What is the best management approach for a 48-year-old female with Hyperlipidemia (HLD), Type 2 Diabetes Mellitus (DM 2), fibromyalgia, and a current smoker, presenting with Postural Orthostatic Tachycardia Syndrome (POTS) symptoms, borderline concentric left ventricular hypertrophy (LVH), and a left ventricular ejection fraction (LVEF) of 45-50%?

Management of POTS-like Symptoms with Borderline LVH and Reduced LVEF

Critical Reassessment Required

This patient does not have POTS and requires immediate discontinuation of midodrine and fludrocortisone, with initiation of guideline-directed heart failure therapy for her borderline concentric LVH with LVEF 45-50%. 1, 2

The current management approach is fundamentally flawed because the patient has been treated for POTS when she actually has structural heart disease with reduced ejection fraction requiring entirely different pharmacotherapy. 1, 2, 3

Why This Is Not POTS

• POTS requires absence of orthostatic hypotension (defined as >20 mm Hg reduction in systolic BP), yet this patient has documented symptomatic hypotension at multiple visits. 1
• The echocardiogram revealed borderline concentric LVH with LVEF 45-50%, which represents structural heart disease and early heart failure with mildly reduced ejection fraction (HFmrEF). 1, 2, 3
• POTS is a diagnosis of exclusion that cannot be made in the presence of cardiac structural abnormalities capable of causing symptoms. 1, 4
• Her tachycardia (103-105 bpm at rest, range 68-154 bpm on monitor) with hypotension suggests compensatory tachycardia from reduced cardiac output, not primary POTS. 1, 3

Immediate Management Changes Required

Discontinue Harmful Medications

• Stop midodrine immediately - vasoconstrictors increase afterload and worsen cardiac function in patients with reduced LVEF by increasing the workload on an already compromised ventricle. 1, 2
• Stop fludrocortisone immediately - mineralocorticoid therapy is appropriate for POTS but contraindicated as initial therapy in heart failure with reduced ejection fraction. 1, 2, 3
• Propranolol discontinuation was correct, but for the wrong reason - beta-blockers are actually indicated in HFmrEF, but the approach needs restructuring. 1, 2, 3

Initiate Guideline-Directed Medical Therapy for HFmrEF

First-line therapy must include ACE inhibitors (or ARBs if ACE inhibitor intolerant) plus beta-blockers, even in mildly symptomatic patients with LVEF 45-50%. 2, 3

• Start an ACE inhibitor (e.g., lisinopril 2.5-5 mg daily initially, titrate to target dose 20-40 mg daily) or ARB if ACE inhibitor causes cough. 1, 2, 3
• Restart a cardioselective beta-blocker using one of the three proven agents: metoprolol succinate (not tartrate) 12.5-25 mg daily initially, carvedilol 3.125 mg twice daily, or bisoprolol 1.25 mg daily, titrated gradually to target doses. 1, 2, 3
• The American College of Cardiology recommends that ACE inhibitors should be started in all patients with reduced LVEF, even when asymptomatic, as they delay symptom onset and decrease risk of death and hospitalization. 3
• Beta-blockers should be initiated even in asymptomatic patients with reduced LVEF to improve mortality and prevent disease progression. 2, 3

Address Volume Status Carefully

• Low-dose loop diuretics (e.g., furosemide 20 mg daily) may be cautiously added if there is clinical evidence of volume overload, but aggressive diuresis should be avoided as it can worsen hypotension. 1
• The patient is described as "euvolemic with no evidence of retaining fluid," suggesting fludrocortisone-induced volume expansion has not occurred, which is appropriate to avoid in this context. 1

Management of Hypotension During GDMT Titration

The 2025 European Society of Cardiology guidelines specifically address low blood pressure in heart failure patients and emphasize that hypotension with minor symptoms is not a reason to withhold or reduce heart failure GDMT. 1

