© 2005 European Society of Cardiology
CRT improves the exercise capacity and functional reserve of the failing heart through enhancing the cardiac flow- and pressure-generating capacity
a Molecular Cardiovascular Medicine, University of Leeds, Leeds General Infirmary Great George Street, Leeds LS1 3EX, UK
b Cardiology Department, Leeds General Infirmary Leeds, LS1 3EX, UK
c Cardiology Department, Bradford Royal Infirmary Bradford, UK
* Corresponding author. Molecular Vascular Medicine, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK. Tel.: +44 113 392 5401; fax: +44 113 392 5395.
 |
Abstract |
|---|
 Top Abstract 1. Introduction2. Methods3. Results4. DiscussionReferences |
|---|
Background: While information on how cardiac resynchronisation therapy (CRT) affects cardiac performance at rest is readily available, the mechanisms whereby CRT alters cardiac function during maximal exercise are unclear.
Aims: We examined the medium-term effects of CRT on cardiac and physical functional reserve of patients with severe heart failure (CHF) and prolonged QRS duration.
Methods: Seventeen consecutive patients with severe CHF (NYHA III–IV) and widened QRS underwent maximal cardiopulmonary exercise testing with non-invasive central haemodynamic measurements before and 6–8 weeks after CRT pacemaker implantation.
Results: After CRT there were significant increases in exercise cardiac output by 19.3% (P=0.0048) from 9.5±3.4 l min–1, peak mean arterial blood pressure by 14.1% (P=0.0001) from 91.3±13.6 mm Hg, and peak cardiac power output by 37.2% (P=0.0008) from 1.92±0.74 W. There were no significant changes in these variables at rest. Exercise duration (+42.3%, P=0.0002), NYHA functional class (P=0.0001) and SF-36 symptom score (P=0.0006) were also significantly improved. Powerful surrogate indicators of prognosis were also significantly improved with CRT: peak O2 consumption (+20.9%, P=0.0007), VE/VCO2 slope (–20.0%, P=0.005) and circulatory power (+42.0%, P=0.0012).
Conclusion: In this cohort of patients, post-implant CRT significantly improved the flow-, pressure- and power-generating capacity of the failing hearts. This may be causally related to the improvements observed in exercise capacity, functional class and symptom scores.
Key Words: Heart failure • Cardiac resynchronisation therapy • Cardiac function • Cardiac power output • Exercise capacity
Received May 7, 2005; Revised September 28, 2005; Accepted November 3, 2005
|
1. Introduction |
|---|
|
TopAbstract1. Introduction2. Methods3. Results4. DiscussionReferences |
|---|
Cardiac resynchronisation therapy (CRT) is unique amongst therapeutic options in being able to improve all major clinical endpoints—symptoms, exercise capacity, hospitalization rates, and longevity—of patients with chronic heart failure and dyssynchronous ventricular contraction [1-4]. If the primary premise of CRT is to improve cardiac pump function through resynchronisation, then an obvious question is to what extent and in what circumstances does CRT improve cardiac pump function? Hitherto, this question has remained unanswered largely due to debates about which parameter(s) would best represent cardiac function.
Several studies have previously established that CRT can improve various aspects related to cardiac dysfunction [5,6], but whether such improvements are causally related to improvements in the actual pump function of the failing ventricle in order to deliver the requisite amount of hydraulic energy to maintain the circulation especially during maximal stress or exercise [7,8], is unknown. Information on how CRT affects central haemodynamic responses and direct indicators of cardiac function during peak exercise is still lacking. The hypothesis to be tested in this study was that CRT implantation is associated with beneficial effects through directly improving the cardiac pump dysfunction, especially during volitional maximal exercise.
|
2. Methods |
|---|
|
TopAbstract1. Introduction2. Methods3. Results4. DiscussionReferences |
|---|
2.1. Patient population
Seventeen consecutive patients awaiting CRT pacemaker implantation in our institution between September 2001 and July 2004 were asked to participate in this prospective follow up study. Standard indications for CRT pacemaker implantation according to published clinical guidelines [9] were followed. Patients included in this study were in New York Heart Association (NYHA) functional classes III and IV. They received optimal medical treatment for CHF and were in a stable condition for more than one month (no hospitalization for heart failure, no change in medication and no change in NYHA class). All had a QRS width >120 ms on their surface ECG. Exclusion criteria included inability to perform treadmill exercise tests, inability to exercise beyond anaerobic threshold, symptomatic angina limiting exercise, coexisting lung or other systemic diseases precluding maximal exercise, inability or unwillingness to provide consent. The study was approved by the Ethics Committee of the Leeds Teaching Hospitals Trust, and informed written consent was obtained from all patients.
