What are the possible differential diagnoses for an elderly female patient with type 2 diabetes (T2D) and systemic hypertension (HTN) presenting with shortness of breath, New York Heart Association (NYHA) class 3, and generalized swelling, including facial puffiness?

Differential Diagnoses for Elderly Female with T2D, HTN, NYHA Class 3 Dyspnea, and Generalized Edema with Facial Puffiness

The most likely diagnosis is acute decompensated heart failure (HFpEF given her risk profile), but you must systematically exclude cardiac, renal, and hepatic causes through targeted evaluation, as this triad of symptoms carries high mortality risk and demands urgent workup. 1, 2

Life-Threatening Cardiac Diagnoses (Evaluate First)

Heart Failure (Most Likely)

• Congestive heart failure—both HFrEF and HFpEF—is the primary diagnosis given bilateral edema, NYHA class 3 dyspnea, and her risk factors (diabetes, hypertension). 1, 2
• HFpEF is particularly common in elderly women with diabetes and hypertension, presenting with orthopnea, paroxysmal nocturnal dyspnea, and bilateral edema. 1, 2
• The combination of dyspnea, generalized edema, and facial puffiness strongly suggests biventricular failure or left-heart backward failure. 3, 2
• Diabetes increases HF risk 4-fold compared to the general population, with prevalence of 9-22% in diabetic patients. 1
• Poor glycemic control accelerates HF development—each 1% increase in HbA1c increases HF risk by 8-36%. 1

Acute Coronary Syndrome

• Women with diabetes presenting with dyspnea require heightened suspicion for unstable angina/NSTEMI, as dyspnea alone carries twice the mortality risk of typical angina and increases sudden cardiac death risk 4-fold. 4, 3
• Women frequently present with "atypical" ACS symptoms, with shortness of breath as the predominant feature rather than classic chest pain. 4, 3
• Diabetes, older age, and history of hypertension are high-risk features mandating cardiac evaluation. 4

Critical Renal Causes

Diabetic Nephropathy with Nephrotic Syndrome

• Kidney failure is a primary noncardiovascular mimic of heart failure presenting identically with dyspnea and edema. 2
• Facial puffiness (periorbital edema) is particularly characteristic of nephrotic syndrome due to severe hypoalbuminemia. 1, 5
• Diabetic nephropathy causes microalbuminuria (≥30 mg/24h) progressing to overt proteinuria, with hypertension markedly accelerating progression. 1
• Transient elevations in urinary albumin can occur with hyperglycemia, heart failure, or acute illness—requiring 2 of 3 positive collections over 3-6 months for diagnosis. 1

Acute Kidney Injury

• Decreased urine output with bilateral edema suggests acute kidney injury, which can contribute to acute myocardial injury and fluid overload. 1, 2
• Chronic renal failure is a specific risk factor for fluid retention and heart failure development. 2

Hepatic Causes

Cirrhosis with Portal Hypertension

• Cirrhotic liver disease presents with ascites, peripheral edema, and potential hepatorenal syndrome. 2
• Decreased oncotic pressure from hepatic synthetic dysfunction causes generalized edema including facial puffiness. 1, 2

Pulmonary Causes

COPD with Cor Pulmonale

• Chronic lung disease with right heart failure (cor pulmonale) presents with dyspnea and bilateral edema. 2, 6
• Pulmonary hypertension from chronic lung disease causes right ventricular failure with systemic congestion. 2

Pulmonary Embolism

• PE must be excluded in any patient with acute dyspnea and bilateral leg edema, which may indicate deep vein thrombosis as the source. 3
• The combination of pleuritic chest pain, dyspnea, and bilateral leg swelling raises suspicion for thromboembolic disease. 3

Mandatory Initial Workup (Do Not Skip)

Immediate Laboratory Tests

• BNP or NT-proBNP measurement—elevated levels warrant echocardiography and strongly suggest heart failure. 1, 4, 2
• Cardiac troponin to evaluate for acute myocardial injury or Type 2 MI from supply-demand mismatch. 1, 3
• Urinalysis with protein-to-creatinine ratio to assess for nephrotic syndrome (ratio >7 indicates severe proteinuria). 1, 2, 5
• Serum creatinine and albumin—albumin <2.3 g/dL with proteinuria confirms nephrotic syndrome. 1, 5
• HbA1c to assess glycemic control, as poor control accelerates both nephropathy and heart failure. 1

Essential Imaging

• ECG to identify acute ischemia, silent MI, left ventricular hypertrophy, or arrhythmia. 3, 2
• Chest X-ray to assess for cardiomegaly, pulmonary edema, pleural effusions, or alternative pulmonary pathology. 4, 3, 2
• Transthoracic echocardiography is "usually appropriate" and must be performed in all patients with dyspnea of suspected cardiac origin to assess ejection fraction, valvular disease, and diastolic dysfunction. 1, 4, 2

Physical Examination Priorities

• Assess for jugular venous distention, S3 gallop, and pulmonary rales—these findings strongly suggest CHF. 1, 2
• Evaluate for hepatojugular reflux, hepatomegaly, and ascites to assess for right heart failure or hepatic congestion. 1, 2
• Check for periorbital edema and assess whether edema is pitting—nephrotic syndrome typically causes generalized pitting edema including facial involvement. 1, 5

Critical Pitfalls to Avoid

• Never assume dyspnea without chest pain is non-cardiac—this assumption leads to underdiagnosis and increased mortality in women with diabetes. 4, 3
• Do not attribute all symptoms to a single diagnosis prematurely, as more than 30% of chronic dyspnea cases are multifactorial. 3
• Never rely on chest X-ray and ECG alone—they have limited sensitivity and must be supplemented with echocardiography and natriuretic peptide measurement. 4
• Do not dismiss facial puffiness as benign—it is a red flag for nephrotic syndrome or severe hypoalbuminemia requiring urgent evaluation. 1, 5
• Avoid assuming "typical" heart failure presentation—elderly diabetic women frequently have HFpEF with preserved ejection fraction on echo but severe symptoms. 1