- Email: [email protected]
Influence of Perindopril on Left Ventricular Remodeling in Essential and Secondary Hypertension
The 7th Annual Scientific Meeting
•
HFSA
S27
094
095
Influence of Perindopril on Left Ventricular Remodeling in Essential and Secondary Hypertension Karine R. Sahakyan,1 Svetlana V. Gurgenyan,1 Susanna Kh. Vatinyan,1 Karine G. Nikogosyan1—1Hypertension, Institute of Cardiology, Yerevan, Armenia
QRS Duration Correlates with Scar Content in Dilated Cardiomyopathy James O. O’Neill,1 Richard C. Brunken,2 Patrick M. McCarthy,1 Tiffany Buda,1 Katherine Hoercher,1 James B. Young,1 Randall C. Starling1—1Kaufman Center for Heart Failure, Cleveland Clinic Foundation, Cleveland, OH; 2Department of Molecular and Functional Imaging, Cleveland Clinic Foundation, Cleveland, OH
Background: To evaluate the relation between the left ventricular hypertrophy (LVH) regression and changes of LV diastolic function under the influence of perindopril in patients (pts) with hypertension. Methods: Fifty-two pts with essential hypertension (EH) and 36with secondary arterial hypertension (SAH) of renal genesis with II-III grade hypertension, LVH and abnormal mitral flow pattern have been studied to assess effect of perindopril (up to 4 mg/day) on left ventricular remodeling. Each subject was underwent two-dimensional and Doppler-echocardiography. LV mass index (LVMI), LV end-diastolic diameter (EDD), septal and posterior wall thickness (SWT, PWT) were evaluated, the following parameters of LV diastolic function were assessed by Doppler echocardiographic analysis of the diastolic transmitral flow: the maximal early- (E) and late – (A) velocity of diastolic filling; the E/ A ratio, the deceleration time (DT) and the isovolumetric relaxation time (IVRT). Examination was performed at baseline and after 48 weeks of treatment with perindopril. Results: In pts with EH systolic BP (SBP) was reduced on average from 190 ⫾ 22 to 136 ⫾ 10 mm Hg., diastolic BP (DBP) from 113 ⫾ 11.2 to 84 ⫾ 12 mm Hg. In pts with SAH there was detected reduction of SBP and DBP from 206 ⫾ 24 to 142 ⫾ 10 mm Hg and 115 ⫾ 11.1 to 86 ⫾ 11 mm Hg, respectively. LVMI was reduced by 14.2 % in EH and by 13.0 % in SAH (p ⬍ 0.01 for both). PWT decreased by 12.2 % in EH (p ⬍ 0.01) and by 7.4 % in SAH (p ⬍ 0.05), SWT by 6 % (p ⬍ 0.05) and 14.6 % (p ⬍ 0.001), respectively. Perindopril treatment produced shortening of IVRT (102.6 ⫾ 4.24 vs 146.8 ⫾ 7.90 ms in EH, and 102.0 ⫾ 2.92 vs 154.0 ⫾ 6.00 ms in SAH, p ⬍ 0.01 for both), DT (180.0 ⫾ 7.42 vs. 230.0 ⫾ 12.9 ms in EH, p ⬍ 0.01 and 184.0 ⫾ 7.86 vs. 204.6 ⫾ 9.60 ms in SAH, p ⬍ 0.05), E (68.8 ⫾ 6.4 vs. 50.0 ⫾ 10.0 cm/s in EH and 56.0 ⫾ 10.3 vs. 46.0 ⫾ 10.0 cm/s in SAH, p ⬍ 0.05 for both), increased E/A ratio (from 0.82 ⫾ 0.10 to 0.96 ⫾ 0.12 in EH and from 0.70 ⫾ 0.04 to 0.86 ⫾ 0.16 in SAH, p ⬍ 0.05 for both) and had trend toward decreasing A (68.8 ⫾ 10.0 vs. 86.2 ⫾ 12.0 cm/s in EH and 70.0 ⫾ 10.4 vs. 82.5 ⫾ 12.3 in SAH cm/s, p ⫽ NS for both). At the end of follow up normal mitral flow pattern was detected in 46.8% pts with EH and 39.2 % pts with SAH. Increased in E/A was related to reduction of SWT in pts with SAH (r ⫽ 0.69, p ⬍ 0.05), while in EH at the account of diminution of the LV EDD (r ⫽ 0.50, p ⬍ 0.05). Conclusion: Perindopril treatment has significantly ptoduced the attenuation of the left ventricular remodeling process in pts with EH and SAH. Diastolic function improvement in pts with SAH was related to the reduction of SWT, while in EH to the reduction of the left ventricular cavity size.