2.2. Cardiopulmonary exercise tests
These were conducted as described in a previous report [10]. In line with previous recommendation [11] all patients performed a preliminary, familiarizing, symptom limited cardiopulmonary exercise (CPX) test, with non-invasive measurement of cardiac output at rest and during exertion. Baseline evaluation was performed before CRT implantation and the test was repeated 6-8 weeks following the procedure. This allowed adequate time for full clinical recovery from the intervention. A symptom-limited exercise test was performed using the modified Bruce protocol to measure the peak O2 consumption (VO2), peak CO2 production (VCO2), ventilatory (anaerobic) threshold, respiratory exchange ratio (RER), heart rate (HR) and exercise duration, using MedGraphics CardiO2 equipment (Medical Graphics Corporation, St Paul, U.S.A.). Blood pressure was measured using manual cuff sphygmomanometry. After >1 h of rest, a second peak single-stage exercise test, targeted for approximately the peak workload attained during the prior incremental test, was then performed to measure peak cardiac output using CO2 re-breathing technique.
2.3. Implantation and programming of atrio-biventricular pacemaker
Implantation was performed according to standard technique of atrio-biventricular pacemaker implantation. The pacemaker was programmed to a base rate of 40 bpm and upper limit 85% of the age-gender maximum predicted heart rate. The atrioventricular delay was optimised using echocardiography, selecting optimal filling time and aortic outflow velocity time integral. Patients in AF received biventricular VVIR pacemakers.
2.4. Quality of life and functional evaluation
The New York Heart Association (NYHA) functional class and the Short Form (SF-36) health survey [12] were assessed during the baseline and follow up CPX test.
2.5. Calculations and statistical analysis
Mean arterial pressure (MAP) was calculated from the standard equation MAP=DBP+0.412(SBP–DBP) [13]. The cardiac power output (CPO) was calculated from the product of mean cardiac output and mean arterial pressure [14]. The span of cardiac performance is depicted by cardiac reserve, which was calculated by subtracting the resting CPO from the peak CPO: cardiac reserve=CPOmax–CPOrest [15]. Peak circulatory power was calculated using the product of peak VO2 and peak arterial blood pressure [16], although MAP was employed to avoid age- or stiffness-related exaggeration of systolic BP. The VE/VCO2 and VE/VO2 slopes were calculated by linear regression analysis using the values of minute ventilation, carbon dioxide output and oxygen consumption as described previously [17].
Based on previous CPX data obtained in our unit, a sample size of 12 subjects would be needed to demonstrate a difference between pre- and post-CRT in the peak exercise oxygen consumption of 150 ml min–1, with a 5% two-sided significance level and 80% power. All data were expressed as mean±SD unless stated differently. Comparison of data obtained before and after CRT implantation was done using a Student's t test for parametric data and the Wilcoxon matched-pairs signed-rank test for non-parametric data. A value of P<0.05 was considered significant. Simple individual linear regression analyses were performed by the Pearson correlation coefficient between individual variables.
|
3. Results |
|---|
|
TopAbstract1. Introduction2. Methods3. Results4. DiscussionReferences |
|---|
3.1. Study population baseline characteristics
All 17 patients completed the incremental exercise test of the exercise protocol before and after CRT implantation. Two patients were not able to perform the second part of the exercise protocol because of exhaustion. Therefore complete haemodynamic data was available in 15 patients. The clinical characteristics of the patients participating in the study are summarized in Table 1. All patients (14 male; age 61±9 years, range 47-77) had severe heart failure with a mean LV ejection fraction of 25±9%. Thirteen patients were in NYHA functional class III, four in NYHA class IV despite optimal medical treatment. The underlying aetiology was ischaemic heart disease in 11 patients and dilated cardiomyopathy in 6 patients. The mean LV end-diastolic diameter was 68±6 mm. Eleven (65%) patients were on beta-blockers, 13 (77%) on angiotensin converting enzyme inhibitors or angiotensin receptor blockers, all (100%) were on diuretics, ten (59%) on digoxin, ten (59%) on nitrates and eleven (65%) on spironolactone. Except for diuretics, which were frequently reduced after CRT implantation, no significant changes were made in the medication during the study. Four patients were able to reduce the loop diuretic dosage by 40-120 mg/day of furosemide after CRT.
|
Fourteen patients were in sinus rhythm and three patients in atrial fibrillation. Fourteen patients had underlying left bundle branch block, and three had a pre-existing standard dual chamber pacemaker with resulting left bundle branch block and required upgrading to CRT on clinical grounds. At baseline, mean QRS interval was 174±38 ms, and this was reduced to 134±32 ms post-CRT. Mean reduction in QRS duration was 39±38 ms.
