Exacerbation of Congestive Heart Failure (CHF): Given the patient's history of CHF and recent hospitalization, worsening shortness of breath, especially when lying flat (orthopnea), is highly suggestive of CHF exacerbation. The recent prolonged hospital stay and procedure could have contributed to fluid overload or decreased mobility, exacerbating CHF.

Pulmonary Embolism (PE): Recent hospitalization, prolonged immobilization, and the presence of a PICC line increase the risk of deep vein thrombosis and subsequent PE, which can cause worsening shortness of breath.
Pneumonia: The patient's history of COPD and recent hospitalization puts him at risk for pneumonia, which could present with worsening shortness of breath.
Chronic Obstructive Pulmonary Disease (COPD) Exacerbation: Given the patient's history of COPD, an exacerbation could be triggered by various factors, including infection or air pollution, leading to worsening shortness of breath.

Cardiac Tamponade: Although less likely, cardiac tamponade is a life-threatening condition that could occur, especially given the patient's history of cardiology procedures. It presents with shortness of breath, orthopnea, and potentially hypotension.
Pulmonary Edema due to Other Causes: Other causes such as renal failure or severe hypertension could lead to pulmonary edema, presenting similarly to CHF exacerbation.
Sepsis: Given the recent history of infection and IV antibiotics, sepsis should be considered, especially if there are signs of systemic inflammation.

Lymphangitic Carcinomatosis: A rare condition where metastatic cancer infiltrates the lymphatic vessels of the lung, causing shortness of breath. Given the patient's age and history of recent hospitalization for a foot infection, although unlikely, it should be considered if other diagnoses are ruled out.
Mitral Stenosis: If not previously diagnosed, mitral stenosis could present with worsening shortness of breath, especially when lying flat, due to increased pressure in the left atrium.

The workup should include:

Chest X-ray to evaluate for signs of CHF, pneumonia, or other pulmonary pathologies.
Electrocardiogram (ECG) to assess for cardiac ischemia or arrhythmias.
Echocardiogram to evaluate cardiac function and rule out tamponade.
Blood tests including complete blood count (CBC), blood cultures, and cardiac biomarkers (e.g., troponin) to assess for infection, sepsis, or cardiac injury.
D-dimer if pulmonary embolism is suspected, although its utility may be limited in this clinical context due to recent hospitalization and potential for false positives.
CT Pulmonary Angiogram (CTPA) if PE is highly suspected after initial workup.
Arterial Blood Gas (ABG) to assess oxygenation and ventilation status.
Physical therapy and mobility assessment to ensure the patient is not experiencing deconditioning that could exacerbate symptoms.