Background: Dilated cardiomyopathy (DCM) is generally associated with global systolic dysfunction, however in advanced states it may manifest regional abnormalities. A broad QRS duration on the surface ECG is also commonly seen, and predicts a poor prognosis. Intraventricular conduction delay may be a manifestation of the myocardiopathic process, rather than primarily due to conduction disease. We quantitatively assessed myocardial scar in patients with dilated (non-ischemic) cardiomyopathy using positron emission tomography (PET). Methods: Patients with DCM, ejection fraction ⬍30% and NYHA class III or IV symptoms underwent pharmacological stress (dipyridamole or dobutamine) Rubidium 82 perfusion/Fluorine-18 FDG PET metabolic studies to assess coronary insufficiency and myocardial tissue viability. Patients were excluded if they had significant coronary disease (defined as any lesion ⬎40%, or ⬎60% in a non-dominant right coronary artery), obstructive valvular disease or had ventricular pacing. Results: Forty patients, mean age 55.9 ⫾ 13 (range 20–75) years, 68% male, were studied. Thirty-six (90%) had idiopathic DCM. Mean QRS duration was 144 ⫾ 39 (range 88–228) msec. Fixed perfusion defects, with decreased FDG uptake, indicating the presence of scar occurred in 36/40 (90%) patients, involving LAD territory in all 36 (100%), RCA territory in 10/36 (28%) and Circumflex territory in 9/36 (25%). Mean scar size was 28 ⫾ 16 (range 3–62)% of total LV mass. In a stepwise multivariate analysis (including age, duration of DCM, aetiology and diabetes), QRS duration correlated with percentage scar, p ⫽ 0.0005, r ⫽ 0.54. Conclusions: These data suggest that regional abnormalities are common in patients with advanced dilated cardiomyopathy. Longer QRS duration predicts less regional metabolic activity and perfusion. This may be related to the worse outcome seen in those with the widest QRS duration.
096
097
Time Dependent Changes in Plasma Matrix Metalloproteinase (MMP) and Tissue Inhibitor of MMP in Patients with Hypertensive Left Ventricular Hypertrophy Michael R. Zile,1 Weems R. Pennington, III1 Amy Hardin,2 Catherine McClure,2 Rupak Mukherjee,2 Francis G. Spinale2—1Cardiology, Medical University of South Carolina and RHJ Department of Veterans Affairs Medical Center, Charleston, SC; 2 Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC
Remodeling of the Intercalated Disks in Desmin-Related Cardiomyopathy Caused by an aB-Crystallin Mutation in Mice Wei Huang,1 Joseph W. Glasford,1 Niels R. Harden,1 Xin Dong,1 A. Martin Gerdes,1 Jeffrey Robbins,2 Xuejun Wang1—1Cardiovascular Research Institute, University of South Dakota, Sioux Falls, SD; 2Department of Pediatrics, University of Cincinnati, Cincinnati, OH
Background: Hypertension causes hypertrophic remodeling in both the cardiac muscle cells and the extracellular matrix (ECM) which surrounds them. Whether and to what extent the ECM proteolytic system which includes matrix metalloproteinases (MMP) and tissue inhibitor of MMP (TIMP) is altered during and contributes to this process has not been defined. A necessary first step in defining the relationship between hypertrophic remodeling and the MMP/TIMP system is quantifying the levels of MMP and TIMP in a population of stable hypertensive patients and determining whether there are time dependent changes in MMP and TIMP in this population. Methods: Fourteen patients (age 58 ⫾ 3, 7 men, 7 woman) with hypertension and