A new functional measure of contractility in human cardiomyopathies

Amy Li, Dane King, Eleanor Kable, Tatsuya Kagemoto, Jolanda van der Velden, Dennis Dooijes, Peter S. Macdonald, Filip Braet, Shin'ichi Ishiwata, Cristobal G. dos Remedios

Research output: Contribution to journalMeeting abstractpeer-review

Abstract

Hypertrophic and familial dilated cardiomyopathies are arguably the most common forms of inherited myocardial dysfunction. Both disease states result in
deterioration of cardiac function and quality of life as a consequence of extensive remodelling of the chamber walls.

Here we use a novel technique SPontaneous Oscillatory Contractions - or SPOCs to assess changes in contraction and relaxation phases using a range of explanted human heart samples. We examine left ventricle (LV) samples from: (1) patients with hypertrophic cardiomyopathy (HCM); (2) patients with familial dilated cardiomyopathy (FDCM); and (3) and aged-matched non-failing donors. The SPOC parameters of interest are: (i) SPOC amplitudes; (ii) the rates of engthening (relaxation); (iii) the rates of shortening (contraction); and (iv) their respective SPOC periods.

On average, samples from HCM patients exhibited significantly slower rates of lengthening and shorter SPOC periods, while FDCM patients displayed significantly longer lengthening and shortening SPOC periods, compared to donors. Impaired shortening is indicative of diastolic dysfunction while impaired shortening indicates a systolic dysfunction. We observed extensive changes in
SPOC parameters that were mutation-specific. The MYBPC3 mutation exhibited
shorter SPOC period and faster shortening rates while the samples with the TNNI3 mutation had a higher amplitude and slower shortening rates. Their SPOC data are consistent with the relatively mild phenotype associated with their respective mutations. Furthermore, SPOC is also sensitive to the progressive deterioration in LV ejection fraction.

SPOC analysis is a promising tool that provides a quantitative insights into cardiac contractility. It may allow us to unravel other significant differences between familial cardiomyopathies and donor hearts. The SPOC data agree
well with patient clinical phenotypes.
Original languageEnglish
Article number189-Plat
Pages (from-to)37A-37A
Number of pages1
JournalBiophysical Journal
Volume104
Issue number2
DOIs
Publication statusPublished - 29 Jan 2013
Externally publishedYes
Event57th Annual Meeting of the Biophysical-Society - Philadelphia, United States
Duration: 2 Feb 20136 Feb 2013

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