3.2. Resting variables
After CRT there were no significant changes in any of the central haemodynamic variables measured at rest. In particular, there was no significant change in resting systolic, diastolic and mean systemic arterial blood pressures before and after CRT. Systemic vascular resistance at rest did not alter after CRT implantation. Resting heart rate, stroke volume and cardiac output were also not significantly different. Consequently, resting left ventricular stroke work and cardiac power output were not significantly different before and after CRT implantation. Similarly, all respiratory and metabolic measurements made at rest showed no significant difference before vs after CRT.
3.3. Exercise variables
3.3.1. Exercise duration and peak VO2
Exercise capacity, haemodynamic and metabolic variables during symptom-limited maximal exercise before and after CRT are shown in Fig. 1. After CRT implantation, the patients were able to increase significantly their exercise duration by 42% (from 374±219 s, P<0.001) and aerobic exercise capacity by 20.9% (peak VO2 from 13.9±3.5 ml kg–1 min–1, P<0.001). There was no significant difference between the peak RER before (1.09±0.09) and after CRT (1.09±0.08). Three of the patients showed a decrease in either exercise duration or peak VO2 after CRT implantation. Twelve (71%) of the patients increased exercise duration by >60 s in absolute values at their respective peak exercise treadmill workloads, and 13 (76%) of the patients increased their peak VO2 by >2 ml kg–1 min–1. The changes in pre- and post-CRT in exercise duration correlated with changes in peak VO2 (r=0.77, P<0.001). The ventilatory (or anaerobic) threshold (VTh) was also improved with CRT (pre-CRT VTh at VO2 of 861±310 and post-CRT 1025±428 ml min–1).
|
P<0.001.3.3.2. Respiratory and metabolic variables
The ventilatory efficiency represented by the VE/VCO2 slope showed a significant improvement with a decrease of 20.0% from 46.9±19.2 (P=0.005) after CRT, although peak exercise ventilation (VE) remained largely unchanged after CRT (Fig. 1A). VE/VO2 slope also improved significantly from 57.7±30.6 to 42.6±11.8 (P=0.01) after CRT. End-tidal pCO2 at peak exercise also showed significant improvement with CRT (from 29±7 to 32±6 mm Hg, P<0.01). Indeed, the end-tidal pCO2 at peak exercise post-CRT became non-significantly different from the resting values before exercise (33±5 mm Hg).
3.3.3. Central haemodynamics
The peak exercise HR increased by 8% from 108.3±19.1 min–1 pre-CRT (P=0.04, Fig. 1B) and heart rate reserve (
HR=peak exercise–resting HR) was slightly enhanced after CRT (34.7±17.8 min–1 pre-CRT vs 42.9±13.3 post-CRT, P=0.01). In terms of the flow generating capacity of the heart, peak cardiac output increased by 19.3% from 9.5±3.4 l min–1 after CRT (P<0.005, Fig. 1B). Interestingly, at peak exercise the stroke volume was greater after CRT implantation but not significant (92.9±29.3 ml vs 102.9±23.5 ml, P=0.157). In terms of cardiac pressure generating capacity, the systolic, diastolic and mean systemic BPs were significantly greater at peak exercise (from 119.7±21.4 to 142.4±23.4, P<0.0001; from 71.3±9 to 77.78±10.4, P=0.0005 and from 91.3±13.6 to 104.4±14.2, P=0.0001, respectively) post-CRT (Fig. 1B) despite the opposite trend observed in the systemic vascular resistance, which was found to be non-significantly lower by 9% at peak exercise after CRT (780±208 dyn s cm–5 post-CRT, P=0.077) (Fig. 1C).
