Clinical Characteristics and One-Year Outcomes in Patients with Cardiac Amyloidosis

Abstract

Abstract:

Background: Light-chain (AL) amyloidosis is a rare disorder causing organ dysfunction through amyloid fibril deposition, with cardiac involvement conferring significant morbidity. This case series describes the clinical profiles, diagnosis, and one-year outcomes of six patients with AL amyloidosis.

Case Presentation: Six patients (median age 58 years, range 41 to 72, two males, four females) presented with congestive cardiac failure (n=2), arthralgia, weight loss, ventricular tachycardia, and melaena at a tertiary center (January 2022–December 2023). Diagnostic evaluations showed elevated serum free light chains, abnormal kappa/lambda ratios, and multi-organ involvement (cardiac, hepatic, renal, gastrointestinal). Cardiac biomarkers (NT-proBNP: 553–>25,000 pg/mL) indicated severe cardiac involvement in four patients. Treatment involved cyclophosphamide, bortezomib, and dexamethasone (CyBorD)-based chemotherapy, with one patient receiving autologous stem cell transplantation (ASCT). Outcomes varied: four patients achieved maintenance therapy, while two with advanced cardiac disease died. Diagnostic delays (2 months–2 years) were found to correlate with poorer outcomes.

Conclusions: This case series highlights AL amyloidosis’s clinical heterogeneity and diagnostic challenges. Early diagnosis using serum free light chain assays is critical for improved outcomes. Advanced cardiac involvement and comorbidities worsen prognosis, underscoring the need for tailored therapies and novel agents like daratumumab.

Background:

Systemic AL amyloidosis, caused by extracellular deposition of monoclonal immunoglobulin light chain-derived amyloid fibrils, affects organs like the heart, liver, and kidneys, leading to high morbidity and mortality [1]. Cardiac involvement, seen in up to 75% of cases, is a major prognostic determinant [2]. Diagnosis is challenging due to nonspecific symptoms (e.g., fatigue, weight loss) and requires specialized tools like serum free light chain (FLC) assays and bone marrow biopsy [3]. Treatment with CyBorD or ASCT aims to suppress light chain production, but outcomes vary based on disease stage and comorbidities [4]. This case series details the clinical characteristics, diagnostics, and one-year outcomes of six patients with AL amyloidosis, emphasizing cardiac involvement and management challenges.

Case Presentation:

Six patients diagnosed with AL amyloidosis at a tertiary care center (January 2022–December 2023) were studied. Data were extracted from electronic medical records, including demographics, comorbidities, symptoms, organ involvement, laboratory findings (haemoglobin, serum creatinine, NT-proBNP, troponin, FLC, 24-hour urine protein), bone marrow plasma cells, left ventricular (LV) function, time to diagnosis, treatment, and one-year outcomes. Descriptive statistics summarized findings. The study followed institutional ethical guidelines, with informed consent obtained.

Patient 1

A 63-year-old female (BMI 26.3 kg/m², no comorbidities) presented with congestive cardiac failure. Laboratory findings: hemoglobin 10.2 g/dL, serum creatinine 0.8 mg/dL, NT-proBNP 7096 pg/mL, troponin 0.26 ng/mL, kappa 6 mg/L, lambda 448 mg/L, kappa/lambda ratio 0.01, 24-hour urine protein 130 mg, bone marrow plasma cells 39%. Baseline LV function was 60%. Liver involvement was noted. Diagnosis was made 2 months post-symptom onset. She tolerated 12 CyBorD cycles and was on maintenance therapy at one-year follow-up.

Patient 2

A 41-year-old female (BMI 26 kg/m², no comorbidities) presented with arthralgia. Laboratory findings: hemoglobin 11.8 g/dL, serum creatinine 0.9 mg/dL, NT-proBNP 553 pg/mL, negative troponin, kappa 6380 mg/L, lambda 9 mg/L, kappa/lambda ratio 708, 24-hour urine protein 250 mg, bone marrow plasma cells 4%. Baseline LV function was 60%. Liver and shoulder joint involvement were noted. Diagnosis took 4 months. She received CyBorD followed by ASCT and was on maintenance therapy at one-year follow-up.

