Evicenter
P&T meetings

RP-A501 (AAV9.LAMP2B)

Danon disease

Regulatory submission
BLA planned for late 2028
Last updated
300 sources

Product information and disease descriptionPlace of product in therapyApproaches to treatmentCurrent treatment options and standard of care

Implantable cardioverter-defibrillators

19 evidence topics · 20 sources

Basis of management recommendations: expert opinion and extrapolation from hypertrophic cardiomyopathy guidelines

“There are currently no consensus clinical practice guidelines and assessment, and management is largely based on expert opinion and extrapolation from hypertrophic cardiomyopathy guidelines.” (opens the source at this quote in a new tab)

“Danon disease represents a small proportion of patients included in historical hypertrophic cardiomyopathy cohorts and has a very distinct clinical profile.” (opens the source at this quote in a new tab)

“Therefore, it is likely inappropriate to apply hypertrophic cardiomyopathy guidelines to patients with Danon disease.” (opens the source at this quote in a new tab)

Consensus statement: low threshold for defibrillator implantation; risk models not validated in Danon disease

“Importantly, neither approach has been validated in individuals with Danon disease.” (opens the source at this quote in a new tab)

“Nevertheless, currently available data support a low threshold for consideration of ICD implantation in patients with Danon disease who have severe LVH, unexplained syncope, and/or nonsustained ventricular tachycardia.” (opens the source at this quote in a new tab)

“Again, in patients with unexplained syncope or presyncope, an implantable loop recorder or direct implantation of an ICD seems reasonable (see sudden cardiac death prevention, later).” (opens the source at this quote in a new tab)

“In cases of marked fibrosis (>15%), consideration for sudden cardiac death prevention and for heart transplantation referral should be made.” (opens the source at this quote in a new tab)

Consensus statement: subcutaneous device and defibrillation threshold testing

“A subcutaneous device should be considered in young individuals who do not require pacing, to minimize the long-term risk of infection and vascular complications with procedures.” (opens the source at this quote in a new tab)

“Defibrillation threshold testing should be considered in individuals with massive hypertrophy.” (opens the source at this quote in a new tab)

Consensus statement: activity restriction with and without a defibrillator

“And last, education to avoid strenuous physical activity and competitive sports is important to decrease the risk of stress-provoked arrhythmia in those without an ICD and the risk of arrhythmic storm in those considered to be protected (by an ICD).” (opens the source at this quote in a new tab)

Italian Society of Cardiology position paper: defibrillator recommendation that names Danon disease

“ICD implantation should be considered in patients with severe left ventricular hypertrophy, non-sustained ventricular tachycardia and/ or unexplained syncope.” (opens the source at this quote in a new tab)

GeneReviews: timely consideration of a defibrillator

“Timely consideration of implantable cardiac defibrillators” (opens the source at this quote in a new tab)

Earlier management proposal: clinical features that prompt defibrillator therapy

“Diagnostic and management guidelines for Danon disease have not been published.” (opens the source at this quote in a new tab)

“Implantable cardioverter-defibrillator (ICD) therapy should be strongly considered in patients with symptomatic arrhythmias, moderate to severe hypertrophy, substantial fibrosis burden on cMRI imaging, and/or family history of premature sudden death.” (opens the source at this quote in a new tab)

AHA/ACC hypertrophic cardiomyopathy guideline: Danon cardiomyopathy outside the guideline's scope

“In these syndromic or infiltrative diseases, although the magnitude and distribution of increased LV wall thickness can be similar to that of HCM, the pathophysiologic mechanisms responsible for hypertrophy, natural history, and treatment strategies are not the same.” (opens the source at this quote in a new tab)

“For these reasons, other cardiac or systemic diseases capable of producing LVH (ie, HCM mimics) will not be addressed in this document.” (opens the source at this quote in a new tab)

“In some circumstances, the genetic test result may alter the management of the index case, such as enzyme replacement therapy in patients with Fabry disease or more aggressive clinical management of patients with Danon disease.” (opens the source at this quote in a new tab)

ESC cardiomyopathy guideline: insufficient data on sudden death risk factors in Danon disease