In terms of cardiac power generating capacity, peak exercise cardiac power output increased by 37% from the pre-CRT value of 1.92±0.74 W (P=0.0008). These changes appear to be concomitant with the changes in VO2 during peak exercise following CRT implantation (Fig. 2). Moreover, the delta changes of the two variables also correlated well (P<0.0001) (Fig. 2). Circulatory power, an indirect measure of cardiac power output, was also increased by a similar extent of 42% following CRT implantation (P=0.0012). The cardiac pumping reserve available for maximal exercise was enhanced by about 55% with CRT from pre-implantation value of 1.18±0.65 W (P=0.0004). Left ventricular stroke work during peak exercise was also significantly enhanced by 26.3% from baseline value of 116±41 g m (P=0.0063) (Fig. 1C). The relative changes in the peak exercise variables are shown in Fig. 1D. The most significant changes statistically and numerically were in exercise duration and CPOmax and cardiac reserve, with around 40% improvement and all P<0.001. Equally statistically significant were changes in VO2max and MAPmax.
|
3.4. Effects of CRT on functional class, quality of life score
The SF-36 quality of life score was assessed in twelve patients and this significantly improved after CRT from 36±18 to 60±20 (P<0.001). NYHA functional class showed a significant improvement from 3.2±0.4 to 2.2±0.8 (P=0.0001, Fig. 3). In total 14 (82%) patients improved their functional class by at least one class. Three patients did not have improvement in NYHA class, and they did not show any significant change in CPOmax following CRT (0.08±0.37 W), whereas those who improved NYHA class also had a significant increase in CPOmax (0.94±0.66 W, P=0.0004).
|
|
4. Discussion |
|---|
|
TopAbstract1. Introduction2. Methods3. Results4. DiscussionReferences |
|---|
This is a novel prospective study exploring non-invasively the impacts of CRT on the central haemodynamics of patients with moderate to severe congestive heart failure and ventricular dyssynchrony during volitional maximal exercise as well as at rest, and it has revealed some mechanistic information that may have important clinical implications. No study to date has examined the haemodynamic response during peak exercise comparing pre- and post-CRT implant data. The results show that in a majority of these patients during medium term follow-up, both the flow- and pressure-generating capacity of the cardiac pump improved after CRT, leading to the ability of the heart to deliver more hydraulic energy into the circulation (power-generating capacity) during maximal exercise. These beneficial haemodynamic effects were significantly associated with improvement in aerobic exercise capacity. The symptomatic status, NYHA functional class and exercise duration were found to be improved in this unselected cohort of consecutive patients receiving CRT. The ventilatory and metabolic variables during peak exercise also showed improvements. The generalized improvements observed across the board are consistent with the hypothesis that CRT indeed produced improvements by directly improving the intrinsic pump dysfunction, and not secondary to unspecified peripheral factors.
In contrast, no statistically significant improvement was observed in the variables measured at rest after CRT. In this study, we have not included patients with heart failure so severe as to require inotropic support, in whom the reversal of ventricular dyssynchronous contraction may manifest with improvement in cardiac function at rest [18]. Haemodynamic studies assessing the effect of CRT on cardiac output at rest have revealed contradictory results. While cardiac output increased by up to 35% at rest in response to CRT in some studies [5,19] the increase was less marked or did not reach statistical significance in other studies [20,21]. In our patient cohort, the manner with which CRT improves cardiac function was clearly evident at peak exercise and not at rest.
This investigation builds on previous work which evaluated the effects of CRT on component aspects of cardiac function (e.g. LV dimensions, LVEF, synchronicity of contraction, LV dp/dtmax, LV instantaneous power index) [22,23], surrogate indicators of cardiac function (e.g. VO2max, BNP, exercise capacity, SNS, NYHA) [2,4,7,24-26], and measurements performed at rest (e.g. resting CO during invasive haemodynamic studies) [5,6,19-22]. It is unclear whether the changes in the respective component parts of the LV would summate and translate into an overall improvement in cardiac function, or whether they might negate each other to result in no improvement in pump function, especially during peak exercise. Taking the premise of CRT benefit as the improvement of contractile synchronicity and thereby enhancing cardiac pump function, our study showed that not only was there a good correlation with cardiac pumping capability and aerobic exercise capacity (Fig. 2A) consistent with our previous report [10], but there was also a good correlation between the changes in pumping capacity induced by CRT with the changes in aerobic exercise capacity (Fig. 2B). Most importantly, these increases were not accompanied by a significant change in systemic vascular resistance (Fig. 1C). This observation is consistent with the notion that CRT improves cardiac function directly, and peripheral effects are secondary phenomena. These observed improvements in cardiac function in turn were associated with patients' improved exercise capacity, ventilatory efficiency, functional class and symptom score.
