CLINICAL RESEARCH: HEART FAILURE
Predicting the Long-Term Effects of Cardiac Resynchronization Therapy on Mortality From Baseline Variables and the Early ResponseA Report From the CARE-HF (Cardiac Resynchronization in Heart Failure) Trial
John Cleland, MD, FRCP, FACC*,*,
Nick Freemantle, PhD ,
Stefano Ghio, MD ,
Friedrich Fruhwald, MD ,
Aparna Shankar, PhD,
Monique Marijanowski, PhD||,
Yves Verboven|| and
Luigi Tavazzi, MD, FESC
* Department of Cardiology, University of Hull, Hull, United Kingdom
Department of Primary Care and General Practice, University of Birmingham, Birmingham, United Kingdom
Department of Cardiology, Policlinico S Matteo, Pavia, Italy
Department of Internal Medicine, Medical University of Graz, Graz, Austria
|| Medtronic Bakken Research Center B.V., Maastricht, the Netherlands.
Manuscript received December 28, 2007;
revised manuscript received March 6, 2008,
accepted April 3, 2008.
* Reprint requests and correspondence: Dr. John G. F. Cleland, Department of Cardiology, University of Hull, Castle Hill Hospital, Castle Road, Cottingham, Kingston upon Hull, HU16 5JQ United Kingdom. (Email: j.g.cleland{at}hull.ac.uk).
Objectives: This study was designed to investigate whether selected baseline variables and early response markers predict the effects of cardiac resynchronization therapy (CRT) on long-term mortality.
Background: Cardiac resynchronization therapy reduces long-term morbidity and mortality in patients with moderate or severe heart failure and markers of cardiac dyssynchrony, but not all patients respond to a similar extent.
Methods: In the CARE-HF (Cardiac Resynchronization in Heart Failure) study, 813 patients with heart failure and markers of cardiac dyssynchrony were randomly assigned to receive or not receive CRT in addition to pharmacological treatment and were followed for a median of 37.6 months. A model including assigned treatment, 15 pre-specified baseline variables, and 8 markers of response at 3 months was constructed to predict all-cause mortality.
Results: On multivariable analysis, plasma concentration of amino terminal pro–brain natriuretic peptide (univariate and multivariable model chi-square test: 105.0 and 48.4; both p < 0.0001) and severity of mitral regurgitation (chi-square test: 44.0 and 17.9; both p < 0.0001) at 3 months, regardless of assigned treatment, were the strongest predictors of mortality. Ischemic heart disease as the cause of ventricular dysfunction (chi-square test: 34.9 and 7.4; p < 0.0001 and p = 0.0066), being in New York Heart Association functional class IV (chi-square test: 18.8 and 9.6; p < 0.0001 and p = 0.0020), or having less interventricular mechanical delay (chi-square test: 29.8 and 8.8; p < 0.0001 and p = 0.0029) at baseline all predicted a worse outcome. However, the reduction in mortality in patients assigned to CRT was similar before (hazard ratio: 0.602; 95% confidence interval: 0.468 to 0.774) and after (hazard ratio: 0.679; 95% confidence interval: 0.494 to 0.914) adjustment for variables measured at baseline and at 3 months.
Conclusions: Patients who have more severe mitral regurgitation or persistently elevated amino terminal pro–brain natriuretic peptide despite treatment for heart failure, including CRT, have a higher mortality. However, patients assigned to CRT had a lower mortality even after adjusting for variables measured before and 3 months after intervention. The effect of CRT on mortality cannot be usefully predicted using such information. (CARE-HF CArdiac Resynchronization in Heart Failure; NCT00170300
[ClinicalTrials.gov]
)
Key Words: heart failure • cardiac resynchronization therapy • randomized controlled trial
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Abbreviations and Acronyms
| | CRT = cardiac resynchronization therapy | | ESVI = end-systolic volume index | | IVMD = interventricular mechanical delay | | LV = left ventricle/ventricular | | LVEF = left ventricular ejection fraction | | MR = mitral regurgitation | | NT-proBNP = amino terminal pro-brain natriuretic peptide |
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|
|
|
|
|
|
|
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|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
|
D. E. Thomas, S. A. Exton, and Z. R. Yousef
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|
|
|
|
|
|
|
G. Frohlich, J. Steffel, D. Hurlimann, F. Enseleit, T. F. Luscher, F. Ruschitzka, W. T. Abraham, and J. Holzmeister
Upgrading to resynchronization therapy after chronic right ventricular pacing improves left ventricular remodelling
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|
|
|
|
|
|
|
P. S. Chan, T. Khumri, E. S. Chung, S. Ghio, K. J. Reid, B. Gerritse, B. K. Nallamothu, and J. A. Spertus
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
S. Masson, R. Latini, E. Carbonieri, L. Moretti, M. G. Rossi, S. Ciricugno, V. Milani, R. Marchioli, J. Struck, A. Bergmann, et al.
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|
|
|
|
|
|
|
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12(4):
382 - 388.
