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Year : 2008  |  Volume : 9  |  Issue : 3  |  Page : 104-108 Table of Contents     

Short Term Effect of Cardiac Resynchronization Therapy on Functional Recovery of Patients with Congestive Heart Failure

Dubai Heart Centre, Dubai Hospital, Dubai, United Arab Emirates

Date of Web Publication17-Jun-2010

Correspondence Address:
Zaky Hosam
P.O. Box 21910, Dubai
United Arab Emirates
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Source of Support: None, Conflict of Interest: None

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Objectives: We investigated the impact of six month cardiac resynchronization therapy (CRT) on echocardiographic and clinical variables in congestive heart failure patients (CHF).
Background: Cardiac resynchronization reduces symptoms and improves left ventricular function in many patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony1. We evaluated its short term effects on reverse remodeling of the left ventricle and on the patient symptoms.
Methods: The evaluated group contains seven patients (1 woman and 6 men). The average age was 62.43 ± 21.9 years. All the patients had CHF with prolonged QRS. The etiology was ischemic in 5 and idiopathic in 2. All patients underwent physical examination and six minutes hall walk test. Echocardiography was done to evaluate basic cardiac function, left ventricular ejection fraction (LVEF, M-mode & Simpson), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), MR severity and dysynchrony by Doppler and tissue Doppler. Results were compared before implantation and six weeks and six month after CRT implantation.
Results: LVEDD and LVESD were reduced after six months, LVEDD was reduced from 75.9 ± 7.4 to 71.0 ± 4.1 mm ± SD (p value 0.04) and LVESD was reduced from 62.4 ± 8.5 to 59.3 ± 7.0 (p value 0.15). Ejection fraction was significantly increased after 6 weeks from 25 ± 7.1% to 31 ± 4.5%, (p value 0.03).The average grade of mitral regurgitation has increased from 1.67 ± 0.82 at baseline to 1.75 ± 0.88 at 6 month follow up, (p value 0.66) by semi-quantitative analysis.
Conclusion: Although the study was performed on a small number of patients, yet we are convinced that Cardiac resynchronization therapy had favorable hemodynamic and clinical results in our heart failure patients.

Keywords: cardiac resynchronization therapy, congestive heart failure, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, mitral regurgitation, LVEF

How to cite this article:
Hosam Z, Hamid H, Mohamed AA, Obaid A. Short Term Effect of Cardiac Resynchronization Therapy on Functional Recovery of Patients with Congestive Heart Failure. Heart Views 2008;9:104-8

How to cite this URL:
Hosam Z, Hamid H, Mohamed AA, Obaid A. Short Term Effect of Cardiac Resynchronization Therapy on Functional Recovery of Patients with Congestive Heart Failure. Heart Views [serial online] 2008 [cited 2023 Dec 7];9:104-8. Available from: https://www.heartviews.org/text.asp?2008/9/3/104/63753

   Introduction Top

Over the past decade, investigators have established that ventricular stimulation of right and left ventricle together (biventricular), or just left ventricular free wall itself, can improve the mechanics and energetics of the failing heart with discoordinate contraction. Cardiac resynchronization therapy (CRT) have gained an established role in the treatment of patients with advanced heart failure due to systolic dysfunction in association with QRS delay .Patients not only feel better and can do more with CRT, but also they live longer and are hospitalized less [1],[2],[3] .

   Methods Top

Our study included 7 patients. All patients gave written informed consent for the procedure and the study. In this study, we had studied the effect of CRT on our patients regarding symptoms, 6 minutes hall walk test and echocardiographic measures of reverse remodeling at 6 weeks and 6 month intervals. The design, inclusion and exclusion criteria of the study are as follows:

   Inclusion criteria Top

  • Patients with CHF of both ischemic and nonischemic origin.
  • NYHA functional class III or IV.
  • On optimal medical therapy
  • LVEF ≤ 0.35
  • LVEDD ≥ 5.5 cm
  • QRS duration ≥ 120 msec.
  • Echocardiographic evidence of intra and inter-ventricular conduction delay.

   Exclusion criteria Top

  • Asymptomatic heart failure patients
  • Reversible risk factors like ischemia or operable valve lesion.

