Response to Letter Regarding Article, “Left Ventricular Untwisting Rate by Speckle Tracking Echocardiography”
We appreciate the interest of Dwivedi et al in our study.1 They raise 3 points with respect to our results. The first deals with their belief that the untwisting rate (UR) should be abnormal in patients with diastolic heart failure (DHF), the second deals with cardiac function in these patients at rest and with exercise, and the third has to do with the underlying mechanisms.
Dwivedi et al base their impression that DHF patients should have a reduced UR on reduced Ea, on other studies showing abnormal UR, and on a report in patients with hypertrophic cardiomyopathy that Dwivedi and colleagues believe showed that peak UR is an independent predictor of τ. We and others have previously shown that the main hemodynamic determinants of Ea are τ, filling pressures, and LV minimal pressure.2,3 Therefore, it is not accurate to base the conclusion of reduced recoil on a reduced Ea alone, particularly when the direct measurement shows a normal/increased UR. The published literature has some studies showing normal UR in patients with normal EF1,4 and others showing abnormal findings (as cited in the letter). DHF patients are not necessarily a homogenous population where all abnormalities have to be present, and it is a simplification to expect that. However, we are in agreement that some patients can have delayed untwisting, as noted in 12 DHF patients in our study,1 where it was associated with a larger left atrial volume and a higher pulmonary artery systolic pressure. This association, however, was not statistically significant because of the small sample size. The letter cites a study4 that did not measure τ in patients. On the other hand, we clearly show in animal experiments that LV end-systolic volume is the strongest determinant of UR, to such an extent that UR was different in experimental stages with different end-systolic volumes, despite having the same τ. In addition, when comparing stages with similar end-systolic volume, peak URs were almost identical despite large and significant differences in τ.1 We noted similar observations in patients.
The assessment of cardiac function with exercise can add important information in most patient groups. This assessment was not carried out in our study because imaging was performed while patients were in acute heart failure. This limitation was clearly acknowledged in the limitations section, wherein we stated that exercise can show abnormalities in DHF patients and cited Notomi et al4 to support this statement, even though the letter by Dwivedi et al states that this information “was not mentioned.”
As to the underlying mechanisms, we hypothesized that changes in titin isoforms play a role because experimental data exist that directly support this mechanism.5 The letter however explains why apical twist would be increased, as seen in our study, rather than the reduced UR as proposed in earlier studies. It contains interesting hypotheses that require proof in DHF patients. In summary, we agree that more data are needed to understand LV function in DHF patients, but it is prudent to keep an open mind as our knowledge increases.
Dr. Khoury has received research support from St. Jude Medical. Dr. Nagueh has received consulting fees from St. Jude Medical and lecture fees from Medtronic. The other authors report no conflicts.
Wang J, Khoury DS, Yue Y, Torre-Amione G, Nagueh SF. Left ventricular untwisting rate by speckle tracking echocardiography. Circulation. 2007; 116: 2580–2586.
Notomi Y, Martin-Miklovic MG, Oryszak SJ, Shiota T, Deserranno D, Popovic ZB, Garcia MJ, Greenberg NL, Thomas JD. Enhanced ventricular untwisting during exercise: a mechanistic manifestation of elastic recoil described by Doppler tissue imaging. Circulation. 2006; 113: 2524–2533.
Bell SP, Nyland L, Tischler MD, McNabb M, Granzier H, LeWinter MM. Alterations in the determinants of diastolic suction during pacing tachycardia. Circ Res. 2000; 87: 235–240.