Rapid progression of cardiac remodeling and apical wall thinning in early age with hypertrophic cardiomyopathy

Author(s):  
Jae Hee Seol ◽  
Ah Young Kim ◽  
Yu Rim Shin ◽  
Jo Won Jung
2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
J W Jung

Abstract Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased left ventricular (LV) wall thickness that is not explained by abnormal loading conditions without a priori assumptions about etiology or myocardial pathology even in neonate, children and adults. The diagnosis of HCM is mainly the detection of increased LV wall thickness by any imaging modality. Due to its diverse etiology, the disease phenotype includes chest pain, palpitation, syncope and heart failure. In most patients, there is a life-long process of progressive and adverse cardiac remodeling, characterized by myocardial fibrosis and wall thinning. However, there was no report about cardiac remodeling of progressive wall thinning in children with HCMP. A 5 year-old boy was evaluated due to familiar HCMP, and finally confirmed with HCMP by echocardiography. His father was diagnosed as asymmetric HCMP and treated with septal alcohol ablation 3 years ago. His family referred for genetic counselling. His symptom was vague because he was very young. Initial electrocardiographic finding was normal sinus rhythm with left ventricular hypertrophy. Ambulatory electrocardiography (ECG) showed isolated premature ventricular contraction. Initial echocardiographic findings revealed asymmetric septal hypertrophy with diffuse hypertrophied LV myocardium, systolic anterior motion of anterior leaflet of mitral valve without LV outflow tract obstruction (LVOTO) and only mild dynamic obstruction on mid-septum of LV. His cardiovascular magnetic resonance imaging (CMR) showed similar to echocardiographic findings and no late gadolinium enhancement (LGE). He started to take medication with beta blocker, and later addon verapamil. After 3 years later, his ambulatory ECG showed non-sustained ventricular tachycardia of 4 episodes. Follow-up echocardiographic findings revealed progressive septal wall thickness from 13mm to 19 mm, marked LVOTO with peak pressure gradient of 128 mmHg and profound dynamic obstruction on mid-septum of LV. Follow-up CMR imaging showed additional progressive apical wall thinning without suspicious or definite LGE on any other myocardium. Urgently he undertook the implantation of implantable cardioverter defibrillatorsfor prevention of sudden cardiac death. Now he is listing and waiting for heart transplantation. Cardiac remodeling is progressively life-long process in most HCMP, but in this case with pediatric HCMP, even though he took medical treatment its progression was rapid cardiac remodeling.


2010 ◽  
Vol 16 (12) ◽  
pp. 950-956 ◽  
Author(s):  
Victoria Moreno ◽  
Diana Hernández-Romero ◽  
Juan Antonio Vilchez ◽  
Antonio García-Honrubia ◽  
Francisco Cambronero ◽  
...  

Author(s):  
Suwen Kumar ◽  
Benjamin Ebner ◽  
Jeniffer Bragg-Gresham ◽  
Peter Farrehi ◽  
Sharlene Day

Background: Prevalence of obstructive sleep apnea (OSA) in hypertrophic cardiomyopathy (HCM) is estimated between 32% and 71%. Individuals with HCM and OSA have increased blood pressure, BMI, , ascending aorta size, left atrial size, left ventricular end diastolic diameter, E/e’ ratio, atrial fibrillation rates and NYHA functional class. It has been suggested that treatment of OSA can decrease the need for septal reduction. However, studies have found no effect of OSA on septal thickness or outflow gradient. It is not known how OSA affects exercise performance or cardiac remodeling assessed by MR. Genetic propensity toward OSA in HCM has not been reported. We propose that OSA predicts decrease exercise tolerance and that cardiac remodeling could be identified using MR. We sought to report on HCM genotype in OSA as well as compare our clinical and echo data with other investigators. Methods: Subjects were identified through our institution’s HCM database. They were surveyed using the STOP-BANG (SB) questionnaire, a validated questionnaire to identify individuals at high risk for OSA. We stratified patients into high risk (HR) and low risk (LR) groups, based on a cut point of greater than or equal to 3 on SB. Demographics and clinical characteristics were extracted from our database. Prevalence and means were compared between the two groups, using Chi-square and t-tests. Differences between the groups were adjusted for age, sex, and BMI using linear mixed models for continuous measures and logistic regression for dichotomous measures. Results: There were 206 respondents, of those 160 (78%) scored high risk for OSA, 60 of which had a history of polysomnogram (PSG) confirming OSA. Having a HR vs. LR SB was associated with a significantly greater likelihood of stroke, CHF hospitalization, NYHA functional class >2, reduced peak VO2, reduced anaerobic threshold and increased LA diameter. Adjusted comparisons for age, gender, and BMI showed that had significantly higher PAWP and LV mass index. Of those with a prior diagnosis of OSA we compared therapy compliant and non-compliant individuals and found they differed on LV mass index (HR=98.7 g/m2 vs. LR=62.0 g/m2, p=0.01). Conclusions: OSA occurs frequently in HCM and is associated with decreased exercise tolerance, worse hemodynamics, poor outcome as well as increased LV mass, which may be attenuated by therapy. OSA is an important and modifiable risk factor in HCM. Prospective evaluation utilizing PSG based diagnosis and positive pressure therapy is warranted.


