Response to Letter Regarding Article, “Role of Left Ventricular Stiffness in Heart Failure With Normal Ejection Fraction”
We would like to thank Dr Kass for his interest in our study, which investigated hemodynamic characteristics of patients with heart failure and normal ejection fraction (HFNEF).1
An important finding in our study was that with increased paced heart rates the patients in the HFNEF group showed a decrease in end-diastolic volume leading to reduced stroke volume, which limited their ability to increase cardiac output and may explain their exertional limitations. These results were in contrast to those in the control group where end-diastolic volumes and stroke volumes were maintained or even increased at faster heart rates.
The comments of Dr Kass focus on the results in our control group, and he refers to previous studies that show (in contrast to ours) a decline in filling at higher heart rates in normal subjects. We feel that the difference in heart rate response between HFNEF and controls in our study is unlikely to be related to calibration problems because our methodology was carefully established and applied identically in both groups.
As a possible explanation, it is known that the observed effect is dependent on pacing rate2 and on volume load3 and therefore may vary in different studies. In our control subjects, who were studied in a supine position, pacing up to 120 bpm (as reported in our article) did not cause a decrease in end-diastolic volume.
Although not reported in the article because it was only tested in a subset of the patients (9 controls, 19 patients with HFNEF), during atrial pacing at 140 bpm a decrease in end-diastolic volume was indeed found in the control group (−18% versus sinus rhythm, P<0.05). However, in the HFNEF group, end-diastolic volume dropped significantly more (−44% versus sinus rhythm, P<0.05) leading to significantly lower end-diastolic volume versus the control group also at 140 bpm (P<0.05). This reflects a cardiac abnormality leading to a more pronounced decrease in stroke volume in HFNEF patients compared with controls, which is in line with previous research from other groups.4
We fully agree with Dr Kass and the editorial comments of Dr Kitzman,5 that the pathophysiology of HFNEF needs further study, and therefore we are looking forward to the results from studies like the Restoration of Chronotropic Competence in Heart Failure Patients With Normal Ejection Fraction (RESET) trial which investigates whether or not atrial pacing could be an appropriate option for HFNEF patients and whether also patients which are characterized by increased left ventricular stiffness will have a benefit from increasing heart rate.
Source of Funding
This study was supported by the Deutsche Forschungsgesellschaft (SFB-TR-19, A2, B5, and Z2).
Westermann D, Kasner M, Steendijk P, Spillmann F, Riad A, Weitmann K, Hoffmann W, Poller W, Pauschinger M, Schultheiss HP, Tschope C. Role of left ventricular stiffness in heart failure with normal ejection fraction. Circulation. 2008; 117: 2051–2060.
Hasenfuss G, Holubarsch C, Hermann HP, Astheimer K, Pieske B, Just H. Influence of the force-frequency relationship on haemodynamics and left ventricular function in patients with non-failing hearts and in patients with dilated cardiomyopathy. Eur Heart J. 1994; 15: 164–170.
Sohn DW, Kim HK, Park JS, Chang HJ, Kim YJ, Zo ZH, Oh BH, Park YB, Choi YS. Hemodynamic effects of tachycardia in patients with relaxation abnormality: abnormal stroke volume response as an overlooked mechanism of dyspnea associated with tachycardia in diastolic heart failure. J Am Soc Echocardiogr. 2007; 20: 171–176.
Kitzman DW. Diastolic dysfunction: one piece of the heart failure with normal ejection fraction puzzle. Circulation. 2008; 117: 2044–2046.