Dr. César Cáceres Monié Hospital Británico

Presentación del tema: "Dr. César Cáceres Monié Hospital Británico"— Transcripción de la presentación:

1 Dr. César Cáceres Monié Hospital Británico
Terapia de Resincronización en la Insuficiencia Cardíaca Mecanismos, Resultados Clínicos y Selección de pacientes This presentation provides an overview of the proposed mechanisms and proven clinical benefits of cardiac resynchronization therapy. Patient selection guidelines and descriptions of both the Medtronic InSync® Model 8040 and InSync ICD® Model 7272 and their approved indications are included at the end of this presentation. It is intended for audiences who manage heart failure patients in their practices and may refer patients for cardiac resynchronization therapy. Dr. César Cáceres Monié Hospital Británico

2 Generalidades La IC es una de las enfermedades más prevalentes en los países desarrollados Pronóstico: malo (a pesar de las nuevas terapias farmacológicas ) 30% IC avanzada: Trastornos de la conducción IV Asincronía en la contractilidad ventricular Deterioro de la CF

3 Prevalencia En EE UU: 1% (0,3-2%)
Aumenta con la edad (5-10% en mayores de 75 a) Es la causa más frecuente de ingreso hospitalario en mayores de 65 años Promedio de internación 7 días, y de 13 días si requieren cuidados intensivos. El 13% reingresa en el primer año Shocken DD, Arrieta MI, Leaverton PE, Ross EA. Prevalence and mortality rate of congestive heart failure in the United States. J Am Coll Cardiol 1992;20:301-6.

4 Pronóstico Malo, progresión IC y > incidencia de MS
Mortalidad:(Bajo tratamiento farmacológico óptimo) IC leve: 20-30% a los 4 años IC leve-moderada: 30-40% a los 4 años IC Severa: 50% en el primer año The CONSENSUS Trial Study Group: effects of enalapril on mortality in severe congestive heart failure: Results of the Cooperative North Scandinavian Survival Study. Group (CONSENSUS). N Engl J Med 1987;316: [

5 IC y T. Conducción Población con IC IC leve1,2 IC mod. o severa 3,4,5
Approximately 15% of all heart failure patients have an inter- or intraventricular conduction delay (QRS > 120 msec)1-2. Over 30% of moderate to severe heart failure patients have a prolonged QRS. The prevalence of conduction defects increases with severity of heart failure.3-5 Shenkman and colleagues found the factors associated with prolonged QRS included: Older age, Male gender, Caucasian race, Lower EF, Higher LVESD 1 Havranek EP, Masoudi FA, Westfall KA, Wolfe P, Ordin DL, Krumholz HM. Spectrum of heart failure in older patients: Results from the National Heart Failure Project. Am Heart J 2002;143: 2 Shenkman HJ, McKinnon JE, Khandelwal AK, et al. Determinants of QRS Prolongation in a Generalized Heart Failure Population: Findings from the Conquest Study [Abstract 2993]. Circulation 2000;102(18 Suppl II) 3 Schoeller R, Andersen D, Buttner P, Oezcelik K, Vey G, Schroder R. First-or second-degree atrioventricular block as a risk factor in idiopathic dilated cardiomyopathy. Am J Cardiol 1993;71: 4 Aaronson KD, Schwartz JS, Chen TM, Wong KL, Goin JE, Mancini DM. Development & prospective validation of a clinical index to predict survival in ambulatory patients referred for cardiac transplant evaluation. Circulation 1997; 95: 5 Farwell D, Patel NR, Hall A, Ralph S, Sulke AN. How many people with heart failure are appropriate for biventricular resynchronization? Eur Heart J 2000;21: 1 Havranek E, Masoudi F, Westfall K, et al. Am Heart J 2002;143: 2 Shenkman H, McKinnon J, Khandelwal A, et al. Circulation 2000;102(18 Suppl II): abstract 2293 3 Schoeller R, Andersen D, Buttner P, et al. Am J Cardiol. 1993;71: 4 Aaronson K, Schwartz J, Chen T, et al. Circulation 1997;95: 5 Farwell D, Patel N, Hall A, et al. Eur Heart J 2000;21:

6 ECG

7 BCRI y cambios hemodinámicos
Alteración de la sincronía Disminución de la contractilidad cardíaca (dP/dT) Reducción de la fracción de eyección Descenso del gasto cardíaco Deterioro hemodinámico y de la CF

8 BCRI y cambios hemodinámicos
Alteración de la sincronía Disminución de la contractilidad cardíaca (dP/dT) Reducción de la fracción de eyección Descenso del gasto cardíaco Deterioro hemodinámico y de la CF

9 BCRI y cambios hemodinámicos
Alteración de la sincronía Disminución de la contractilidad cardíaca (dP/dT) Reducción de la fracción de eyección Descenso del gasto cardíaco Deterioro hemodinámico y de la CF

10 BCRI y cambios hemodinámicos
Alteración de la sincronía Disminución de la contractilidad cardíaca (dP/dT) Reducción de la fracción de eyección Descenso del gasto cardíaco Deterioro hemodinámico y de la CF

11 BCRI y cambios hemodinámicos
Alteración de la sincronía Disminución de la contractilidad cardíaca (dP/dT) Reducción de la fracción de eyección Descenso del gasto cardíaco Deterioro hemodinámico y de la CF

12 BCRI y cambios hemodinámicos
Desarrolla y o aumenta IM Alteración de los músculos papilares, Retraso de la contracción en la pared lateral. Asincronía AV Menor aporte AI al VI Aumento de presión AI Aumento del VFDVI Aumenta o desarrolla la presencia de IM por alteración de la función de los músculos papilares, y retraso de la contracción en la pared lateral. Asincronía AV con menor aporte de la aurícula al llenado ventricular, lo que aumenta la presión de la AI y el volumen telediastólico del VI La prolongación de la sístole lleva a una reducción del tiempo de llenado que puede empeorar o condicionar la aparición de disfunción diastólica. Asincronía interventricular: disminuye el volumen de eyección del VD derecho y empeore la situación global del paciente

13 BCRI y cambios hemodinámicos
Sístole prolongada Reducción del tiempo de llenado VI Condiciona aparicion de DD Asincronía interventricular: Disminucion del Vol. ey VD Empeora la situación global del paciente Aumenta o desarrolla la presencia de IM por alteración de la función de los músculos papilares, y retraso de la contracción en la pared lateral. Asincronía AV con menor aporte de la aurícula al llenado ventricular, lo que aumenta la presión de la AI y el volumen telediastólico del VI La prolongación de la sístole lleva a una reducción del tiempo de llenado que puede empeorar o condicionar la aparición de disfunción diastólica. Asincronía interventricular: disminuye el volumen de eyección del VD derecho y empeore la situación global del paciente

14 En síntesis: el BCRI Contracción de VD preceden a la del VI
El septum se desplaza contra el VI Se prolonga la contracción, la eyección y relajación VI Retraso en la apertura y cierre aórtico y mitral Sitios tardiamente despolarizados Empeora el vol.sist. Mayor regurgitación mitral

15 Mortalidad , IC y BRI Incremento de la mortalidad en 1 año en pacientes con BCRI (QRS > 140 ms) Significativo incremento en la mortalidad si se toma poblaciones según la edad, subgrupos de efermedad cardíaca, severidad en la IC, y el tratamiento con drogas N=5517 20 HR* 1.70 ( ) BRI=1391 * HR = Hazard Ratio 15 16.1 11.9 Mortalidad anual (%) HR * 1.58 ( ) 10 This slide was developed using data from Italian Network on CHF Registry, established in 1995 in 150 cardiology centers distributed throughout Italy. The group defined complete LBBB as a QRS duration greater than 140 ms. The graph displays 1-year unadjusted mortality for all patients, and for those with complete LBBB. Hazard Ratios (HR) with 95% Confidence Interval are labeled. A Hazard Ratio of 1.70 for all-cause mortality means a 70% greater risk of death with LBBB. With respect to sudden cardiac death, patients with LBBB have a 58% greater risk than the general patient group. Of interest is 25% of the patients had a QRS duration greater than 140 msec. This may reflect the fact that these patients were seen in cardiology centers, were likely sicker than the HF population at large and therefore were more likely to have LBBB. Baldasseroni S, Opasich C, Gorini M, Lucci D, Marchionni N, Marini M, Campana C, Perini G, Deorsola A, Masotti G, Tavazzi L, Maggioni AP. Left bundle-branch block is associated with increased 1-year sudden and total mortality rate in 5517 outpatients with congestive heart failure: A report from the Italian Network on Congestive Heart Failure. Am Heart J 2002;143: 7.3 5 5.5 Muerte total Muerte Súbita Causa de Muerte Baldasseroni S, Opasich C, Gorini M, et al. Am Heart J 2002;143:

16 BCRI: mortalidad al año 16.1%
I.C y BCRI N: (1 año) Isquémica: (45 %) Idiopatica: (36 %) Hipertensiva: (12 %) Otras causas: (5%) BCRI presente (25%) BCRI: mortalidad al año 16.1% Report from the Italian network on congestive heat failure

17 I.C y BCRI QRS: > 120 N= 600 Mortalidad total Muerte súbita
34 % 49 % 17 % 25 % F. Ey: > 30 % F. Ey: < 30 % 41 % 51 % 21 % 29 % QRS: > 120 Georgetown University Medical Center Veterans Affairs Cooperative Studies Program Am Heart J. 2002

18 QRS ancho e Incremento de la mortalidad
Vesnarinone Study1 (VEST study analysis) QRS Duration (msec) <90 90-120 >220 NYHA Clase II-IV 3,654 ECGs Edad, creatinina, LVEF, frecuencia cardíaca, ancho del QRS, son predictores independientes de la mortalidad Riesgo relativo en 5x de pacientes con QRS ancho vs. QRS angosto The VEST Study demonstrated QRS duration was found to be an independent predictor of mortality. Patients with wider QRS (> 200 ms) had five times greater mortality risk than those with the narrowest (< 90 ms). Resting ECG is a powerful yet accessible and inexpensive marker of prognosis in patients with DCM and CHF. ACC 1999; Abstract: 847-4 The Resting Electrocardiogram Provides a Sensitive and Inexpensive Marker of Prognosis in Patients with Chronic Congestive Heart Failure Venkateshwar K. Gottipaty, Steven P. Krelis, Fei Lu, Elizabeth P. Spencer, Vladimir Shusterman, Raul Weiss, Susan Brode, Amie White, Kelley P. Anderson, B.G. White, Arthur M. Feldman For the VEST investigators; University of Pittsburgh, Pittsburgh PA, USA 1 Gottipaty V, Krelis S, Lu F, et al. JACC 1999;33(2) :145 [Abstr847-4].

19 I.C y BCRI MORTALIDAD GLOBAL: % BCRI RIESGO DE MUERTE SÚBITA: %

20 Implicancia de los Estudios
El BRI es un marcador independiente de muerte total y de muerte súbita

21 Prolongación del intervalo PR
Dism. el tiempo de llenado VI Aum. de la reg.VA pre-sistólica Dism. del Vol de Ey VI

22 I.Mitral en la I.C I.C. >I.C. Remodelado esférico Insuficiencia
Dilatación del anillo mitral Distorsion de la implantación de los músculos papilares >I.C. Insuficiencia mitral

23 Disincronía ventricular
This animation shows the normal heart changing into a dilated, remodeled heart, followed by a depiction of a mechanical perspective of ventricular dysynchrony. An ECG showing intra- or interventricular conduction delays is displayed along the bottom. Animation Filename: “Clip1-Vdysynchrony.mpg.” The animation can be started by positioning the mouse-cursor over the image and clicking once. To stop or restart the animation video at anytime, click once on the image.

24 Desincronización cardíaca
Eléctrica : BRI alteración Inter e Intra ventricular Estructural: Ruptura de la matriz de colágeno con < fuerza mecánica Mecánica: Por Anormalidad del movimiento regional Introduces “new” terms used in this slide series. Ventricular dysynchrony is defined as the effect caused by intra- and inter-ventricular conduction defects or bundle branch block. Read Dr. Tavazzi’s editorial referenced here for a summary of the three potential causes of ventricular dysynchrony. Cardiac resynchronization is defined as the therapeutic intent of atrial synchronized biventricular pacing for patients with heart failure and ventricular dysynchrony. The intent of the therapy is to resynchronize the ventricular activation sequence, and to better coordinate atrial-ventricular timing to improve pumping efficiency. Cardiac resynchronization therapy is currently indicated for the reduction of symptoms of moderate to severe heart failure (NYHA Function Class III or IV) in those patients who remain symptomatic despite stable, optimal medical therapy, and have a left ventricular ejection fraction  35% and a QRS duration 130 ms. An ICD is also available for patients with a standard ICD indication who also meet the above listed criteria. Using atrial-synchronized biventricular pacing in combination with optimal drug therapy has been shown to significantly improve a patient’s symptoms. 1 Tavazzi L. Eur Heart J 2000;21:

25 BCRI por estimulación VD
Sub estudios del MOST y del MADIT II y Los resultados del estudio DAVID demostraron que: La estimulación crónica en ápex de ventrículo derecho, puede tener efectos negativos la función ventricular Sweeney M, et al. Adverse effects of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation 2003;107: Wilkoff BL, Cook JR, Epstein AE, Greene HL, Hallstrom AP, Hsia H, et al. Dual-chamber pacing or ventricular back-up pacing in patients with an implantable defibrillator: the Dual Chamber and VVI implantable defibrillator (DAVID) trial. JAMA 2002;288:

26 Además… MPD VD en IC Disincronía ventricular Empeora la IC
Aumenta las hospitalizaciones Mayor incidencia de efectos adversos Sweeney M. (MOST) trial Circulation Wilkoff BL (DAVID) trial. JAMA 2002

27 Objetivo de la TRC en la IC
Trastornos de conducción Alteraciones de la motilidad parietal Contractilidad Llenado ventricular Reflujo mitral Mejorar Clinical findings show that heart failure patients suffer from conduction disturbances, regional wall motion abnormalities, mitral regurgitation that impacts filling, contractility and, ultimately, cardiac output. Van Orden Wallace Critical Care. 1998 Hochleitner M. Am J Cardiol. 1992

28 Objetivo de la TRC Resincronizacion Cardíaca Mejorar la Conducción AV
Mejorar la sincronia intraventricular Mejorar la Conducción AV Mejorar la sincronia interventricular Heart failure patients have problems with ventricular remodeling (progressive LV dilitation and loss of contractile function). The goal in treating these patients is to prevent remodeling or reverse it, if possible. This slide reflects the three proposed mechanisms of benefit attributed to cardiac resynchronization therapy. Below is an article that describes the mechanisms in detail. The next few slides will give a brief overview of the 3 proposed mechanisms. Yu C-M, Chau E, Sanderson J, Fan K, Tang M, Fung W, Lin H, Kong S, Lam Y, Hill M, Lau C.P. Tissue doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 2002;105: Study of 25 HF pts (65+12 yrs, NYHA III-IV, LVEF <40%, QRS>140 ms) both ischemic and non-ischemic, receiving biventricular pacing therapy for 3 months, then biventricular pacing stopped. Pts assessed serially up to 3 mo after pacing and when pacing was withheld for 4 wks. Results after 3 mo of biventricular pacing: improvement of ejection fraction, dP/dt, and myocardial performance index; decrease in mitral regurgitation, LV end-diastolic ( to ml) and end-systolic volume ( to ml); and improved 6-min hall-walk distance and quality of life score. Mechanisms of benefits: (1) improved (intraventricular) LV synchrony; (2) improved interventricular synchrony; and (3) shortened isovolumic contraction time but increased diastolic filling time. Benefits are pacing dependent, because withholding pacing resulted in loss of cardiac improvements. Improvement of LV mechanical synchrony found to be the predominant mechanism. Conclusion: Biventricular pacing reverses LV remodeling and improves cardiac function. Yu C-M, Chau E, Sanderson J, et al. Circulation 2002;105:

29 Mecanismos Propuestos de la TRC
La estimulación del VI permite que se inicie la contracción antes, lo que aumenta el tiempo de llenado. Reducción de la discinesia septal (movimiento paradojal del septum MPS) Reducción de la insuficiencia mitral presistólica.

