A Case Series on Patients of Cardiac Amyloidosis with Varying Initial Clinical Presentation in a Tertiary Health Care Cardiology Outpatient Service, Kerala

Antony P Pathadan; Suresh Davis; Ramdas Nayak; Jacob George; Sahala Abbas; Latha K Abraham

Case Series

Austin Cardio & Cardiovasc Case Rep. 2022; 8(1): 1050.

A Case Series on Patients of Cardiac Amyloidosis with Varying Initial Clinical Presentation in a Tertiary Health Care Cardiology Outpatient Service, Kerala

Antony P Pathadan¹; Suresh Davis²; Ramdas Nayak¹; Jacob George¹; Sahala Abbas⁴*; Latha K Abraham³

¹Department of Cardiology, Rajagiri Hospital, India

²Department of Cardiology, Diploma in Diabetology, Rajagiri Hospital, India

³Department of Pathology, Rajagiri Hospital, India

⁴Department of Cardiology, Medical Officer, Rajagiri Hospital, India

*Corresponding author: Sahala Abbas Department of Cardiology, Medical Officer, Rajagiri Hospital, Kerala, India.

Received: February 22, 2023 Accepted: March 29, 2023 Published: April 05, 2023

Abstract

The study aims to assess the outcome of early diagnosis in cardiac amyloidosis and to emphasize the need for high clinical index of suspicion even before onset of cardiac symptoms. Recent advances in immunohistochemical markers, molecular and genetic studies carry early diagnostic and grave prognostic significance. This study concludes a significant inverse relationship between time of diagnosis after the onset of cardiac symptoms and percentage survival rate of the affected individuals.

Introduction

Cardiac Amyloidosis (CA) has emerged as an underdiagnosed cause of Heart Failure (HF) that is associated with significant morbidity and mortality, particularly in later stages of disease [1,2]. Heart failure with amyloidosis is associated with higher odds of in-hospital mortality, 30-day readmission, and a longer length of hospital stay. It may be the presenting feature of the disease or may be identified while investigating a patient presenting with other organ involvement.

Small, single-centric studies have estimated the prevalence of Cardiac Amyloidosis as 13% among patients with {HF with preserved ejection fraction} [3,4]. Most cases of Cardiac Amyloidosis are of either transthyretin type, which may be acquired in older individuals or inherited in younger patients, or acquired monoclonal immunoglobulin light chain (AL) type.

Significant advances in non-invasive diagnostic testing [5,6] and targeted amyloid therapeutics [7] have piqued clinical enthusiasm; however, diagnostic delays of up to 34 months still persist [8,9]. Amyloidosis being a systemic disorder, biopsies can be obtained from several sites, including the heart {in ATTR -transthyretin amyloidosis}, due to predominant cardiac involvement), abdominal fat pad, bone marrow (as part of work-up for plasma cell dyscrasia in suspected AL amyloidosis), or kidney [1].

Prognosis in amyloidosis depends predominantly on the degree of cardiac involvement. Atrial fibrillation is common and is assosiated with poor prognosis. Though the prognosis is better in ATTR amyloidosis, both types of amyloidosis carry a high risk of mortality. As a result, timely diagnosis is critical to allow treatment initiation in earlier stages of disease, where inhibition of amyloid fibril formation has greater clinical benefit. Treatment for amyloidosis has evolved significantly over the past several years [7]. Treatment follows two parallel paths:

A) Treating the consequence of organ dysfunction and attempting to slow the progression of disease with chemotherapy against the plasma cells.

B) Cardiac specific treatment including {diuretics/salt restriction} and managing arrhythmias.

Currently available therapies include transthyretin stabilizers and transthyretin synthesis inhibitors for transthyretin amyloidosis, chemotherapy and autologous stem cell transplantation for light chain amyloidosis, and cardiac transplantation for selected patients with advanced HF [10]. ACE-Inhibitors, Angiotensin Receptor Blockers and Beta blockers are poorly tolerated and may result in profound hypotension. Pacemakers are frequently required due to assosiated conduction disease .As the disease is irreversible with high mortality, a cardiac transplant may be considered in indicated patients.

