Skip to main content

Advertisement

SpringerLink
Log in

Safety and Efficacy of Carvedilol Therapy for Patients with Dilated Cardiomyopathy Secondary to Muscular Dystrophy

  • Original
  • Published:
Pediatric Cardiology Aims and scope Submit manuscript

Abstract

Background

By the age of 20 years, almost all patients with Duchenne’s or Becker’s muscular dystrophy have experienced dilated cardiomyopathy (DCM), a condition that contributes significantly to their morbidity and mortality. Although studies have shown carvedilol to be an effective therapy for patients with other forms of DCM, few data exist concerning its safety and efficacy for patients with muscular dystrophy. This study aimed to evaluate the safety and efficacy of carvedilol for patients with DCM.

Methods

A clinical trial at an outpatient clinic investigated 22 muscular dystrophy patients, ages 14 to 46 years, with DCM and left ventricular ejection fraction (LVEF) less than 50%. Carvedilol up-titrated over 8 weeks then was administered at the maximum or highest tolerated dose for 6 months. Baseline and posttreatment cardiac magnetic resonance imaging (CMR), echocardiography, and Holter monitoring were recorded.

Results

Carvedilol therapy was associated with a modest but statistically significant improvement in CMR-derived ejection fraction (41% ± 8.3% to 43% ± 8%; p < 0.02). Carvedilol also was associated with significant improvements in both the mean rate of pressure rise (dP/dt) during isovolumetric contraction (804 ± 216 to 951 ± 282 mmHg/s; p < 0.05) and the myocardial performance index (0.55 ± 0.18 to 0.42 ± 0.15; p < 0.01). A trend toward improved shortening fraction, E/E’ ratio, and isovolumetric relaxation time also was observed. Two patients had runs of nonsustained ventricular tachycardia exceeding 140 beats per minute (bpm) before carvedilol administration. Ventricular tachycardia exceeding 140 bpm was not observed after carvedilol therapy. Carvedilol was well tolerated, and no serious adverse events were identified.

Conclusions

Carvedilol therapy appears to be safe for patients with DCM secondary to muscular dystrophy and produces a modest improvement in systolic and diastolic function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Article Open access 10 May 2019

Sven Dittrich, Erika Graf, … on behalf of the German Competence Network for Congenital Heart Defects and the Treat-NMD Neuromuscular Network Investigators list of additional local Investigators and co-workers of the German Competence Network for Congenital Heart Defects and the Treat-NMD Neuromuscular Network

References

  1. Alfakih K, Plein S, Thiele H, Jones T, Ridgway JP, Sivananthan MU (2003) Normal human left and right ventricular dimensions for MRI as assessed by turbo gradient echo and steady-state free precession imaging sequences. J Magn Reson Imaging 17:323–329

    Article  PubMed  Google Scholar 

  2. Bruns LA, Chrisant MK, Lamour JM, Shaddy RE, Pahl E, Blume ED, Hallowell S, Addonizio L, Canter CE (2001) Carvedilol as therapy in pediatric heart failure: an intial multicenter experience. J Pediatr 138:511

    Google Scholar 

  3. Cox GF, Kunkel LM (1997) Dystrophies and heart disease. Curr Opin Cardiol 12:329–343

    Article  PubMed  CAS  Google Scholar 

  4. Duboc D, Meune C, Lerebours G, Deveaux JY, Vaksmann G, Becane HM (2005) Effect of peridopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy. J Am Coll Cardiol 45:855–857

    Article  PubMed  CAS  Google Scholar 

  5. Francis GS, Benedict C, Johnstone DE, Kirlin PC, Nicklas J, Lang C, Kubo SH, Rudin-Toretsky E, Salim Y (1990) Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. Circulation 82:1724–1729

    PubMed  CAS  Google Scholar 

  6. Frishman WH (1998) Carvedilol N Engl J Med 339:1759–1765

    Google Scholar 

  7. Grothues F, Smith GC, Moon JCC, Bellenger NG, Collins P, Klein HU, Pennell DJ (2002) Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. Am J Cardiol 90:29–34

    Article  PubMed  Google Scholar 

  8. Hiramatsu S, Maekawa K, Hioka T: Female carrier of Duchenne muscular dystrophy presenting with secondary dilated cardiomyopathy: a case report. J Cardiol 200 38(Suppl):35–40