4.1. Study limitations
In view of positive results in the MIRACLE, MUSTIC, CARE-HF and other randomised-controlled trials (RCT) [1-4], it was considered no longer ethically acceptable to withhold the benefits of CRT from patients participating in this study, thus ruling out the ability to use the RCT design. The results of this study would need to be interpreted in light of this methodological limitation. Nevertheless, by enrolling unselected consecutive patients able to exercise from the waiting list for CRT implantation at our institution, the patient cohort and their results can be viewed as those typically encountered in real-life everyday cardiological practice.
Although statistically significant results were obtained in key test results, the relatively small patient numbers precluded the possibility of making any inference about patient selection such as those with atrial fibrillation, lesser degrees of dyssynchrony or QRS prolongation, ischaemic vs dilated cardiomyopathy aetiologies.
4.2. Clinical implications
The bottom line objective of cardiac therapeutics is to preserve or improve cardiac function. The results from this study strongly suggest that CRT is a useful therapeutic modality to achieve such an objective. The results from this study have shown that the most powerful surrogate indicators of prognosis such as CPOmax [7,27], peak circulatory power [16], VO2max and VE/VCO2 slope [17] were all shown to be improved by CRT. Whether such across-the-board improvements in surrogate prognostic indicators can possibly be translated into actual improvement in prognosis has been given some credence by the recently published CARE-HF positive results [1].
In practical terms, this study has shown that the absence of significant changes in pump function observed at rest does not necessarily mean that there is not going to be any improvements during exercise. Assessment of patients undergoing CRT implantation requires both stress testing and the measurement of variables that reflect both the flow- and pressure-generating capacity of the heart. We suggest that cardiopulmonary exercise stress testing with non-invasive measurement of central haemodynamics including cardiac power output is feasible and an attractive alternative to currently used methods for the evaluation of patients receiving CRT. More and larger studies need to be conducted to help determine if exercise haemodynamics could be used to investigate and identify patients most likely to respond to CRT.
|
Acknowledgement |
|---|
We are grateful for the excellent technical support we have received in this study from the Cardiac Non-Invasive Unit of the Leeds General Infirmary, and to the patient participants who have volunteered their valuable time and energy.
|
References |
|---|
|
TopAbstract1. Introduction2. Methods3. Results4. DiscussionReferences |
|---|
- Cleland J.G., Daubert J.C., Erdmann E., et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med (2005) 352(15):1539–1549.
[Abstract/Free Full Text] - Abraham W.T., Fisher W.G., Smith A.L., et al. Cardiac resynchronization in chronic heart failure. N Engl J Med (2002) 346(24):1845–1853.
[Abstract/Free Full Text] - Bradley D.J., Bradley E.A., Baughman K.L., et al. Cardiac resynchronization and death from progressive heart failure: a meta-analysis of randomized controlled trials. JAMA (2003) 289(6):730–740.
[Abstract/Free Full Text] - Bristow M.R., Krause-Steinrauf H., Nuzzo R., et al. Cardiac-resynchronisation therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med (2004) 350(21):2140–2150.
[Abstract/Free Full Text] - Leclercq C., Cazeau S., Le Breton H., et al. Acute hemodynamic effects of biventricular DDD pacing in patients with end-stage heart failure. J Am Coll Cardiol (1998) 32(7):1825–1831.
[Abstract/Free Full Text] - Nelson G.S., Berger R.D., Fetics B.J., et al. Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundle-branch block. Circulation (2000) 102(25):3053–3059.
[Abstract/Free Full Text] - Cotter G., Williams S.G., Vered Z., Tan L.B. Role of cardiac power in heart failure. Curr Opin Cardiol (2003) 18(3):215–222.[CrossRef][Web of Science][Medline]
- Tan L.B., Littler W.A., Murray R.G. Beneficial haemodynamic effects of intravenous dopexamine in patients with low-output heart failure. J Cardiovasc Pharmacol (1987) 10(3):280–286.[Web of Science][Medline]
- Gregoratos G., Abrams J., Epstein A.E., et al. ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices—summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). J Am Coll Cardiol (2002) 40(9):1703–1719.
[Free Full Text] - Cooke G.A., Marshall P., Al Timman J.K., et al. Physiological cardiac reserve: development of a non-invasive method and first estimates in man. Heart (1998) 79(3):289–294.
[Abstract/Free Full Text] - Elborn J.S., Stanford C.F., Nicholls D.P. Reproducibility of cardiopulmonary parameters during exercise in patients with chronic cardiac failure. The need for a preliminary test. Eur Heart J (1990) 11(1):75–81.
