What is the next step in managing a patient with a history of orthostatic hypotension, currently on Florinef (fludrocortisone) and midodrine, who recently experienced episodes of supraventricular tachycardia (SVT) and syncopal symptoms, but with no evidence of leukocytosis, anemia, or acute coronary syndrome (ACS)?

From the Guidelines

For a patient with a storied history of orthostatic hypotension who is already on Florinef and midodrine, with recent episodes of SVT on Holter monitoring but no current dysrhythmias, and negative workup for other causes of syncope, I recommend optimizing the current medication regimen and considering additional management options to reduce morbidity, mortality, and improve quality of life. The patient's current medication regimen should be optimized by ensuring adequate dosing of Florinef (fludrocortisone) 0.1-0.2 mg daily and midodrine 5-10 mg three times daily, avoiding evening doses to prevent supine hypertension, as recommended by the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope 1. Consider adding compression stockings (30-40 mmHg) extending to at least the thigh level to improve venous return, as this has been shown to be beneficial in patients with syncope and OH 1. Increased salt intake (8-10g daily) and adequate hydration (2-3 liters daily) should be emphasized, as encouraging increased salt and fluid intake may be reasonable in selected patients with neurogenic OH 1. For additional pharmacologic options, consider pyridostigmine 30-60 mg three times daily, which can help with neurogenic orthostatic hypotension without worsening supine hypertension, as it may be beneficial in patients with syncope due to neurogenic OH who are refractory to other treatments 1. Droxidopa 100-600 mg three times daily is another option for neurogenic orthostatic hypotension if other measures are insufficient, as it can be beneficial in patients with syncope due to neurogenic OH 1. Further workup should include autonomic testing (tilt table test, Valsalva maneuver, sudomotor testing) to better characterize the orthostatic hypotension, as recommended by the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope 1. Consider referral to an autonomic specialist if not already involved, and for the SVT episodes, an electrophysiology consultation may be warranted to determine if ablation would be beneficial, especially if episodes correlate with syncope. Patient education on positional changes (rising slowly, avoiding prolonged standing) and recognizing prodromal symptoms is essential for preventing syncopal episodes and falls. Some key points to consider in the management of this patient include:

• Optimizing the current medication regimen to prevent supine hypertension
• Adding compression stockings to improve venous return
• Encouraging increased salt and fluid intake
• Considering additional pharmacologic options such as pyridostigmine and droxidopa
• Further workup with autonomic testing and referral to an autonomic specialist if necessary
• Patient education on positional changes and recognizing prodromal symptoms.

From the FDA Drug Label

Midodrine should be used cautiously in patients with urinary retention problems, as desglymidodrine acts on the alpha-adrenergic receptors of the bladder neck Midodrine should be used with caution in orthostatic hypotensive patients who are also diabetic, as well as those with a history of visual problems who are also taking fludrocortisone acetate, which is known to cause an increase in intraocular pressure and glaucoma. Patients should be told that certain agents in over-the-counter products, such as cold remedies and diet aids, can elevate blood pressure, and therefore, should be used cautiously with midodrine, as they may enhance or potentiate the pressor effects of midodrine The patient is likely experiencing continuation of orthostatic hypotension. Given the patient's current medication regimen, which includes midodrine and fludrocortisone acetate, caution should be exercised to avoid exacerbating supine hypertension.

• The patient should be advised to take their last daily dose of midodrine 3 to 4 hours before bedtime to minimize nighttime supine hypertension.
• The patient should also be cautioned about the potential for drug interactions with over-the-counter products, such as cold remedies and diet aids, which can elevate blood pressure.
• Consideration should be given to monitoring the patient's renal function and hepatic function prior to initiating therapy and subsequently, as appropriate 2.
• The patient's blood pressure should be closely monitored, especially when concomitantly administering drugs that increase blood pressure.

From the Research

Patient's Condition

The patient has a storied history with orthostatic hypotension and is currently on Florinef and midodrine at home. Recent tests, including a 7-day Holter monitor and laboratory analysis, have ruled out other potential causes of the patient's syncopal symptoms, such as leukocytosis, acute blood loss anemia, and ACS.

Current Treatment

The patient is currently taking midodrine, which has been shown to be effective in managing orthostatic hypotension 3. Midodrine is a prodrug that undergoes enzymatic hydrolysis to the selective alpha 1-adrenoceptor agonist desglymidodrine, which increases standing systolic blood pressure and improves standing time and energy level.

Additional Treatment Options

Other treatment options for orthostatic hypotension include:

• Fludrocortisone, which is a mineralocorticoid that increases blood volume and blood pressure 4
• Pyridostigmine, which facilitates cholinergic neurotransmission in autonomic ganglia 5
• Droxidopa, which is a synthetic precursor of norepinephrine that can increase blood pressure 6
• Nonpharmacologic strategies, such as dietary modifications, compression garments, physical maneuvers, and avoiding environments that exacerbate symptoms 7, 6

Considerations

When considering additional treatment options, it is essential to weigh the potential benefits and harms of each treatment. For example, fludrocortisone has been shown to have concerning long-term effects 6. Additionally, the patient's current medication regimen and medical history should be taken into account to minimize potential interactions and adverse effects.

Further Evaluation

Further evaluation of the patient's condition may include:

• Head-up tilt-table testing to confirm the diagnosis of orthostatic hypotension and assess treatment response 7, 6
• Monitoring of blood pressure and heart rate to assess the effectiveness of treatment 6
• Evaluation of the patient's underlying medical conditions and potential causes of orthostatic hypotension 5