  9. Ishikawa K (1997) Cardiac involvement in progressive muscular dystrophy of the Duchenne type. Jpn Heart J 38:163–179

    PubMed  CAS  Google Scholar 

  10. Ishikawa Y, Bach JR, Minami R (1999) Cardioprotection for Duchenne’s muscular dystrophy. Am Heart J 137:895–902

    Article  PubMed  CAS  Google Scholar 

  11. Jefferies JL, Eidem BW, Belmont JW, Craigen WJ, Ware SM, Fernbach SD, Neish SR, O’Brian Smith E, Towbin JA (2005) Genetic predictors and remodeling of dilated cardiomyopathy in muscular dystrophy. Circulation 112:2799–2804

    Article  PubMed  Google Scholar 

  12. Kajimoto K, Ishigake K, Okumura K, Tomimatsu H, Nakazawa M, Saito K, Osawa M, Nakanishi T (2006) Beta-blocker therapy for cardiac dysfunction in patients with muscular dystrophy. Circ J 70:991–994

    Article  PubMed  CAS  Google Scholar 

  13. Kantor HL, Krishnan SC (1995) Cardiologic problems in patients with neurologic disease. Cardiol Clin 13:179–208

    PubMed  CAS  Google Scholar 

  14. Kennedy JD, Staples A.J., Brooks PD, Parsons DW, Sutherland AD, Martin AJ, Stern LM, Foster BK (1995) Effect of spinal surgery on lung function in Duchenne muscular dystrophy. Thorax 50:1173–1178

    Article  PubMed  CAS  Google Scholar 

  15. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pelikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, St John Sutton M, Stewart WJ (2005) Recommendations for chamber quantification: a report from the American Society of Echocardiography’s guidelines and standards committee and the chamber quantification writing group. J Am Soc Echocardiogr 18:1440–1463

    Article  PubMed  Google Scholar 

  16. Lorenz CH, Walker ES, Morgan VL, Klein SS, Graham TP Jr (1999) Normal human right and left ventricular mass, systolic function, and gender differences by cine magnetic resonance imaging. J Cardiovasc Magn Reson 1:7–21

    Article  PubMed  CAS  Google Scholar 

  17. Ommen SR, Nishimura SA, Applerton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ (2000) Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 102:1788–1794

    PubMed  CAS  Google Scholar 

  18. Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P (2001) Effect of carvedilol on survival in severe heart failure. N Engl J Med 344:1651–1658

    Article  PubMed  CAS  Google Scholar 

  19. Parthenakis FI, Kanakaraki MK, Kanoupakis EM, Skalidis EI, Diakakis GF, Filippou OK, Vardas PE (2002) Value of Doppler index combining systolic and diastolic myocardial performance in predicting cardiopulmonary exercise capacity in patients with congestive heart failure: effects of dobutamine. Chest 121:1935–1941

    Article  PubMed  Google Scholar 

  20. Rhodes J, Udelson JE, Marx GR, Schmidt CH, Konstam MA, Hijazi ZM, Bova SA, Fulton DR (1993) A new noninvasive method for the estimation of peak dP/dt. Circulation 88:2693–2699

    PubMed  CAS  Google Scholar 

  21. Saito T, Matsumura T, Miyai I, Nozaki S, Shinno S (2001) Carvedilol effectiveness for left ventricular-insufficient patients with Duchenne muscular dystrophy. Rinsho Shinkeigaku 41:691–694

    PubMed  CAS  Google Scholar 

  22. Schleman KA, Lindenfeld JA, Lowes BD, Bristow MR, Ferguson D, Wolfel EE, Abraham WT, Zisman LS (2001) Predicting response to carvedilol for the treatment of heart failure: a multivariate retrospective analysis. J Card Fail 7:4–12

    Article  PubMed  CAS  Google Scholar 

  23. Shaddy RE, Curtin EL, Sower B, Tani LY, Burr J, LaSalle B, Boucek MM, Mahoney L, Hsu DT, Pahl E, Burch GH, Schlenker-Herceg R (2002) The pediatric randomized carvedilol trial in children with chronic heart failure: rationale and design. Am Heart J, 144:383–389

