Journal of the Practice of Cardiovascular Sciences

ORIGINAL ARTICLE
Year
: 2021  |  Volume : 7  |  Issue : 2  |  Page : 121--127

Cardiac amyloidosis in India: A clinicopathological study


Harsh Agarwal1, Tamoghna Ghosh1, Sudheer Arava2, Ruma Ray2, Sandeep Seth3,  
1 Undergraduate, All India Institute of Medical Sciences, New Delhi, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
3 Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
Sandeep Seth
Department of Cardiology, All India Institute of Medical Sciences, New Delhi
India

Abstract

Background: Cardiac amyloidosis (CA) has been rarely reported from India. We aim to describe the experience of diagnosing and treating cardiac amyloid over three decades from a tertiary care center in India. Materials and Methods: Medical records were screened starting from 1987 up to 2019 and patients with histopathological diagnosis of CA were identified. The demographics, clinical presentation, investigations available, prognosis, and outcomes were retrospectively reviewed and analyzed. Results: A total of 40 patients were enrolled, out of which 26 (65%) were males. Median age at presentation was 51 years with a range of 33–65 years. Fatigue, weakness, and shortness of breath were the most common presenting symptoms. Clinical features of systemic amyloidosis including periorbital ecchymosis and macroglossia were present in 7.5% and 10% patients, respectively. Median survival from diagnosis was 2.1 years. Conclusions: Cardiac amyloid is a rarely diagnosed cause of restrictive cardiomyopathy in India and usually fatal. The patients in India are younger than the West. Endomyocardial biopsy is usually required to make a diagnosis of cardiac involvement though magnetic resonance imaging and nuclear imaging may raise a suspicion of cardiac amyloid.



How to cite this article:
Agarwal H, Ghosh T, Arava S, Ray R, Seth S. Cardiac amyloidosis in India: A clinicopathological study.J Pract Cardiovasc Sci 2021;7:121-127


How to cite this URL:
Agarwal H, Ghosh T, Arava S, Ray R, Seth S. Cardiac amyloidosis in India: A clinicopathological study. J Pract Cardiovasc Sci [serial online] 2021 [cited 2021 Dec 4 ];7:121-127
Available from: https://www.j-pcs.org/text.asp?2021/7/2/121/325226


Full Text



 Introduction



Cardiac amyloid is an uncommon cause of restrictive cardiomyopathy (RCMP). The diagnosis is important both for prognosis and treatment. Among patients with systemic amyloid, cardiac involvement is a bad prognostic markers as 40% of patients die from heart failure or rhythm disturbances. In a endomyocardial biopsy (EMB) series from mayo clinic of 454 patients, 7% (30) had evidence of systemic/cardiac amyloid.[1] In a histopathological series from India, of RCMP, 18 (25%) of a series of seventy patients biopsied with a diagnosis of restrictive heart disease had cardiac amyloid.[2]

Any part of the heart can be involved in amyloidosis. Importantly, myocardial deposition of amyloid leads to infiltrative cardiomyopathy, stiffening, diastolic dysfunction, and consequent restrictive cardiomyopathy.[3],[4],[5] Structural and functional changes on echocardiography can suggest the presence of amyloid, but cardiac magnetic resonance and nuclear imaging provide important complementary information on amyloid burden and the amyloid subtype, respectively.

Data from India are lacking regarding cardiac amyloid except for isolated case reports. Most diseases in India have a different profile as compared from the West.

This study discusses various clinicopathological as well as investigational features of forty patients who presented with cardiac involvement of amyloidosis in a tertiary care center in India.

 Materials and Methods



The present study is a retrospective analysis of forty histopathologically diagnosed cases of CA encountered between 1987 and 2019. Patient records were accessed from the pathology record files and then clinical record files were accessed to retrieve clinical, electrocardiogram (ECG), and echocardiogram data. EMB had been performed in all these patients.

The pathology data were classified for amyloid distribution based on hematoxylin and eosin staining and Congo red staining into interstitial and vascular deposits. The ECG was screened for rhythm disturbances and voltage heights. The echocardiograms were reviewed for ventricular wall hypertrophy and function. Patients/their families were contacted for their current status.

