Upgrade to Resynchronization Therapy. Saeed Oraii MD, Cardiologist Interventional Electrophysiologist Tehran Arrhythmia Clinic May 2016

Transcription

1 Upgrade to Resynchronization Therapy Saeed Oraii MD, Cardiologist Interventional Electrophysiologist Tehran Arrhythmia Clinic May 2016

2 Event Free Survival (%) CRT Cardiac resynchronization therapy (CRT) is an established therapy for patients with cardiomyopathy, ventricular dyssynchrony, and moderate-to-severe heart failure (HF) despite appropriate pharmacologic therapy. 100% Randomized clinical 95% 90% trials have demonstrated 85% the efficacy of CRT in 80% 75% this patient population. 70% P = Relative risk = 0.60; 95% CI (0.37, 0.96) CRT Control Months After Randomization

3 Pacing Induced Dyssynchrony Extremely wide QRS complexes are frequently observed in patients who are chronically paced via a right ventricular (RV) lead for bradycardic indications.

4 Pacing in ICD Patients Retrospective analyses suggest that 15 50% of ICD patients have an accepted indication for dual chamber pacing at the time of ICD system implantation. Indications for dual chamber pacing may arise later in a significant portion of ICD patients who do not require pacing at implantation. Geelen P, et al. The value of DDD pacing in patients with an implantable cardioverter defibrillator. PACE 1997; 20: Higgins SL, et al. Indications for implantation of a dual-chamber pacemaker combined with an implantable cardioverterdefibrillator. Am J Cardiol 1998; 81:

5 Adverse Effects of RV Pacing Multiple trials have shown that RV pacing may be associated with worsening of HF, even when used in conjunction with physiologic (dualchamber) pacing modes. This is mostly attributed to dyssynchrony imposed on ventricular function by RV apical pacing. Wilkoff BL, et al. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 2002;288: Sweeney MO, et al. Adverse effect 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:

6 Risk of Heart Failure The MOST study, reported a <2% hospitalization for heart failure linked to pacing over 2 years when baseline left ventricular (LV) function prior to pacing was normal and in the absence of preexisting cardiac pathology. Where there was preexisting pathology, there was a marked increase in the risk of heart failure hospitalization, by up to 50%. Lamas GA, et al. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med 2002; 346:

7 Possible Mechanisms The altered pattern of activation may lead to several histological and functional adjustments of the left ventricle, including: Inhomogeneous thickening of the ventricular myocardium Myofibrillar disarray, Fibrosis Disturbances in ion-handling protein expression Myocardial perfusion defects Alterations in sympathetic tone and Mitral regurgitation (MR) Polychronis Dilaveris. Upgrade to biventricular pacing in patients with pacing-induced heart failure: can resynchronization do the trick? Europace (2006) 8,

8 Dyssynchrony RV pacing results in interventricular dyssynchrony, leading to a ms. delay in LV activation. Intraventricular dyssynchrony also results from the complete reversion of ventricular activation sequence (apex to base instead of base to apex). Vassalo J, et al. Left ventricular endocardial activation during right ventricular pacing: effect of underlying heart disease. J Am Coll Cardiol 1986;7:

9 Pathophysiology RV apical pacing leads to a heterogeneous distribution of workload: Lower strain (workload), in the early-activated region than in the late-activated regions Early-activated regions tend to become thinner over time, as opposed to late-activated ones, which show a progressive increase in wallthickness. Prinzen FW, et al. Asymmetric thickness of the left ventricular wall resulting from asynchronous electric activation study in dogs with ventricular pacing and in patients with left bundle branch block. Am Heart J 1995;130:

10 Pathophysiology The regional heterogeneity of myocardial hypertrophy results in remodeling of the LV, which alters its contractile and hemodynamic efficiency. The primary causative factor of this remodeling seems to be the alteration of force vectors, which entails an alteration of mechanical stress distribution in the ventricle. A role of a neuro-endocrine mechanisms cannot be excluded.

11 Mechanism of MR There appears to be a complex mechanism: The altered sequence of activation of the components of the mitral apparatus and the dyssynchronized transfer of forces from the papillary muscles through the chordae tendinae to the mitral leaflets lead to poor coaptation and thus to regurgitation during ventricular systole. The appearance or aggravation of pre-existing MR may contribute to the development or deterioration of HF in paced patients.

