Cardiac resynchronization therapy: Difference between revisions
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{{CMG}}; {{AOEIC}}: Bhaskar Purushottam, M.D. [mailto:bpurushottam@gmail.com] | {{CMG}}; {{AOEIC}}: Bhaskar Purushottam, M.D. [mailto:bpurushottam@gmail.com] | ||
'''''Synonyms and Keywords:''''' CRT | |||
==Overview== | ==Overview== | ||
Cardiac resynchronization therapy (CRT) is an evidence based device treatment for [[congestive heart failure]]. CRT is indicated in those patients with symptomatic [[congestive heart failure]] despite optimal medical therapy who have a reduced [[left ventricular ejection fraction]](an LVEF ≤ 35%), and a wide QRS (≥ 0.12 sec). It involves timed atrioventricular and biventricular pacing, which can improve left ventricular function, heart failure symptoms and may be associated with a reduction in mortality. | Cardiac resynchronization therapy (CRT) is an evidence based device treatment for [[congestive heart failure]]. CRT is indicated in those patients with symptomatic [[congestive heart failure]] despite optimal medical therapy who have a reduced [[left ventricular ejection fraction]](an LVEF ≤ 35%), and a wide QRS (≥ 0.12 sec). It involves timed atrioventricular and biventricular pacing, which can improve left ventricular function, heart failure symptoms and may be associated with a reduction in mortality. | ||
Revision as of 00:42, 12 September 2011
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief:: Bhaskar Purushottam, M.D. [2]
Synonyms and Keywords: CRT
Overview
Cardiac resynchronization therapy (CRT) is an evidence based device treatment for congestive heart failure. CRT is indicated in those patients with symptomatic congestive heart failure despite optimal medical therapy who have a reduced left ventricular ejection fraction(an LVEF ≤ 35%), and a wide QRS (≥ 0.12 sec). It involves timed atrioventricular and biventricular pacing, which can improve left ventricular function, heart failure symptoms and may be associated with a reduction in mortality.
Indications
The ACC / AHA guidelines indicate that CRT is recommended for those patients with all of the following: [1]
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1. Patients with an left ventricular ejection fraction less than or equal to 35%, QRS duration greater than or equal to 0.12 seconds, sinus rhythm and NYHA class 3 or 4 heart failure symptoms on optimal medical therapy (considered a class 1 indication with level A evidence) 2. Patients with an left ventricular ejection fraction less than or equal to 35%, QRS duration greater than or equal to 0.12 seconds, atrial fibrillation and NYHA class 3 or 4 heart failure symptoms on optimal medical therapy (considered a class 2a indication with level B evidence) 3. Patients with an left ventricular ejection fraction less than or equal to 35%, NYHA class 3 or 4 heart failure symptoms on optimal medical therapy and who have frequent dependence on ventricular pacing (considered a class 2a indication with level B evidence) 4. Patients with an left ventricular ejection fraction less than or equal to 35%, NYHA class 1 or 2 heart failure symptoms on optimal medical therapy and who are undergoing implantation of a permanent pacemaker and or ICD with anticipated frequent ventricular pacing (considered a class 2b indication with level C evidence) |
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Contraindications
The ACC / AHA guidelines indicate that CRT is not indicated in the following patients: [1]
- Patients who are asymptomatic with a reduced LVEF who have no other indications for pacing.
- Patients who have a limited life expectancy due to a non-cardiac condition.
- Patients who have a limited functional capacity due to a chronic non-cardiac condition.
Pathophysiologic Basis For CRT
Left ventricular systolic dysfunction is often accompanied by impaired electromechanical coupling, which may further diminish the left ventricular systolic function. The types of electromechanical dyssynchrony are atrioventricular, interventricular, intraventricular and intramural delay[2]. Atrioventricular dyssynchrony results in a late diastolic ventriculoatrial gradient and so called "pre-systolic" mitral regurgitation. Interventricular dyssynchrony is the time delay between the contraction of the left and right ventricles and this is calculated by measuring the difference in the time of onset of systolic flow in the aortic and pulmonic valve. A time difference greater than or equal to 40 milliseconds is indicative of interventricular dyssynchrony. There are several echocardiographic techniques to measure intraventricular dyssynchrony, which include M mode echocardiography, tissue Doppler imaging, tissue strain, strain rate analysis and speckle tracking echocardiography. Intramural dyssynchrony is the dyssynchrony within the myocardial wall and it has been measured using speckle tracking echocardiography[3]. However, the most common abnormalities are prolonged atrio-ventricular and ventricular conduction, which causes regional mechanical delay within the left ventricle.
