Clinical trial NCT06129331: Aortic Stenosis and Cardiac Amyloidosis
Official title: Aortic Stenosis and Cardiac Amyloidosis: A Pragmatic, Streamlined International
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cardiac Amyloidosis
Aortic Stenosis
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: Allina Health System
name: Royal Free Hospital NHS Foundation Trust
name: Columbia University
name: Medical University of South Carolina
name: Laval University
name: Vilnius University Hospital Santaros Klinikos
name: Université Catholique de Louvain
name: Wolfson Medical Center
name: IRCCS Azienda Ospedaliero-Universitaria di Bologna
name: University of Trieste
First posted: 2023-11-13
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a dual pathology of significant aortic stenosis and concomitant cardiac amyloidosis

Brief summary: The dual pathology of aortic stenosis (AS) and cardiac amyloidosis (CA) is increasingly recognized. Even tough efforts have been undertaken to bring cohorts together, the largest cohort of AS-ATTR to date is \<50 patients. It is the aim of the present international, multi-center registry to collect \~300 patients with AS-CA creating a big enough cohort to allow

1. thorough characterization of this condition
2. assessment of log-term clinical outcomes of AS-CA
3. assessment of effectiveness of amyloid-specific treatment on top of valve replacement

Detailed description: Calcific aortic stenosis (AS) and transthyretin (ATTR) cardiac amyloidosis are both conditions commonly affecting the elderly. Bone scintigraphy using amyloid-avid tracers (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, DPD; 99mTc-pyrophosphate; or 99mTc-hydroxymethylene diphosphonate) represents the key imaging modality for non-invasive ATTR diagnosis. Recent studies have used this technology to screen AS patients and demonstrated that AS and ATTR may coexist in 8 to 16%. This is substantially higher than in non-cardiac referrals for bone scintigraphy (range 1-3% in individuals \>80 years), which is considered the most accurate approach to estimate the ATTR prevalence in the general population. While the dual burden of AS and ATTR might suggest adverse prognostic implications, it has been shown that AS-ATTR and lone AS patients benefit equally from transcatheter aortic valve replacement (TAVR) with comparable 1- and 2-year survival rates. Yet, data on long-term outcomes are still missing.

With increased recognition and valvular treatment of AS-ATTR, the disease course after TAVR becomes a key issue. Our data suggest significantly different remodeling between lone AS and AS-ATTR, with the latter being transformed into a "lone-ATTR" cardiomyopathy phenotype at one-year post-TAVR. Novel ATTR-specific treatments are now available, with the potential to further improve prognosis in AS-ATTR on top of valvular replacement. However, patients with significant AS were not included in the ATTR-ACT trial, and treatment effectiveness in this patient population therefore remains unclear. Also, despite increased ATTR screening globally, the case numbers for dual AS-ATTR of individual centers are still low.

The present international multi-center study is therefore designed to provide detailed characterization of dual AS-ATTR, inform about long-term clinical outcomes and assess the effect of ATTR specific treatment.

Eligibility criteria: Inclusion Criteria:

* Patients with significant AS and a concomitant diagnosis of cardiac amyloidosis who are eligible for inclusion as per local permissions

Exclusion Criteria:

* Patients without significant AS (less than moderate AS)
* Patients with other subtypes of cardiac amyloidosis (e.g., light chain)

Primary outcomes:
measure: Phenotyping of AS with "early" ATTR infiltration (DPD grade 1) versus "advanced" ATTR cardiomyopathy (DPD grade 2/3)
timeFrame: 0 months
measure: All cause mortality in AS-CA with versus without CA-specific treatment
timeFrame: 60 months
measure: Hospitalization for heart failure in AS-CA with versus without CA-specific treatment
timeFrame: 60 months
measure: Cardiovascular mortality in AS-CA with versus without CA-specific treatment
timeFrame: 60 months
Secondary outcomes:
measure: Natural history of AS-ATTR after valve replacement
timeFrame: 60 months
measure: Composite of hospitalization for heart failure and/or death in AS-CA with versus without CA-specific treatment
timeFrame: 60 months
measure: Heart failure hospitalzation rate in AS-CA with versus without CA-specific treatment
timeFrame: 36 months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
city: London
country: United Kingdom
facility: University College London
Study officials:
References:
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