12 Alternative Pacing Sites There are reports of preservation of LV systolic function with RV septal pacing as opposed to RV apical pacing in patients without HF. This was not confirmed by studies in the failing heart. Karpawich PP, Mital S. Comparative left ventricular function following atrial, septal, and apical single chamber heart pacing in the young. Pacing Clin Electrophysiol 1997;20: Gold MR, et al. The acute hemodynamic effects of right ventricular septal pacing in patients with congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 1997;79:

13 RV Septal Pacing It has been shown that implanting the pacing lead at the site of the RV septal surface causing the shortest paced QRS may result in improved LV systolic performance. However, the latter findings were relatively minor and unlikely to have any significant clinical impact as in the effects on LV ejection fraction. Schwaab B, et al. Septal lead implantation for the reduction of paced QRS duration using passive-fixation leads. Pacing Clin Electrophysiol 2001;24:28 33.

14 RVOT Pacing The RV outflow tract was also proposed as an alternative site of RV pacing, associated with increased cardiac output when compared with RV apical pacing in acute pacing studies. This was not confirmed conclusively either with long-term pacing studies. De Cock CC, et al. Hemodynamic benefits of right ventricular outflow tract pacing: Comparison with right ventricular apex pacing. Pacing Clin Electrophysiol. 1998;21: Victor F, et al. Optimal right ventricular pacing site in chronically implanted patients: a prospective randomized crossover comparison of apical and outflow tract pacing. J Am Coll Cardiol 1999;33:311 6.

15 CRT LV or biventricular (BiV) pacing has been proposed as an adjunctive treatment for patients with advanced HF complicated by RV pacing induced discoordinate contraction. Both short-term and a growing number of long-term clinical trials have reported on the mechanisms and short- and mid-term efficacy of this approach, with encouraging results. Mehra MR, Greenberg BH. Cardiac resynchronization therapy: caveat medicus! J Am Coll Cardiol 2004;43:

16 Pacing QRS Duration A QRS duration over 200 ms has been arbitrarily proposed to suggest the upgrade of RV pacing in HF patients to BiV pacing. Such a wide QRS has been suggested to correspond with notable inter- or intra-lv mechanical dyssynchrony. Bordachar P, et al. Interventricular and intra-left ventricular electromechanical delays in right ventricular paced patients with heart failure: implications for upgrading to biventricular stimulation. Heart 2003;89:

17 Pacing QRS Duration It should be noted, however, that improved mechanical synchrony and function do not necessarily require increased electrical synchrony. More recent data dispute the correlation between electrical features (QRS duration) and the degree of electromechanical ventricular dyssynchrony in RV paced patients. Leclercq C, et al. Systolic improvement and mechanical resynchronization does not require electrical synchrony in the dilated failing heart with left bundle-branch block. Circulation 2002;106:

18 Intraventricular Dyssynchrony RV pacing-induced intraventricular dyssynchrony is more common than interventricular dyssynchrony. The major cause of LV function impairment is likely to be the presence of intra-lv dyssynchrony. Auricchio A, et al. Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. The Pacing Therapies for Congestive Heart Failure Study Group. The Guidant Congestive Heart Failure Research Group. Circulation 1999;99:

19 Echocardiographic Dyssynchrony Echo documented dyssynchrony is an approach to patient selection and gives new insight into the possible mechanisms of improvement.

20 Intra-ventricular Dyssynchrony BiV pacing results in the improvement of intra- LV rather than of interventricular synchrony. RV-paced patients who present with an abnormally increased intra-lv dyssynchrony should benefit more from BiV upgrading

21 CRT Upgrade Studies Five studies compared the clinical outcomes of patients who received an upgrade to CRT with those who received a de novo CRT implant. During a follow-up of 3 38 months, upgraded patients showed improvement similar to the de novo patients ESC Guidelines on cardiac pacing and cardiac resynchronization therapy

22 The RAFT Upgrade Substudy The success rate was 95.2% for de novo versus 96.3% for study upgrade and 90.0% for substudy CRT attempts (upgrade within 6 months after presentation of study results). Vidal Essebag et al. Incidence, Predictors, and Procedural Results of Upgrade to Resynchronization Therapy. The RAFT Upgrade Substudy. Circ Arrhythm Electrophysiol. 2015;8:

23 The Rate of CRT Upgrade This varies widely among studies. In a retrospective single center study, the upgrade rates at 1, 3, and 5 years were 0.03%, 2.4%, and 5.1%, respectively. Scott P A et al. Rates of Upgrade of ICD Recipients to CRT in Clinical Practice and the Potential Impact of the More Liberal Use of CRT at Initial Implant. Pacing and Clinical Electrophysiology Volume 35, Issue 1, pages 73 80, January 2012.

24 The Rate of CRT Upgrade In the European CRT Survey of 2367 implant procedures, 29.2% were identified as having an upgrade from pacemaker to CRT-P or ICD to CRT-D. Bogale Nigussie et al. The European Cardiac Resynchronization Therapy Survey: comparison of outcomes between de novo cardiac resynchronization therapy implantations and upgrades. European Journal of Heart Failure Volume 13, Issue 9, pages , 2011.