Methods

The study was a retrospective study with one year follows up of the patients conducted in the department of cardiology, Rajagiri hospital. The study subjects included all patients who were diagnosed with cardiac amyloidosis in Rajagiri hospital from time period August 2020 to August 2021. The relevant cinical information were obtained from electronic case report of the patient. Cinical details that were collected included age, gender, BMI(kg/m2), associated comorbidities, intial presenting symptoms and assessment of of liver, spleen and other organ involvement was done. The haemoglobin, serum creatinine, NT proBNP, 24 hour urine protein ratio, troponin, baseline LV function at the time of diagnosis was studied. Genetic study done by the patient was analasyed. Fat pad biopsy, immunohistochemistry slides of the patients available in department of pathology was studied for identifying the type of amyloidosis. The data was then entered in spread sheets of Microsoft Office Excel and the variables were compared quantitatively and qualitatively. The treatment details in relation to number of chemotherapy cycles [CyboR-D based chemotherapy), stem cell transplantation were collected from the department of hematology. The treatment follow of the patient was continued for a period of one year by simultaneously entering them in the spreadsheet and the results were tabularised as in (Table 1). These patients were furthur divided according to revised Mayo prognostic index 2012.

Figure 1: Echocardiogram of patient with cardiac amyloidosis showing biatrial enlargement.

    
    
    Figure 1: Echocardiogram of patient with cardiac amyloidosis showing biatrial enlargement.

Figure 2: Apple green bifringence wit congo red stain of abdominal fat pad biopsy specimen.

    
    
    Figure 2: Apple green bifringence wit congo red stain of abdominal fat pad biopsy specimen.

Table 1: One year follow up details of the patients included in the study.




  
    Basic    Characterstics
    1
    2
    3
    4
    5
    6
    7
    8
  
  
    Age (years)
    63 years
    41 years
    72 years
    63 years
    53 years
    51 years
    68 years
    69 years
  
  
    Gender
    Female
    Female
    Male
    Male
    Female
    Female
    Male
    Male
  
  
    BMI (kg/m2)
    26.3
    26
    16
    63
    21
    22
    22
    26
  
  
    Comorbidities
    Nil
    Nil
    CAD ,

      COPD
    CKD,

      CLD
    DLP    hypothyroidism
    DM
    Nil
    Hypothyroidism    Hypertension Dyslipidemia 
  
  
     
      Initial    presentation
     
      CCF
     
      Arthralgia
     
      weight loss
     
      VT
     
      CCF
     
      weight

        loss,

        malaena
    Difficulty

      in walking

      since

      5years worsened

      in past 1 year.
    Recurrent    syncope,

      limb

      weakness

      and

      spasticity.
  
  
    Other

      organ    involvement
    liver
    Shoulder    joint , liver
    Lung- type 2    respiratory failure
    Gastroparesis-antral    ulcers
    liver ,spleen
    Liver,

      chronic    proctitis, chronic deodinitis
    Hypotonia Sensori-motor    axonal polyneuropathy

      gastric ulcer
    Chronic 

      Sensori-motor    polyneuropathy- 
  
  
    Hemoglobin(g/dl)
    10.2
    11.8
    13.4
    10.4
    13.2
    11.4
    15
    12
  
  
    Serum    creatinine
    0.8
    0.9
    1.2
    2.7
    4.4
    0.9
    0.7
    1.2
  
  
    NT proBNP
    7096
    553
    5058
    15,070
    > 25,000
    4311
    279
    500
  
  
    Troponin
    0.26
    negative
    0.12.
    0.14
    0.8
    0.05
    negative
    negative
  
  
    DFLC

      (kappa    -3.3-19) Lamda -5.7-26}
    Kappa-6

      Lamda-448
    Kappa-6380

      Lamda-9
    Kappa-20

      Lamda-874
    Kappa-12

      Lamda-4401
    Kappa -20

      Lamda-133
    Kappa-1123

      Lamda-35
    Kappa -17.44

      Lamda -12.61
    Kappa -23

      Lamda -12
  
  
    FreeKappa    /lamda

      ratio    {0.26-1.65}
    0.01
    708
    0.02
    0.002
    0.15
    31.4
    1.38
    1.9
  
