Letter by Connelly et al Regarding Article, “Diastolic Stiffness of the Failing Diabetic Heart: Importance of Fibrosis, Advanced Glycation End Products, and Myocyte Resting Tension”
To the Editor:
We would like to congratulate van Heerebeek and colleagues on the recent article “Diastolic Stiffness of the Failing Diabetic heart.”1 The authors provide evidence that increased myocyte stiffness is the principal abnormality in diabetic subjects with heart failure and a normal ejection fraction and that fibrosis and advanced glycation end-products contribute to diabetic subjects with heart failure and a reduced ejection fraction. We are concerned that these data may be interpreted as indicating that fibrosis does not contribute to diabetic subjects with heart failure and a normal ejection fraction. Animal studies suggest that fibrosis contributes to this syndrome,2 and previous data from these same investigators indicate that, when compared with control subjects, collagen volume fraction is increased approximately 2-fold in both diabetic and nondiabetic subjects with heart failure and a normal ejection fraction.3 Together, these studies suggest that fibrosis and dysfunction are linked attributes of heart failure and a normal ejection fraction, regardless of its cause. Accordingly, the development of both antifibrotic and antihypertrophic strategies remain key pharmacological goals for patients with heart failure and a normal ejection fraction, regardless of the cause, along with optimal medical management of cardiovascular risk factors.
Sources of Funding
The work of the authors is supported by the Canadian Institutes of Health Research and the National Health and Medical Research Council of Australia. Dr Connelly is supported by a TACTICS Scholarship (Canada) and a National Health and Medical Research Council Neil Hamilton Fairley Scholarship (440712).
Drs Gilbert and Krum have filed patent applications for novel antifibrotic compounds. Dr Connelly reports no conflicts.
van Heerebeek L, Hamdani N, Handoko ML, Falcao-Pires I, Musters RJ, Kupreishvili K, Ijsselmuiden AJ, Schalkwijk CG, Bronzwaer JG, Diamant M, Borbely A, van der Velden J, Stienen GJ, Laarman GJ, Niessen HW, Paulus WJ. Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension. Circulation. 2008; 117: 43–51.
Connelly KA, Kelly DJ, Zhang Y, Prior DL, Martin J, Cox AJ, Thai K, Feneley MP, Tsoporis J, White KE, Krum H, Gilbert RE. Functional, structural and molecular aspects of diastolic heart failure in the diabetic (mRen-2)27 rat. Cardiovasc Res. 2007; 76: 280–291.
van Heerebeek L, Borbely A, Niessen HW, Bronzwaer JG, van der Velden J, Stienen GJ, Linke WA, Laarman GJ, Paulus WJ. Myocardial structure and function differ in systolic and diastolic heart failure. Circulation. 2006; 113: 1966–1973.