What are the differential diagnoses for a patient with metabolic acidosis and cardiac dysfunction, aside from thiamine deficiency?

Differential Diagnoses for Metabolic Acidosis with Cardiac Dysfunction

When evaluating a patient with metabolic acidosis and cardiac dysfunction beyond thiamine deficiency, you must systematically consider infiltrative cardiomyopathies, endocrine/metabolic derangements, toxic exposures, and infectious causes—each requiring specific diagnostic workup and targeted treatment.

Infiltrative and Storage Diseases

Cardiac amyloidosis should be high on your differential, particularly if the patient presents with restrictive cardiomyopathy features progressing to dilated phenotype with systolic dysfunction 1. These patients may have low QRS voltage despite increased left ventricular wall thickness, which is a key distinguishing feature 1.

• Hemochromatosis can cause dilated cardiomyopathy in advanced stages and may present with metabolic acidosis due to multi-organ iron deposition affecting hepatic and pancreatic function 1.
• Cardiac sarcoidosis should be considered, especially if there is evidence of progressive atrioventricular conduction delay or ventricular arrhythmias 1.
• Storage diseases (Pompe, Danon, PRKAG2 mutations) characteristically show extreme left ventricular hypertrophy with Sokolow scores ≥50 mm and may have pre-excitation or progressive AV block 1.

Endocrine and Metabolic Causes

Multiple endocrine deficiencies can mimic or exacerbate heart failure and metabolic acidosis, requiring systematic screening 1:

• Hypothyroidism and hypoparathyroidism can cause primary myocardial dysfunction that mimics cardiomyopathy 1.
• Adrenal insufficiency is critical to identify—patients in heart failure should be treated empirically for adrenal insufficiency until proven otherwise 1.
• Diabetes mellitus with ketoacidosis causes metabolic acidosis and can precipitate cardiac dysfunction through altered cardiac metabolism, lipotoxicity, and microvascular disease 1.
• Hypogonadism may exacerbate heart failure symptoms and is the most common endocrinopathy in certain at-risk populations 1.

Nutritional Deficiencies Beyond Thiamine

Other vitamin and cofactor deficiencies must be excluded, as they are easily treatable and can present similarly 1:

• Carnitine deficiency is common and has been associated with clinical improvement when replaced 1.
• Selenium deficiency can cause dilated cardiomyopathy 1.
• Vitamin B12, copper, and vitamin E deficiencies should be assessed, particularly if neurological symptoms are present 2.
• Extreme vitamin D deficiency (25-hydroxyvitamin D <10 ng/dL) warrants replacement given the benign nature of therapy 1.

Toxic and Drug-Induced Causes

Cardiotoxic exposures are reversible causes that must be identified urgently 1:

• Alcohol can cause toxic cardiomyopathy and metabolic acidosis 1.
• Chemotherapeutic agents (anthracyclines, trastuzumab) cause dose-dependent cardiotoxicity 1.
• Recreational drugs (cocaine, amphetamines) can precipitate acute cardiac dysfunction 1.
• Medications including NSAIDs, corticosteroids, and negative inotropic agents may trigger decompensation 1.

Infectious and Inflammatory Causes

Sepsis is the second-leading cause of death in certain high-risk populations and may precipitate heart failure 1:

• Myocarditis presents with acute reduction in cardiac function, often with chest pain, diffuse ST-T wave changes, and elevated cardiac enzymes—features that distinguish it from other causes 1.
• Infective endocarditis can cause acute valve dysfunction and metabolic derangements 1.
• Pneumonia and other systemic infections are common precipitants of acute decompensation 1.

Hepatic Causes

Hepatic encephalopathy with cirrhosis can present with altered mental status and metabolic acidosis 1:

• Check plasma ammonia levels—a normal value makes hepatic encephalopathy unlikely 1.
• Consider portosystemic shunts causing metabolic derangements even without significant liver dysfunction 1.
• Hepatic myelopathy is a rare complication characterized by rapidly progressing spastic paraparesis that requires differentiation from thiamine, B12, and copper deficiency 1.

Autoimmune and Systemic Diseases

Systemic autoimmune diseases commonly cause dilated cardiomyopathy 1:

• Systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, scleroderma, and polyarteritis nodosa should be considered 1.
• These may present with multi-organ involvement including renal dysfunction contributing to metabolic acidosis 1.

Mitochondrial Disorders

Mitochondrial diseases present with lactic acidosis, cardiac dysfunction, and multi-system involvement 1:

• Look for sensorineural deafness, diabetes, retinal disease, and progressive AV conduction delay 1.
• These patients often have short PR intervals or pre-excitation patterns on ECG 1.

Critical Pitfalls to Avoid

• Never administer glucose before thiamine in any patient with suspected nutritional deficiency, as this can precipitate or worsen Wernicke-Korsakoff syndrome 2.
• Do not attribute all symptoms to a single diagnosis—multiple deficiencies and comorbidities frequently coexist, particularly in malnourished or critically ill patients 1.
• Empiric thiamine administration remains appropriate even while pursuing other diagnoses, given its safety profile and the catastrophic consequences of delayed treatment in deficiency states 3, 4, 5.
• Measure ammonia levels in patients with altered mental status and liver disease—normal levels argue against hepatic encephalopathy and should prompt consideration of alternative diagnoses 1.
• Screen for endocrine dysfunction systematically in any patient with unexplained cardiomyopathy, as these are treatable causes that significantly impact prognosis 1.