   Patient's evaluation before the procedure Top

  1. History taking to assess the NYHA functional class, to ensure that the patient is on maximal medical therapy and complies well with medication and absence of treatable causes for the heart failure.
  2. Examining the chest, heart and abdomen for signs of heart failure and underlying etiology.
  3. 6 minutes hall walk test for ambulant patients.
  4. ECG: for PR interval and QRS width.
  5. CXR: for cardiac silhouette and lung field evaluation.
  6. Echocardiography.

   A. Echocardiographic measurements Top

Transthoracic echocardiography was performed shortly before pacemaker implantation and then after six weeks and six months when patients were paced with the optimal mode and settings. Left atrial and left ventricular diameters were determined using M-mode echocardiography under two-dimensional guidance in the parasternal long-axis view according to the recommendation of chamber quantification by the American society of echocardiography 2006[4]. The end of diastole was defined by the largest diameter while the end of systole was defined by the smallest cavity area before mitral valve opening. Biplane left ventricular end systolic volume (LVESV) and left ventricular end diastolic volume (LVEDV) were respectively calculated from the two-chamber and four-chamber views, according to the modified Simpson's rule. Measurements were averaged from three cardiac cycles. Left ventricular EF was calculated as: (LVEDV - LVESV)/ LVEDV x1005. Mitral regurgitation (MR) was semiquantitatively graded on a 4-point scale (grades 0 to 3) using color-coded Doppler signals, the maximal jet area was measured in the parasternal and apical views4. Final analysis was performed off-line (from videotape) by two independent observers after manual recalibration on a Phillips sonos 7500 ultrasound scanner.

   B. Evidence of dysynchrony Top

Aortic (AO) pre-ejection time ≥ 140 msec from onset of QRS to start of aortic ejection was calculated to diagnose intraventricular conduction delay [6] . Measuring pulmonary pre-ejection time and confirming interventricular conduction delay by a difference between AO pre ejection and pulmonary pre ejection of more than 40 msec was done [6] . Tissue Doppler evidence of desynchrony in the form delayed longitudinal contraction by ≥ 70 msec between the basal septum and the basal lateral wall in the 4 chamber view and evidence of post systolic motion was also done [7] .

   Pacing protocol and Operative procedure Top

The implantation of atrio-biventricular pacemakers was done through creation of a pocket in the delto-pectoral groove. Pacing leads were inserted in the right atrial appendage, right ventricular apex and coronary sinus. For LV pacing, we tried to reach mid lateral wall position. Cases which had ICD implantation, defibrillation threshold testing twice at 10 joules less than the maximumal output of the device was done. All leads were tested for threshold of pacing, impedance, and RA and RV leads for P wave and R wave sensing. Testing for pherenic nerve stimulation at 10 volts was done for all leads.

One case with persistent left superior vena cava with no apparent tributary had epicardial lead implantation through minimal thoracotomy by the cardiac surgeon. Postoperative programming for the atrioventricular (A-V) delay and ventriculo-ventricular (V-V) delay using echocardiography for optimization. ICD cases were programmed on the VF zone where indicated for primary prevention of sudden cardiac death.

Follow up: The Following steps were repeated in 6 weeks and 6 month follow-up:

  1. History taking, examination and 6 minutes hall walk test.
  2. Echocardiography measurements of LVEDD, LVESD, LVEF, and mitral regurgitation (MR).
  3. Doppler examination for mitral inflow to optimize the A-V delay and for left ventricular out flow tract (LVOT) to optimize the V- V delay.
  4. The pacemakers have been interrogated and tested for threshold, impedance, and sensitivity of all leads and percent pacing.
  5. ICD cases were interrogated for possible shocks or any attack of dysrrhythmia.

   Concomitant drug treatment Top

For patients to be included in the study, they had to be in a stable NYHA functional class III without a change in medication or in class IV without the need for intravenous inotropic drugs during the last month.

   Statistical analysis Top

Statistical analysis was performed using SPSS 13 software (statistical Package for Social Science) for windows. Results were expressed as mean ± SD or mean (range) as appropriate using Student's t-test & Wilcoxon test wherever applicable. A p-value of less than 0.05 (two - tailed) was considered statistically significant.

