What are the signs and symptoms of amyloid cardiac involvement?

Signs and Symptoms of Cardiac Amyloidosis

Cardiac amyloidosis presents with a constellation of cardiac symptoms including dyspnea, orthopnea, paroxysmal nocturnal dyspnea, edema, fatigue, exercise intolerance, dizziness/lightheadedness, syncope, palpitations, and chest pain, which are often accompanied by systemic manifestations depending on the type of amyloidosis. 1

Cardiac Symptoms

• Heart Failure Symptoms:

  • Dyspnea (shortness of breath) 1
  • Orthopnea (difficulty breathing when lying flat) 1
  • Paroxysmal nocturnal dyspnea 1
  • Peripheral edema (leg swelling) 1
  • Fatigue and exercise intolerance 1
  • Bloating 1

• Cardiovascular Manifestations:

  • Dizziness/lightheadedness 1
  • Syncope (fainting) 1
  • Palpitations 1
  • Chest pain 1
  • Electrical conduction abnormalities and arrhythmias 1
  • Intolerance to ACE inhibitors, ARBs, or beta blockers 1

Laboratory Findings

• Biomarker Abnormalities:
  • Elevated NT-proBNP levels (>332 ng/L), often disproportionate to the degree of heart failure 1
  • Elevated troponin levels 1
  • In AL amyloidosis: abnormal free light chain ratio 1, 2

Imaging Findings

• Echocardiographic Features:

  • Diffuse ventricular wall thickening (>12 mm) with no other known cardiac cause 1, 3
  • Restrictive filling pattern (diastolic dysfunction) 3, 2
  • Preserved left ventricular ejection fraction (≥40%) in early stages 1, 2
  • Characteristic "granular sparkling" appearance of myocardium 3, 2
  • Pericardial effusion 3, 2
  • Atrial enlargement 3
  • Thickened interatrial septum and atrioventricular valves 2
  • "Apical sparing" pattern on 2D longitudinal strain 2

• Electrocardiographic Findings:

  • Low voltage QRS complexes (more common in AL than ATTR amyloidosis) 1, 2
  • Pseudoinfarct pattern (Q waves without prior myocardial infarction) 1
  • Poor R-wave progression 4
  • Conduction abnormalities 1

Associated Systemic Manifestations

• Neurological Symptoms:

  • Sensorimotor neuropathy 1
  • Autonomic dysfunction (orthostatic hypotension, erectile dysfunction, sweating abnormalities) 1
  • Carpal tunnel syndrome (particularly in males with ATTR) 1

• Gastrointestinal Symptoms:

  • Diarrhea 1
  • GI dysmotility 1
  • Malabsorption 1

• Other Clinical Clues:

  • History of lumbar spinal stenosis 1
  • Previous orthopedic procedures 1
  • Spontaneous biceps tendon rupture 1
  • Swollen tongue and xerostomia (dry mouth) in AL amyloidosis 2
  • Bleeding tendencies (in AL amyloidosis) 2
  • Proteinuria/nephrotic syndrome (in AL amyloidosis) 2

Prognostic Indicators

• Development of congestive heart failure significantly worsens prognosis (median survival shortens to 6 months) 3
• Elevated cardiac biomarkers (NT-proBNP and troponins) are used for staging and prognostication 1
• Increasing diuretic dose requirements and worsening NYHA functional class indicate disease progression 1

Clinical Pitfalls

• Cardiac amyloidosis is frequently misdiagnosed as:
  • Hypertrophic cardiomyopathy 1
  • Undifferentiated heart failure with preserved ejection fraction (HFpEF) 1
  • Low-flow, low-gradient aortic stenosis 1
• Cardiac involvement may be present without overt cardiac symptoms in 37% of patients 3
• Hypertension that resolves over time may be a clue to developing cardiac amyloidosis 1
• Cardiac amyloidosis should be considered in any patient with unexplained heart failure, particularly with preserved ejection fraction and increased wall thickness 1, 4