echocardiographically proven hypertrophic remodeling were prospectively studied at baseline and after six months using echocardiography and echoDoppler techniques. Plasma MMP-2, MMP-9, TIMP-1, TIMP-2 levels were determined using high sensitivity immunoassays at baseline and after six months. Results: At baseline, these patients had significant hypertrophic remodeling with increased left ventricular (LV) wall thickness, increased LV mass, and normal LV end diastolic volumes. This hypertrophic remodeling was accompanied by a normal fractional shortening but a decreased transmitral doppler E/A ratio. As a group there were no significant changes in these structural or functional measurements over six month period of follow-up (Table 1). In addition, as a group, while there were no significant changes in plasma MMP-2, MMP-9, TIMP-1, TIMP2 levels, both MMP 2 and 9 fell and TIMP 1 and 2 rose over the six-month follow-up period (Table 1). Examined individually, 5 patients had an increase in mass (41.5 ⫾ 11.6 gm; p ⬍ 0.05) while 6 patients had a decrease in mass (-77.1 ⫾ 22.6 gm; p ⬍ 0.05). These changes in mass were not correlated with changes in blood pressure but were correlated with changes in TIMP-1 (r ⫽ 0.63; p ⬍ 0.05) plasma levels such that TIMP levels fell as mass fell, and TIMP levels rose as mass rose. Conclusion: These data support the conclusion that even in a stable population of patients with hypertensive LV hypertrophy, myocardial remodeling continues and appears to be associated with changes in the MMP and TIMP proteolytic system. Table 1. LV structure and function measurements vs plasma MMP and TIMP levels.
Systolic blood pressure Diastolic blood pressure LV Diastolic volume (ml) Wall thickness (cm) Mass(gm) Fractional Shortening(%) E/A IVRT(ms) MMP-2(ng/mL) MMP-9(ng/mL) TIMP-1(ng/mL) TIMP-2(ng/mL)
Baseline
LVH
138 ⫾ 2 78 ⫾ 2 107.1 ⫾ 11.1 1.4 ⫾ 0.1 340 ⫾ 30 44 ⫾ 1 0.9 ⫾ 0.1 84 ⫾ 3 1064.0 ⫾ 83.0 28.3 ⫾ 10.2 64.3 ⫾ 3.8 48.3 ⫾ 11.8
136 ⫾ 4 75 ⫾ 2 111.3 ⫾ 8.6 1.4 ⫾ 0.1 322 ⫾ 27 39 ⫾ 2 0.9 ⫾ 0.1 78 ⫾ 5 908.5 ⫾ 60.3 22.6 ⫾ 5.9 65.6 ⫾ 6.6 49.6 ⫾ 10.9
Background: Desmin-related myopathies (DRM) are characterized by aberrant desmin-aggregation in muscle cells. DRM often affect the heart and resultant cardiomyopathy (DRC) is usually the cause of death. Both human genetic linkage and experimental studies have demonstrated that DRC can be caused by mutations in both the desmin and the αB-crystallin (CryAB) genes. The intercalated disks, containing desmosomes, fascia adherentes and gap junctions, are a characteristic structure in cardiac muscle and play an important role in the propagation of both mechanical and electro-chemical signals among adjacent cardiac myocytes. Arrhythmia is frequently observed in DRC patients. Previous studies on R120G-CryAB and wild type (WT-) CryAB transgenic (TG) mice showed that cardiac-specific moderate overexpression of WT-CryAB is benign, but expression of R120G-CryAB leads to aberrant desmin and CryAB aggregation and cardiomyopathy. The Line 134 R120G-CryAB TG mice develop concentric cardiac hypertrophy at 3 months and congestive heart failure at 6 months. Most of them die within 7 months of age. Therefore, to explore the pathological basis of arrhythmia and mechanical malfunction associated with DRC, we have investigated changes in the composition and distribution of intercalated disk proteins in the R120G-CryAB TG mouse model of DRC. Methods: Line 134 R120GCryAB and Line 11 WT-CryAB TG mice