Patient 3

A 72-year-old male (BMI 16 kg/m², coronary artery disease, chronic obstructive pulmonary disease) presented with weight loss. Laboratory findings: hemoglobin 13.4 g/dL, serum creatinine 1.2 mg/dL, NT-proBNP 5058 pg/mL, troponin 0.12 ng/mL, kappa 20 mg/L, lambda 874 mg/L, kappa/lambda ratio 0.02, 24-hour urine protein 146 mg, bone marrow plasma cells 2%. Baseline LV function was 55%. Lung involvement caused type 2 respiratory failure. Diagnosis took 1 year. He was intolerant to CyBorD and died within one year from disease progression.

Patient 4

A 63-year-old male (BMI 63 kg/m², chronic kidney disease, early cirrhosis) presented with ventricular tachycardia. Laboratory findings: hemoglobin 10.4 g/dL, serum creatinine 2.7 mg/dL, NT-proBNP 15,070 pg/mL, troponin 0.14 ng/mL, kappa 12 mg/L, lambda 4401 mg/L, kappa/lambda ratio 0.002, 24-hour urine protein 1785 mg, bone marrow plasma cells 26%. Baseline LV function was 35%. Gastrointestinal involvement (gastroparesis, ulcers) was noted. Diagnosis took 2 years. He was intolerant to CyBorD and died within one year.

Patient 5

A 53-year-old female (BMI 21 kg/m², dyslipidemia, hypothyroidism) presented with congestive cardiac failure. Laboratory findings: hemoglobin 13.2 g/dL, serum creatinine 4.4 mg/dL, NT-proBNP >25,000 pg/mL, troponin 0.8 ng/mL, kappa 20 mg/L, lambda 133 mg/L, kappa/lambda ratio 0.15, 24-hour urine protein 5481 mg, bone marrow plasma cells 4%. Baseline LV function was 40%. Liver and spleen involvement were noted. Diagnosis took 4 months. She tolerated 12 CyBorD cycles and was on maintenance therapy at one-year follow-up.

Patient 6

A 51-year-old female (BMI 22 kg/m², diabetes mellitus) presented with weight loss and malena. Laboratory findings: hemoglobin 11.4 g/dL, serum creatinine 0.9 mg/dL, NT-proBNP 4311 pg/mL, troponin 0.05 ng/mL, kappa 1123 mg/L, lambda 35 mg/L, kappa/lambda ratio 31.4, 24-hour urine protein 1689 mg, bone marrow plasma cells 7%. Baseline LV function was 60%. Liver, proctitis, and duodenitis were noted. Diagnosis took 8 months. She initiated CyBorD and was on maintenance therapy at one-year follow-up.

Discussion:

This case series illustrates the clinical heterogeneity of AL amyloidosis, with presentations ranging from congestive cardiac failure to malena. The median age (58 years, range 41–72) and gender distribution (four females, two males) align with AL amyloidosis epidemiology [5]. Cardiac involvement, indicated by elevated NT-proBNP and troponin, was prominent in four patients, correlating with poor prognosis in Patients 3 and 4 (NT-proBNP 5058 and 15,070 pg/mL, respectively), who died from cardiac arrest [1]. Diagnostic delays (2 months–2 years) were common, with shorter delays (Patients 1 and 5) linked to better outcomes, emphasizing the need for early FLC assay use [3]. Treatment success varied: four patients achieved maintenance therapy, while comorbidities and advanced disease led to intolerance and death in two cases. Patient 2’s successful ASCT suggests efficacy in select patients [4]. Limitations include small sample size, limiting generalizability. Novel therapies like daratumumab and advanced imaging may improve outcomes [2,7].

Conclusions:

AL amyloidosis presents diverse clinical challenges, particularly with cardiac involvement. Early diagnosis using FLC assays and tailored therapies are crucial. Advanced disease and comorbidities worsen prognosis, necessitating further research into novel treatments and diagnostic strategies.

References

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