Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06607471
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-09-07
Brief Title:
Multimodal and Multidisciplinary Approach to Optimize Diagnostic Prognostic and Therapeutic Management of Patients with Non-ischemic Cardiomyopathies and Arrhythmogenic-inflammatory Phenotypes a Multicenter Observational Retrospective and Prospective Registry Study
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Multimodal and Multidisciplinary Approach to Optimize Diagnostic Prognostic and Therapeutic Management of Patients with Non-ischemic Cardiomyopathies and Arrhythmogenic-inflammatory Phenotypes a Multicenter Observational Retrospective and Prospective Registry Study
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
AINICM
Brief Summary:
Non-ischemic cardiomyopathies NICM represent a heterogeneous group of pathologies characterized by absence of obstructive disease of the epicardial coronary vessels and distinct structural and functional changes of the myocardium The main identified forms include dilated cardiomyopathy DCM hypertrophic cardiomyopathy HCM restrictive cardiomyopathy RCM and arrhythmogenic cardiomyopathy proper ACM More recently further forms of cardiomyopathy have been described less common and not uniquely classifiable including uncompressed myocardium LVNC peripartum cardiomyopathy PPCM structural correlates of arrhythmogenic mitral valve prolapse AMVP Anderson-Fabry disease AFD NICM associated with multi- system neuromuscular or autoimmune diseases lysosomal diseases glycogenosis mitochondrial cytopathies and canal diseases with structural substrates Finally there are overlap forms characterized by the sharing in the same subject of characteristic aspects of two or more of the above- mentioned diseases and of the undefined forms which to date do not reach the diagnostic criteria for any of the above-mentioned diseases
To the best of current knowledge there are two points discovered in scientific research namely the description of the arrhythmogenic and inflammatory phenotypes in a broad sense which are summarized here with the acronym AINICM In detail
1 Arrhythmic manifestations account for the arrhythmogenic component of AINICM which is not limited to ACM proper In fact most of the above diseases have a non-arrhythmic clinical presentation and a prevailing tendency to evolve towards a picture of cardiovascular decompensation Although sudden arrhythmic death has been described throughout the spectrum of AINICM early arrhythmic manifestations of such diseases have an unknown prevalence an uncertain association with different disease genotypes and phenotypes and still uncertain predictivity of long-term arrhythmic risk At the same time optimal diagnostic and therapeutic pathways in arrhythmias associated with AINICM are still being studied
2 Myocardial inflammation M-Infl accounts for the inflammatory component of AINICM and has recently been described in association with many AINICM on a genetic basis including undefined and arrhythmic forms The data is of high interest not only in the diagnostic but also in prognostic and therapeutic field In fact on the one hand the presence of M-Infl seems to have a physio- pathological role in AINICM on the other as already known in myocarditis the optimal therapeutic paths of arrhythmias may differ in patients with and without M-Infl in particular also in the light of the preliminary data available in adult and paediatric AINICM the inflammatory forms are expected to respond better to immunosuppressive therapy the arrhythmogenic ones to an ablative therapy with frequent need of implantation of cardiac devices
Based on the clinical presentation NICM patients will be divided into arrhythmic AINICM and non-arrhythmic patients as study and control groups respectively The AINICM group will include presentation with ventricular fibrillation VF either sustained or non-sustained ventricular tachycardia VT NSVT frequent premature ventricular complexes PVC supraventricular arrhythmias SVA and bradyarrhythmias BA Clinical presentations other than arrhythmic including chest pain and heart failure will define the control group In parallel as shown in Figure 1 patients with any evidence of M-Infl will be compared with those showing no signs of M-Infl
To the best of current knowledge there are two points discovered in scientific research namely the description of the arrhythmogenic and inflammatory phenotypes in a broad sense which are summarized here with the acronym AINICM In detail
1 Arrhythmic manifestations account for the arrhythmogenic component of AINICM which is not limited to ACM proper In fact most of the above diseases have a non-arrhythmic clinical presentation and a prevailing tendency to evolve towards a picture of cardiovascular decompensation Although sudden arrhythmic death has been described throughout the spectrum of AINICM early arrhythmic manifestations of such diseases have an unknown prevalence an uncertain association with different disease genotypes and phenotypes and still uncertain predictivity of long-term arrhythmic risk At the same time optimal diagnostic and therapeutic pathways in arrhythmias associated with AINICM are still being studied
2 Myocardial inflammation M-Infl accounts for the inflammatory component of AINICM and has recently been described in association with many AINICM on a genetic basis including undefined and arrhythmic forms The data is of high interest not only in the diagnostic but also in prognostic and therapeutic field In fact on the one hand the presence of M-Infl seems to have a physio- pathological role in AINICM on the other as already known in myocarditis the optimal therapeutic paths of arrhythmias may differ in patients with and without M-Infl in particular also in the light of the preliminary data available in adult and paediatric AINICM the inflammatory forms are expected to respond better to immunosuppressive therapy the arrhythmogenic ones to an ablative therapy with frequent need of implantation of cardiac devices
Based on the clinical presentation NICM patients will be divided into arrhythmic AINICM and non-arrhythmic patients as study and control groups respectively The AINICM group will include presentation with ventricular fibrillation VF either sustained or non-sustained ventricular tachycardia VT NSVT frequent premature ventricular complexes PVC supraventricular arrhythmias SVA and bradyarrhythmias BA Clinical presentations other than arrhythmic including chest pain and heart failure will define the control group In parallel as shown in Figure 1 patients with any evidence of M-Infl will be compared with those showing no signs of M-Infl