  
    
      Hour Urine Protein (<150)
    
    130
    250
    146
    1785
    5481
    1689
    NA
    NA
  
  
    Bone marrow    plasma cells

      (% nucleated    marrow cells)
    39%
    4%
    2%
    26%
    4%
    7%
    2%
    8%
  
  
    Baseline LV    function
    60%
    60%
    55%
    35%
    40%
    60%
    60%
    60%
  
  
    Genetic study
    Not done
    Not done
    Not done
    Not done
    Not done
    Not done
    TTR+ on exon 5 hetrozygous -heriditary    amyloidosis {autosomal dominant}.
    TTR+ on exon 5 hetrozygous -heriditary amyloidosis    {autosomal dominant }.

      PMP22(-) Exon5hetrozygous -heriditary amyloidosis    {autosomal dominant}.
  
  
    Time from

      onset

      of symptoms

      to

      diagnosis    (months)
     
      2 months
     
      4 months
     
      1 year
     
      2 year
     
      4 months
     
      8 months
     
      1 year
     
      8 months
  
  
    Treatment    regimen

      (CyboR-D

      based    chemotherapy)
    Tolerated 

      12 cycles

      of    chemotherapy
    Chemotherapy    followed

      by stem cell    transplantation
    Initiated

      on    chemotherapy, but could not tolerate
    Initiated

      on    chemotherapy,

      But couldn�t tolerate
    Tolerated

      12 cycles

      of    chemotherapy
    Initiated

      on    chemotherapy
    Intiated

      on chemotherapy
    Tolerated 

      12cycles

      of    chemotherapy
  
  
    One year

      follow up    details
    On    maintainance
    On    mainatainance
    Cardiac    arrest
    Cardiac    arrest
    On    maintenance
    On    maintenance
    On maintainance
    On

      mainatainance



Table 1: One year follow up details of the patients included in the study.

Discussion

A total of 8 patients were included in the study. The predominant age group affected was 60-70 years with mean age group as 60 years. Cardiac involvement in amyloidosis presents commonly with arrhythmias and/or rapidly progressing heart failure or occasionally with polyneuropathy, arthralgia or gastrointestinal symptoms. Once a patient develops cardiac symptoms, they usually have large amount of amyloid in the heart. Amyloid deposit in the atrium causes an irregular surface that makes these patients prone to thrombus formation, irrespective of atrial fibrillation development. Amyloid fibrils cause stiffening of heart which explains restrictive physiology found on echocardiogram.

Genetic study encouraged early diagnosis. Patients diagnosed with short duration of symptoms had good prognosis even though they presented in heart failure. Meanwhile patients diagnosed with long duration of symptoms had poor prognosis even though they were not in failure. A better treatment outcome in seen in patients who had stem cell transplantation following chemotherapy. The patients with assosiated multiorgan failure couldn’t tolerate chemotherapy and succumbed to death while the rest are on maintainance on one year follow up.

Thus we could see in our study, a significant inverse relationship between time of diagnosis after the onset of cardiac symptoms and their life expectancy rate and could conclude high clinical index of suspicion is needed for early diagnosis and good outcome.

Author Statements

Acknowledgement

The authors express sincere gratitude to Dr Mobin Paul, Department of Hemato Oncology, Rajagiri hospital for sincere guidance and moral support throughout the course of their work.

Funding

No funding sources

Conflict of Interest

None declared.

Informed Consent

Written informed consent was obtained from the patient.

References

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Citation: Pathadan AP, Davis S, Nayak R, George J, Abbas S, et al. A Case Series on Patients of Cardiac Amyloidosis with Varying Initial Clinical Presentation in a Tertiary Health Care Cardiology Outpatient Service, Kerala. Austin Cardio & Cardiovasc Case Rep. 2023; 8(1): 1050.

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