2004 ◽  
Vol 287 (3) ◽  
pp. H1303-H1311 ◽  
Author(s):  
David Engel ◽  
Ronald Peshock ◽  
Robert C. Armstong ◽  
Natarajan Sivasubramanian ◽  
Douglas L. Mann

Although cardiac myocyte apoptosis has been detected in explanted hearts from patients with end-stage dilated and ischemic cardiomyopathy, the relative contribution of apoptotic cell death to left ventricular (LV) remodeling and cardiac decompensation is not known. To determine whether progressive cardiac myocyte apoptosis contributes to the transition from a hypertrophic to a dilated cardiac phenotype that is observed in transgenic myosin heavy chain secreted TNF (MHCsTNF) mice with cardiac restricted overexpression of tumor necrosis factor (TNF), we assessed cardiac myocyte apoptosis (using a DNA ligase technique) in MHCsTNF mice and littermate control mice in relation to serial changes in LV structure, which was assessed using MRI. The prevalence of cardiac myocyte apoptosis increased progressively from 4 to 12 wk as the hearts of the MHCsTNF mice underwent the transition from a concentric hypertrophic to a dilated cardiac phenotype. Treatment of the MHCsTNF mice with the broad-based caspase inhibitor N-[(1,3-dimethylindole-2-carbonyl)-valinyl]-3-amino4-oxo-5-fluoropentanoic acid significantly decreased cardiac myocyte apoptosis and significantly attenuated LV wall thinning and adverse cardiac remodeling. Additional studies suggested that the TNF-induced decrease in Bcl-2 expression and activation of the intrinsic mitochondrial death pathway were responsible for the cardiac myocyte apoptosis observed in the MHCsTNF mice. These studies show that progressive cardiac myocyte apoptosis is sufficient to contribute to adverse cardiac remodeling in the adult mammalian heart through progressive LV wall thinning.


1997 ◽  
Vol 79 (8) ◽  
pp. 1137-1141 ◽  
Author(s):  
Toshihiro Ino ◽  
Kei Nishimoto ◽  
Mataichi Okubo ◽  
Katsumi Akimoto ◽  
Keijiro Yabuta ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3180
Author(s):  
Somy Yoon ◽  
Ulrich Gergs ◽  
Julie R. McMullen ◽  
Gwang Hyeon Eom

Heat shock protein (HSP) 70 is a molecular chaperone that regulates protein structure in response to thermal stress. In addition, HSP70 is involved in post-translational modification and is related to the severity of some diseases. Here, we tested the functional relevance of long-lasting HSP70 expression in a model of nonischemic heart failure using protein phosphatase 2 catalytic subunit A (PP2CA)-expressing transgenic mice. These transgenic mice, with cardiac-specific overexpression of PP2CA, abruptly died after 12 weeks of postnatal life. Serial echocardiograms to assess cardiac function revealed that the ejection fraction (EF) was gradually decreased in transgenic PP2CA (TgPP2CA) mice. In addition, PP2CA expression exacerbated systolic dysfunction and LV dilatation, with free wall thinning, which are indicators of fatal dilated cardiomyopathy. Interestingly, simultaneous expression of HSP70 in double transgenic mice (dTg) significantly improved the dilated cardiomyopathy phenotype of TgPP2CA mice. We observed better survival, preserved EF, reduced chamber enlargement, and suppression of free wall thinning. In the proposed molecular mechanism, HSP70 preferentially regulates the phosphorylation of AKT. Phosphorylation of AKT was significantly reduced in TgPP2CA mice but was not significantly lower in dTg mice. Signal crosstalk between AKT and its substrates, in association with HSP70, might be a useful intervention for patients with nonischemic heart failure to suppress cardiac remodeling and improve survival.


2002 ◽  
Vol 143 (4) ◽  
pp. 690-695 ◽  
Author(s):  
Masami Shimizu ◽  
Hidekazu Ino ◽  
Kazuyasu Okeie ◽  
Masato Yamaguchi ◽  
Kenshi Hayashi ◽  
...  

2005 ◽  
Vol 7 (4) ◽  
pp. 684-688 ◽  
Author(s):  
Ok Young Park ◽  
Youngkeun Ahn ◽  
Woo Seok Park ◽  
Ji Hyun Lim ◽  
Hyung Wook Park ◽  
...  

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