Friedreich's ataxia(FRDA), which occurs in 1/50000 live births, is the most prevalent inherited neuromuscular disorder. Nearly all FRDA patients develop cardiomyopathy at some point in their lives. The clinical ma...Friedreich's ataxia(FRDA), which occurs in 1/50000 live births, is the most prevalent inherited neuromuscular disorder. Nearly all FRDA patients develop cardiomyopathy at some point in their lives. The clinical manifestations of FRDA include ataxia of the limbs and trunk, dysarthria, diabetes mellitus, and cardiac diseases. However, the broad clinical spectrum makes FRDA difficult to identify.The diagnosis of FRDA is based on the presence of suspicious clinical factors, the use of the Harding criteria and, more recently, the use of genetic testing for identifying the expansion of a triplet nucleotide sequence. FRDA is linked to a defect in the mitochondrial protein frataxin; an epigenetic alteration interferes with the folding of this protein, causing a relative deficiency of frataxin in affected patients. Frataxins are small essential proteins whose deficiency causes a range of metabolic disturbances, including oxidative stress, iron-sulfur cluster deficits, and defects in heme synthesis, sulfur amino acid metabolism, energy metabolism, stress responses, and mitochondrial function. The cardiac involvement seen in FRDA is a consequence of mitochondrial proliferation as well as the loss of contractile proteins and the subsequent development of myocardial fibrosis. The walls of the left ventricle become thickened, and different phenotypic manifestations are seen, including concentric or asymmetric hypertrophy and(less commonly) dilated cardiomyopathy. Dilated cardiomyopathy and arrhythmia are associated with mortality in patients with FRDA, whereas hypertrophic cardiomyopathy is not. Systolic function tends to be low-normal in FRDA patients, with an acute decline at the end of life.However, the literature includes only a few long-term prospective studies of cardiac progression in FRDA, and the cause of death is often attributed to heart failure and arrhythmia postmortem. Cardiomyopathy tends to be correlated with the clinical neurologic age of onset and the nucleotide triplet repeat length(i.e.,markers of phenotypic disease severity) rather than the duration of disease or the severity of neurologic symptoms. As most patients are wheelchair-bound within15 years of diagnosis, the clinical determination of cardiac involvement is often complicated by comorbidities. Researchers are currently testing targeted therapies for FRDA, and a centralized database, patient registry, and natural history study have been launched to support these clinical trials. The present review discusses the pathogenesis, clinical manifestations, and spectrum of cardiac disease in FRDA patients and then introduces gene-targeted and pathology-specific therapies as well as screening guidelines that should be used to monitor cardiac disease in this mitochondrial disorder.展开更多
BACKGROUND Phrenic nerve(PN)injury is one of the recognized possible complications following epicardial ablation of ventricular tachycardia(VT).High-output pacing is a widely used maneuver to establish a relationship ...BACKGROUND Phrenic nerve(PN)injury is one of the recognized possible complications following epicardial ablation of ventricular tachycardia(VT).High-output pacing is a widely used maneuver to establish a relationship between the PN and the ablation catheter tip.An absence of PN capture is usually considered an indication that it is safe to ablate,and that successful ablation may be performed at adjacent sites.However,PN capture may impact the procedural outcome.Only a few cases have been reported in the literature that avoid PN injury by using different techniques.CASE SUMMARY Three patients with a previous history of myocarditis and one patient with ischemic cardiomyopathy underwent epicardial ablation for drug-refractory VT.Before the procedure,transthoracic echocardiogram,coronary angiogram,and cardiac magnetic resonance imaging were performed on all patients.Under general anesthesia,endo/epicardial three-dimensional anatomical and substrate maps of the left ventricle were accomplished.Before radiofrequency delivery,the course of the PN was identified by provoking diaphragmatic stimulation with high-output pacing from the distal electrode of the ablation catheter.In every case,a scar region with late potentials was mapped along the PN course.After obtaining another epicardial access,a second introducer sheath was placed,and a vascular balloon catheter was inserted into the epicardial space and inflated with saline solution to separate the PN from the epicardium.Once the absence of PN capture had been proven,radiofrequency was applied to aim for complete late potential elimination and avoid VT induction.CONCLUSION PN injury can occur as one of the complications following epicardial VT ablation procedures,and may prevent successful ablation of these arrhythmias.PN displacement by using large balloon catheters into the epicardial space seems to be feasible and reproducible,avoid procedure-related morbidity,and improve ablation success when performed in selected centers and by experienced operators.展开更多
