Can conditions such as amyloidosis cause both heart failure with pitting edema and nocturnal diarrhea in an older adult with comorbidities like hypertension or diabetes?

Amyloidosis as a Unifying Diagnosis for Heart Failure with Pitting Edema and Nocturnal Diarrhea

Yes, cardiac amyloidosis—particularly transthyretin (ATTR) amyloidosis—can cause both heart failure with pitting edema and nocturnal diarrhea through simultaneous cardiac and autonomic nervous system involvement. This presentation is especially important to recognize in older adults, as it is frequently misdiagnosed as generic heart failure with preserved ejection fraction 1.

Clinical Presentation of Cardiac Amyloidosis

Cardiac Manifestations

• Heart failure symptoms include dyspnea, orthopnea, paroxysmal nocturnal dyspnea, edema, fatigue, exercise intolerance, dizziness/syncope, and palpitations 1.
• Physical examination findings reveal elevated jugular venous pressure, hepatomegaly, ascites, and peripheral pitting edema—the classic signs of right-sided heart failure 2, 3.
• The edema in cardiac amyloidosis is characteristically pitting and cool, associated with elevated jugular venous pressure, distinguishing it from non-cardiac causes 4.

Gastrointestinal and Autonomic Manifestations

• Autonomic dysfunction is a prominent feature, particularly in ATTR amyloidosis, manifesting as orthostasis, erectile dysfunction, sweating abnormalities, and diarrhea 1.
• The diarrhea occurs due to autonomic neuropathy affecting gastrointestinal motility and can present as nocturnal symptoms 1.
• These autonomic symptoms may precede or accompany cardiac symptoms, making the diagnosis challenging 1.

Diagnostic Approach

High-Risk Features Requiring Evaluation

• Age >60 years (especially males for wild-type ATTR) with unexplained heart failure 1, 5.
• Disproportionately elevated NT-proBNP relative to clinical heart failure severity 1.
• Intolerance to ACE inhibitors, ARBs, or beta-blockers due to autonomic dysfunction 1.
• Associated findings: carpal tunnel syndrome (particularly in males), lumbar spinal stenosis, spontaneous biceps tendon rupture, or prior orthopedic procedures 1.
• Hypertension that resolves over time as amyloid infiltration progresses 1.

Essential Diagnostic Workup

• Echocardiography showing increased left ventricular wall thickness (often >12mm), normal or small ventricular cavities, enlarged atrial cavities, and characteristic "granular sparkling" appearance of myocardium 2, 5.
• Electrocardiography revealing low voltage despite increased wall thickness (pseudoinfarction pattern), conduction abnormalities, or arrhythmias 6, 3.
• NT-proBNP and troponin levels that are markedly elevated and disproportionate to clinical presentation 1.
• Tissue biopsy (endomyocardial, gingival, or abdominal fat pad) with Congo red staining showing apple-green birefringence under polarized light 2.
• Nuclear imaging (technetium-99m pyrophosphate scintigraphy) can diagnose ATTR cardiac amyloidosis non-invasively when combined with absence of monoclonal protein 1.

Management Considerations

Heart Failure Treatment Modifications

• Avoid aggressive diuresis in the absence of clear volume overload, as excessive diuresis can paradoxically reduce stroke volume and cardiac output in restrictive physiology 4.
• Use loop diuretics cautiously only when there is objective evidence of congestion (elevated JVP, pulmonary rales, orthopnea) 4.
• Discontinue calcium channel blockers (particularly amlodipine), as they bind to amyloid fibrils and worsen outcomes 4.
• Digoxin should be avoided as it also binds to amyloid fibrils and increases toxicity risk 1.

Disease-Specific Therapy

• Tafamidis (VYNDAQEL 80 mg or VYNDAMAX 61 mg orally once daily) is FDA-approved for treatment of ATTR cardiomyopathy to reduce cardiovascular mortality and hospitalization 7.
• For AL amyloidosis, high-dose melphalan with autologous stem cell transplantation is the treatment of choice in appropriate candidates 3.
• For hereditary ATTR, liver transplantation may be curative as transthyretin is synthesized in the liver 3.

Prognosis and Monitoring

Survival Differences by Type

• Senile systemic amyloidosis (wild-type ATTR) has median survival of 75 months with slowly progressive heart failure 5.
• AL amyloidosis has median survival of only 11 months with rapidly progressive heart failure, suggesting a toxic component from circulating light chains 5.
• Despite thicker ventricular walls in ATTR, the severity of heart failure is typically less than in AL amyloidosis 5.

Critical Pitfalls to Avoid

• Misdiagnosis as hypertrophic cardiomyopathy or generic heart failure with preserved ejection fraction is common and delays appropriate treatment 1.
• Failure to recognize the multisystem nature of amyloidosis leads to missed diagnosis when only cardiac symptoms are considered 1.
• Overlooking autonomic symptoms (including nocturnal diarrhea) as unrelated to cardiac disease prevents recognition of the unifying diagnosis 1.