[Abstract/Free Full Text] - Hobbs F.D., Kenkre J.E., Roalfe A.K., Davis R.C., Hare R., Davies M.K. Impact of heart failure and left ventricular systolic dysfunction on quality of life: a cross-sectional study comparing common chronic cardiac and medical disorders and a representative adult population. Eur Heart J (2002) 23(23):1867–1876.
[Abstract/Free Full Text] - Meaney E., Alva F., Moguel R., Meaney A., Alva J., Webel R. Formula and nomogram for the sphygmomanometric calculation of the mean arterial pressure. Heart (2000) 84:64.
[Free Full Text] - Tan L.B. Clinical and research implications of new concepts in the assessment of cardiac pumping performance in heart failure. Cardiovasc Res (1987) 21(8):615–622.
[Abstract/Free Full Text] - Tan L.B. Evaluation of cardiac dysfunction, cardiac reserve and inotropic response. Postgrad Med J (1991) 67(Suppl_1):S10–S20.[Web of Science][Medline]
- Cohen-Solal A., Tabet J.Y., Logeart D., et al. A non-invasively determined surrogate of cardiac power (circulatory power) at peak exercise is a powerful prognostic factor in chronic heart failure. Eur Heart J (2002) 23:806–814.
[Abstract/Free Full Text] - Chua T.P., Ponikowski P., Harrington D., et al. Clinical correlates and prognostic significance of the ventilatory response to exercise in chronic heart failure. J Am Coll Cardiol (1997) 29(7):1585–1590.[Abstract]
- Cowburn P.J., Patel H., Jolliffe R.E., Wald R.W., Parker J.D. Cardiac resynchronisation therapy: an option for inotrope-supported patients with end-stage heart failure? Eur J Heart Fail (2005) 7(2):215–217.
[Abstract/Free Full Text] - Yu C.M., Chau E., Sanderson J.E., 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(4):438–445.
[Abstract/Free Full Text] - Mansourati J., Etienne Y., Gilard M., et al. Left ventricular-based pacing in patients with chronic heart failure: comparison of acute hemodynamic benefits according to underlying heart disease. Eur J Heart Fail (2000) 2(2):195–199.
[Abstract/Free Full Text] - Duncan A., Wait D., Gibson D., Daubert J.C. Left ventricular remodelling and haemodynamic effects of multisite biventricular pacing in patients with left ventricular systolic dysfunction and activation disturbances in sinus rhythm: sub-study of the MUSTIC (Multisite Stimulation in Cardiomyopathies) trial. Eur Heart J (2003) 24(5):430–441.
[Abstract/Free Full Text] - Leclercq C., Kass D.A. Retiming the failing heart: principles and current clinical status of cardiac resynchronization. J Am Coll Cardiol (2002) 39(2):194–201.
[Abstract/Free Full Text] - Popovic Z.B., Grimm R.A., Perlic G., et al. Noninvasive assessment of cardiac resynchronization therapy for congestive heart failure using myocardial strain and left ventricular peak power as parameters of myocardial synchrony and function. J Cardiovasc Electrophysiol (2002) 13(12):1203–1208.[CrossRef][Web of Science][Medline]
- Lamp B., Vogt J., Schmidt H., Horstkotte D. Impact of cardiopulmonary exercise testing on patient selection for cardiac resynchronisation therapy. Eur Heart J (2004) (Suppl (D)):D5–D9.
- Molhoek S.G., Bax J.J., van Erven L., et al. Atrial and brain natriuretic peptides as markers of response to resynchronisation therapy. Heart (2004) 90(1):97–98.
[Free Full Text] - Grassi G., Vincenti A., Brambilla R., et al. Sustained sympathoinhibitory effects of cardiac resynchronization therapy in severe heart failure. Hypertension (2004) 44(5):727–731.
[Abstract/Free Full Text] - Williams S.G., Cooke G.A., Wright D.J., et al. Peak exercise cardiac power output; a direct indicator of cardiac function strongly predictive of prognosis in chronic heart failure. Eur Heart J (2001) 22(16):1496–1503.
[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. E. Thomas, Z. R. Yousef, and A. G. Fraser A critical comparison of echocardiographic measurements used for optimizing cardiac resynchronization therapy: stroke distance is best Eur J Heart Fail, August 1, 2009; 11(8): 779 - 788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Y. Patwala, P. R. Woods, L. Sharp, D. F. Goldspink, L. B. Tan, and D. J. Wright Maximizing Patient Benefit From Cardiac Resynchronization Therapy With the Addition of Structured Exercise Training: A Randomized Controlled Study J. Am. Coll. Cardiol., June 23, 2009; 53(25): 2332 - 2339. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||