and their non-TG (NTG) littermates (6 months old) were used for collecting data reported here. The abundance of desmosome, fascia adherens, and gap junction proteins in ventricular myocardium was determined by immunoblotting and the distribution of these proteins was investigated by immunofluorescent confocal microscopy. Results: The total protein levels of pan-cadherin were not significant changed among the 3 groups while desmoplakin, α-catenin, and β-catenin were significantly increased in both the cytosolic and the membrane-skeleton fractions in the R120G-CryAB TG heart. Phosphorylated (Thr41/Ser45) β-catenin was increased only in the cytosolic fraction. Connexin43 is significantly down-regulated in the R120G-CryAB TG ventricles while connexin40 was not detectable in any of the 3 groups. Immunostaining of the cryosections of the ventricles showed that changes of these proteins at the polar membrane (the intercalated disk sites) were consistent with the immunoblot data. An additional confocal microscopic feature for the distribution of both mechanical and gap junctional proteins in the R120G-CryAB TG ventricles is that immunostaining of α-catenin, β-catenin, and connexin43 at the lateral membrane appeared to be substantially increased, compared to NTG and WT-CryAB TG groups. For all proteins examined, no remarkable difference was observed between NTG and WT-CryAB TG mouse groups. Conclusion: The intercalated disks undergo significant remodeling in the mutant CryAB-induced DRC; the remodeling may be caused by disruption of the desmin filaments and may contribute to progression to congestive heart failure.
•
HFSA
S27
094
095
Influence of Perindopril on Left Ventricular Remodeling in Essential and Secondary Hypertension Karine R. Sahakyan,1 Svetlana V. Gurgenyan,1 Susanna Kh. Vatinyan,1 Karine G. Nikogosyan1—1Hypertension, Institute of Cardiology, Yerevan, Armenia
QRS Duration Correlates with Scar Content in Dilated Cardiomyopathy James O. O’Neill,1 Richard C. Brunken,2 Patrick M. McCarthy,1 Tiffany Buda,1 Katherine Hoercher,1 James B. Young,1 Randall C. Starling1—1Kaufman Center for Heart Failure, Cleveland Clinic Foundation, Cleveland, OH; 2Department of Molecular and Functional Imaging, Cleveland Clinic Foundation, Cleveland, OH
Background: To evaluate the relation between the left ventricular hypertrophy (LVH) regression and changes of LV diastolic function under the influence of perindopril in patients (pts) with hypertension. Methods: Fifty-two pts with essential hypertension (EH) and 36with secondary arterial hypertension (SAH) of renal genesis with II-III grade hypertension, LVH and abnormal mitral flow pattern have been studied to assess effect of perindopril (up to 4 mg/day) on left ventricular remodeling. Each subject was underwent two-dimensional and Doppler-echocardiography. LV mass index (LVMI), LV end-diastolic diameter (EDD), septal and posterior wall thickness (SWT, PWT) were evaluated, the following parameters of LV diastolic function were assessed by Doppler echocardiographic analysis of the diastolic transmitral flow: the maximal early- (E) and late – (A) velocity of diastolic filling; the E/ A ratio, the deceleration time (DT) and the isovolumetric relaxation time (IVRT). Examination was performed at baseline and after 48 weeks of treatment with perindopril. Results: In pts with EH systolic BP (SBP) was reduced on average from 190 ⫾ 22 to 136 ⫾ 10 mm Hg., diastolic BP (DBP) from 113 ⫾ 11.2 to 