文摘Friedreich's ataxia(FRDA), which occurs in 1/50000 live births, is the most prevalent inherited neuromuscular disorder. Nearly all FRDA patients develop cardiomyopathy at some point in their lives. The clinical manifestations of FRDA include ataxia of the limbs and trunk, dysarthria, diabetes mellitus, and cardiac diseases. However, the broad clinical spectrum makes FRDA difficult to identify.The diagnosis of FRDA is based on the presence of suspicious clinical factors, the use of the Harding criteria and, more recently, the use of genetic testing for identifying the expansion of a triplet nucleotide sequence. FRDA is linked to a defect in the mitochondrial protein frataxin; an epigenetic alteration interferes with the folding of this protein, causing a relative deficiency of frataxin in affected patients. Frataxins are small essential proteins whose deficiency causes a range of metabolic disturbances, including oxidative stress, iron-sulfur cluster deficits, and defects in heme synthesis, sulfur amino acid metabolism, energy metabolism, stress responses, and mitochondrial function. The cardiac involvement seen in FRDA is a consequence of mitochondrial proliferation as well as the loss of contractile proteins and the subsequent development of myocardial fibrosis. The walls of the left ventricle become thickened, and different phenotypic manifestations are seen, including concentric or asymmetric hypertrophy and(less commonly) dilated cardiomyopathy. Dilated cardiomyopathy and arrhythmia are associated with mortality in patients with FRDA, whereas hypertrophic cardiomyopathy is not. Systolic function tends to be low-normal in FRDA patients, with an acute decline at the end of life.However, the literature includes only a few long-term prospective studies of cardiac progression in FRDA, and the cause of death is often attributed to heart failure and arrhythmia postmortem. Cardiomyopathy tends to be correlated with the clinical neurologic age of onset and the nucleotide triplet repeat length(i.e.,markers of phenotypic disease severity) rather than the duration of disease or the severity of neurologic symptoms. As most patients are wheelchair-bound within15 years of diagnosis, the clinical determination of cardiac involvement is often complicated by comorbidities. Researchers are currently testing targeted therapies for FRDA, and a centralized database, patient registry, and natural history study have been launched to support these clinical trials. The present review discusses the pathogenesis, clinical manifestations, and spectrum of cardiac disease in FRDA patients and then introduces gene-targeted and pathology-specific therapies as well as screening guidelines that should be used to monitor cardiac disease in this mitochondrial disorder.
基金support to Michela Grande, BEng, Abbott, Milan, Italy
文摘BACKGROUND Phrenic nerve(PN)injury is one of the recognized possible complications following epicardial ablation of ventricular tachycardia(VT).High-output pacing is a widely used maneuver to establish a relationship between the PN and the ablation catheter tip.An absence of PN capture is usually considered an indication that it is safe to ablate,and that successful ablation may be performed at adjacent sites.However,PN capture may impact the procedural outcome.Only a few cases have been reported in the literature that avoid PN injury by using different techniques.CASE SUMMARY Three patients with a previous history of myocarditis and one patient with ischemic cardiomyopathy underwent epicardial ablation for drug-refractory VT.Before the procedure,transthoracic echocardiogram,coronary angiogram,and cardiac magnetic resonance imaging were performed on all patients.Under general anesthesia,endo/epicardial three-dimensional anatomical and substrate maps of the left ventricle were accomplished.Before radiofrequency delivery,the course of the PN was identified by provoking diaphragmatic stimulation with high-output pacing from the distal electrode of the ablation catheter.In every case,a scar region with late potentials was mapped along the PN course.After obtaining another epicardial access,a second introducer sheath was placed,and a vascular balloon catheter was inserted into the epicardial space and inflated with saline solution to separate the PN from the epicardium.Once the absence of PN capture had been proven,radiofrequency was applied to aim for complete late potential elimination and avoid VT induction.CONCLUSION PN injury can occur as one of the complications following epicardial VT ablation procedures,and may prevent successful ablation of these arrhythmias.PN displacement by using large balloon catheters into the epicardial space seems to be feasible and reproducible,avoid procedure-related morbidity,and improve ablation success when performed in selected centers and by experienced operators.
