Differential Diagnosis

The patient presents with a complex array of symptoms including progressive shortness of breath, generalized fatigue, significant weight loss, orthopnea (indicated by sleeping on three pillows), numbness and tingling in the hands, dizziness upon standing, constipation, irregularly irregular pulse, orthostatic hypotension, enlarged tongue, crackles at lung bases, and pitting edema. These symptoms suggest a multisystem disease process. Here's a categorized differential diagnosis:

• Single Most Likely Diagnosis

  • Amyloidosis: This condition is characterized by the deposition of amyloid proteins in various tissues, leading to organ dysfunction. The patient's symptoms, such as enlarged tongue (macroglossia), numbness and tingling in the hands (possibly carpal tunnel syndrome due to amyloid deposition), orthostatic hypotension, and heart failure symptoms (shortness of breath, orthopnea, and edema), are consistent with systemic amyloidosis, particularly AL (primary) amyloidosis or transthyretin amyloidosis (wild-type or hereditary).

• Other Likely Diagnoses

  • Hemochromatosis: Although less likely given the specific constellation of symptoms, hemochromatosis can lead to heart failure, fatigue, and potentially neuropathy. However, the absence of specific findings like skin pigmentation changes makes it less likely.
  • Sarcoidosis: This condition can cause heart failure, neuropathy, and systemic symptoms like fatigue and weight loss. However, the presence of an enlarged tongue and specific patterns of numbness are not typical for sarcoidosis.

• Do Not Miss Diagnoses

  • Viral Myocarditis: Although the presentation might not be typical, myocarditis can lead to heart failure and arrhythmias. Given the potential for severe outcomes, it's crucial not to miss this diagnosis.
  • Drug-induced Myocardial Injury: Certain drugs can cause cardiomyopathy or myocardial injury leading to heart failure. Given the patient's age and potential for polypharmacy, this is an important consideration.

• Rare Diagnoses

  • Hypovolemic Shock: The patient's symptoms of orthostatic hypotension and dizziness could suggest hypovolemia, but the presence of edema and heart failure symptoms makes this less likely.
  • Other rare conditions such as familial amyloid polyneuropathy or specific types of storage diseases could also be considered but are less likely given the patient's age and presentation.