Heart transplantation is considered the best treatment modality for advanced heart disease. While old age has conventionally been considered a contraindication for heart transplantation due to the reported adverse eff...Heart transplantation is considered the best treatment modality for advanced heart disease. While old age has conventionally been considered a contraindication for heart transplantation due to the reported adverse effect of advanced age, however donor hearts' shortage continues to stimulate the discussion about the recipient's upper age limit. Our study was based on a retrospective analysis for the results of 52(18%) patients aged 60 years and older undergoing heart transplantation between May 2008 and December 2015, and these patients were compared with 236(82%) adult recipients who were younger than 60 years at the time of transplantation and during the same period. In older group, 71% were males with the mean age of 63.38±3.55 years, and in younger group, 83.4% were males with a mean age of 43.72±11.41 years(P=0.27). Dilated cardiomyopathy was the most common indication for transplantation among patients in both groups(P=0.147). In older group, the 3-month survival rate was higher than that in younger group(P=0.587), however the 6-month survival rate showed no significant difference(P=0.225). Although the 1-year survival rate was higher in older group(P=0.56), yet the 3-year survival rate between the two groups showed no statistically significant difference(P=0.48). According to our experience among older heart transplant candidates who were 60 years and older, we believe that advanced age should not be an excluding criterion to cardiac transplantation.展开更多
Cardiomyopathy is a pathological condition characterized by cardiac pump failure due to myocardial dysfunction and the major cause of advanced heart failure requiring heart transplantation.Although optimized medical t...Cardiomyopathy is a pathological condition characterized by cardiac pump failure due to myocardial dysfunction and the major cause of advanced heart failure requiring heart transplantation.Although optimized medical therapies have been developed for heart failure during the last few decades,some patients with cardiomyopathy exhibit advanced heart failure and are refractory to medical therapies.Desmosome,which is a dynamic cell-to-cell junctional component,maintains the structural integrity of heart tissues.Genetic mutations in desmo-somal genes cause arrhythmogenic cardiomyopathy(AC),a rare inheritable disease,and predispose patients to sudden cardiac death and heart failure.Recent advances in sequencing technologies have elucidated the genetic basis of cardiomyopathies and revealed that desmosome-related cardiomyopathy is concealed in broad cardiomyopathies.Among desmosomal genes,mutations in PKP2(which encodes PKP2)are most frequently identified in patients with AC.PKP2 deficiency causes various pathological cardiac phenotypes.Human cardiomyocytes differentiated from patient-derived induced pluripotent stem cells(iPSCs)in combination with genome editing,which allows the precise arrangement of the targeted genome,are powerful experimental tools for studying disease.This review summarizes the current issues associated with practical medicine for advanced heart failure and the recent advances in disease modeling using iPSC-derived cardiomyocytes targeting desmosome-related cardiomyopathy caused by PKP2 deficiency.展开更多
文摘Heart transplantation is considered the best treatment modality for advanced heart disease. While old age has conventionally been considered a contraindication for heart transplantation due to the reported adverse effect of advanced age, however donor hearts' shortage continues to stimulate the discussion about the recipient's upper age limit. Our study was based on a retrospective analysis for the results of 52(18%) patients aged 60 years and older undergoing heart transplantation between May 2008 and December 2015, and these patients were compared with 236(82%) adult recipients who were younger than 60 years at the time of transplantation and during the same period. In older group, 71% were males with the mean age of 63.38±3.55 years, and in younger group, 83.4% were males with a mean age of 43.72±11.41 years(P=0.27). Dilated cardiomyopathy was the most common indication for transplantation among patients in both groups(P=0.147). In older group, the 3-month survival rate was higher than that in younger group(P=0.587), however the 6-month survival rate showed no significant difference(P=0.225). Although the 1-year survival rate was higher in older group(P=0.56), yet the 3-year survival rate between the two groups showed no statistically significant difference(P=0.48). According to our experience among older heart transplant candidates who were 60 years and older, we believe that advanced age should not be an excluding criterion to cardiac transplantation.
基金Supported by JSPS KAKENHI,No.20K21602,No.21H02915,and No.22K19526the Japan Agency for Medical Research and Development,No.21bm0804008h0005+2 种基金the Cell Science Research Foundationthe Grant for Basic Research of the Japanese Circulation Society(2018)SENSHIN Medical Research Foundation.
文摘Cardiomyopathy is a pathological condition characterized by cardiac pump failure due to myocardial dysfunction and the major cause of advanced heart failure requiring heart transplantation.Although optimized medical therapies have been developed for heart failure during the last few decades,some patients with cardiomyopathy exhibit advanced heart failure and are refractory to medical therapies.Desmosome,which is a dynamic cell-to-cell junctional component,maintains the structural integrity of heart tissues.Genetic mutations in desmo-somal genes cause arrhythmogenic cardiomyopathy(AC),a rare inheritable disease,and predispose patients to sudden cardiac death and heart failure.Recent advances in sequencing technologies have elucidated the genetic basis of cardiomyopathies and revealed that desmosome-related cardiomyopathy is concealed in broad cardiomyopathies.Among desmosomal genes,mutations in PKP2(which encodes PKP2)are most frequently identified in patients with AC.PKP2 deficiency causes various pathological cardiac phenotypes.Human cardiomyocytes differentiated from patient-derived induced pluripotent stem cells(iPSCs)in combination with genome editing,which allows the precise arrangement of the targeted genome,are powerful experimental tools for studying disease.This review summarizes the current issues associated with practical medicine for advanced heart failure and the recent advances in disease modeling using iPSC-derived cardiomyocytes targeting desmosome-related cardiomyopathy caused by PKP2 deficiency.