with biventricular pacing. Various short-term animal andclinical hemodynamic studies showed significant improve-ment in cardiac function when both right and left ventricles ofa diseased heart with conduction disturbance were preexcited(biventricular pacing),6and similar findings were observedrecently with univentricular left ventricular stimulation inthe compromised heart with conduction block.7Central toall these studies was that dyssynchronous contraction associ-ated with disturbed left ventricular conduction improved withdirect left ventricular pacing.A series of large randomized trials, includingCOMPANION,8CARE-HF,9MADIT-CRT,10and RAFT,11have documented the safety and efficacy of biventricular car-diac reynchronization pacing in patients with various degreesof severity of heart failure. All the studies involved patientswith wide QRS complexes, with the best results observed inthose with left bundle-branch block. Cardiac guideline recom-mendations followed in 2008,12with a recent update in 201213emphasizing the importance of wide QRS and left ventricularconduction disturbance as the best substrate for CRT efficacy.The article by Thibault et al14in Circulation involves asmall randomized trial of CRT in patients with heart failureand narrow QRS (<120 ms) using exercise duration at 1 yearas the primary end point. The Thibault trial was designed in2002 and initiated in 2003, and it appears to be based on anobservational study reported in 2003 by Achilli et al.15TheAchilli study enrolled patients with refractory heart failure(HF) and incomplete left bundle-branch block (narrow QRS)together with echocardiographic evidence of interventricularand intraventricular asynchrony. There were 38 patients withQRS >120 ms and 14 patients had a narrow QRS <120 ms.The CRT benefit was similar in patients with wide or narrowQRS. It should be emphasized that the authors put the wordnarrow in quotes (“narrow”) in the title and throughout thearticle when referring to QRS <120 ms because many of thepatients had QRS durations <100 ms. The authors concludedthat “cardiac resynchronization therapy may be helpful inpatients with echocardiographic evidence of interventricularand intraventricular asynchrony and incomplete left bundle-branch block”.15It is surprising that Thibault et al.14initiated their studybased on limited findings in the literature, and their studydid not include echocardiographic evidence of dyssynchrony.The average QRS duration was 104+9 ms, with many of theenrolled patients with QRS <100 ms. There were 12 enrollingcenters, and the study ran for 8 years from 2003 to 2011 witha total enrollment of only 85 patients in the study. That meansthat, on average, each center enrolled <1 patient per centerper year. It is surprising that the Data and Safety MonitoringBoard waited 8 years to terminate the study because of futilityand safety concerns.After Thibault et al initiated their study but beforepublication in Circulation, there were several reports ofvariable CRT efficiacy in heart failure patients with narrowQRS complexes. In a small observational study by Bleeker etal16involving 66 studied patients with low ejection fractionand left ventricular dyssynchrony on tissue doppler imagaing,the 33 patients with QRS <120 ms had left ventricular reverseremodeling with CRT comparable with the 33 patients withQRS complex >120 ms. A larger randomized trial by Beshaiet al17involved 172 patients with the primary end point anincrease in peak oxygen consumption of at least 1.0 mL perkilogram of body weight per minute during cardiopulmonaryexercise testing at 6 months after randomization. The CRT-treated patients did not improve peak oxygen consumptionwhen compared with the nontreated control group. The resultsof this randomized study were not very encouraging that CRTwould be beneficial in patients with narrow QRS complexes.What have we learned from the large MADIT-CRT trialregarding CRT efficacy and QRS duration? CRT was sig-nificantly more effective when the QRS duration was >150ms than in the 130 to 149 ms range,10and female patients(Circulation. 