 Results



The data of forty patients could be reviewed. Majority of the patients were males (65%). Age range was found to be 33–65 years of age with a median age of 51 years [Figure 1]. The mean standard deviation duration of symptoms was 5.2 + 2.1 months [Figure 2]. The most common symptoms reported were dyspnea on exertion, fatigue, and weakness. Comorbidities included hypothyroidism (10%), hypertension (5%), and diabetes mellitus (12.5%). At initial presentation, majority of the patients had minimal symptoms [[Table 1], New York Heart Association (NYHA) I = 33%, NYHA II 42%]. Hallmark features of periorbital ecchymosis and macroglossia were present in 7.5% and 10% of patients, respectively.{Figure 1}{Figure 2}{Table 1}

Majority of the patients had ECG abnormalities (95.2%). Low limb leads' voltage (low voltage on the ECG defined as a peak-to-peak QRS amplitude of <5 mm in the limb leads and/or <10 mm in the precordial leads) was found in 80.9% of patients. First-degree AV block, second-degree AV block, and left bundle branch block were found in one patient each. Poor R wave progression was found to be in 9.5% of patients [Table 2] and [Figure 3].{Figure 3}{Table 2}

On echocardiography [Figure 4], majority of the patients had ventricular hypertrophy (90%), with 55% having isolated left ventricular (LV) hypertrophy, whereas 35% of patients had biventricular hypertrophy and a presentation like a RCMP [Table 3]. Ten percent of the patients showed biatrial enlargement. Thirty five percent of patients had decreased LV ejection fraction, whereas 5% patients showed decreased right ventricular ejection. Five percent of patients showed thickened atrial septum [Table 4].{Figure 4}{Table 3}{Table 4}

Data on magnetic resonance imaging (MRI) were available in this series from three patients. It showed diffuse subendocardial perfusion defects seen in basal to apical LV and thickened IAS and lateral wall of RA with diffuse patchy areas of LV and septal subendocardial to transmural myocardial Late Gadolinium Enhancement (LGE) in all of the three patients [Figure 5].{Figure 5}

Histopathology findings

On EMB, all the patients had deposition of extracellular eosinophilic material which was further confirmed by Congo red (exhibiting apple green birefringence on polarized microscopy) and crystal violet (showing metachromasia). Predominant interstitial deposition was noted in 33 biopsies. The rest of the seven cases showed prominent vascular deposition of amyloid. Twenty five out of 40 biopsied revealed both vascular and interstitial amyloid deposits [Figure 6],[Figure 7],[Figure 8],[Figure 9],[Figure 10]. No amyloid typing was done.{Figure 6}{Figure 7}{Figure 8}{Figure 9}{Figure 10}

Abdominal fat pad biopsy was performed in six patients, of which five had amyloid deposition suggesting systemic involvement. Four patients underwent bone marrow aspiration and biopsy, of which two showed increase number of plasma cells (20% and 22%, respectively) [Figure 11]. Amyloid deposition was not seen in bone marrow biopsy specimens. Bone marrow biopsy revealed plasma cells suggestive of multiple myelome in a few patients [Figure 12] and they were aggressively treated with steroids and melphelan.{Figure 11}{Figure 12}

On comparing findings in different NYHA classes [Table 5], it was found that all (100%) NYHA III-IV patients showing invariably low limb voltages, interstitial and vascular positive amyloid deposits on EMB, and LV hypertrophy and RCMP feature, 80% of them showing biventricular hypertrophy and decreased ejection fraction. One patient, who was Class IV had syncope, received a pacemaker but died in hospital due to pacing failure within 3 days of pacemaker implant with the pacemaker interrogation showing pacing spikes but no capture (probably due to electromechanical dissociation due to cardiac amyloid).{Table 5}

Data on mortality were available on seven patients out of 21 patients for whom we could collect follow-up and clinical information [Table 6],[Table 7] and [Figure 12] and [Figure 13]. The median (range) survival was 25 (5–49) months. The patients who died had a median age of 48 years and died within 2 years of diagnosis.{Figure 13}{Table 6}{Table 7}

 Discussion



In this retrospective clinicopathological study, we have described the findings of forty patients of cardiac amyloidosis (CA) who were all diagnosed by EMB. Most of them were diagnosed clinically by low voltages along with LV or biventricular hypertrophy on echocardiogram. They had normal or low LV function. Those presenting with NYHA Classes III and IV had a poor prognosis with worse ECG and histopathological findings and a median survival from diagnosis of about 2 years.