30 Mecanismos de la TRC Estimulación en VI La activación Ventricular
se inicia antes Mejora el flujo transmitral Mejora el llenado

31 La activación Ventricular
Mecanismos de la TRC Estimulación en VI La activación Ventricular se inicia antes Insuficiencia mitral Mejora el llenado

32 Mecanismos de la TRC Estimulación en VI La activación Ventricular
se inicia antes Evita el movimiento paradojal del SIV Mejora el llenado

33 Terapia de Resincronización Cardíaca
Complementa el optimo manejo clínico y farmacológico Intenta sincronizar la secuencia de activación: Auriculo-ventricular Interventricular Intraventricular Introduces “new” terms used in this slide series. Ventricular dysynchrony is defined as the effect caused by intra- and inter-ventricular conduction defects or bundle branch block. Read Dr. Tavazzi’s editorial referenced here for a summary of the three potential causes of ventricular dysynchrony. Cardiac resynchronization is defined as the therapeutic intent of atrial synchronized biventricular pacing for patients with heart failure and ventricular dysynchrony. The intent of the therapy is to resynchronize the ventricular activation sequence, and to better coordinate atrial-ventricular timing to improve pumping efficiency. Cardiac resynchronization therapy is currently indicated for the reduction of symptoms of moderate to severe heart failure (NYHA Function Class III or IV) in those patients who remain symptomatic despite stable, optimal medical therapy, and have a left ventricular ejection fraction  35% and a QRS duration 130 ms. An ICD is also available for patients with a standard ICD indication who also meet the above listed criteria. Using atrial-synchronized biventricular pacing in combination with optimal drug therapy has been shown to significantly improve a patient’s symptoms. 1 Tavazzi L. Eur Heart J 2000;21:

34 Sincronía intra ventricular
Mejorando la sincronia Intraventricular1,2  dP/dt 1,3,4 FE1,5  Presión de pulso  VS y VM  IM1  VFS VI  Ps AI We have discussed how improvement in the intraventricular synchrony improves cardiac function. Now, let’s discuss mitral regurgitation. Yu et al found that mechanical mitral regurgitation (MR) decreased due to improved LV synchronicity, secondary to decreased distortion of the mitral valve during systole. This decrease in mitral regurgitation led to decreased left-atrial pressure, which led to a decrease in left ventricular end diastolic volume (LVEDV)1. Yu C-M, Chau E, Sanderson J, Fan K, Tang M, Fung W, Lin H, Kong S, Lam Y, Hill M, Lau C.P. Tissue doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 2002;105: Video Filename: “mitral-regurg.avi.” The animation can be started by positioning the mouse-cursor over the image and clicking once. To stop or restart the animation video at anytime, click once on the image. Note in the video clips, that with cardiac resynchronization off, the mitral regurgitation (blue jet seen filling the left atrium) is significant. When cardiac resynchronization is turned on, the mitral regurgitation has markedly decreased. 1 Yu C-M, Chau E, Sanderson J, et al. Circulation 2002;105: 2 Søgaard P, Kim W, Jensen H, et al. Cardiology 2001;95: 3 Kass D Chen-Huan C, Curry C, et al. Circulation 1999;99: 4 Auricchio A, Ding J, Spinelli J, et al. J Am Coll Cardiol 2002;39: 5 Stellbrink C, Breithardt O, Franke A, et al. J Am Coll Cardiol 2001;38:

35 Optimizando el retardo AV:
Sincronía AV Optimization of the AV interval is thought to have a positive, albeit less significant than intraventricular synchrony, effect on improved hemodynamics. Yu et al. found that an optimized AV delay effectively reduced the extended isovolumic contraction time (IVCT) observed in this patient population without change in the contraction time or isovolumic relaxation time. This reduction in IVCT reduced the time available for pre-systolic mitral regurgitation, and allowed more time during the cardiac cycle for left ventricular diastolic filling. This reduced MR (wasted presystolic time after atrial filling) with an accompanying reduction in LA pressure resulted in an acute reduction in left ventricular end-diastolic volume. Yu C-M, Chau E, Sanderson J, Fan K, Tang M, Fung W, Lin H, Kong S, Lam Y, Hill M, Lau C.P. Tissue doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 2002;105: Kindermann M, Frohlig G, Doerr T, Schieffer H. Optimizing the AV delay in DDD pacemaker patients with high degree AV block: mitral valve doppler versus impedance cardiography. Pacing Clin Electrophysiol 1997; 20(I): Breithardt O, Stellbrink C, Franke A, Balta O, Diem B, Bakker P, Sack S, Auricchio A, for the PATH-CHF Study Group, and Pochet T, Salo R, for the Guidant Congestive Heart Failure Research. Acute effects of cardiac resynchronization therapy on left ventricular Doppler indices in patients with congestive heart failure. Am Heart J 2002;143:34-44 Study of 32 pts w/ advanced HF (59±6 yrs, NYHA III, QRS>120 ms,PR interval>150 ms) 4 wks after implant of cardiac resynchronization therapy (CRT) system. Doppler echocardiography in 3 separate CRT modes (RV, LV,and BV stimulation) at 3 different atrioventricular delays (short, intermediate, and long). CRT resulted in significant improvement of Doppler parameters such as filling time ( baseline to ms BV), aortic velocity time integral ( cm to cm LV),and myocardial performance index (MPI; to BV). Most improvement observed w/ LV and BV stimulation at short and intermediate atrioventricular delays ( ms), independent of ischemic or idiopathic origin. Discussion of effect of AV delay, effect of pacing site, effects on systolic time intervals and MPI, diastolic vs. systolic Doppler parameters, response to CRT according to HF, and the limitations of the study. Sogaard P, Kim W, Jensen Henrik, Mortensen P, Pedersen A, Kristensen B, Egeblad H. Impact of acute biventricular pacing on left ventricular performance and volumes in patients with severe heart failure. J Am Coll Cardiol 2001;38:1957–1965. Study of 25 patients with QRS >120 ms, NYHA Class III or IV on standard medical HF therapy. Tissue velocity imaging (TVI) and 3-dimensional echocardiography was used to evaluate the effect of acute bi-V pacing on LV performance and volumes in patients with severe HF and BBB. Bi-V pacing significantly improved extent of contracting myocardium in synchrony by 15.4% and the duration of contraction synchrony by 17% (p<0.05 for both). LVEDV and LVESV decreased by 7 +/- 4.5% and 13 +/- 6% (p<0.01) and EF increased by /- 9% (p<0.01). Conclusion: Bi-V pacing improves LV systolic performance and reduces LV volumes during short-term treatment. Video Filename: “mitral-flow.avi.” The animation can be started by positioning the mouse-cursor over the image and clicking once. To stop or restart the animation video at anytime, click once on the image. Note on the video clips. With resynchronization Off, the E and A-waves are fused and the diastolic filling time is short. With resynchronization On, note less fusion of the E and A-waves and improved diastolic filling time. Mejorar la Sincronia AV Presión en la AI llenado Diast VI  VFS VI Optimizando el retardo AV:  IM1,4 1 Yu C-M, Chau E, Sanderson J, et al. Circulation 2002;105: 2 Kindermann M, Frohlig G, Doerr T, et al. Pacing Clin Electrophysiol 1997; 20(I): 3 Breithardt O, Stellbrink C, Franke A, et al. Am Heart J 2002;143:34-44 4 Søgaard P, Kim W, Jensen H, et al. Cardiology 2001;95:

36 Sincronía inter ventricular
Septum VI Mejorando la sincronia interventricular1,2  Llenado Diast VI Vol sist VD The last proposed mechanism, improved interventricular synchrony, appears to be the least important mechanism and has been the least studied. The benefit may be due to ventricular interdependence.1 When both ventricles contract appropriately with respect to the “shared” septum, the net result is improved forward flow. This improved ventricular contraction results in improved perfusion and return of blood to the heart for appropriate diastolic filling (overall system improvement). Yu C-M, Chau E, Sanderson J, Fan K, Tang M, Fung W, Lin H, Kong S, Lam Y, Hill M, Lau C.P. Tissue doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 2002;105: According to Yu’s article, in the RV there was also delay in the the time to peak sustained systolic contraction (Ts) to a magnitude similar to that of the septum during biventricular pacing, resulting in simultaneous peak contraction with the LV (i.e interventricular synchrony was also achieved). The still images of the M-mode echos above illustrate how the LV freewall contracts toward a stable septum with cardiac resynchronization On versus away from the septum with cardiac resynchronization Off. Kerwin W, Botvinick E, O’Connell W, et al. Ventricular contraction abnormalities in dilated cardiomyopathy: effect of biventricular pacing to correct interventricular dysynchrony. J Am Coll Cardiol 2000;35: 13 pts with DCM, NYHA Class II-IV HF, IVCD, and sinus rhythm underwent multiple gated equilibrium blood pool scintigraphy to determine if BiV pacing would improve synchrony of RV and LV contraction and thus result in improved LVEF. The study showed that the degree of interventricular dysynchrony present in NSR correlated with LVEF. During BiV pacing, interventricular contractile synchrony improved overall. The degree of interventricular dysynchrony present in NSR correlated with the magnitude of improvement in synchrony during BiV pacing. LVEF increased in all 13 pts during BiV pacing and correlated significantly with improvement in RV/LV synchrony during BiV pacing. Conclusion: Improvement in interventricular synchrony during BiV pacing correlate with acute improvement in LVEF. In this still echo picture, note with resynchronization OFF, the LV wall moves away from the interventricular septum during systole. With resynchronization ON, the LV wall moves toward the interventricular septum. 1 Yu C-M, Chau E, Sanderson J, et al. Circulation 2002;105: 2 Kerwin W, Botvinick E, O’Connel W, et al. JACC 2000;35:1221-7

37 Mecanismos propuestos: Mejorar la sincronia intraventricular
40 80 120 100 200 300 LV Pressure (mm Hg) LV Volume (mL) RV Apex RV Septum LV Free Wall Biventricular ----- NSR Control VDD Pacing Adapted from Kass et al. In addition, David Kass at Johns Hopkins showed that LV or BiV pacing decreased end systolic volumes. PV loops displayed here are from a single patient with LBBB in Kass’s acute study. In these PV loops, the red line indicates normal sinus rhythm (NSR) control and the yellow line indicates VDD pacing. It is also noteable that each site shown here was at the optimal AV interval. Minimal changes were seen with RV pacing, but increased stroke work and lowered end systolic volumes were seen with LV or BiV pacing. Kass D, Chen-Huan C, Curry C, Talbot M, Berger R, Fetics B, Nevo E. Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 1999;99: Kass D Chen-Huan C, Curry C, et al. Circulation 1999;99:

38 Sumario de los mecanismos propuestos
Sincronia Intra ventriciular Sincronia AV Sincronia Inter venticular Presión en la AI Presión de Llenado VI  Vol Ey VD  VTS VI  VTD VI Remodelado Inverso Resincronización cardíaca  IM  dP/dt,  FE,  VM  Presión de pulso These paragraphs highlight some of the key findings from Yu’s study (see slide reference). Intraventricular synchrony As a result of improved synchrony, systole becomes more effective and therefore, ejection fraction (EF), cardiac output (CO) and other parameters of cardiac function are improved. Left ventricular end-systolic volume (LVESV) is reduced. Mitral regurgitation (MR) attributable to distortion of the mitral apparatus is reduced by synchronizing the contractions and left atrial (LA) pressure is reduced. LV end-diastolic pressure and volume (LVEDV) are decreased. Atrioventricular synchrony A second mechanism is the shortening of the isovolumic contraction time (IVCT) after optimization of the atrioventricular delay. The effective diastolic filling time is increased, which in turn increases the stroke volume. In addition, LA pressure is reduced due to decreases in presystolic mitral regurgitation. Interventricular synchrony A less important mechanism is the improvement of interventricular synchrony between the right and left ventricles. This benefit may mediate through ventricular interdependence. This results in the gain in RV cardiac output, thereby augmenting the LV filling, resulting in overall improved cardiac function. The end effect of reverse remodeling will additionally improve cardiac synchrony and decrease secondary mitral regurgitation, forming a positive feedback loop. Benefits are dependent upon pacing Withholding pacing resulted in loss of cardiac improvements. Improvement in diastolic filling time, isovolumic contraction time, and myocardial performance index (MPI) were lost immediately since they were largely dependent upon control of AV synchrony. Benefits on ejection fraction and cardiac output were lost over 4 weeks which suggest strongly that pacing is the cause of LV remodeling. Improvements in Quality of Life score and walking distance were maintained for at least 4 weeks after pacing was suspended. These observations provide strong evidence that cardiac resynchronization therapy is the cause of LV reverse remodeling. Yu C-M, Chau E, Sanderson J, et al. Circulation 2002;105:

39 Sincronizacion AV y la estimulación Biventricular
Acceso trasnvenoso (+) convencional AD (+) convencional VD (+) VI a traves del SC Cable AD CRT Cable de VI A specially designed pacing lead is passed through the coronary sinus into a cardiac vein on the left lateral freewall. A standard pacing lead is placed in the right atrium. If the patient is indicated for an ICD and receives a device that combines both VT/VF therapies with cardiac resynchronization, a standard defibrillation lead is placed in the right ventricle. Otherwise a standard pacing lead is in placed in the right ventricle. Cable VD

40 This animation shows the placement of a left heart lead via the coronary sinus. On-screen annotations are included during the playing of the video clip. Animation Filename(s): “Clip2-AttainLV.mpg.” The animation can be started by positioning the mouse-cursor over the image and clicking once. To stop or restart the animation video at anytime, click once on the image.

41 Resincronización cardíaca
The animation illustrates cardiac resynchronization with the Medtronic InSync® system. During resynchronization, notice the stabilization of the septal wall and the restoration of a more coordinated ventricular systolic contraction. A dilated heart with ventricular dysynchrony appears toward the end of the video to further highlight the paradoxical septal wall motion that occurs when CRT therapy is not applied. Animation Filename: “Clip3-CardiacResynch.mpg.” The animation can be started by positioning the mouse-cursor over the image and clicking once. To stop or restart the animation video at anytime, click once on the image.

42 ECG

43 ECG post implante

44 RX Torax post implante

45 Desincronización ventricular
MPS Reducción dP/dt Reduccion de FEy y del VM Reducción del tiempo de llenado diastólico Reducción de la presion de pulso4 Mayor duracion de la IM Key Messages: Ventricular dysynchrony has been associated with paradoxical septal wall motion, reduced dP/dt max, prolonged mitral regurgitation duration, and reduced diastolic filling times in studies comparing patients with left bundle branch block with normals or with comparable patients without LBBB. Grines C, Bashore T, Boudoulas H, et al. Functional abnormalities in isolated left bundle branch block: the effect of interventricular asynchrony. Circulation 1989;79: Using simultaneous ECG, phonocardiogram, radionuclide ventriculograms, and 2D and M-mode echoes, Grines et al studied 18 patients with LBBB (and no other underlying cardiac disease) compared with 10 normals. In LBBB patients she found significant delays in LV systolic and diastolic events, reduced diastolic filling times, abnormal interventricular septal wall motion, and a loss of septal contribution to global ejection fraction. This study concluded that a LBBB causes a delay in the left ventricular depolarization resulting in delayed left ventricular contraction and relaxation compared with the right ventricle. Delay in left ventricular systole results in a delay in left ventricular diastole, which may contribute to displacement of the interventricular septum. In addition, asynchronous right-left ventricular contraction and relaxation may produce dynamic alterations in transseptal pressure and volume that may be responsible for the abnormal septal deflections. This abnormal septal motion results in an altered regional ejection fraction with decreased septal contribution to global left ventricular performance. Xiao Lee C, Gibson D. effect of left bundle branch block on diastolic function in dilated cardiomyopathy. Br Heart J 1991;66: Xiao H, Brecker S, Gibson D. Effects of abnormal activation on the time course of left ventricular pressure pulse in dilated cardiomyopathy. Br Heart J 1992;68: Yu C-M, Chau E, Sanderson J, et al. Tissue Doppler Echocardiographic Evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 2002;105: Animation Filename: “4-chamber.avi.” The animation can be started by positioning the mouse-cursor over the image and clicking once. To stop or restart the animation video at anytime, click once on the image. In this video clip, when cardiac resynchronization is off in a patient with a LBBB, the interventricular septum is not able to contribute to the global ejection fraction and is displaced. When cardiac resynchronization is ON, the interventricular septum appears more stable and is able to contribute to the global ejection fraction. 1 Grines CL, Bashore TM, Boudoulas H, et al. Circulation 1989;79: 2 Xiao, HB, Lee CH, Gibson DG. Br Heart J 1991;66: 3 Xiao HB, Brecker SJD, Gibson DG. Br Heart J 1992;68: 4 Yu C-M, Chau E, Sanderson JE, et al. Circulation. 2002;105:

46 Moderada o severa insuficiencia cardíaca (NYHA Class III/IV)
TRC: Indicaciones Moderada o severa insuficiencia cardíaca (NYHA Class III/IV) QRS  130 ms Fracción de eyección 35% Sintomáticos a pesar de estabilidad con una óptima terapia con drogas. DISCLOSURE FOR INSYNC SYSTEM (InSync 8040 Generator / 9790 Programmer / Attain Models 2187, 2188, and 4193 Leads) Indications: The Medtronic InSync Model 8040 device is indicated for the reduction of the symptoms of moderate to severe heart failure (NYHA Functional Class III or IV) in those patients who remain symptomatic despite stable, optimal medical therapy, and have a left ventricular ejection fraction 35% and a QRS duration 130ms. The Medtronic Model 9790 Programmer is a portable, microprocessor-based instrument used to program Medtronic implantable devices. The Attain LV Model 2187 and the Attain OTW Model 4193 leads have application as part of a Medtronic biventricular pacing system. The Attain CS Model 2188 lead has application where permanent atrial, or dual chamber pacing systems are indicated, or as part of a Medtronic biventricular pacing system. Contraindications: Asynchronous pacing is contraindicated in the presence (or likelihood) of competitive or intrinsic rhythms. Unipolar pacing is contraindicated in patients with an implanted defibrillator or cardioverter-defibrillator (ICD) because it may cause unwanted delivery or inhibition of defibrillator or ICD therapy. The Attain Models 2187, 2188, and 4193 leads are contraindicated for patients with coronary venous vasculature that is inadequate for lead placement, as indicated by venogram. For the Model 4193 lead, do not use steroid eluting leads in patients for whom a single dose of 1.0 mg dexamethasone sodium phosphate may be contraindicated. Warnings and Precautions: Patients implanted with a Medtronic InSync system should avoid sources of magnetic resonance imaging, diathermy, high sources of radiation, electrosurgical cautery, external defibrillation, lithotripsy, and radiofrequency ablation. These may result in electrical reset of the device and may result in inappropriate sensing and/or therapy. Certain programming and device operations may not provide cardiac resynchronization. Elective Replacement Indicator (ERI) results in the device switching to VVI pacing at 65 ppm. In this mode, patients may experience loss of cardiac resynchronization therapy and / or loss of AV synchrony. For this reason, the device should be replaced prior to ERI being set. An implantable defibrillator may be implanted concomitantly with an InSync system, provided implant protocols are followed for device and defibrillator lead placement and device configuration. Leads and stylets should be handled with great care at all times. When using a Model 4193 lead, only use compatible stylets (stylets with downsized knobs and are 3 cm shorter than the lead length). Chronic repositioning or removal of leads may be difficult because of fibrotic tissue development. The clinical study was not designed to evaluate the removal of left ventricular leads from the coronary venous vasculature. Output pulses, especially from unipolar leads, may adversely affect device sensing capabilities. Previously implanted pulse generators, implantable cardioverter defibrillators, and leads should generally be explanted. Back-up pacing should be readily available during implant. Use of leads may cause heart block. Do not force the guide catheter and/or leads if significant resistance is encountered. Use of the leads may cause trauma to the heart. Use care when handling guide wires. Damage to the guide wire may prevent the guide wire from performing accurate torque response control and may cause vessel damage. Do not use excessive force to remove a guide wire from a lead. Refer to the literature packaged with the guide wire for additional information on guide wires. For the Model 4193 lead, it has not been determined if whether the warnings, precautions, or complications usually associated with injectable dexamethasone sodium phosphate apply to the use of this highly localized, controlled-release device. For a list of potential adverse effects, refer to the Physician’s Desk Reference. See the appropriate technical manuals for detailed information regarding instructions for use, indications, contraindications, warnings and precautions, and potential adverse events. Caution: Federal law (USA) restricts these devices to sale by or on the order of a physician.

47 TRC diminuye arrítmias?
Pacientes clase III/IV con estimulación biventricular Disminución significativa en la cantidad de eventos ectópicos y el nro de eventos de TV Decremento de eventos de FA Conclusion: La resincronización cardíaca promueve la disminucion de la actividad ectópica ventricular en pacientes sin indicación de CDI Walker S, Levy T, Rex S, Brant S, Allen J, Ilsley C, Paul V. Usefulness of suppression of ventricular arrhythmia by biventricular pacing in severe congestive cardiac failure. Am J Cardiol 2000;86: Holter analysis of 20 NYHA Class III/IV, 8 in chronic AF undergoing HIS ablation, and both RV and LV leads implant; 12 in normal sinus rhythm and RA, RV and LV leads place. Compared ectopic events during BiV and control (no pacing for NSR, RV pacing for AF). Randomized cross-over design. Results from NSR group shown here. Similar results for chronic AF pts not shown. Walker S, Levy T, Rex S, et al. Am J Cardiol 2000;

48 TRC diminuye arrítmias?
Pacientes indicacion de TRC + TV/FV (sub-analisis estudio Ventak CHF)1 (Estudio mundial InSync) 2 Menor número de episodio durante la estimulacion biventricular Higgins S, Yong P, Scheck D, McDaniel M, Bollinger F, Vadecha M, Desai S, Meyer D for the Ventak CHF Investigators. Biventricular pacing diminishes the need for implantable defibrillator therapy. J Am Coll Cardiol 2000;36: Analysis of 32 of 54 pts with HF and ICD indications enrolled in randomized Ventak CHF study in the US. Study was a 3 month crossover design. 13/32 (41%) received appropriate therapy for VT at least once during the 6 month period. 5/32 (16%) had at least 1 episode while programmed o BiV, 11/32 (34%), had at least 1 episode while programmed to no pacing, and 3/32 (9%) received therapy in both periods. The mean number of episodes in the BiV pacing period was 0.6±2.1 compared with 1.4±3.5 in the no pacing period, p=0.035. Kuhlkamp V, et al. for the InSync 7272 ICD World Wide Investigators. Initial experience with an implantable cardioverter-defibrillator incorporating cardiac resynchronization therapy. J Am Coll Cardiol 2002;39: Analysis of 84 pts with HF and standard ICD indications enrolled in InSync ICD European study. Patients were required to have symptomatic heart failure despite appropriate therapy, LVEF < 35%, QRS > 130 ms and LVEDD > 55 mm. 81 patients were successfully implanted with an LV lead. Of the patients, 26 experienced 472 episodes of spontaneous sustained ventricular tachyarrhythmias. 339 episodes in 17 patients were detected in the VT zone, 107 episodes in 8 patients in the fast VT zone and 26 episodes in 8 patients in the VF zone. Double-counting of sensed events did NOT occur. 26 patients (33%) experienced at least one episode of sustained VT or VF. 1 Higgins S, Yong P, Scheck D, et al. J Am Coll Cardiol 2000;36: 2 Kuhlkamp V, et al., for the InSync 7272 ICD World Wide Investigators. J Am Coll Cardiol 2002;39;

49 HF and CRT Clinical Studies – Observational and Randomized
Note: This graphic is not all-inclusive of all studies and all device manufacturers. It lists some of the larger or key studies to date. Early studies of CRT have demonstrated improvement in patient symptoms and exercise capacity, but have been limited by small numbers of enrolled patients, uncontrolled or poorly controlled study designs and unblinded or single-blinded nature of follow-up. : Mechanistic and longer-term observational studies : Randomized, placebo-controlled studies to assess exercise capacity, functional capacity and Quality of Life : Randomized trials to assess combined mortality and hospitalization