2013;127:1093-1094.)© 2013 American Heart Association, Inc.Circulation is available at http://circ.ahajournals.orgDOI: 10.1161/CIRCULATIONAHA.113.001363The opinions expressed in this article are not necessarily those of theeditors or of the American Heart Association.From the University of Rochester Medical Center, Rochester, NY.Correspondence to Arthur J. Moss, MD, Professor of Medicine(Cardiology), Heart Research Follow-Up Program, University ofRochester Medical Center, 265 Crittenden Blvd, CU 420653, Rochester,NY 14642-0653. E-mail heartajm@heart.rochester.eduNarrow QRS Is Not the Right Substrate forCardiac Resynchronization TherapyArthur J. Moss, MDEditorial
  2. 2. 1094  Circulation  March 12, 2013were the only ones who achieved significant CRT benefitwith QRS of 130 to 149 ms.18Heart failure patients with leftbundle-branch block conduction obtained excellent benefitfrom CRT, and there was no appreciable benefit from CRTin patients with right bundle-branch block or intraventricularconduction delay.19It is quite clear that CRT does not achieve a favorableresult in patients with QRS durations <120 ms. On the otherhand, mechanical left ventricular dyssynchrony, an impor-tant myocardial substrate for effective CRT, is exacerbatedby abnormal excitation of the left ventricle with a wide QRSduration, especially when a left bundle branch conductiondisturbance is present. Although many factors influence thecardiac responsiveness to CRT (lead position, type of cardio-myopathy [ischemic versus nonischemic], extent and severityof the myocardial damage, and sex), wide QRS complex andleft bundle-branch block are excellent electric biomarkers foridentification of heart failure patients who are likely to benefitfrom resynchronization therapy.DisclosuresDr Moss reports a research grant from Boston Scientific to theUniversity of Rochester, of which he is a principal investigator.References 1. Wiggers C. The muscular reactions of the mammalian ventricles to artifi-cial surface stimulation. Am J Physiol 1925;73:346–378. 2. Mirowski M, Mower MM, Langer A, Heilman MS, Schreibman J. Achronically implanted system for automatic defibrillation in active con-scious dogs: experimental model for treatment of sudden death from ven-tricular fibrillation. Circulation. 1978;58:90–94. 3. Mirowski M, Reid PR, Mower MM, Watkins L, Gott VL, Schauble JF,Langer A, Heilman MS, Kolenik SA, Fischell RE, Weisfeldt ML. Termi-nation of malignant ventricular arrhythmias with an implanted automaticdefibrillator in human beings. N Engl J Med. 1980;303:322–324. 4. Mower MM. Method and apparatus for treating hemodynamic dysfunc-tion. Patent issued May 29,1990. 5. Cazeau S, Ritter P, Bakdach S, LazarusA, Limousin M, Henao L, MundlerO, Daubert JC, Mugica J. Four chamber pacing in dilated cardiomyopathy.Pacing Clin Electrophysiol. 1994;17(11 Pt 2):1974–1979. 6. Kass DA, Chen CH, Curry C, Talbot M, Berger R, Fetics B, Nevo E.Improved left ventricular mechanics from acute VDD pacing in patientswith dilated cardiomyopathy and ventricular conduction delay. Circula-tion. 1999;99:1567–1573. 7. Thibault B, Ducharme A, Harel F, White M, O’Meara E, Guertin MC,Lavoie J, Frasure-Smith N, Dubuc M, Guerra P, Macle L, Rivard L, RoyD, Talajic M, Khairy P. Left ventricular versus simultaneous biventricularpacing in patients with heart failure and a QRS complex >/=120 millisec-onds. Circulation. 2011;124:2874–2881. 8. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De MarcoT, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, FeldmanAM; Comparison of Medical Therapy, Pacing, and Defibrillation in HeartFailure (COMPANION) Investigators. Cardiac-resynchronization therapywith or without an implantable defibrillator in advanced chronic heart fail-ure. N Engl J Med. 2004;350:2140–2150. 9. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, KappenbergerL, Tavazzi L; Cardiac Resynchronization-Heart Failure (CARE-HF)Study Investigators. The effect of cardiac resynchronization on morbidityand mortality in heart failure. N Engl J Med. 2005;352:1539–1549. 10. Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, EstesNA III, Foster E, Greenberg H, Higgins SL, Pfeffer MA, Solomon SD,Wilber D, Zareba W; MADIT-CRT Trial Investigators. Cardiac-resynchro-nization therapy for the prevention of heart-failure events. N Engl J Med.2009;361:1329–1338. 11. Tang AS, Wells GA, Talajic M, Arnold MO, Sheldon R, Connolly S,Hohnloser SH, Nichol G, Birnie DH, Sapp JL, Yee R, Healey JS, RouleauJL; Resynchronization-Defibrillation for Ambulatory Heart Failure TrialInvestigators. Cardiac-resynchronization therapy for mild-to-moderateheart failure. N Engl J Med. 2010;363:2385–2395. 12. Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA, III, Freedman RA,Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, HlatkyMA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW,Sweeney MO, Smith SC, Jr., Jacobs AK, Adams CD, Anderson JL, BullerCE, Creager MA, Ettinger SM, Faxon DP, Halperin JL, Hiratzka LF, HuntSA, Krumholz HM, Kushner FG, Lytle BW, Nishimura RA, Ornato JP,Riegel B, Tarkington LG, Yancy CW. ACC/AHA/HRS 2008 guidelinesfor device-based therapy of cardiac rhythm abnormalities: A report ofthe American College of Cardiology/American Heart Association TaskForce on Practice Guidelines (writing committee to revise the ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers andantiarrhythmia devices): Developed in collaboration with the americanassociation for thoracic surgery and society of thoracic surgeons. Circula-tion. 2008;117:e350–408. 13. Epstein AE, Dimarco JP, Ellenbogen KA, Estes NA, III, Freedman RA,Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, HlatkyMA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW,Sweeney MO. 2012 ACCF/AHA/HRS focused update incorporated intothe ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiacrhythm abnormalities: a report of the American College of CardiologyFoundation/American Heart Association Task Force on Practice Guide-lines and the Heart Rhythm Society. Circulation. 2013 Jan 22;127:e283–352. doi: 10.1161/CIR.0b013e318276ce9b. Epub 2012 Dec 19. 14. Thibault B, Harel F, Ducharme A, White M, Ellenbogen K, Frasure-SmithN, Roy D. Cardiac resynchronization therapy in patients with heart failureand a QRS complex <120 milliseconds: the Evaluation of Resynchroni-zation Therapy for Heart Failure (LESSER-EARTH) trial. Circulation.2013;127:873–881. 15. Achilli A, Sassara M, Ficili S, Pontillo D, Achilli P, Alessi C, De SpiritoS, Guerra R, Patruno N, Serra F. Long-term effectiveness of cardiac resyn-chronization therapy in patients with refractory heart failure and “narrow”QRS. J Am Coll Cardiol. 2003;42:2117–2124. 16. Bleeker GB, Holman ER, Steendijk P, Boersma E, van der Wall EE,Schalij MJ, Bax JJ. Cardiac resynchronization therapy in patients with anarrow QRS complex. J Am Coll Cardiol. 2006;48:2243–2250. 17. Beshai JF, Grimm RA, Nagueh SF, Baker JH II, Beau SL, Greenberg SM,Pires LA, Tchou PJ; RethinQ Study Investigators. Cardiac-resynchroniza-tion therapy in heart failure with narrow QRS complexes. N Engl J Med.2007;357:2461–2471. 18. Arshad A, Moss AJ, Foster E, Padeletti L, Barsheshet A, Goldenberg I,Greenberg H, Hall WJ, McNitt S, Zareba W, Solomon S, Steinberg JS;MADIT-CRT Executive Committee. Cardiac resynchronization therapyis more effective in women than in men: the MADIT-CRT (MulticenterAutomatic Defibrillator Implantation Trial with Cardiac Resynchroniza-tion Therapy) trial. J Am Coll Cardiol. 2011;57:813–820. 19. Zareba W, Klein H, Cygankiewicz I, Hall WJ, McNitt S, Brown M,Cannom D, Daubert JP, Eldar M, Gold MR, Goldberger JJ, GoldenbergI, Lichstein E, Pitschner H, Rashtian M, Solomon S, Viskin S, Wang P,Moss AJ; MADIT-CRT Investigators. Effectiveness of Cardiac Resyn-chronization Therapy by QRS Morphology in the Multicenter AutomaticDefibrillator Implantation Trial-Cardiac Resynchronization Therapy(MADIT-CRT). Circulation. 2011;123:1061–1072.Key Words: Editorials ■ cardiac resynchronization therapy