In a 53‑year‑old woman with hypertension, hyperlipidemia, type 2 diabetes mellitus, obesity, gastro‑esophageal reflux disease, gastroparesis on glucagon‑like peptide‑1 receptor agonist therapy (e.g., semaglutide), a prior small fixed apical infarct, mild (<50 %) circumflex stenosis on coronary computed tomography angiography, a strong family history of premature myocardial infarction, mild obstructive sleep apnea (apnea‑hypopnea index 8.8) and recurrent substernal chest pain radiating to the right that is relieved by a second dose of sublingual nitroglycerin but not improved with metoprolol succinate, is it appropriate to obtain a cardiac magnetic resonance imaging study with stress perfusion and late‑gadolinium enhancement and to switch her anti‑anginal therapy to diltiazem 120 mg daily?

Cardiac MRI and Diltiazem Switch in Recurrent Angina with Mild CAD

Yes, cardiac MRI with stress perfusion and late gadolinium enhancement is appropriate, and switching from metoprolol to diltiazem 120 mg daily is reasonable in this patient with recurrent nitroglycerin-responsive chest pain despite non-obstructive coronary disease on CTA.

Rationale for Cardiac MRI

Cardiac MRI with stress perfusion is the recommended non-invasive test for women with suspected chronic coronary syndrome and non-obstructive coronary artery disease, particularly when functional assessment of ischemia is needed 1. Your patient has:

• Recurrent substernal chest pain radiating to the right, occurring 1-2 times every couple weeks
• Pain relieved by a second dose of sublingual nitroglycerin (suggesting true ischemia)
• Prior fixed apical infarct on nuclear stress test
• Mild (<50%) circumflex stenosis on CTA
• Strong family history of premature MI (father in 30s, relative in 50s)
• Multiple cardiovascular risk factors (HTN, HLD, DM2, obesity)

Why Cardiac MRI Over Repeat Nuclear Stress Test

Stress perfusion cardiac MRI is superior to SPECT for detecting microvascular ischemia and provides comprehensive tissue characterization in a single study 1. The cardiac MRI will:

• Detect microvascular dysfunction: Women with non-obstructive CAD frequently have microvascular ischemia (circumferential perfusion defects at stress that resolve at rest), which explains anginal symptoms despite <50% stenosis 1
• Characterize the apical infarct: Late gadolinium enhancement will define the extent and transmurality of the fixed apical defect seen on prior nuclear imaging 1
• Assess for inducible ischemia: Stress perfusion will identify territory-specific ischemia from the circumflex stenosis or diffuse subendocardial ischemia from microvascular disease 1
• Evaluate ventricular function comprehensively: Including right ventricular function, wall motion abnormalities, and diastolic parameters 1

Non-invasive imaging for myocardial ischemia, such as stress perfusion cardiovascular MRI, is the recommended initial test in women with chronic coronary syndrome 1.

Rationale for Switching to Diltiazem

Diltiazem is an appropriate alternative anti-anginal agent when beta-blockers fail to control symptoms, particularly in patients with diabetes and suspected microvascular disease 2.

Why Diltiazem Over Continued Metoprolol

• Metoprolol did not improve her chest pain and caused chronic fatigue (a common beta-blocker side effect)
• Diltiazem reduces heart rate and cardiac inotropy (similar to beta-blockers) while providing additional coronary vasodilation, which may be beneficial for microvascular ischemia 2
• Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) are effective for angina and have decades of favorable clinical experience in ischemic heart disease 2
• There is no major evidence of significant difference between drug classes for blood pressure control in IHD patients, provided target BP is achieved 2

Critical Safety Consideration

You must monitor for bradycardia and AV conduction abnormalities when initiating diltiazem, especially given her recent metoprolol use 3. Although she has discontinued metoprolol, ensure:

• Baseline ECG shows no AV block or bradycardia
• Heart rate is >60 bpm at baseline
• No history of sick sinus syndrome
• Follow-up ECG and heart rate check within 1-2 weeks of starting diltiazem 3

Combination therapy with diltiazem and beta-blockers carries risk of severe bradycardia and conduction abnormalities, but since you are switching (not combining), this risk is mitigated 3.

Additional Management Considerations

Address the Mild Sleep Apnea

CPAP titration should be pursued for her AHI of 8.8, as even mild obstructive sleep apnea:

• Exacerbates hypertension
• Increases cardiovascular risk
• May contribute to her chronic fatigue
• Can worsen nocturnal ischemia

Optimize GERD Management

Her gastroparesis and GERD (worsened by prior GLP-1 therapy) complicate the clinical picture 4. Since she stopped Ozempic due to side effects:

• Continue aggressive PPI therapy
• Small, frequent meals (already advised)
• Consider adding H2-blocker at bedtime if nocturnal symptoms persist
• Do not rely on nitroglycerin response to distinguish cardiac from esophageal pain, as esophageal spasm may also respond to nitroglycerin 5, 6

Glycemic Control Without GLP-1 Agonists

Consider metformin as first-line therapy for glucose control in this patient with type 2 diabetes and ischemic heart disease 7. Metformin:

• Does not worsen gastroparesis or GERD
• Has cardiovascular benefits
• Is recommended as first-line therapy in diabetic patients with cardiovascular disease 7

Algorithmic Approach to Her Chest Pain

Follow this sequence:

1. Cardiac MRI with stress perfusion and late gadolinium enhancement → Will definitively characterize:

   • Extent of prior infarction
   • Presence and territory of inducible ischemia
   • Microvascular dysfunction
   • Ventricular function and wall motion 1

2. If cardiac MRI shows significant inducible ischemia → Consider:

   • Invasive coronary angiography with fractional flow reserve (FFR) of the circumflex lesion
   • Possible revascularization if FFR <0.80 1

3. If cardiac MRI shows microvascular ischemia without obstructive disease → Optimize medical therapy:

   • Continue diltiazem 120 mg daily
   • Add long-acting nitrate (isosorbide mononitrate) if symptoms persist
   • Consider ranolazine as third-line agent 2

4. If cardiac MRI is negative for ischemia → Refocus on non-cardiac causes:

   • Upper endoscopy for persistent GERD symptoms
   • Esophageal manometry if esophageal spasm suspected
   • Musculoskeletal evaluation 5, 8

Critical Pitfalls to Avoid

• Do not assume her symptoms are purely GERD-related despite her gastroparesis history; nitroglycerin-responsive chest pain in a patient with known CAD and multiple risk factors warrants functional cardiac imaging 5, 6
• Do not delay cardiac MRI while empirically treating GERD; her strong family history and prior infarct mandate definitive ischemia evaluation 1
• Do not combine diltiazem with beta-blockers without careful monitoring, as this increases risk of severe bradycardia and AV block 3
• Do not dismiss the possibility of microvascular angina in women with non-obstructive CAD; this is a common and under-recognized cause of persistent angina 1