50 CRT mejora la QoL y la CF QoL NYHA PATH-CHF1 (n=41) + +
InSync (Europe)2 (n=103) InSync ICD (Europe)3 (n=84) MUSTIC4 (n=67) + MIRACLE5 (n=453) MIRACLE ICD6 (n=364) Follow-up data from both controlled and uncontrolled studies document symptomatic improvement in patients treated with cardiac resynchronization therapy. Most notably, MUSTIC, MIRACLE and MIRACLE ICD trials document that cardiac resynchronization is safe, well tolerated by patients, and clinically beneficial. These studies reported improvements in patient Quality of Life, exercise capacity, and NYHA functional class for patients receiving cardiac resynchronization therapy as well as improvement in many echocardiagraphic parameters. + Statistically significant improvement with CRT (p  0.05)  Not statistically significant or No statistical analysis performed on data Blank Indicates test neither performed nor reported 1 Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol 2002;39: 2 Gras D, Leclercq C, Tang A, et al. Eur J Heart Failure 2002;4: 3 Kuhlkamp V. JACC 2002;39: 4 Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol 2002;40: 5 Abraham W, Fisher W, Smith A, et al. N Engl J Med. 2002;346: 6 Leon A. NASPE Scientific Sessions – Late Breaking Clinical Trials. May 2002; Medtronic Inc. data on file

51 CRT la capacidad ante el ejercicio
6 Min Walk Peak VO2 Exercise Time PATH-CHF1 (n=41) InSync (Europe)2 (n=103) + InSync ICD (Europe)3 (n=84) + MUSTIC4 (n=67) +  MIRACLE5 (n=453) MIRACLE ICD6 (n=364)  Key Message: Results from studies, both observational and randomized, controlled are concordant in their finding that CRT improves exercise capacity measured parameters. Note: A subset of the MIRACLE and MIRACLE ICD patients provided paired data for these parameters. + Statistically significant improvement with CRT (p  0.05)  Not statistically significant or No statistical analysis performed on data Blank Indicates test neither performed nor reported 1 Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol 2002;39: 2 Gras D, Leclercq C, Tang A, et al. Eur J Heart Failure 2002;4: 3 Kuhlkamp V. JACC 2002;39: 4 Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol 2002;40: 5 Abraham W, Fisher W, Smith A, et al. N Engl J Med. 2002;346: 6 Leon A. NASPE Scientific Sessions – Late Breaking Clinical Trials. May 2002; Medtronic Inc., data on file

52 CRT Mejora la FSVI y la IM
LVEF MR Other PATH-CHF1 (n=41) + LVEDP LV dP/dtmax InSync (Europe)2 (n=103) + + Filling Time InSync ICD (Europe)3 (n=84) MUSTIC4 (n=67)   LVEDD,LVESD  Filling Time MIRACLE5 (n=453) + LVEDD, LVEDV, LVESV MIRACLE ICD6 (n=362) + LVESV, LVEDV Key Message: Results from studies, both observational and randomized, controlled are concordant in their finding that CRT improves many secondary efficacy endpoints measured by echocardiographic parameters. The MIRACLE ICD data reported here was presented at the 2002 ACC Scientific Sessions (n=362 here, rather than n=364 reported by Dr. Leon at the 2002 NASPE scientific session.) Note: A subset of the MIRACLE and MIRACLE ICD patients provided paired data for the echo parameters. Statistically significant improvement with CRT (p  0.05)  Not statistically significant or No statistical analysis performed on data Blank Indicates test neither performed nor reported 1 Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol 2002;39: 2 Gras D, Leclercq C, Tang A, et al. Eur J Heart Failure 2002;4: 3 Kuhlkamp V. JACC 2002;39: 4 Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol 2002;40: 5 Abraham W, Fisher W, Smith A, et al. N Engl J Med. 2002;346: 6 Young J. ACC Scientific Sessions – Late Breaking Clinical Trials III. March 2002; Medtronic Inc., data on file

53 Resultados sustentables
NYHA QoL 6 Minute Walk Peak VO2 InSync European and Canadian Study1 (n=67, followed to 12 months) + PATH-CHF Study2 (n=29, followed to 12 months) MUSTIC Study3 (n=42 in sinus rhythm group, n=33 in atrial fibrillation group followed to 12 months)  Results from the InSync prospective observational multi-center European and Canadian study (67 patients followed to 12 months), the PATH-CHF (multi-center, patient-blinded, sequential-treatment, randomized, crossover) study (29 patients followed to 12 months), and the MUSTIC (multicenter, randomized, controlled; 75 patients followed to 12 months) showed sustained long term improvements in NYHA functional class, quality of life and 6 minute walk distance. Peak VO2 improvements were sustained in the the PATH-CHF study but no statistically significant improvement between control and therapy groups was measured in the MUSTIC study at 12 months. Statistically significant improvement with CRT (p  0.05)  No statistically significant improvement with CRT Blank Indicates test neither performed nor reported 1 Gras D, Leclercq C, Tang A, et al. Eur J Heart Fail 2002;4: 2 Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol 2002;39: 3 Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol 2002;40:

54 Beneficios relativos en hospitalización de la terapia de resincronización
1 año antes del implante , 22 pacientes, con HF fueron hopitalizados con un promedio de 18,5 días Al año de seguimiento pos implante 9 pacientes hospitalizados con un promedio de 4.5 días Grupo de Ritmo Sinusal: 7 veces menos en la hopitalizacion (12 meses de seguimiento) Grupo AF : 4 veces menos en la hospitalización de pacientes con HF (12 meses de seguimiento) Número de hospitalización significativamente menor (p = 0.02) Duración en la hospitalización de pacientes con HF significativamente menor (p = 0.05) PATH-CHF1 MUSTIC2 MIRACLE3 MIRACLE ICD4 Heart failure related hospitalizations were studied and recorded in the trials listed on this slide. Each of these studies documented either reduced hospitalization or reduced length of stay for patients receiving cardiac resynchronization therapy. Note: P-values were not calculated for the PATH-CHF and MUSTIC trial data. 1 Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol 2002;39: 2 Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol 2002;40: 3 Abraham W, Fisher W, Smith A, et al. N Engl J Med. 2002;346: 4 Leon A. DeLurgioD, Smith A, et al. PACE 2002;25(4), Part II:647

55 Comparacion con trials con droga : Digoxin, ACE-I y Beta bloqueantes Therapies
Change from baseline in 6 Change from baseline in Change from baseline in minute walk distance CPX Duration QoL (MLWHF) Score † ‡ 40 90 5 * 30 † 20 60 * Improvement 10 -5 meters score seconds 30 ‡ * -10 -10 -15 NS -20 -30 ‡ -30 -20 Dig BB CRT Dig ACE CRT ACE BB CRT (1) (2) (6) Key points: 1) CRT is used as an adjunct with these medications to treat heart failure. 2) CRT provides the same or greater level of improvement in these endpoints. It is important to point out that those patients receiving cardiac resynchronization therapy were on optimal medical therapy (MIRACLE trial – 90% on ACEI, 60% on beta-blockers). These graphs show results from randomized, controlled trials of ACE-I , beta-blockers, and CRT for heart failure related to changes in 6 minute walk, QoL (MLWHF), and exercise duration. In the first graph, note the patients on Digoxin and those receiving CRT significantly improved (p < .01) their 6 minute hall walk over control compared to those patients on beta blockers. In the second graph, the CRT patients (MIRACLE – 90% already on an ACEI) could perform longer on CPX testing (P<0.001) over control compared to those on Digoxin and an ACEI. In the third graph, patients on an ACE inhibitor and receiving CRT had a highly significant change (p < .001) in their QoL score (marked improvement since score went down). Patients on Beta blockers improved but when compared to the control, it was not significant. Key Message: Cardiac resynchronization therapy shows an incremental benefit over medical therapy on these HF endpoints. Note that these drugs were approved by the FDA because they improved survival or combined survival and hospitalization. (1) (3) (6) (4) (5) (6) * P † P ‡ P.001 Control Treatment 1 N Engl J Med 1993;329:1-7 (RADIANCE) 2 Circulation 1996;94: (PRECISE) 3 JAMA 1988;259: 4 Am J Cardiol 1993;71: (SOLVD Treatment) 5 J Cardiac Failure 1997;3: 6 N Engl J Med. 2002;346:

56 Estudios en CRT

57 Terapia de Resincronización Caríaca Selección de pacientes y dispositivos, Implante y seguimiento

58 Indicaciones IC Mod. o sev. (Clase III/IV NYHA) QRS  130 ms
F. Ey 35% Sintomaticos bajo terapia farmacológica óptima DISCLOSURE FOR INSYNC SYSTEM (InSync 8040 Generator / 9790 Programmer / Attain Models 2187, 2188, and 4193 Leads) Indications: The Medtronic InSync Model 8040 device is indicated for the reduction of the symptoms of moderate to severe heart failure (NYHA Functional Class III or IV) in those patients who remain symptomatic despite stable, optimal medical therapy, and have a left ventricular ejection fraction 35% and a QRS duration 130ms. The Medtronic Model 9790 Programmer is a portable, microprocessor-based instrument used to program Medtronic implantable devices. The Attain LV Model 2187 and the Attain OTW Model 4193 leads have application as part of a Medtronic biventricular pacing system. The Attain CS Model 2188 lead has application where permanent atrial, or dual chamber pacing systems are indicated, or as part of a Medtronic biventricular pacing system. Contraindications: Asynchronous pacing is contraindicated in the presence (or likelihood) of competitive or intrinsic rhythms. Unipolar pacing is contraindicated in patients with an implanted defibrillator or cardioverter-defibrillator (ICD) because it may cause unwanted delivery or inhibition of defibrillator or ICD therapy. The Attain Models 2187, 2188, and 4193 leads are contraindicated for patients with coronary venous vasculature that is inadequate for lead placement, as indicated by venogram. For the Model 4193 lead, do not use steroid eluting leads in patients for whom a single dose of 1.0 mg dexamethasone sodium phosphate may be contraindicated. Warnings and Precautions: Patients implanted with a Medtronic InSync system should avoid sources of magnetic resonance imaging, diathermy, high sources of radiation, electrosurgical cautery, external defibrillation, lithotripsy, and radiofrequency ablation. These may result in electrical reset of the device and may result in inappropriate sensing and/or therapy. Certain programming and device operations may not provide cardiac resynchronization. Elective Replacement Indicator (ERI) results in the device switching to VVI pacing at 65 ppm. In this mode, patients may experience loss of cardiac resynchronization therapy and / or loss of AV synchrony. For this reason, the device should be replaced prior to ERI being set. An implantable defibrillator may be implanted concomitantly with an InSync system, provided implant protocols are followed for device and defibrillator lead placement and device configuration. Leads and stylets should be handled with great care at all times. When using a Model 4193 lead, only use compatible stylets (stylets with downsized knobs and are 3 cm shorter than the lead length). Chronic repositioning or removal of leads may be difficult because of fibrotic tissue development. The clinical study was not designed to evaluate the removal of left ventricular leads from the coronary venous vasculature. Output pulses, especially from unipolar leads, may adversely affect device sensing capabilities. Previously implanted pulse generators, implantable cardioverter defibrillators, and leads should generally be explanted. Back-up pacing should be readily available during implant. Use of leads may cause heart block. Do not force the guide catheter and/or leads if significant resistance is encountered. Use of the leads may cause trauma to the heart. Use care when handling guide wires. Damage to the guide wire may prevent the guide wire from performing accurate torque response control and may cause vessel damage. Do not use excessive force to remove a guide wire from a lead. Refer to the literature packaged with the guide wire for additional information on guide wires. For the Model 4193 lead, it has not been determined if whether the warnings, precautions, or complications usually associated with injectable dexamethasone sodium phosphate apply to the use of this highly localized, controlled-release device. For a list of potential adverse effects, refer to the Physician’s Desk Reference. See the appropriate technical manuals for detailed information regarding instructions for use, indications, contraindications, warnings and precautions, and potential adverse events. Caution: Federal law (USA) restricts these devices to sale by or on the order of a physician.

59 NO respondedores Alrededor de un 30% de pacientes que no mejoran con la estimulación biventricular Explicaciones posibles: Patrones de activación distintos Cardiopatía subyacente Efecto o no sobre la insuficiencia mitral

60 Predictores ¿Cuál es el mejor?
Ancho del QRS Doppler tisular Clase Funcional Yu CM, Lin H, Zhang Q, Sanderson JE. High prevalence of left ventricular systolic and diastolic asynchrony in patients with congestive heart failure and normal QRS duration. Heart 2003;89:54-60 Cleland JGF, Kappenberger LJ, Tavazzi L, Klein W, Erdmann E. Design and methodology of the CARE-HF trial. A randomised trial of cardiac resynchronization in patients with heart failure and ventricular dyssynchrony. Eur J Heart Fail 2001;3:481-9. Huneycutt DC, Langberg J, Leon AR, Sith AL. Experience with cardiac resynchronization in heart failure patients requiring inotropic support [abstract]. PACE 2003;26:1041 Nada es concluyente

61 Indicaciones de la TRC - D
Indicación de CDI Moderada o severa insuficiencia cardíaca (NYHA Class III/IV) QRS  130 ms Fraccion de eyección 35% Sintomaticos a pesar de estabilidad con una optima terapìa de drogas CDI CRT The indications listed are the approved labeling as determined by the FDA. Indications: The InSync ICD system is intended to provide ventricular antitachycardia pacing and ventricular defibrillation for automated treatment of life threatening ventricular arrhythmias, and for the reduction of the symptoms of moderate to severe heart failure (NYHA Functional Class III or IV) in those patients who remain symptomatic despite stable, optimal medical therapy (as defined in the clinical trials section), and have a left ventricular ejection fraction less than or equal to 35% and a QRS duration greater than or equal to 130 ms. Contraindications: The InSync ICD system is contraindicated in: -          Patients whose ventricular tachyarrhythmias may have transient or reversible causes. -          Patients with incessant VT or VF -          Patients who have a unipolar pacemaker Warnings/Precautions: -          Changes in patient’s disease and/or medications may alter the efficacy of the device’s programmed parameters. -          Patients should avoid sources of magnetic and electromagnetic radiation, including MRI, ditheramy, and electrosurgical units, to avoid possible underdetection, inappropriate therapy delivery, and/or electrical reset of the device. -          Certain programming and device operations may not provide cardiac resynchronization. -          Do not place transthoracic defibrillation paddles directly over the device. See the appropriate technical manuals for detailed information regarding instructions for use, indications, contraindications, warnings and precautions, and potential adverse events.

62 Técnica de implante TRC – D ¿Diferente?
Inserción de los tres cables (AD, VD, VI) Estimulación de AD Estimulación de VD Inducción de FV Colocación del catéter de VI a través del SC Medición de los umbrales y programación final Implante TRC- D Similar al de TRC y CDI Implantation involves placement of a device into the upper chest along with three leads. The implant is typically done under local anesthesia with the patient sedated. Three leads are implanted: Standard transvenous pacing leads are placed in the right atrium and ventricle, while a specially designed transvenous left ventricular lead is inserted into the distal cardiac vein via the coronary sinus. The goal is to place the LV lead in a mid-cardiac position on the left lateral freewall with good physical and electrical separation from the RV lead. This separation helps to optimize resynchronization to correct the ventricular contraction pattern.

63 TRC vs TRC CDI El paciente candidato a la TRC tiene también un riesgo aumentado de MS La evidencia es controvertida CARE-HF: disminuye significativamente la MS Dos metanalisis: no la disminuye significativamente Rivero-Ayerza M, Theuns D, Garcia-garcia HM, Boersma E, Simoons M, Jordaens LJ. Effects of cardiac resynchronization therapy on overall mortality and mode of death: a meta-analysis of randomized controlled trials. Eur Heart J 2006;27: 2682–2688  Mc Alister EA, Ezekowitz JA, Wiebe N et al. Systematic review: cardiac resynchronization in patients with symptomatic heart failure. Ann Intern Med 2004;141:381–390.