84 ⫾ 12 mm Hg. In pts with SAH there was detected reduction of SBP and DBP from 206 ⫾ 24 to 142 ⫾ 10 mm Hg and 115 ⫾ 11.1 to 86 ⫾ 11 mm Hg, respectively. LVMI was reduced by 14.2 % in EH and by 13.0 % in SAH (p ⬍ 0.01 for both). PWT decreased by 12.2 % in EH (p ⬍ 0.01) and by 7.4 % in SAH (p ⬍ 0.05), SWT by 6 % (p ⬍ 0.05) and 14.6 % (p ⬍ 0.001), respectively. Perindopril treatment produced shortening of IVRT (102.6 ⫾ 4.24 vs 146.8 ⫾ 7.90 ms in EH, and 102.0 ⫾ 2.92 vs 154.0 ⫾ 6.00 ms in SAH, p ⬍ 0.01 for both), DT (180.0 ⫾ 7.42 vs. 230.0 ⫾ 12.9 ms in EH, p ⬍ 0.01 and 184.0 ⫾ 7.86 vs. 204.6 ⫾ 9.60 ms in SAH, p ⬍ 0.05), E (68.8 ⫾ 6.4 vs. 50.0 ⫾ 10.0 cm/s in EH and 56.0 ⫾ 10.3 vs. 46.0 ⫾ 10.0 cm/s in SAH, p ⬍ 0.05 for both), increased E/A ratio (from 0.82 ⫾ 0.10 to 0.96 ⫾ 0.12 in EH and from 0.70 ⫾ 0.04 to 0.86 ⫾ 0.16 in SAH, p ⬍ 0.05 for both) and had trend toward decreasing A (68.8 ⫾ 10.0 vs. 86.2 ⫾ 12.0 cm/s in EH and 70.0 ⫾ 10.4 vs. 82.5 ⫾ 12.3 in SAH cm/s, p ⫽ NS for both). At the end of follow up normal mitral flow pattern was detected in 46.8% pts with EH and 39.2 % pts with SAH. Increased in E/A was related to reduction of SWT in pts with SAH (r ⫽ 0.69, p ⬍ 0.05), while in EH at the account of diminution of the LV EDD (r ⫽ 0.50, p ⬍ 0.05). Conclusion: Perindopril treatment has significantly ptoduced the attenuation of the left ventricular remodeling process in pts with EH and SAH. Diastolic function improvement in pts with SAH was related to the reduction of SWT, while in EH to the reduction of the left ventricular cavity size.
Background: Dilated cardiomyopathy (DCM) is generally associated with global systolic dysfunction, however in advanced states it may manifest regional abnormalities. A broad QRS duration on the surface ECG is also commonly seen, and predicts a poor prognosis. Intraventricular conduction delay may be a manifestation of the myocardiopathic process, rather than primarily due to conduction disease. We quantitatively assessed myocardial scar in patients with dilated (non-ischemic) cardiomyopathy using positron emission tomography (PET). Methods: Patients with DCM, ejection fraction ⬍30% and NYHA class III or IV symptoms underwent pharmacological stress (dipyridamole or dobutamine) Rubidium 82 perfusion/Fluorine-18 FDG PET metabolic studies to assess coronary insufficiency and myocardial tissue viability. Patients were excluded if they had significant coronary disease (defined as any lesion ⬎40%, or ⬎60% in a non-dominant right coronary artery), obstructive valvular disease or had ventricular pacing. Results: Forty patients, mean age 55.9 ⫾ 13 (range 20–75) years, 68% male, were studied. Thirty-six (90%) had idiopathic DCM. Mean QRS duration was 144 ⫾ 39 (range 88–228) msec. Fixed perfusion defects, with decreased FDG uptake, indicating the presence of scar occurred in 36/40 (90%) patients, involving LAD territory in all 36 (100%), RCA territory in 10/36 (28%) and Circumflex territory in 9/36 (25%). Mean scar size was 28 ⫾ 16 (range 3–62)% of total LV mass. In a stepwise multivariate analysis (including age, duration of DCM, aetiology and diabetes), QRS duration correlated with percentage scar, p ⫽ 0.0005, r ⫽ 0.54. Conclusions: These data suggest that regional abnormalities are common in patients with advanced dilated cardiomyopathy. Longer QRS duration predicts less regional metabolic activity and perfusion. This may be related to the worse outcome seen in those with the widest QRS duration.