This mechanical delay is responsible for ventricular dyssynchrony, which can result in the following hemodynamic abnormalities[4]:
- Reduced left ventricular systolic function, decreased dP/dT and cardiac output
- Delayed contraction of lateral and posterior left ventriclular wall with abnormal septal motion
- Increased myocardial energy expenditure
- Adverse remodeling with increased left ventricular dilatation left ventricular end systolic volume
- Functional mitral regurgitation
- Delayed mitral valve opening
- Reduced left ventricular filling time with increased left atrial pressures
- Distorted mitral valve annulus
- Delayed aortic valve opening and closure with reduced systolic ejection time
Landmark Trials
The several landmark trials which led to the acceptance of CRT as a non-pharmacological treatment approach for heart failure almost exclusively enrolled patients with sinus rhythm and a left bundle branch block (especially, with a QRS duration greater than or equal to 0.15 seconds). However, QRS duration greater than or equal to 0.12 seconds has been used a measure for dyssynchrony and a criterion for selection of patients for CRT. It is thought that when the QRS duration is prolonged there is delayed activation of the ventricular myocardium with dyssynchronous contraction between the left and right ventricle (interventricular dyssynchrony) and within the left ventricle itself (intraventricular dyssynchrony). However, left ventricular mechanical dyssynchrony is shown to occur independent of QRS duration by echocardiographic parameters (predominantly tissue Doppler and speckle tracking imaging), which measure inter and intra left ventricular conduction delay. By such parameters, nearly half of the heart failure patients with normal QRS duration have evidence of mechanical dyssynchrony and one fifth of heart failure patients with QRS duration greater than or equal to 0.15 seconds reveal no evidence of mechanical dyssynchrony[5][6]. It has also been shown that mechanical dyssynchrony measured by echocardiographic techniques is predictive of cardiac events in heart failure patients independent of their QRS duration[6]. Therefore, using QRS duration, which is an electrical measure of conduction delay may not be the most reliable marker of ventricular dyssynchrony. The RethinQ[7] trial failed to show any benefit from CRT in heart failure patients with a NYHA class 3, left ventricular ejection fraction less than or equal to 35%, narrow QRS duration(less than or equal to 0.13 seconds) with mechanical dyssynchrony as measured by tissue Doppler imaging and M-mode echocardiography. One of the major limitations of this study was the selection criteria for mechanical dyssynchrony. Currently, there are several studies underway which are looking at different echocardiographic techniques to predict intra left ventricular mechanical dyssynchrony accurately. Till we have a feasible, convenient, reproducible and accurate technique to measure mechanical intra left ventricular dyssynchrony, QRS duration will be used as a measure of dyssynchrony in selecting patients for CRT. CRT in responders can reverse the above mentioned hemodynamic abnormalities to a certain extent with associated clinical and functional benefit.
Efficacy in Clinical Trials
PATH-CHF[8], MUSTIC SR[9][10], MUSTIC AF[11], MIRACLE[12], COMPANION[13], CARE-HF[14], MIRACLE-ICD[15], CONTAK-CD[16], RHYTHM-ICD and HOBIPACE[17] landmark trials demonstrated the following beneficial effects of CRT:
- Reduced mortality (24% to 36% benefit)
- Reduced hospitalizations (30% decrease)
- Improved 6 minute walk test (50 to 70 meter increase)
- Improved 105 -point Minnesota scale (greater than or equal to 10 point reduction of heart failure symptoms)
- Improved NYHA class
- Increase in peak oxygen consumption
Atrial Fibrillation and CRT
Challenges Posed by Atrial Fibrillation and CRT
Atrial fibrillation poses several challenges to effective biventricular pacing[18].
- The intrinsic, intermediate-to-high irregular atrial fibrillation rhythm reduces the number of biventricular paced captured beats.
