Systolic Myocardial Mechanics in Hypertrophic Cardiomyopathy: Novel Concepts and Implications for Clinical Status

Carasso, Shemy; Yang, Hua; Woo, Anna; Vannan, Mani A.; Jamorski, Michal; Wigle, E. Douglas; Rakowski, Harry

doi:10.1016/j.echo.2007.10.021

Cited by 192 publications

(183 citation statements)

References 44 publications

Supporting

Mentioning

154

Contrasting

Unclassified

Order By: Relevance

“…Ejection fraction (EF) was also significantly higher in HCM compared with WT mice, which is consistent with reports on HCM patients (19,20), and indicates cardiac hypertrophy in D166V mice. These HCM-induced abnormalities observed in Tg-D166V mice were reversed or significantly improved in Homo-and Hetero-rescue mice (Table 1).…”

Section: Resultssupporting

confidence: 80%

Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in mice

Yuan

Muthu

Kazmierczak

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

127

View full text Add to dashboard Cite

Myosin light chain kinase (MLCK)-dependent phosphorylation of the regulatory light chain (RLC) of cardiac myosin is known to play a beneficial role in heart disease, but the idea of a phosphorylation-mediated reversal of a hypertrophic cardiomyopathy (HCM) phenotype is novel. Our previous studies on transgenic (Tg) HCM-RLC mice revealed that the D166V (Aspartate166 →Valine) mutation-induced changes in heart morphology and function coincided with largely reduced RLC phosphorylation in situ. We hypothesized that the introduction of a constitutively phosphorylated Serine15 (S15D) into the hearts of D166V mice would prevent the development of a deleterious HCM phenotype. In support of this notion, MLCK-induced phosphorylation of D166V-mutated hearts was found to rescue some of their abnormal contractile properties. Tg-S15D-D166V mice were generated with the human cardiac RLC-S15D-D166V construct substituted for mouse cardiac RLC and were subjected to functional, structural, and morphological assessments. The results were compared with Tg-WT and Tg-D166V mice expressing the human ventricular RLC-WT or its D166V mutant, respectively. Echocardiography and invasive hemodynamic studies demonstrated significant improvements of intact heart function in S15D-D166V mice compared with D166V, with the systolic and diastolic indices reaching those monitored in WT mice. A largely reduced maximal tension and abnormally high myofilament Ca 2+ sensitivity observed in D166V-mutated hearts were reversed in S15D-D166V mice. Lowangle X-ray diffraction study revealed that altered myofilament structures present in HCM-D166V mice were mitigated in S15D-D166V rescue mice. Our collective results suggest that expression of pseudophosphorylated RLC in the hearts of HCM mice is sufficient to prevent the development of the pathological HCM phenotype.cardiomyopathy | hemodynamics | myocardial contraction | X-ray structure | myosin RLC

show abstract

Section: Resultssupporting

confidence: 80%

Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in mice

Yuan

Muthu

Kazmierczak

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

127

View full text Add to dashboard Cite

show abstract

“…So, we used TDI and 2-D STE to measure strain and strain rate as a parameter of systolic function. [19] had measured systolic myocardial function in 72 HCM patients using strain parameters (2-dimensional velocity vector imaging) and they found higher circumferential strain (−34±9 vs. −29±8, p<.05) and lower longitudinal strain (−16±4 vs. −21±4, p<.05) in patients with HCM as compared with control subjects. On the other hand, Paraskevaidis et al, [20] showed significant difference in longitudinal strain but insignificant difference in radial and circumferential strain.…”

Section: Strain Imagingmentioning

confidence: 99%

Evaluation of Subtle Left Ventricular Systolic Abnormalities in Adult Patients with Hypertrophic Cardiomyopathy

Shetty

Samanth

Nayak

et al. 2014

JCDR

View full text Add to dashboard Cite

“…Benek takibi (speckle tracking) ekokardiyografi tekniği ile miyokardın burkulma hareketleri kantitatif olarak incelenebilmektedir. Hipertrofik kardiyomiyopatili hastalarda SV orta bölgesinin dönüşü saat yönünde iken normal bireylerde ise ters yönde olmaktadır (30). 'Strain rate' görüntüleme tekniği ile hipertansiyona bağlı gelişen SV hipertrofisi ile HKM'ye bağlı SV hipertrofisi ayırt edilebilmektedir (31).…”

Section: Strain (Gerilme) Görüntülemeunclassified

Hipertrofik kardiyomiyopatili hastaların risk sınıflandırmasında görüntüleme yöntemlerinin yeri

Tülüce¹,

Emren²,

Tülüce³

et al. 2015

Ege Tıp Dergisi

View full text Add to dashboard Cite

Hipertrofik kardiyomiyopati (HKM) genetik geçişli bir kalp hastalığıdır. Genç sporcularda ani kardiyak ölümün (AKÖ) en sık nedenidir. Bu ölümlerin önlenebilmesi için hekimler büyük özen göstermektedir. Ani kardiyak ölüm açısından yüksek riskli hastalar implante edilebilen kardiyoverter defibrilatör tedavisi için adaydırlar. Ani kardiyak ölüm açısından yüksek riskli bu bireylerin saptanabilmesi için yapılan risk sınıflandırmasında kardiyak görüntüleme yöntemleri önemli bilgiler sağlamaktadır. Görüntüleme yöntemleri ile elde edilen bilgilerin doğru yorumlanması ve önlemlerin alınması bu hastalar için hayat kurtarıcı olması nedeniyle büyük önem taşımaktadır. Teknolojideki gelişmeler yüksek riskli hastaların erken tespitine önemli katkılar sağlamaktadır. Bu derlemede biz HKM'li hastaların risk sınıflandırmasında görüntüleme yöntemlerinin yeri ve önemini değerlendirdik.Anahtar Sözcükler: Hipertrofik kardiyomiyopati, ani kardiyak ölüm, kalp görüntüleme yöntemleri. Abstract Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder. It is the most common reason of sudden cardiac death (SCD) in young athletes. Prevention of these deaths is

show abstract

Systolic Myocardial Mechanics in Hypertrophic Cardiomyopathy: Novel Concepts and Implications for Clinical Status

Cited by 192 publications

References 44 publications

Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in mice

Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in mice

Evaluation of Subtle Left Ventricular Systolic Abnormalities in Adult Patients with Hypertrophic Cardiomyopathy

Hipertrofik kardiyomiyopatili hastaların risk sınıflandırmasında görüntüleme yöntemlerinin yeri

Contact Info

Product

Resources

About