096
097
Time Dependent Changes in Plasma Matrix Metalloproteinase (MMP) and Tissue Inhibitor of MMP in Patients with Hypertensive Left Ventricular Hypertrophy Michael R. Zile,1 Weems R. Pennington, III1 Amy Hardin,2 Catherine McClure,2 Rupak Mukherjee,2 Francis G. Spinale2—1Cardiology, Medical University of South Carolina and RHJ Department of Veterans Affairs Medical Center, Charleston, SC; 2 Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC
Remodeling of the Intercalated Disks in Desmin-Related Cardiomyopathy Caused by an aB-Crystallin Mutation in Mice Wei Huang,1 Joseph W. Glasford,1 Niels R. Harden,1 Xin Dong,1 A. Martin Gerdes,1 Jeffrey Robbins,2 Xuejun Wang1—1Cardiovascular Research Institute, University of South Dakota, Sioux Falls, SD; 2Department of Pediatrics, University of Cincinnati, Cincinnati, OH
Background: Hypertension causes hypertrophic remodeling in both the cardiac muscle cells and the extracellular matrix (ECM) which surrounds them. Whether and to what extent the ECM proteolytic system which includes matrix metalloproteinases (MMP) and tissue inhibitor of MMP (TIMP) is altered during and contributes to this process has not been defined. A necessary first step in defining the relationship between hypertrophic remodeling and the MMP/TIMP system is quantifying the levels of MMP and TIMP in a population of stable hypertensive patients and determining whether there are time dependent changes in MMP and TIMP in this population. Methods: Fourteen patients (age 58 ⫾ 3, 7 men, 7 woman) with hypertension and echocardiographically proven hypertrophic remodeling were prospectively studied at baseline and after six months using echocardiography and echoDoppler techniques. Plasma MMP-2, MMP-9, TIMP-1, TIMP-2 levels were determined using high sensitivity immunoassays at baseline and after six months. Results: At baseline, these patients had significant hypertrophic remodeling with increased left ventricular (LV) wall thickness, increased LV mass, and normal LV end diastolic volumes. This hypertrophic remodeling was accompanied by a normal fractional shortening but a decreased transmitral doppler E/A ratio. As a group there were no significant changes in these structural or functional measurements over six month period of follow-up (Table 1). In addition, as a group, while there were no significant changes in plasma MMP-2, MMP-9, TIMP-1, TIMP2 levels, both MMP 2 and 9 fell and TIMP 1 and 2 rose over the six-month follow-up period (Table 1). Examined individually, 5 patients had an increase in mass (41.5 ⫾ 11.6 gm; p ⬍ 0.05) while 6 patients had a decrease in mass (-77.1 ⫾ 22.6 gm; p ⬍ 0.05). These changes in mass were not correlated with changes in blood pressure but were correlated with changes in TIMP-1 (r ⫽ 0.63; p ⬍ 0.05) plasma levels such that TIMP levels fell as mass fell, and TIMP levels rose as mass rose. Conclusion: These data support the conclusion that even in a stable population of patients with hypertensive LV hypertrophy, myocardial remodeling continues and appears to be associated with changes in the MMP and TIMP proteolytic system. Table 1. LV structure and function measurements vs plasma MMP and TIMP levels.