- Even in atrial fibrillation patients who have a normal ventricular response rate, there is the occurrence of spontaneous, fusion and pseudofusion beats, which once again minimize the biventricular pacing.
- Rapid heart rates reduce diastolic filling time and hence reduce stroke volume.
- Irregular rhythm negatively impacts left ventricular function.
Solutions to the Challenges Posed by Atrial Fibrillation and CRT
- Rate control with negative chronotropic agents
- Atrioventricular junction ablation and device mediated treatment, such as ‘Ventricular Rate Regularization. The OPISTE[19] and PAVE[20] trials confirmed the clinical benefits of atrioventricular ablation with adequate rate control. The PAVE study showed a greater benefit of biventricular pacing. On the basis of these trials and recent observational data, atrioventricular junction ablation may represent a fundamental tool in improving cardiac resynchronization response.
Cardiac Resynchronization Therapy in Minimal Heart Failure
Procedure
CRT involves a procedure similar to that of a pacemaker placement. In addition to that of the routine implantation of the atrial and right ventricular lead, a third lead is introduced into the coronary sinus and the lateral or posterior branch is accessed for stimulation of the left ventricle. Previously, an epicardial left ventricular lead was implanted after a limited lateral throacotomy. Such epicardial lead implantation is associated with high capture thresholds, suboptimal position for resynchronization, a far more invasive procedure, risk of general anaesthesia and standard complications associated with thoracotomy. However, this approach may be used if the coronary sinus or the appropriate branch cannot be accessed due to anatomical variations, vein stenosis, coronary sinus injury, tortuosity of the coronary sinus and distortion of the ostium.
Complications
The performance of the CRT procedure itself can be associated with several complications, such as bleeding, infection, pneumothorax (0.9% in CRT trials, Medicare registry[21] reported 1.2%), lead dislodgement, myocardial injury, coronary sinus dissection (1.3%) or perforation (1.3%)(complication rate related to coronary veins has been reported in 2%) and pericardial tamponade. Pocket erosion, hematomas (2.4%; in routine clinical practice, the actual incidence of pocket hematomas is probably higher as the trials only reported those hematomas, which needed surgical intervention), lead fracture, lead dislodgements (CRT trials demonstrated a rate verying from 2.9% to 10.6%; the MIRACLE-ICD[15] study demonstrated a higher occurence of lead dislodgement with left ventricular lead than right atrial and right ventricular leads-6.8%, 15 and 0.6% respectively) and device infection are common post procedural complications. It is important to note that early re-intervention of pocket hematomas is associated with a 15-fold increase in infection[22]. Given the proximity of the posterior wall of the left ventricle to the phrenic nerve, there remains the risk of inappropriate phrenic nerve stimulation. For CRT patients, the average in-hospital mortality is 0.3% and the 30 day mortality is 0.7%. Reynolds et al.[21] showed a 1.1% in-hospital mortality in 30,984 Medicare patients undergoing CRT. This disparity in the in-hospital mortality rates can be explained by the strict inclusion criteria of the trials, where the patients are more healthier than the patients in real life practice.[23]
Non-responders
30% of the CRT recipients are considered non-responders. A patient is considered a non-responder if there are no significant clinical or functional improvement after CRT as measured in the landmark trials (as mentioned above under clinical benefits). There are several plausible causes to explain a non-responder. As mentioned earlier, not all patients with QRS duration greater than or equal to 0.12 seconds have mechanical dyssynchrony. Unfortunately, the PROSPECT[24] trial which set out to examine the various echocardiographic parameters to predict CRT response was not successful. Some of the major limitations in the study were the technical difficulties in obtaining the dyssynchrony parameters and the discrepancies among the different centers. The other reasons could be lead placement in regions of the left ventricle which is not dyssynchronous or fibrosis with no live myocardium. In fact, anterior left ventricular lead placement has been associated with worsening hemodynamics. Also, lack of sufficient biventricular pacing could result in a non-responder secondary to high left ventricular capture thresholds, lead dislodgement, a long atrioventricular delay, atrial tachyarrhythmias with rapid ventricular response and frequent premature ventricular contractions. Lack of optimal atrioventricular and ventricular to ventricular (i.e., right ventricle to left ventricle) timing can result in a non-responder.
