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Analysis of Calcium Score of Severe Aortic Stenosis in Patients With and Without Cardiac Amyloidosis (CAUSATIVE Study)

Recruiting
Conditions
Aortic Stenosis, Severe
Amyloidosis Cardiac
Registration Number
NCT06066632
Lead Sponsor
University Hospital of Ferrara
Brief Summary

The concomitant presence of cardiac amyloidosis (CA) in patients with aortic stenosis (AS) may challenge the estimation of stenosis degree. In patients with dual pathology (AS + CA) the most frequent AS hemodynamic profile is paradoxical low-flow, low-gradient AS.

In this setting, estimating stenosis degree with cardiac ultrasound may be challenging and aortic valve calcium score estimation by cardiac CT is a valuable exam.

Preliminary findings from small case series showed that patients with severe AS and CA presented less valvular calcium deposition compared to patients with severe AS alone. On this basis, confirmation of these findings would have a huge clinical impact on diagnosis, choice of treatment strategy and understanding of the pathophysiology of these patients.

The aim of the study is to study the correlation between valvular calcium score (assessed by EKG-gated CT) and effective orifice area (assessed through echocardiogram) according to cardiac amyloidosis presence (in the overall population and among hemodynamic phenotypes of cardiac amyloidosis).

As secondary endpoints the study will sought to assess TAVI/SAVR efficacy, procedural complications, in-hospital mortality, all-cause death and heart failure hospitalization at 1 year, according to absence or presence of CA.

Detailed Description

Aortic stenosis (AS) is the most common valvular pathology in the elderly population, and there is an anticipated increase in prevalence and associated costs for treating this condition in the future. In a non-negligible percentage of cases (approximately 15%), another pathology is associated, namely cardiac amyloidosis, especially in the wild-type ATTR form. Patients with both pathologies (AS+ATTR) have a worse prognosis compared to those with AS alone. Based on the available data up to now, ATTR-associated amyloidotic cardiomyopathy does not appear to significantly influence the immediate outcome of TAVI or short-term outcomes. However, among patients with amyloidosis, there is an increased frequency of heart failure in subsequent follow-ups. The mechanism behind this dual pathology remains unclear. Epidemiological similarities (advanced age) alone do not explain the association. It is possible that there is a direct causal link between amyloidosis and aortic stenosis (amyloidosis as a co-cause or contributing factor to valvular stenosis), or that the elevated intramyocardial strain due to degenerative valvular stenosis promotes amyloidogenesis and myocardial infiltration. Understanding the extent of valvular calcifications in individual cases would provide better insights into the pathogenesis of this dual pathology. There are also diagnostic implications. Amyloidosis could potentially complicate the accurate classification of the severity of aortic pathology. For example, patients with AS+ATTR often exhibit a "low-flow low-gradient" paradoxical hemodynamic profile. In these cases, estimating the valve area with an echocardiogram is challenging, and evaluating the valvular calcium score through CT assumes an important diagnostic role. Preliminary studies suggest that, for the same degree of stenosis severity, there may be a lower quantity of calcium in the valves of patients with AS+ATTR compared to those with AS alone. Preliminary studies suggest that, for the same degree of stenosis severity, there may be a lower quantity of calcium in the valves of patients with AS+ATTR compared to those with AS alone. In a 1:1 propensity matching of over 300 patients (mostly without aortic stenosis), those with amyloidosis had lower aortic valvular calcium scores (p\<0.01). In a small series of 13 cases with AS+ATTR, 12 had aortic valvular calcium scores below the severity cut-offs recommended by the guidelines. If confirmed, traditionally used calcium score cut-offs may be inadequate, with significant implications for treatment selection and therefore prognosis.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
480
Inclusion Criteria
  • signed informed consent
  • age ≥65 years old
  • severe AS
  • planned or performed TAVI/SAVR
  • at least one red-flag suggestive of CA
  • availability of EKG-gated CT
  • availability of echocardiogram performed before TAVI/SAVR
  • availability of bone scintigraphy performed within 1 year from CT
Exclusion Criteria

• suboptimal acoustic window that may undermine the assessment of AS severity and phenotype profiling

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Correlation between valvular calcium score and effective orifice area.Up to 12 months

Correlation between valvular calcium score (assessed by EKG-gated CT) and effective orifice area (assessed through echocardiogram) according to cardiac amyloidosis presence (in the overall population and among hemodynamic phenotypes of cardiac amyloidosis).

Secondary Outcome Measures
NameTimeMethod
In-hospital MortalityAt an average of 12 months

In-hospital Mortality will be assessed from hospital records

All-cause Mortality and Heart Failure HospitalizationAt an average of 12 months

The composite of all-cause Mortality and Heart Failure Hospitalization will be assessed through clinical follow-up, hospital records, and telephone follow-up.

Procedural ComplicationsAt an average of 12 months

Procedural complications will be assessed as per VARC definitions

TAVI/SAVR efficacyAt time of post-procedural echocardiographic assessment (through study completion, an average of 1 month)

Echocardiographic effective orifice valvular area (EROA) will be assessed and reported in cm2.

Trial Locations

Locations (1)

University Hospital of Ferrara

🇮🇹

Ferrara, Italy

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