Prevalence, Predictors and Diagnosis of Cardiac Amyloidosis in Patients with Aortic Stenosis

Syed Bukhari

doi:10.37871/jbres1796

ISSN: 2766-2276

Medicine Group . 2023 September 13;4(9):1277-1280. doi: 10.37871/jbres1796.

Subject area(s)

Cardiovascular Diseases

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Mini Review

Prevalence, Predictors and Diagnosis of Cardiac Amyloidosis in Patients with Aortic Stenosis

Syed Bukhari*

Department of Medicine, Temple University Hospital, Jeanes Campus, USA

*Corresponding author: Syed Bukhari, Department of Medicine, Temple University Hospital, Jeanes Campus, USA E-mail:

Received: 23 August 2023 | Accepted: 12 September 2023 | Published: 13 September 2023

How to cite this article: Bukhari S. Prevalence, Predictors and Diagnosis of Cardiac Amyloidosis in Patients with Aortic Stenosis. 2023 Sep 13; 4(9): 1277-1280. doi: 10.37871/jbres1757, Article ID: jbres1757

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Abstract

Cardiac amyloidosis and aortic stenosis often share a common clinical phenotype, and are associated with morbidity and mortality if untreated. Cardiac amyloidosis is present in ~15% of patients with aortic stenosis. Clinical suspicion for cardiac amyloidosis in aortic stenosis is often raised based on history (bilateral carpal tunnel syndrome, severe lumbar spinal stenosis, spontaneous biceps rupture), chronic troponin elevation, electrocardiographic features (low-voltage criteria, pseudoinfarct pattern), echocardiogram (bilateral ventricular hypertrophy, abnormal longitudinal strain) and magnetic resonance imaging (late gadolinium enhancement, elevated T1 and T2). Eventual diagnosis of cardiac amyloidosis is based either on pyrophosphate nuclear scintigraphy or tissue biopsy depending on which subtype of cardiac amyloidosis is suspected.

Introduction

Cardiac Amyloidosis (CA) is a restrictive cardiomyopathy resulting from myocardial amyloid fibril deposition [1,2]. The amyloid deposits primarily originate either from transthyretin (ATTR), which is a transporter protein produced in the liver, or from light chain immunoglobulins (AL) secreted by the plasma cells in bone marrow [3,4]. ATTR is further subdivided into wild-type (wtATTR) and variant (vATTR) depending on the absence or presence of mutation in the TTR gene, respectively [5,6]. While ATTR is diagnosed noninvasively with Tc-pyrophosphate scintigraphy, diagnosis of AL always requires tissue confirmation [7-9].

Calcific Aortic Stenosis (AS), like CA, is a common disease in the elderly population, and co-existence of CA and AS is not infrequent. Both CA and AS have several clinical features in common, making the diagnosis of CA difficult. Studies have indicated that CA in AS (CA-AS), if untreated, is associated with increased risk of heart failure, mortality, and treatment futility with aortic valve replacement [10]. In this mini-review, we discuss about the prevalence, predictors and diagnosis of CA-AS.

Prevalence of CA-AS

The prevalence of CA-AS is reported to range from 6% to 16% [11-13]. In a study of 407 patients (age 83.4 ± 6.5 years; 49.8% men) who were referred for Transcatheter Aortic Valve Replacement (TAVR) at Barts Heart Centre, London, United John Radcliffe Hospital, Oxford, and Vienna General Hospital, Vienna, CA was diagnosed in 48 (11.8%) patients, and CA-AS had worse clinical presentation and a trend toward worse prognosis, unless treated [11]. In another study of 200 patients aged ≥75 with severe AS referred for Transcatheter Aortic Valve Implantation (TAVI), CA-AS was found in 26 (13%) [12]. TAVI significantly improved outcome in CA-AS, while periprocedural complications and mortality were similar to lone AS, suggesting that TAVI should not be denied to patients with CA-AS [12]. Another study showed that occult wtATTR had a prevalence of 6% among patients with AS aged >65 years undergoing surgical aortic valve replacement and was associated with a poor outcome [13].

Predictors of CA-AS

There are several features that can predict CA in a patient with AS. Bilateral carpal tunnel syndrome has been associated with CA, and is known to precede CA by ~6-10 years [14,15]. There are other orthopedic manifestations including trigger finger, spontaneous rupture of the biceps tendon and severe lumbar spinal stenosis that are commonly associated with CA, and hence could help predict CA-AS [16-18]. Chronic troponin elevation is often noted due to myocardial injury caused by amyloid fibrils. In addition, CA is also associated with a high prevalence of atrial fibrillation, and is also noted to have a significantly elevated thromboembolic risk [19-21].

There are specific electrocardiographic features that are associated CA. These include low-voltage QRS, first degree atrioventricular block, pseudo-infarct pattern, fascicular and bundle branch block [22]. On echocardiogram, biventricular thickness is often associated with CA. In addition, the discrepancy between echocardiographic findings of ventricular hypertrophy and low voltage QRS on electrocardiogram can help to distinguish CA from other mimics including AS and hypertrophic cardiomyopathy [23-25].

Diagnostic Evaluation of CA-AS

The diagnostic evaluation starts with speckled-tracking echocardiography. The presence of abnormal longitudinal strain and ‘cherry-on-top’ apical sparing pattern raises strong suspicion for CA [7]. Apical sparing pattern is not seen in lone AS.

Cardiac MRI (CMR) is more useful than echocardiogram in diagnosing CA. Importantly, while CMR can distinguish CA from other etiologies of left ventricular thickness, including Fabry’s disease and lone AS, it cannot differentiate between ATTR and AL [7]. Late gadolinium enhancement is pathognomonic for CA. In addition, elevated extracellular volume, and elevated T1 and T2 are other reliable markers that can help consolidate the diagnosis of CA [7].

The only reliable way of non-invasively diagnosing ATTR is Tc-pyrophosphate scintigraphy [26,27]. Tc-pyrophosphate scintigraphy cannot diagnose AL. However, due to mild uptake of the tracer in AL, blood and urine protein electrophoresis and immunofixation are simultaneously ordered to rule out the possibility of AL [28,29]. Positive Tc-pyrophosphate scan and absence of paraproteinemia establishes the diagnosis of ATTR. The diagnosis of AL requires tissue biopsy, often either endomyocardial or bone marrow tissue. TAVR should not be withheld in CA-AS, as it can adversely impact prognosis [30,31].

Conclusion

CA and AS are diseases of the elderly, and can co-exist, but it could be challenging to diagnose CA-AS. It is important to identify predictors of CA-AS, and have knowledge of diagnostic algorithm to timely diagnose and treat CA, which impacts survival in AS patients.