Unmet Needs
The following are remaining unmet needs:
- The identification of patients who would definitely benefit from CRT (i.e. reducing the number of non-responders). Different imaging modalities and dyssynchrony parameters may accurately reveal mechanical dyssynchrony and therefore predict a CRT responder, especially in patients with a narrow QRS complex.
- Further confirmatory evidence regarding the benefit of atrioventricular ablation versus pharmacological rate control in optimizing the clinical benefits is needed. In addition to atrioventricular and Ventricular-Ventricular optimization, other device based changes need to be explored so as to reap the complete benefits of CRT.
References
- ↑ 1.0 1.1 Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO, Smith SC, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Faxon DP, Halperin JL, Hiratzka LF, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura RA, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW (2008). "ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons". Circulation. 117 (21): e350–408. doi:10.1161/CIRCUALTIONAHA.108.189742. PMID 18483207. Retrieved 2011-01-15. Unknown parameter
|month=ignored (help) - ↑ Auricchio A, Abraham WT (2004). "Cardiac resynchronization therapy: current state of the art: cost versus benefit". Circulation. 109 (3): 300–7. doi:10.1161/01.CIR.0000115583.20268.E1. PMID 14744954.
- ↑ Bank AJ, Kaufman CL, Burns KV, Parah JS, Johnson L, Kelly AS; et al. (2010). "Intramural dyssynchrony and response to cardiac resynchronization therapy in patients with and without previous right ventricular pacing". Eur J Heart Fail. 12 (12): 1317–24. doi:10.1093/eurjhf/hfq162. PMID 20864481.
- ↑ Ho JK, Mahajan A (2010). "Cardiac resynchronization therapy for treatment of heart failure". Anesth Analg. 111 (6): 1353–61. doi:10.1213/ANE.0b013e3181fa3408. PMID 21059745.
- ↑ Bader H, Garrigue S, Lafitte S, Reuter S, Jaïs P, Haïssaguerre M; et al. (2004). "Intra-left ventricular electromechanical asynchrony. A new independent predictor of severe cardiac events in heart failure patients". J Am Coll Cardiol. 43 (2): 248–56. PMID 14736445.
- ↑ 6.0 6.1 Cho GY, Song JK, Park WJ, Han SW, Choi SH, Doo YC; et al. (2005). "Mechanical dyssynchrony assessed by tissue Doppler imaging is a powerful predictor of mortality in congestive heart failure with normal QRS duration". J Am Coll Cardiol. 46 (12): 2237–43. doi:10.1016/j.jacc.2004.11.074. PMID 16360052.
- ↑ Beshai JF, Grimm RA, Nagueh SF, Baker JH, Beau SL, Greenberg SM; et al. (2007). "Cardiac-resynchronization therapy in heart failure with narrow QRS complexes". N Engl J Med. 357 (24): 2461–71. doi:10.1056/NEJMoa0706695. PMID 17986493.
- ↑ Auricchio A, Stellbrink C, Sack S, Block M, Vogt J, Bakker P; et al. (1999). "The Pacing Therapies for Congestive Heart Failure (PATH-CHF) study: rationale, design, and endpoints of a prospective randomized multicenter study". Am J Cardiol. 83 (5B): 130D–135D. PMID 10089855.
- ↑ Cazeau S, Leclercq C, Lavergne T, Walker S, Varma C, Linde C; et al. (2001). "Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay". N Engl J Med. 344 (12): 873–80. doi:10.1056/NEJM200103223441202. PMID 11259720.
- ↑ Linde C, Leclercq C, Rex S, Garrigue S, Lavergne T, Cazeau S; et al. (2002). "Long-term benefits of biventricular pacing in congestive heart failure: results from the MUltisite STimulation in cardiomyopathy (MUSTIC) study". J Am Coll Cardiol. 40 (1): 111–8. PMID 12103264.
- ↑ Leclercq C, Walker S, Linde C, Clementy J, Marshall AJ, Ritter P; et al. (2002). "Comparative effects of permanent biventricular and right-univentricular pacing in heart failure patients with chronic atrial fibrillation". Eur Heart J. 23 (22): 1780–7. PMID 12419298.
