What are the differential diagnoses for a patient with a 12-lead electrocardiogram (ECG) showing sinus rhythm with a borderline short PR interval, rSr′ pattern in lead V1, and mild ST-segment depressions in inferior leads, in the absence of prior ECG for comparison?

Differential Diagnosis of ECG Findings

The most critical immediate concern is acute coronary syndrome (ACS), specifically diffuse subendocardial ischemia or left main/proximal LAD disease, given the diffuse ST depressions with ST elevation in aVR—this pattern demands urgent troponin measurement, echocardiography, and cardiology consultation regardless of other findings. 1

High-Priority Life-Threatening Diagnoses

Acute Coronary Syndrome

• Diffuse ST-segment depression in inferior and lateral leads (V4-6) combined with ST elevation in aVR is a high-risk pattern indicating either left main coronary artery disease, proximal LAD occlusion, or severe three-vessel disease. 1
• This pattern represents diffuse subendocardial ischemia and carries significant mortality risk requiring immediate intervention 1
• The absence of pathological Q waves does not exclude acute MI, as 1-4% of patients with entirely normal or nonspecific ECGs ultimately have AMI 2
• ST depression may be the only manifestation of posterior or circumflex territory ischemia 1

Structural Heart Disease Requiring Urgent Evaluation

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

• The rSr' pattern in V1 is a recognized finding in ARVC, though not the most specific 3
• T-wave inversion in right precordial leads V1-V3 occurs in 29% of ARVC patients and is the most frequent ECG abnormality 3
• Any suspected ARVC based on ECG requires immediate echocardiography as minimum evaluation, with cardiac MRI being superior for detection 3
• The presence of ST-segment depression extending to lateral leads would suggest left ventricular involvement in ARVC 3

Hypertrophic Cardiomyopathy (HCM)

• ST-segment depression associated with other non-voltage criteria for LV hypertrophy (such as the 2mm P wave amplitude suggesting left atrial enlargement) raises concern for HCM 1
• ST-segment depression, either isolated or with other abnormalities, mandates echocardiography to exclude pathological LV hypertrophy and structural heart disease 1
• HCM characteristically shows ST-T abnormalities combined with voltage criteria and left atrial enlargement 1

Intermediate-Risk Diagnoses

Conduction System Variants and Abnormalities

Incomplete Right Bundle Branch Block (IRBBB)

• The rSr' pattern in V1 with QRS duration ~90ms is consistent with IRBBB 4
• This can be a benign normal variant but requires differentiation from pathological causes 4
• The differential diagnosis of rSr' in V1-V2 ranges from benign variants to life-threatening conditions including Brugada syndrome and ARVC 4

Borderline Short PR Interval (~115ms)

• While the lower limit of normal PR is typically 120ms, a borderline short PR without clear pre-excitation is less concerning 1
• True pre-excitation (Wolff-Parkinson-White) can cause ST-segment abnormalities that mimic ischemia 5
• Accelerated AV nodal conduction from excess catecholamines (e.g., pheochromocytoma) can shorten PR interval 6
• The absence of delta waves makes WPW less likely, but intermittent pre-excitation can occur 5

Atrial Abnormality

• P wave amplitude of 2mm meets criteria for right atrial enlargement when present in leads II, III, aVF 1
• This finding suggests underlying structural heart disease, particularly conditions causing right heart strain 1
• In the context of rSr' pattern, this raises concern for pulmonary hypertension or right ventricular pathology 1

Lower-Risk but Important Considerations

Brugada Syndrome

• The rSr' pattern in V1 can be seen in Brugada syndrome, though the classic Type 1 pattern shows coved ST elevation ≥2mm 7
• Recording V1-V2 in higher intercostal spaces (2nd and 4th) may unmask Brugada pattern 7
• The absence of characteristic ST elevation makes this less likely but does not exclude it 7

Electrolyte Abnormalities

• Diffuse ST-segment depression can occur with severe electrolyte disturbances 7
• The clinical context and basic metabolic panel are essential for evaluation 1

Medication Effects

• A thorough review of prescription and over-the-counter medications is essential, as many drugs can cause ST-T abnormalities 1
• Digitalis, antiarrhythmics, and psychotropic medications commonly cause nonspecific ST changes 1

Critical Diagnostic Algorithm

Immediate Actions (Within 10 Minutes):

1. Obtain serial troponin measurements immediately and at 3-6 hours 1
2. Perform urgent echocardiography to assess for wall motion abnormalities, LVEF, structural disease, and RV function 3, 8
3. Repeat ECG every 15-30 minutes if initial troponin negative but high clinical suspicion 1

If Troponin Elevated or Positive:

• Activate cardiac catheterization team for likely ACS with diffuse subendocardial ischemia 1
• The ST elevation in aVR with diffuse ST depression indicates high-risk anatomy 1

If Troponin Negative but Abnormal Echo:

• Proceed to cardiac MRI for definitive evaluation of cardiomyopathy (ARVC, HCM) 3
• Consider 24-hour Holter monitoring for ventricular arrhythmias 3

If Initial Workup Non-Diagnostic:

• Exercise stress testing may reveal additional abnormalities or provoke ischemia 1
• Consider electrophysiology study if conduction abnormalities persist with symptoms 8

Common Pitfalls to Avoid

• Never dismiss diffuse ST depression with ST elevation in aVR as "nonspecific"—this is a high-risk pattern for left main or severe multivessel disease 1
• Do not attribute all ST changes to the rSr' pattern or IRBBB without excluding ischemia 1
• Overreliance on a borderline or nonspecifically abnormal ECG in a patient with concerning symptoms is dangerous—history remains paramount 2
• The absence of prior ECG makes comparison impossible, lowering diagnostic certainty and mandating more aggressive evaluation 1
• A completely normal or minimally abnormal ECG does not exclude significant pathology, as 1-4% of AMI patients have normal initial ECGs 2