   Results Top

In this study, 7 patients were recruited and one of them was a female. The mean age was 62.43 years ± 21.9 years. Five patients had ischemic cardiomyopathy and 2 had nonischemic cardiomyopathy. One of them had persistent left superior vena cava with no tributary. In this case Left ventricular epicardial lead was implanted by mini-thoracotomy by the cardiac surgeon, however unfortunately during the follow up, we found that he developed exit block with the highest output of the Frontier Saint Jude pacemaker of 7.5 volts and pulse width of 1.5 msec, no LV capture was detected and was considered a non-responder.

One out of 7 patients had 45% CRT delivered most of the time due to frequent PVCs, three had 92% CRT delivery and three had 100% CRT delivery all the time.

Patient's mean ± (SD) NYHA functional class was 3.14 ± (0.38) at baseline and dropped to a mean of 2.14 ± (0.38) at 6 weeks (P value 0.02) and remained steady upto 6 months .There were statistically significant changes denoting sustained benefit attained at 6 weeks [Table 1] .

The 6 minutes hall walk test has increased in 6 weeks and 6 months follow up. However when analyzed using paired t test, it revealed no statistically significant change between the baselines and both the 6 weeks and the 6 months follow up. This could be explained by the small number of cases recruited in the study.

Although the changes in the 6 minutes walk test was statistically insignificant, the distance walked at the 6 weeks increased in comparison to the baseline and increased further at the 6 months follow up [Figure 1] and [Figure 2].

Mitral incompetence did not show significant change when the baseline was compared to the 6 weeks and the 6 months follow up.

The end diastolic diameter at baseline versus 6 weeks showed near significant change (p value 0.6); and baseline versus 6 months follow up, the end diastolic diameter showed statistically significant reduction using paired t-test. The end systolic diameter decreased when comparing the baseline follow up to 6 weeks and 6 months, the change was not significant statistically [Table 1].

When the ejection fraction was compared at baseline to 6 weeks, the increase in EF was significant; and to 6 months follows up, there was an increase in the Ejection fraction but the change was statistically insignificant. We can conclude that the benefit in 6 weeks was sustained at 6 months.

   Discussion Top

In this study, most of the changes in the parameters measured go in line with the major randomized trials. Some of the results were statistically insignificant mostly due to the small number recruited.

The mean NYHA functional class improved significantly when comparing the baseline data to 6 weeks data and also improved significantly when comparing the baseline to 6 months follow up which goes in agreement with most of the short term randomized trials [8],[9],[10],[11],[12] .

In our study, the 6 minutes hall walk test distance has increased in both the 6 weeks and the 6 months follow up, but was not statistically significant; in comparison to other trials where the increase in the distance walked was significant [8],[9],[10],[11],[16] . We believe that the small number of cases is the reason behind the non significant result.

The functional mitral incompetence did not change significantly in our cohort although others [10],[13] documented the significant decrease in functional mitral incompetence for the patients receiving CRT.

The ejection fraction showed significant improvement in baseline versus 6 weeks and nonsignificant increase in the baseline versus 6 months. That increase was also observed in other trials [10],[14] where the ejection fraction increased significantly at 6 months follow up.

The end diastolic diameter decreased significantly in 6 months follow up and near significantly (p value 0.6) in 6 weeks follows up. Also other investigators [8],[9],[10],[11] showed statistically significant decrease in the end diastolic diameter.

The end systolic diameter in this study decreased nonsignificantly both in the 6 weeks and 6 months follow up, although by stllebrink and colleagues14 as well as others [10],[11],[12],[15] decreased significantly in the 6 months follow up.

   Conclusion Top

Cardiac resynchronization therapy on short term follow up evaluation proved beneficial on the patients' symptoms, exercise capacity and evidence of inducing LV reverse remodeling by echocardiography.

   Study Limitation Top

The major limitation of this study was the small number of patients recruited that could explain why some of the results were not statistically significant.