25 AF in Paced Patients Upgrading of an already implanted RV pacing system to BiV pacing in patients with HF and atrial fibrillation reversed dyssynchrony. It improved ventricular performance and dimensions, quality of life and symptoms of HF in the same manner as described in patients with sinus rhythm and left bundle branch block who undergo BiV pacing. Leon AR, et al. Cardiac resynchronization in patients with congestive heart failure and chronic atrial fibrillation. Effect of upgrading to biventricular pacing after chronic right ventricular pacing. J Am Coll Cardiol 2002;39: Erol-Yilmaz A, et al. Reversed remodeling of dilated left sided cardiomyopathy after upgrading from VVIR to VVIR biventricular pacing. Europace 2002;4:445 9.

26 Paced Patients with AF Improvement in functional class, increased EF, decrease in end-systolic and end-diastolic diameters, decrease in the number of hospitalizations and improved quality of life scores were demonstrated in this patient population. A 40% decrease in the MR area was reported in one of the two studies Valls-Bertault V, Fatemi M, et al. Assessment of upgrading to biventricular pacing in patients with right ventricular pacing and congestive heart failure after atrioventricular junctional ablation for chronic atrial fibrillation. Europace 2004; 6:

27 CRT-P vs. CRT-D The use of CRT-D already exceeds that of CRT-P in many countries. There is no evidence, however, from individual randomized trials nor from metaanalyses to suggest that CRT-D improves survival more than CRT-P in the primary prevention setting.

28 CARE-HF Study CRT-P improves left ventricular function and potentially reduces the risk of subsequent SCD. This is consistent with data from CARE-HF suggesting that CRT-P per se reduces SCD as well as total mortality. 60% 50% 40% 30% 20% 10% Primary Endpoint p< % 55% Secondary Endpoint All-cause Mortality p< % 30% 0% Eur Heart J 2006;27: CRT Control CRT Control

29 COMPANION Study In the COMPANION study, survival curves between CRT-D and CRT-P were parallel beyond 9 months, suggesting that the incremental benefit of ICD may be short-lived. Michael R. Bristow et al. Cardiac-Resynchronization Therapy with or without an Implantable Defibrillator in Advanced Chronic Heart Failure. N Engl J Med 2004; 350:

30 CRT-P vs. CRT-D In deciding which device to implant in clinical practice, the physician will need to take into account clinical circumstances as well as societal, cultural, and financial factors of the individual countries. Keep in mind that CRT-D seems to be associated with a higher risk of device-related complications as compared with CRT-P.

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32 Complications A higher risk of acute complications versus a de novo implant are reported. This includes venous access issues, the risk of damage or extraction of old leads, the higher risk of infection, and the additional time that may be required.

33 Technical Considerations Upgrades from RV pacing to CRT systems now comprise nearly 20% of CRT implants Upgrading of previously implanted RV pacing systems has been attempted in the past by the use of different techniques, either using a variety of configurations of leads and connectors or by implanting new pulse generators. Rosen B. D. Resynchronization Therapy Upgrades: Turning Coach into First Class. J Cardiovasc Electrophysiol, Vol. 15, pp

34 Techniques Most studies have involved systems connecting both ventricular leads to a common internal current source. This entails the risk of an impedance mismatch that could result in only RV or only LV pacing, rather than both. Connecting two independent channels adds further programmability of the RV LV stimulation delay.

35 Need for Contralateral Lead Placement Fox D. Upgrading Patients with Chronic Defibrillator Leads to a Biventricular System and Reducing Patient Risk: Contralateral LV Lead Placement. PACE 2006;29: l

36 Difficult Case

37 Subclavian Occlusion

38 Access from Right Side

39 Unstable Lead

40 Stenting of CS

41 Stenting of CS

42 Stable Lead Position

43 Lead Tunneled to Left Side

44 Lead Tunneled to Left Side

45 Final Position

46 Final Message Given that dyssynchrony is the problem, or at least a prominent part of it, with pacinginduced or pacing-aggravated HF, resynchronization is a theoretically sound target to pursue. The upgrading approach to the treatment of already paced HF patients is at least feasible, relatively safe and most likely beneficial.

47 Recs Modified 2012 Cardiac Resynchronization Therapy in Patients With Systolic Heart Failure Who Need Pacing I IIa IIb III CRT can be useful for patients on GDMT who have LVEF less than or equal to 35% and are undergoing new or replacement device placement with anticipated requirement for significant (>40%) ventricular pacing ACCF/AHA/HRS Focused Update of the 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities. Modified recommendation (wording changed to indicate benefit based on ejection fraction and need for pacing rather than NYHA class; class changed from IIb to IIa).

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49 Tehran Arrhythmia Center