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|
|
|
|
|
|
|
F. Cabrera-Bueno, M. J. Molina-Mora, J. Alzueta, J. Pena-Hernandez, M. Jimenez-Navarro, J. Fernandez-Pastor, A. Barrera, and E. de Teresa
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Eur Heart J Cardiovasc Imaging,
March 1, 2010;
11(2):
131 - 137.
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[Full Text]
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|
|
|
|
|
|
|
M. Bertini, V. Delgado, D. W. den Uijl, G. Nucifora, A. C.T. Ng, R. J. van Bommel, C. J. W. Borleffs, G. Boriani, M. J. Schalij, and J. J. Bax
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Circ Cardiovasc Imaging,
January 1, 2010;
3(1):
86 - 93.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Albouaini, A. Alkarmi, and D. J. Wright
Cardiac resynchronisation therapy: what a hospital practitioner needs to know?
Postgrad. Med. J.,
January 1, 2010;
86(1011):
12 - 17.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G.F. Cleland, J. J.V. McMurray, J. Kjekshus, J. H. Cornel, P. Dunselman, C. Fonseca, A. Hjalmarson, J. Korewicki, M. Lindberg, N. Ranjith, et al.
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J. Am. Coll. Cardiol.,
November 10, 2009;
54(20):
1850 - 1859.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. W.X. Foley, F. Leyva, and M. P. Frenneaux
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Europace,
November 1, 2009;
11(suppl_5):
v58 - v65.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. van Bommel, J. J. Bax, W. T. Abraham, E. S. Chung, L. A. Pires, L. Tavazzi, P. J. Zimetbaum, B. Gerritse, N. Kristiansen, and S. Ghio
Characteristics of heart failure patients associated with good and poor response to cardiac resynchronization therapy: a PROSPECT (Predictors of Response to CRT) sub-analysis
Eur. Heart J.,
October 2, 2009;
30(20):
2470 - 2477.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. W.L. De Boeck, A. J. Teske, M. Meine, G. E. Leenders, M. J. Cramer, F. W. Prinzen, and P. A. Doevendans
Septal rebound stretch reflects the functional substrate to cardiac resynchronization therapy and predicts volumetric and neurohormonal response
Eur J Heart Fail,
September 1, 2009;
11(9):
863 - 871.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. M. Marcus, E. Keung, and M. M. Scheinman
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J. Am. Coll. Cardiol.,
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54(9):
777 - 787.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Agricola, A. Ielasi, M. Oppizzi, P. Faggiano, L. Ferri, A. Calabrese, E. Vizzardi, O. Alfieri, and A. Margonato
Long-term prognosis of medically treated patients with functional mitral regurgitation and left ventricular dysfunction
Eur J Heart Fail,
June 1, 2009;
11(6):
581 - 587.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M Cubbon and K. K A Witte
Cardiac resynchronisation therapy for chronic heart failure and conduction delay
BMJ,
April 28, 2009;
338(apr28_2):
b1265 - b1265.
[Full Text]
|
|
|
|
|
|
|
J. K. Oh and C. Miyazaki
Rock 'n Roll Ventricle of the Dyssynchronous Heart: Clinical Significance of Rocking Motion in Selection of Patient for Cardiac Resynchronization Therapy
J. Am. Coll. Cardiol. Img.,
April 1, 2009;
2(4):
387 - 389.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kubanek, K. M. Goode, V. Lanska, A. L. Clark, and J. G.F. Cleland
The prognostic value of repeated measurement of N-terminal pro-B-type natriuretic peptide in patients with chronic heart failure due to left ventricular systolic dysfunction
Eur J Heart Fail,
April 1, 2009;
11(4):
367 - 377.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G.F. Cleland and D. Cullington
Digoxin: Quo Vadis?
Circ Heart Fail,
March 1, 2009;
2(2):
81 - 85.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Mullens, T. Verga, R. A. Grimm, R. C. Starling, B. L. Wilkoff, and W.H. W. Tang
Persistent Hemodynamic Benefits of Cardiac Resynchronization Therapy With Disease Progression in Advanced Heart Failure
J. Am. Coll. Cardiol.,
February 17, 2009;
53(7):
600 - 607.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G.F. Cleland, L. Tavazzi, J.-C. Daubert, A. Tageldien, and N. Freemantle
Cardiac Resynchronization Therapy: Are Modern Myths Preventing Appropriate Use?
J. Am. Coll. Cardiol.,
February 17, 2009;
53(7):
608 - 611.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. N. DeMaria, O. Ben-Yehuda, J. J. Bax, G. K. Feld, B. H. Greenberg, W. Y.W. Lew, J. A.C. Lima, A. S. Maisel, S. M. Narayan, D. J. Sahn, et al.
Highlights of the Year in JACC 2008
J. Am. Coll. Cardiol.,
January 27, 2009;
53(4):
373 - 398.
[Full Text]
[PDF]
|
|
|
|