   References Top

1.Leclercq C, Kass D A: Retiming the failing heart: principles and current clinical status of cardiac resynchronization. J AM Coll Cardiol 2002; 39:194-201.  Back to cited text no. 1      
2.Cleland JGF, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Freemantle N, Gras D, Kappenberger L, Tavazzi L, Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med (2005) 352:1539-1549 .  Back to cited text no. 2      
3.Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM, for the Comparison of Medical Therapy, Pacing, Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med (2004) 350:2140-2150.  Back to cited text no. 3      
4.Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I: Recommendation for quantification of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr 1989; 2:358-367.  Back to cited text no. 4      
5.Feigenbaum H, Armstrong W, Rayan T, Evaluation of systolic and diastolic function of the left ventricle (6) 142-144 Echocardiography; Lippincot Williams & Wilkins Sixth Edition, 2005.  Back to cited text no. 5      
6.Greenberg J, Delurgio DBM, Mera F: Left Ventricular Lead Location in biventricular pacing with variable RV-LV Timing does not affect optimal stroke volume. NASPE 2002:151.  Back to cited text no. 6      
7.Yu CM, Chau E, Sanderson JE. , 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; 105:438-445.  Back to cited text no. 7      
8.Auricchio A, Stellbrink C, Sack S, Block M, Vogt J, Bakker P, Huth C, Schondube F, Wolfhard U, Bocker D, Krahnefeld O, Kirkels H, Pacing Therapies in Congestive Heart Failure (PATH-CHF) Study Group: Long-term of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. J Am Coll Cardiol 2002; 39:2026-2033.  Back to cited text no. 8      
9.Cazeau S, Leclercq C, Lavergne T, Walker S, Varma C, Linde C, Garrigue S, Kappenberger L, Haywood GA, Santini M, Bailleul C, Daubert JC, Multisite Stimulation in Cardiomyopathies (MUSTIC) Study Investigators: Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 2001; 344:873-880.  Back to cited text no. 9      
10.Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, Kocovic DZ, Packer M, Clavell AL, Hayes DL, Ellestad M, Trupp RJ, Underwood J, Pickering F, Truex C, McAtee P, Messenger J, MIRACLE Study Group. Cardiac resynchronization in chronic heart failure. N Engl J Med (2002) 346:1845-1853.  Back to cited text no. 10      
11.Thackray S, Coletta A, Jones P, Dunn A, Clark AL, Cleland JG Clinical trials update: Highlights of the Scientific Sessions of Heart Failure 2001, a meeting of the Working Group on Heart Failure of the European Society of Cardiology. CONTAK-CD, CHRISTMAS, OPTIME-CHF. Eur J Heart Fail, Aug 2001; 3(4): 491-4.  Back to cited text no. 11      
12.Young JB, Abraham WT, Smith AL, et al., for the Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) Trial Investigators. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial. JAMA 2003; 289:2685-2694.  Back to cited text no. 12      
13.Ole A. Breithardt, Anil M. Sinha, Ehud Schwammenthal, Nadim Bidaoui, Kai U. Markus, Andreas Franke, and Christoph StellbrinkAcute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure. Am. Coll. Cardiol., Mar 2003; 41: 765 - 770.  Back to cited text no. 13      
14.Stellbrink C, Breithardt OA, Franke A, et al. Impact of cardiac resynchronization therapy using hemodynamically optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction disturbances. J Am Coll Cardiol 2001; 38:1957-65.  Back to cited text no. 14      
15.Leslie A. Saxon, Teresa De Marco, Jill Schafer, Kanu Chatterjee, Uday N. Kumar, and Elyse Foster ,for the VIGOR congestive heart failure investigators, Effects of Long-Term Biventricular Stimulation for Resynchronization on Echocardiographic Measures of Remodeling Circulation, Mar 2002; 105: 1304 - 1310.  Back to cited text no. 15      
16.Cleland JG, Daubert JC: Effects of cardiac resynchronization therapy with sequential Biventricular pacing on Doppler-derived left ventricular stroke volume, functional status and exercise capacity in patients with ventricular dysfunction and conduction delay. The US In Sync III trial. Pacing clin Electrophysiology 2002; 24:558.  Back to cited text no. 16      


  [Figure 1], [Figure 2]

  [Table 1]


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