- ↑ Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E; et al. (2002). "Cardiac resynchronization in chronic heart failure". N Engl J Med. 346 (24): 1845–53. doi:10.1056/NEJMoa013168. PMID 12063368. Review in: ACP J Club. 2002 Nov-Dec;137(3):82
- ↑ Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T; et al. (2004). "Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure". N Engl J Med. 350 (21): 2140–50. doi:10.1056/NEJMoa032423. PMID 15152059. Review in: ACP J Club. 2004 Nov-Dec;141(3):60
- ↑ Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L; et al. (2005). "The effect of cardiac resynchronization on morbidity and mortality in heart failure". N Engl J Med. 352 (15): 1539–49. doi:10.1056/NEJMoa050496. PMID 15753115. Review in: ACP J Club. 2005 Sep-Oct;143(2):29
- ↑ 15.0 15.1 Young JB, Abraham WT, Smith AL, Leon AR, Lieberman R, Wilkoff B; et al. (2003). "Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial". JAMA. 289 (20): 2685–94. doi:10.1001/jama.289.20.2685. PMID 12771115.
- ↑ Higgins SL, Hummel JD, Niazi IK, Giudici MC, Worley SJ, Saxon LA; et al. (2003). "Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias". J Am Coll Cardiol. 42 (8): 1454–9. PMID 14563591.
- ↑ Kindermann M, Hennen B, Jung J, Geisel J, Böhm M, Fröhlig G (2006). "Biventricular versus conventional right ventricular stimulation for patients with standard pacing indication and left ventricular dysfunction: the Homburg Biventricular Pacing Evaluation (HOBIPACE)". J Am Coll Cardiol. 47 (10): 1927–37. doi:10.1016/j.jacc.2005.12.056. PMID 16697307.
- ↑ Gasparini M, Regoli F, Galimberti P, Ceriotti C, Cappelleri A (2009). "Cardiac resynchronization therapy in heart failure patients with atrial fibrillation". Europace. 11 Suppl 5: v82–6. doi:10.1093/europace/eup273. PMC 2768583. PMID 19861396.
- ↑ Brignole M, Gammage M, Puggioni E, Alboni P, Raviele A, Sutton R; et al. (2005). "Comparative assessment of right, left, and biventricular pacing in patients with permanent atrial fibrillation". Eur Heart J. 26 (7): 712–22. doi:10.1093/eurheartj/ehi069. PMID 15618036.
- ↑ Doshi RN, Daoud EG, Fellows C, Turk K, Duran A, Hamdan MH; et al. (2005). "Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the PAVE study)". J Cardiovasc Electrophysiol. 16 (11): 1160–5. doi:10.1111/j.1540-8167.2005.50062.x. PMID 16302897.
- ↑ 21.0 21.1 Reynolds MR, Cohen DJ, Kugelmass AD, Brown PP, Becker ER, Culler SD; et al. (2006). "The frequency and incremental cost of major complications among medicare beneficiaries receiving implantable cardioverter-defibrillators". J Am Coll Cardiol. 47 (12): 2493–7. doi:10.1016/j.jacc.2006.02.049. PMC 1800827. PMID 16781379.
- ↑ Klug D, Balde M, Pavin D, Hidden-Lucet F, Clementy J, Sadoul N; et al. (2007). "Risk factors related to infections of implanted pacemakers and cardioverter-defibrillators: results of a large prospective study". Circulation. 116 (12): 1349–55. doi:10.1161/CIRCULATIONAHA.106.678664. PMID 17724263.
- ↑ van Rees JB, de Bie MK, Thijssen J, Borleffs CJ, Schalij MJ, van Erven L (2011). "Implantation-related complications of implantable cardioverter-defibrillators and cardiac resynchronization therapy devices a systematic review of randomized clinical trials". J Am Coll Cardiol. 58 (10): 995–1000. doi:10.1016/j.jacc.2011.06.007. PMID 21867832.
- ↑ Chung ES, Leon AR, Tavazzi L, Sun JP, Nihoyannopoulos P, Merlino J; et al. (2008). "Results of the Predictors of Response to CRT (PROSPECT) trial". Circulation. 117 (20): 2608–16. doi:10.1161/CIRCULATIONAHA.107.743120. PMID 18458170.