Detailed Description:
This study aims to collect clinical data of both retrospective and prospective patients with suspected or proven NICMs in a registry The scope of the registry is to answer multiple unsolved questions in the field of AINICM as described below
1 Improving the diagnostic workup While genetic test and cardiac magnetic resonance CMR constitute the gold standard dagnostic techniques for NICM it is known that A the yield of genetic test is low in NICM B the diagnostic performance of CMR may be limited in AINICM because of cardiac device-related artifacts andor irregular heartbeat In this setting alternative diagnostic techniques namely computed tomography CT scan positron emission tomography PET electroanatomical map EAM and endomyocardial biopsy EMB may be clinically helpful as recommended for the investigation of many arrhythmogenic substrates
2 Identifying disease-specific signatures Genotype-phenoype associations are expected to benefit from a multimodal and multiparametric approach in order to allow etiology-specific features in AINICM Most of the current signatures are limited to combined genotype-CMR studies Signatures would likely benefit from implementing additional parameters including arrhythmia features and myocadial inflammatory status
3 Working our models for risk prediction Outcomes and arrhythmic risk stratification remain uncertain for most NICM Based on an advanced multimodal workup multiparametric risk scores may be created and subsequenlty validated in order to predict the arrhythmic risk of specific cardiomyopathies This would improve and refine the scores currently available for a limited number of NICM such as HCM classic right ventricular ACM or cardiomyopathies secondary to LMNA gene mutation Parameters from clinical arrhythmology and cardiac electrophysiology as well as those related to inflammation may improve the current status of the art about risk prediction
4 Tailoring treatment strategies A multimodal ie by use of multiple diagnostic techniques and multidisciplinary ie by means of a team of cardiac electrophysiologists cardiologists radiologists geneticists immunologists cardiac pathologists pediatricians model may help improving therapeutic strategies in AINICM as already demonstrated in myocarditis In detail treatment options will include guideline-directed cardiological treatment implantable cardiac devices antiarrhythmic drugs immunomodulating agents and catheter ablation of arrhythmias In this setting the coordinating center is an internationally recognized third-level referral center for the management of ventricular arrhythmias and already has advanced facilities including a dedicated multidisciplinary disease unit for myocarditis and inflammatory cardiomyopathies In this setting preliminary evidence suggests a potential benefit from targeting M-Infl even in NICM and AINICM
5 Allowing direct comparison among specific NICM subgroups Extensive inclusion criteria allowing the entry of all NICM in a common registry with homogeneous variables would enable the direct comparison of different AINICM types by means of multiparametric and multimodal characterization for the first time including both the electrophysiological and inflammatory viewpoints This is expected to significantly advance the status of knowledge in the field of NICM
1 Improving the diagnostic workup While genetic test and cardiac magnetic resonance CMR constitute the gold standard dagnostic techniques for NICM it is known that A the yield of genetic test is low in NICM B the diagnostic performance of CMR may be limited in AINICM because of cardiac device-related artifacts andor irregular heartbeat In this setting alternative diagnostic techniques namely computed tomography CT scan positron emission tomography PET electroanatomical map EAM and endomyocardial biopsy EMB may be clinically helpful as recommended for the investigation of many arrhythmogenic substrates
2 Identifying disease-specific signatures Genotype-phenoype associations are expected to benefit from a multimodal and multiparametric approach in order to allow etiology-specific features in AINICM Most of the current signatures are limited to combined genotype-CMR studies Signatures would likely benefit from implementing additional parameters including arrhythmia features and myocadial inflammatory status
3 Working our models for risk prediction Outcomes and arrhythmic risk stratification remain uncertain for most NICM Based on an advanced multimodal workup multiparametric risk scores may be created and subsequenlty validated in order to predict the arrhythmic risk of specific cardiomyopathies This would improve and refine the scores currently available for a limited number of NICM such as HCM classic right ventricular ACM or cardiomyopathies secondary to LMNA gene mutation Parameters from clinical arrhythmology and cardiac electrophysiology as well as those related to inflammation may improve the current status of the art about risk prediction
4 Tailoring treatment strategies A multimodal ie by use of multiple diagnostic techniques and multidisciplinary ie by means of a team of cardiac electrophysiologists cardiologists radiologists geneticists immunologists cardiac pathologists pediatricians model may help improving therapeutic strategies in AINICM as already demonstrated in myocarditis In detail treatment options will include guideline-directed cardiological treatment implantable cardiac devices antiarrhythmic drugs immunomodulating agents and catheter ablation of arrhythmias In this setting the coordinating center is an internationally recognized third-level referral center for the management of ventricular arrhythmias and already has advanced facilities including a dedicated multidisciplinary disease unit for myocarditis and inflammatory cardiomyopathies In this setting preliminary evidence suggests a potential benefit from targeting M-Infl even in NICM and AINICM
5 Allowing direct comparison among specific NICM subgroups Extensive inclusion criteria allowing the entry of all NICM in a common registry with homogeneous variables would enable the direct comparison of different AINICM types by means of multiparametric and multimodal characterization for the first time including both the electrophysiological and inflammatory viewpoints This is expected to significantly advance the status of knowledge in the field of NICM
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None