• Focus on assessing symptoms and organ perfusion rather than blood pressure numbers alone - low BP does not always correlate with impaired perfusion. 1
• SBP <80 mmHg or hypotension causing major symptoms is the critical threshold that warrants careful attention and potential adjustment of medical treatment. 1
• For persistent low BP in mildly symptomatic patients with adequate perfusion, start with low doses of GDMT and titrate gradually: begin with ACE inhibitor or ARB at low dose, then add low-dose beta-blocker. 1
• Measure BP both supine and standing to establish whether orthostatic hypotension (drop of 20 mmHg systolic and/or 10 mmHg diastolic within 3 minutes of standing) correlates with symptoms. 1

Addressing Comorbidities That Worsen Outcomes

Smoking Cessation (Critical Priority)

• Current smoking status significantly worsens prognosis in patients with structural heart disease and must be addressed with intensive cessation counseling and pharmacotherapy. 1

Diabetes Management

• Optimize glycemic control as diabetes is associated with poorer prognosis in patients with LVH and heart failure. 1
• The American Heart Association emphasizes that cardiometabolic risk factors (obesity, hypertension, diabetes, obstructive sleep apnea) are highly prevalent and associated with poorer prognosis, highlighting the importance of intensive risk factor modification. 1

Hyperlipidemia Control

• Continue statin therapy for secondary prevention given the presence of structural heart disease. 1

Screen for Sleep Apnea

• Assessment for symptoms of sleep-disordered breathing is recommended, with referral to sleep medicine specialist if present, as sleep apnea affects a significant proportion of patients with cardiac disease and is associated with greater symptom burden. 5

Diagnostic Workup Still Needed

Evaluate for Coronary Artery Disease

• Consider stress testing or coronary angiography to exclude ischemic cardiomyopathy as the cause of LVH and reduced LVEF, particularly given her diabetes, hyperlipidemia, and smoking history. 3
• The American Heart Association recommends considering coronary revascularization if demonstrable myocardial ischemia is present, as this can improve ventricular function. 3

Assess for Hypertension

• Verify blood pressure control - while she presents with hypotension in clinic, her history of HLD and DM2 suggests possible underlying hypertension that may have contributed to LVH development. 1, 2
• Target blood pressure <130/80 mmHg once GDMT is established and hypotensive episodes resolve. 1, 2

Rule Out Other Causes of Cardiomyopathy

• Thyroid function tests to exclude thyroid disease. 4, 6
• Consider cardiac MRI if etiology of cardiomyopathy remains unclear after initial workup. 3

Why the Tilt Table Test Was Appropriately Declined

• The patient correctly declined tilt table testing because she has structural heart disease that explains her symptoms, making POTS testing irrelevant and potentially misleading. 1, 4
• Tilt table testing is only indicated when cardiac causes have been excluded and symptoms remain unexplained. 1

Common Pitfalls to Avoid

• Misclassifying structural heart disease as POTS leads to inappropriate treatment with vasoconstrictors and mineralocorticoids that worsen cardiac function. 1, 2, 3
• Delaying neurohormonal blockade (ACE inhibitors and beta-blockers) in reduced LVEF loses the critical window for preventing disease progression. 2, 3
• Declaring beta-blocker failure prematurely - propranolol was discontinued after only brief trial; cardioselective beta-blockers at appropriate doses for heart failure should be attempted. 1, 2, 3
• Focusing on blood pressure numbers rather than clinical perfusion - the 2025 ESC guidelines emphasize that low BP alone is not a contraindication to GDMT if perfusion is adequate. 1
• Ignoring smoking cessation - this modifiable risk factor dramatically impacts prognosis in structural heart disease. 1

Monitoring and Follow-up

• Reassess in 2-4 weeks after initiating ACE inhibitor and beta-blocker to evaluate symptom response, blood pressure tolerance, and renal function. 1, 3
• Repeat echocardiogram in 3-6 months to assess response to GDMT and determine if LVEF improves, remains stable, or declines. 3
• If LVEF decreases to ≤35% despite optimal medical therapy, consider ICD therapy for primary prevention of sudden cardiac death. 3
• Monitor for atrial arrhythmias, which can exacerbate cardiomyopathy and require specific management. 3