Our patients of cardiac amyloid could not be subcharacterized into subtypes, but the most common type of cardiac amyloid is systemic AL amyloid whereas transthyretin CA is less common and occurs in the elderly (age >70 years, 90% male). It can be associated with B-cell dyscrasias such as multiple myeloma, lymphoma, or macroglobulinemia, but majority are benign monoclonal gammopathies with multiorgan infiltration. It occurs usually above the age of 50 years but can occur as early as the third decade.[6],[7],[8],[9],[10] In our series, the youngest patient was 33 years, the age range was 33–65 years, and the median age was 51 years which is similar to Western data. Cardiac amyloid distribution (AL type) is similar in men and women (>60% men) which is similar to our data.[11]

The patients with cardiac amyloid present with congestive heart failure, conduction blocks, and ventricular hypertrophy picked up on screening of multiple myeloma patients. Patients presenting late have a poorer prognosis.[12] In a series of 168 patients, low voltage on limb leads (54%) and pseudoinfarct patterns (28%) were the most common ECG findings.[13] In our series, 81% had low voltages and 9.5% had a pseudoinfarct pattern. Bradyarrhythmia in that series[13] was in 13%, while in our series, it was 19%. In our series, only 5% of the ECG were normal, the rest having either changes in voltage or some conduction abnormalities.

In a series of 28 patients describing the echocardiographic features of cardiac amyloid, there was LV hypertrophy in 88%, normal ventricular dimensions in all, and reduced ventricular function in 62%.[14],[15],[16],[17],[18] In our series, 90% of the patients had ventricular hypertrophy, 35% had LV dysfunction, and 10% had interatrial septal thickening. Ventricular septal speckling was not commonly mentioned in the echocardiogram reports reviewed.

MRI was available in some of these patients since this was a study spanning three decades. Diffuse thickening and patchy late gadolinium uptake were picked up in some of the patients. The most frequent pattern described on MRI is global transmural or subendocardial LGE.[10],[19],[20] Newer advanced techniques are also used now but are not the subject of the current paper.

Our series reports patients of cardiac amyloid where the diagnosis was based on EMB; therefore, all had features of amyloidosis on biopsy. In a published series of 108 patients of cardiac amyloid, 85% showed amyloid deposition in the interstitium. Vascular deposition was also there in 72%. In an autopsy series of 47 hearts with cardiac amyloid, the findings were graded based on the extent of amyloid deposits and vascular involvement. Clinically, significant amyloid was associated with more than 10% amyloid deposition and involvement of intramyocardial arterioles. In another study of 216 patients, multivariate analysis showed that NYHA class, kidney function, amyloid load, and response to chemotherapy were independent predictors of survival, and the responders had a better survival (16.2 vs. 1.4 months).[21],[22],[23],[24],[25] In our series of forty patients, 82% of the patients had interstitial amyloid deposits, and vascular deposits were there in 63% denoting a sick subgroup of patients. Patients in our series who were Class III and IV were characterized by a significantly higher prevalence of low limb voltages (100%), conduction system problems (8%), interstitial amyloid deposits (100%), vascular deposits (100%), biventricular or LV hypertrophy (100%), and reduced ejection fraction (80%). This is similar to the published literature wherein low voltages on limb leads, significant hypertrophy, higher NYHA class, significant interstitial and vascular amyloid deposits, and reduced ejection fraction all portend a bad prognosis. In this series, the median survival of the patients was 25 months from diagnosis.

Limitations of the study

This is a retrospective study based on chart reviews along with a limited follow-up which could be done of some of the patients, since the study spanned data over a 30-year period. We could get data on survival only on some of the patients, but these data were similar to published literature. We did not get data on chemotherapy, MRI details using the newer techniques. Subclassification of amyloidosis could not be done on endomyocardial biopsies due to nonavailability of appropriate immunohistochemical stains.

 Conclusions



In this study of cardiac amyloidosis in India, we found that the disease presents with heart failure with preserved ejection fraction with unexplained ventricular hypertrophy, low limb voltages on ECG. The diagnosis is made by doing an EMB from the right ventricle. Overall, the prognosis of the disease is not very good though most patients have received chemotherapy. The median survival of patients is 2 years. The markers of poor prognosis include sicker patients, more extensive and vascular amyloid deposits, and more significant hypertrophy with poor cardiac function on echocardiography.

Acknowledgments

The authors express their sincere gratitude to the Department of Cardiology and Department of Pathology, All India Institute of Medical Sciences, New Delhi, India, for their encouragement and motivation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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