“Recently, data from a large multicentre European registry have shown that Danon disease runs a malignant phenotype, but there are insufficient data to identify candidate risk factors for sudden death.” (opens the source at this quote in a new tab)

“Heart failure therapy, antiarrhythmic therapy, and indications for the implantation of devices are included in Section 6.10.” (opens the source at this quote in a new tab)

Device use in the International Danon Disease Registry: 116 participants

“38.8% (n=45) of patients had a CIED throughout the study period” (opens the source at this quote in a new tab)

“Within patients who received a CIED, 2 male patients (3.8%) were implanted with pacemakers alone; the remaining patients were implanted with an automatic implantable cardioverter defibrillator, of which 5.2% (n=2) were for secondary prevention.” (opens the source at this quote in a new tab)

Device use and indications in a European registry: 57 participants

“A total of 38 (67%) patients received an implantable device (Table 2): permanent pacemaker, implantable cardiac defibrillator (ICD) or cardiac resynchronization therapy with an ICD (CRT-D).” (opens the source at this quote in a new tab)

“The most common (21/29) indication for ICD/CRT implantation was primary prevention.” (opens the source at this quote in a new tab)

“Eight were implanted for a secondary prevention after sustained ventricular tachycardia (n=4) or resuscitation for cardiac arrest due to ventricular fibrillation (n=4).” (opens the source at this quote in a new tab)

Appropriate device interventions in the European registry

“Appropriate ICD/CRTD intervention for sustained ventricular” (opens the source at this quote in a new tab)

“arrhythmia (VT or VF) was reported in 6 patients (3 of each gender), 4 of whom were implanted for primary prevention (Table 2).” (opens the source at this quote in a new tab)

Appropriate shocks in a multicenter cohort with pre-excitation: 13 participants

“Over median follow-up of 842 days (interquartile range 138-1678), 11 patients (85%) had ICD placement, and 6 (46.1%) underwent heart transplantation.” (opens the source at this quote in a new tab)

“No patients required therapy for ventricular tachycardia, and 2 patients (15%) had paroxysmal atrial fibrillation.” (opens the source at this quote in a new tab)

Appropriate shocks in a single-center series: 10 participants

“Implantable cardioverter defibrillator was placed in five patients for primary prevention with no patients receiving an appropriate discharge.” (opens the source at this quote in a new tab)

“Over a follow-up of 5.3 years, five underwent heart transplantation.” (opens the source at this quote in a new tab)

Sustained ventricular arrhythmia in a three-family series: 7 participants

“In four patients, ICD implantation was performed for primary prevention of sudden cardiac death.” (opens the source at this quote in a new tab)

“However, sustained ventricular arrhythmias were not documented in any of the patients.” (opens the source at this quote in a new tab)

Failure of defibrillation: one death among 7 participants

“Two others experienced sudden unexpected major arrhythmic events: one died suddenly (age 12) from ventricular fibrillation refractory to implantable cardioverter-defibrillator (ICD) therapy” (opens the source at this quote in a new tab)

“The ICD elicited a defibrillation shock (arrow) which failed to interrupt ventricular fibrillation (280 beats/min).” (opens the source at this quote in a new tab)

“This event was repeated 5 times until ICD capacity was extinguished and death occurred.” (opens the source at this quote in a new tab)

Transvenous device unable to defibrillate and subcutaneous device effective: single case

“We describe a case in which a TV-ICD was unable to defibrillate induced ventricular fibrillation (VF), but a wholly subcutaneous system (S-ICD) was successful in terminating induced VF and spontaneous ventricular tachycardia.” (opens the source at this quote in a new tab)

“These findings have relevance to the selection of device therapy in the management of these individuals and a wider group of young patients with severe hypertrophic cardiomyopathy.” (opens the source at this quote in a new tab)

Inappropriate shocks: single case

“Nine months after implantation, he received two inappropriate shocks due to R-wave double counting during sinus tachycardia.” (opens the source at this quote in a new tab)

Age at defibrillator implantation and frequency across published cohorts

“Mean age at ICD implantation was 23 years (range 9-61) for males and 32 years (range 9-54) for females.” (opens the source at this quote in a new tab)

“ICD implantation: Males 6-50% Females 18-38%” (opens the source at this quote in a new tab)