64 Estudios: MS , CDI y TRC MADIT, MUSTT y MADIT II : eficacia CDI en prevención primaria de la MS cardíaca en pacientes con infarto de miocardio previo y deterioro de la FSVI COMPANION y SCD-HeFT: CDI reduce la mortalidad en pacientes con IC y  deterioro de la función sistólica ventricular izquierda, independientemente de la etiología Conclusión: La elección TRC o TRC-D debería basarse en: Expectativa de vida del pc Estado general y funcional.

65 Indicaciones TRC: Indicación "clase I" con nivel de evidencia "A”
IC en CF III-IV de la NYHA a pesar del tratamiento farmacológico óptimo, Fracción de eyección del VI ≤35%, VI dilatado (diámetro de fin de diástole > 55 mm o > 30 mm/m2 o > 30 mm/m de altura), Ritmo sinusal y Complejo QRS ≥ 120 ms TRC-D: Indicación "clase I" con nivel de evidencia "B“ Indicación de TRC y Expectativa de vida con buen estado funcional mayor a 1 año Cleland JGF, Daubert JC, Erdmann E et al. [CARE-HF] Trial). N Engl J Med 2005;352:1539–1549 Bristow MR, Saxon LA, Boehmer J et al., (COMPANION). N Engl J Med 2004;350:2140–2150 Freemantle N, Tharmanathan P, Meta-analysis. Eur J Heart Fail 2006;8:433–440.

66 Indicacion de TRC y FA "clase IIa" con nivel de evidencia "C”
IC en CF III-IV de la NYHA a pesar de tratamiento farmacológico óptimo, Fracción de eyección del VI ≤35%, VI dilatado (diámetro de fin de diástole > 55 mm o > 30 mm/m2 o > 30 mm/m de altura) y FA permanente con adecuado control de la frecuencia cardíaca que asegure estimulación biventricular permanente (preferentemente ablación del nódulo AV) Daubert JC. Atrial fibrillation and heart failure: a mutually noxious association. Europace 2004;. Gasparini M, Auricchio A, Regoli F et al. Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation. J Am Coll Cardiol 2006;48: 734–743.

67 TRC y QRS < 120 ms "clase IIb" con nivel de evidencia "C“
IC en CF III-IV de la NYHA a pesar de tratamiento farmacológico óptimo, Fracción de eyección del VI ≤35%, VI dilatado (diámetro de fin de diástole > 55 mm o > 30 mm/m2 o > 30 mm/m de altura) Asincronía de contracción intraventricular izquierda evaluada por métodos de imágenes (ecocardiografía, RMN) Ritmo sinusal o FA permanente Yu C-M, Chan Y-S, Zhang Q et al. Benefits of cardiac resynchronization therapy for heart failure patients with narrow QRS complexes and coexisting systolic asynchrony by echocardiography. J Am Coll Cardiol 2006;48:2251–2257. Chung ES, Leon AR, Tavazzi L, Sun J-P, Nihoyannopoulos P, Merlino J, Abraham WT, Ghio S, Leclercq C, Bax J. J, Yu C-M, Gorcsan III J, St John Sutton M, De Sutter J, Murillo J. Results of the Predictors of Response to CRT (PROSPECT) Trial. Circ 2008;117:

68 TRC y BRD y QRS > 140 ms "clase IIb" con nivel de evidencia "C"
IC en CF III-IV de la NYHA a pesar de tratamiento farmacológico óptimo, Fracción de eyección del VI ≤35%, VI dilatado (diámetro de fin de diástole > 55 mm o > 30 mm/m2 o > 30 mm/m de altura) Asincronía VI evaluada por Eco o RMN Ritmo sinusal o FA permanente Garrigue S, Reuter S, Labeque J, et al Usefulness of Biventricular Pacing in Patients With Congestive Heart Failure and Right Bundle Branch Block. Am J Cardiol 2001;88:

69 Eco post implante Objetivos
Optimizar el intervalo AV (ayudar al cierre mitral) Optimizar del intervalo VV

70 No se ha establecido ninguna contraindicación formal
Contraindicaciones No se ha establecido ninguna contraindicación formal Precauciones, escaso beneficio en: IC aguda IC con dependencia de catecolaminas. Cicatriz extensa de la pared lateral IC con BCRD (demostrar disincronía) .

71 Seguimiento Objetivos: Lograr el 100% de (+) biventricular
Maximizar el tiempo de llenado diastólico Optimizando el Intervalo AV Standard medical management of heart failure patients as well as device management should continue as defined by practice guidelines and clinician judgment. Typically a physician who specializes in implantable devices should monitor the device operation. At follow-up, close attention should be paid to the ventricular high rate diagnostics from the device since advanced HF patients have a significant risk of developing ventricular arrhythmias. The rate histogram can be evaluated the first month to ensure cardiac resynchronization is being applied throughout the range of patient activities. Special considerations may need to be taken to ensure coordination of medical management with device operation. Interrogation of device information and lead status occur per device guidelines. Diagnostic information reviewed for presence of potential arrhythmias (AT/AF, VT/VF). Rate Histograms to evaluate appropriateness of CR therapy (percentage of V-pacing) throughout the range of patient activity.

72 Seguimiento Incluyen: Med. de umbrales de sensado AD/ VD / VI
Med. de umbrales de estimulación AD / VD / VI Optimización AV (VTI Aórtico) Optimización del intervalo VI / VD Programaciones especificas A typical follow up for an InSync device includes the same sort of system testing one would expect for a normal pacemaker; Sensing Tests Biventricular Pacing Threshold LV / RV Pacing Threshold AV Optimization Proper Programming Note that AV optimization is performed using echocardiography, and that proper programming of the device will differ in many respects from proper programming of a typical pacemaker. The InSync device uses the old Thera™ -style programmer interface. Sensing tests can be done in the usual manner using the Sensing Test Option.

73 Umbrales 1 2 3 1.-Usar el ultimo umbral de captura biventricular
This strip indicates the first phase of threshold testing. The threshold should be reported as the lowest output which consistently captures the ventricle(s). In this case, the first loss of capture occurred at 0.35 ms. Note the following changes which occur at the first Loss of Capture: Morphology changes on surface ECG VP-VR pattern arises on Marker Channel™. [This occurs because only one ventricle was captured, so the non-captured ventricle was activated cell-to-cell across the septum and sensed on the lead which did not capture!] VEGM demonstrates a sensed deflection following the paced event. [for the same reason as the VP-VR marker] One important issue that arises immediately is—which lead lost capture? While vectorcardiography may offer some help in estimating which lead lost capture, there are serious limitations using vectorcardiographic techniques in patients whose hearts are dilated, hypertrophic, rotated, twisted and paced from both the RV apex and the LV mid-base. There is a single technique which produces consistent results. At each implant, while lead testing is in process, a template of RV-only pacing, LV-only pacing, biventricular pacing and intrinsic rhythm should be recorded. These pacing templates should be placed in the patient's follow up chart so that comparisons can be made between the template and ECG morphology during threshold testing. If you are still having trouble identifying ECG morphology changes at threshold (sometimes they can be quite subtle) use the occurrence of VP-VR markers or changes in VEGM to locate the threshold. 1.-Usar el ultimo umbral de captura biventricular 2.-Disminuir amplitud de salida 3.- Perdida de captura VI

74 Umbrales 1 2 1.-Disminuir amplitud de salida
Stepping down on ventricular output continues during the threshold test until capture of both ventricles is completely lost. Since subtle changes may be difficult to assess while watching a dynamic ECG, one should use the printed threshold strip to review and determine loss of capture and threshold. In some cases the morphology , Marker Channel™ and EGM changes may be very subtle. In these cases it will be necessary to use a 12 lead ECG to determine where changes in morphology occur. 1.-Disminuir amplitud de salida 2.- Perdida de captura de ambas cámaras

75 Resincronización cardíaca
Intenta normalizar los tiempos de llenado de las cámaras del corazón Si bien se llama CRT ventricular, se tiende a resincronizar todas las cámaras del corazón Objetivo mejorar la calidad de vida

76 Gracias por su atención
Hemodinamia