    Article  PubMed  CAS  Google Scholar 

  24. Shaddy RE, Tani LY, Gidding SS, Pahl E, Orsmond GS, Gilbert EM, Lemes V (1999) Beta-blocker treatment of dilated cardiomyopathy with congestive heart failure in children: a multi-institutional experience. J Heart Lung Transplant 18:269–274

    Article  PubMed  CAS  Google Scholar 

  25. Steare SE, Dubowitz V, Benatar A (1992) Subclincial cardiomyopathy in Becker muscular dystrophy. Br Heart J 68:304–308

    Article  PubMed  CAS  Google Scholar 

  26. Tei C (1995) New noninvasive index for combined systolic and diastolic ventricular function. J Cardiol 26:135–136

    PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors gratefully acknowledge the skillful clinical assistance of Elizabeth Brown, RN; Julianne Evangelista, PNP; Shay Dillis, PNP; and Terry Saia, PNP. They also are indebted to the patients who volunteered to participate in the study. This study was supported by an investigator-initiated grant from Glaxo-SmithKline. No other conflicts of interest exist.

Author information

Authors and Affiliations

  1. Department of Cardiology, Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA, 02115, USA

    J. Rhodes, R. Margossian, S. D. Colan, K. J. Jenkins, T. Geva & A. J. Powell

  2. Department of Neurology, Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA, 02115, USA

    B. T. Darras

Authors
  1. J. Rhodes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Margossian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. T. Darras
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. D. Colan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. J. Jenkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T. Geva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. J. Powell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Rhodes.

Appendix

Appendix

Carvedilol in Muscular Dystrophy Questionnaire

Name: Date:

  1. 1.

    Do you ever become short of breath or have trouble breathing?

    1. a.

      No, never

    2. b.

      Yes, but not every day

    3. c.

      Yes, about once every day

    4. d.

      Yes, many times a day

  2. 2.

    Do you have trouble breathing when you lie flat?

    1. a.

      No, not at all

    2. b.

      Yes, and I therefore usually lie on a pillow

    3. c.

      Yes, and I therefore usually lie on more than one pillow

    4. d.

      Yes, and I therefore avoid lying down.

  3. 3.

    Have you ever had pneumonia?

    1. a.

      No, never

    2. b.

      Yes, but not in the past 6 months

    3. c.

      Yes, and once within the past 6 months

    4. d.

      Yes, and more than once in the past 6 months

  4. 4.

    Do you ever have chest pain?

    1. a.

      No, never

    2. b.

      Yes, but less than once a month

    3. c.

      Yes, about 1 to 3 times a month

    4. d.

      Yes, at least once a week but not every day

    5. e.

      Yes, at least once a day

  5. 5.

    Do you ever feel that your heart is beating abnormally or irregularly?

    1. a.

      No, never

    2. b.

      Yes, but less than once a month

    3. c.

      Yes, about 1 to 3 times a month

    4. d.

      Yes, at least once a week but not every day

    5. e.

      Yes, at least once a day

  6. 6.

    Do you ever use supplemental oxygen?

    1. a.

      No, never

    2. b.

      Yes, but less than once a month

    3. c.

      Yes, about 1 to 3 times a month

    4. d.

      Yes, at least once a week but not every day

    5. e.

      Yes, every day, but not all day

    6. f.

      Yes, all the time

  7. 7.

    Do you use mechanical support for your breathing?

    1. a.

      No, and I do not have headaches in the morning

    2. b.

      No, but I do have headaches in the morning

    3. c.

      Yes, I use facial continuous positive airway pressure (CPAP) or biphasic positive airway pressure (BIPAP)

    4. d.

      Yes, I use mechanical ventilation at night

    5. e.

      Yes, I use mechanical ventilation almost all the time.

  8. 8.

    Compared with 6 months ago, would you say your overall health status is

    1. a.

      About the same

    2. b.

      A little better

    3. c.

      A lot better

    4. d.

      A little worse

    5. e.

      A lot worse

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rhodes, J., Margossian, R., Darras, B.T. et al. Safety and Efficacy of Carvedilol Therapy for Patients with Dilated Cardiomyopathy Secondary to Muscular Dystrophy. Pediatr Cardiol 29, 343–351 (2008). https://doi.org/10.1007/s00246-007-9113-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-007-9113-z

Keywords

Search

Navigation