A patient with normal resting left‑ventricular ejection fraction (~60%), moderate left‑ventricular hypertrophy, ascending aorta 4.2 cm, estimated right‑ventricular systolic pressure 26 mmHg (likely underestimated by septal flattening), who terminated a stress test after 1 minute 59 seconds because of fatigue, dyspnea and oxygen saturation drop to 87%, with peak heart rate 121 bpm (below age‑predicted 131 bpm) and no ECG or wall‑motion evidence of ischemia—what is the most likely cause of the exercise intolerance and what are the appropriate next diagnostic and management steps?

Pulmonary Hypertension with Exercise-Induced Desaturation is the Most Likely Cause

This patient's severely reduced exercise tolerance (2.5 METs, termination at 1:59 minutes), oxygen desaturation to 87% after only 1.5 minutes of walking, and echocardiographic evidence of pulmonary hypertension (septal flattening indicating underestimated RVSP) point to pulmonary vascular disease or heart failure with preserved ejection fraction (HFpEF) as the primary cause of exercise intolerance, not coronary ischemia.

Primary Diagnostic Interpretation

Why Ischemia is Ruled Out

• The stress test met appropriate termination criteria due to progressive oxygen desaturation to 87% in a symptomatic patient, which is a standard indication to stop testing 1
• All cardiac walls became hyperdynamic with exercise and ejection fraction increased from 60% to 70%, definitively excluding ischemia as the cause 1
• No ECG changes, chest pain, or wall motion abnormalities occurred during stress, further confirming absence of obstructive coronary disease 1

Evidence Pointing to Pulmonary Hypertension and/or HFpEF

• Septal flattening during systole is pathognomonic for elevated right ventricular systolic pressure, indicating the reported RVSP of 26 mmHg significantly underestimates true pulmonary artery pressure 1
• The combination of moderate left ventricular hypertrophy, normal diastolic function at rest, and severe exercise intolerance with desaturation is characteristic of HFpEF with pulmonary hypertension 1
• Achieving only 2.5 METs represents severely reduced functional capacity—normal individuals should achieve 8-12 METs depending on age and gender 1
• The oxygen desaturation from 94% to 87% after minimal exertion (1.5 minutes) indicates either pulmonary vascular disease, severe diastolic dysfunction with elevated filling pressures causing pulmonary congestion, or intrinsic lung disease 1

Appropriate Next Diagnostic Steps

Immediate Priority Testing

• Perform formal cardiopulmonary exercise testing (CPET) with arterial blood gas monitoring to definitively characterize the mechanism of exercise limitation and quantify gas exchange abnormalities 1

  • CPET is the gold standard for evaluating causes of exercise intolerance when cardiac ischemia is excluded 1
  • Breath-by-breath monitoring of VO₂, VCO₂, minute ventilation, and arterial oxygen saturation will distinguish cardiac from pulmonary from deconditioning causes 1
  • An elevated VE/VCO₂ slope (>34) would indicate heart failure or pulmonary vascular disease 1

• Obtain right heart catheterization to directly measure pulmonary artery pressures, pulmonary capillary wedge pressure, and calculate pulmonary vascular resistance 1

  • This is essential because echocardiographic RVSP is clearly underestimated (septal flattening indicates true RVSP is likely ≥50 mmHg) 1
  • Distinguishes pre-capillary pulmonary hypertension (pulmonary arterial hypertension, chronic thromboembolic disease) from post-capillary (left heart disease) 1
  • Wedge pressure >15 mmHg at rest or >25 mmHg with exercise confirms HFpEF 1

Secondary Evaluation

• Perform diastolic stress echocardiography (if not already done adequately) to assess E/e′ ratio with exercise 1

  • Exercise E/e′ >13 (septal) or >14 (average) indicates elevated left ventricular filling pressures and confirms HFpEF 1
  • Since this patient has grade 1 diastolic dysfunction at rest (normal LA pressure), exercise testing is specifically indicated to unmask elevated filling pressures 1
  • The patient likely has "unstable" diastolic dysfunction that becomes symptomatic only with exertion 1

• Obtain high-resolution chest CT with pulmonary embolism protocol to evaluate for chronic thromboembolic disease, interstitial lung disease, or other parenchymal abnormalities 1

  • Desaturation with minimal exercise raises concern for pulmonary vascular or parenchymal disease 1

• Complete pulmonary function tests with diffusing capacity (DLCO) if not already performed 1

  • Severely reduced DLCO can occur in pulmonary vascular disease and heart failure 1
  • Helps distinguish restrictive lung disease from cardiovascular causes 1

Management Approach Based on Findings

If HFpEF with Pulmonary Hypertension is Confirmed

• Optimize volume status with diuretics targeting euvolemia
• Initiate SGLT2 inhibitor therapy (proven mortality benefit in HFpEF)
• Consider mineralocorticoid receptor antagonist if ejection fraction remains preserved
• Aggressive blood pressure control given existing hypertension (137/88 mmHg at rest)
• Treat the moderate left ventricular hypertrophy as a therapeutic target 2

If Pre-Capillary Pulmonary Hypertension is Found

• Refer to pulmonary hypertension specialist for consideration of pulmonary vasodilator therapy
• Evaluate for chronic thromboembolic disease (potentially surgically correctable)
• Screen for connective tissue disease, HIV, portal hypertension, and other secondary causes

If Intrinsic Lung Disease is Identified

• Refer to pulmonology for disease-specific management
• Consider supplemental oxygen for exertional desaturation

Critical Clinical Pitfalls to Avoid

• Do not pursue coronary angiography based on this stress test—the hyperdynamic wall motion with exercise definitively excludes flow-limiting coronary disease 1
• Do not dismiss the septal flattening finding—this is objective evidence that pulmonary pressures are significantly elevated and the tricuspid regurgitation jet underestimates true RVSP 1
• Do not attribute symptoms to deconditioning alone—while 2.5 METs is low, the oxygen desaturation and septal flattening indicate true cardiopulmonary pathology 1
• Do not repeat standard exercise testing—the patient has already demonstrated inability to exercise adequately, and further exercise ECG testing will not provide additional diagnostic information 1

Prognostic Considerations

• Severely reduced exercise capacity (<5 METs) is associated with significantly increased mortality risk regardless of underlying cause 1
• The combination of left ventricular hypertrophy and exercise intolerance carries particularly poor prognosis if left untreated 2
• Early identification and treatment of pulmonary hypertension and/or HFpEF can improve both symptoms and outcomes 1