Systolic blood pressure Diastolic blood pressure LV Diastolic volume (ml) Wall thickness (cm) Mass(gm) Fractional Shortening(%) E/A IVRT(ms) MMP-2(ng/mL) MMP-9(ng/mL) TIMP-1(ng/mL) TIMP-2(ng/mL)
Baseline
LVH
138 ⫾ 2 78 ⫾ 2 107.1 ⫾ 11.1 1.4 ⫾ 0.1 340 ⫾ 30 44 ⫾ 1 0.9 ⫾ 0.1 84 ⫾ 3 1064.0 ⫾ 83.0 28.3 ⫾ 10.2 64.3 ⫾ 3.8 48.3 ⫾ 11.8
136 ⫾ 4 75 ⫾ 2 111.3 ⫾ 8.6 1.4 ⫾ 0.1 322 ⫾ 27 39 ⫾ 2 0.9 ⫾ 0.1 78 ⫾ 5 908.5 ⫾ 60.3 22.6 ⫾ 5.9 65.6 ⫾ 6.6 49.6 ⫾ 10.9
Background: Desmin-related myopathies (DRM) are characterized by aberrant desmin-aggregation in muscle cells. DRM often affect the heart and resultant cardiomyopathy (DRC) is usually the cause of death. Both human genetic linkage and experimental studies have demonstrated that DRC can be caused by mutations in both the desmin and the αB-crystallin (CryAB) genes. The intercalated disks, containing desmosomes, fascia adherentes and gap junctions, are a characteristic structure in cardiac muscle and play an important role in the propagation of both mechanical and electro-chemical signals among adjacent cardiac myocytes. Arrhythmia is frequently observed in DRC patients. Previous studies on R120G-CryAB and wild type (WT-) CryAB transgenic (TG) mice showed that cardiac-specific moderate overexpression of WT-CryAB is benign, but expression of R120G-CryAB leads to aberrant desmin and CryAB aggregation and cardiomyopathy. The Line 134 R120G-CryAB TG mice develop concentric cardiac hypertrophy at 3 months and congestive heart failure at 6 months. Most of them die within 7 months of age. Therefore, to explore the pathological basis of arrhythmia and mechanical malfunction associated with DRC, we have investigated changes in the composition and distribution of intercalated disk proteins in the R120G-CryAB TG mouse model of DRC. Methods: Line 134 R120GCryAB and Line 11 WT-CryAB TG mice and their non-TG (NTG) littermates (6 months old) were used for collecting data reported here. The abundance of desmosome, fascia adherens, and gap junction proteins in ventricular myocardium was determined by immunoblotting and the distribution of these proteins was investigated by immunofluorescent confocal microscopy. Results: The total protein levels of pan-cadherin were not significant changed among the 3 groups while desmoplakin, α-catenin, and β-catenin were significantly increased in both the cytosolic and the membrane-skeleton fractions in the R120G-CryAB TG heart. Phosphorylated (Thr41/Ser45) β-catenin was increased only in the cytosolic fraction. Connexin43 is significantly down-regulated in the R120G-CryAB TG ventricles while connexin40 was not detectable in any of the 3 groups. Immunostaining of the cryosections of the ventricles showed that changes of these proteins at the polar membrane (the intercalated disk sites) were consistent with the immunoblot data. An additional confocal microscopic feature for the distribution of both mechanical and gap junctional proteins in the R120G-CryAB TG ventricles is that immunostaining of α-catenin, β-catenin, and connexin43 at the lateral membrane appeared to be substantially increased, compared to NTG and WT-CryAB TG groups. For all proteins examined, no remarkable difference was observed between NTG and WT-CryAB TG mouse groups. Conclusion: The intercalated disks undergo significant remodeling in the mutant CryAB-induced DRC; the remodeling may be caused by disruption of the desmin filaments and may contribute to progression to congestive heart failure.