In a patient with sinus rhythm, marked sinus arrhythmia, a short PR interval, and a gallop on examination, what is the most likely diagnosis, its underlying pathology, and the recommended follow‑up?

Likely Diagnosis: Wolff-Parkinson-White (WPW) Syndrome with Possible Cardiomyopathy

The combination of sinus rhythm with marked sinus arrhythmia, short PR interval, and a gallop strongly suggests Wolff-Parkinson-White syndrome with underlying ventricular dysfunction, requiring urgent echocardiography and electrophysiology referral to prevent sudden cardiac death.

Clinical Reasoning and Pathophysiology

The short PR interval (<120 ms) is the critical diagnostic clue that narrows the differential diagnosis significantly. When combined with a gallop rhythm (S3 or S4), this presentation raises immediate concern for two concurrent processes:

Primary Diagnosis: WPW Syndrome

• WPW pattern is defined by PR interval <120 ms, presence of a delta wave (slurred initial QRS upstroke), and QRS duration >120 ms, resulting from an accessory pathway that bypasses the AV node and causes abnormal ventricular pre-excitation 1
• The accessory pathway creates a direct electrical connection between atria and ventricles, allowing rapid conduction that can degenerate into ventricular fibrillation during atrial fibrillation, with sudden death occurring as the first presentation in approximately 50% of cases who experience cardiac arrest 2
• WPW occurs in approximately 1 in 250 individuals and affects 0.1-0.3% of the general population, with most patients having structurally normal hearts initially 1, 3

Secondary Concern: Ventricular Dysfunction

• The presence of a gallop rhythm indicates either ventricular hypertrophy (S4) or ventricular dysfunction (S3), which in the context of WPW may represent tachycardia-induced cardiomyopathy from unrecognized recurrent arrhythmias 2
• For specific locations of accessory pathways with overt anterograde conduction, there may be reduction in LV systolic performance due to anomalous LV depolarization, which can reduce exercise capacity even without tachyarrhythmias 3
• WPW is associated with structural abnormalities including Ebstein's anomaly and hypertrophic cardiomyopathy, both of which can produce gallop rhythms 2

Marked Sinus Arrhythmia Component

• Marked sinus arrhythmia in adults may reflect enhanced vagal tone or underlying autonomic dysfunction, which can coexist with WPW but does not change the primary management approach 1
• The sinus arrhythmia itself is typically benign but should not distract from the more urgent concern of the short PR interval and gallop 1

Mandatory Immediate Workup

Step 1: Confirm WPW Pattern on 12-Lead ECG

• Obtain a 12-lead ECG immediately to identify the delta wave, measure exact PR interval, assess QRS duration, and look for secondary ST-T wave changes that are typically discordant to the major QRS deflection 1, 4
• Manual ECG interpretation is mandatory because automated systems are unreliable and frequently produce erroneous diagnoses in pre-excitation syndromes 5
• Distinguish between isolated short PR (benign) and WPW pattern (high-risk), as the presence or absence of a delta wave completely changes management 2

Step 2: Urgent Echocardiography

• Transthoracic echocardiography is mandatory to evaluate for Ebstein's anomaly, hypertrophic cardiomyopathy, left ventricular hypertrophy, systolic dysfunction, and valvular disease, all of which are associated with WPW or can explain the gallop 1, 2
• Assess left ventricular ejection fraction, wall thickness, chamber dimensions, and left atrial size to determine if tachycardia-induced cardiomyopathy has developed 5
• The gallop rhythm mandates structural assessment regardless of WPW findings, as it indicates either pressure overload (S4) or volume overload/systolic dysfunction (S3) 5

Step 3: Risk Stratification for Sudden Death

• Exercise stress testing is the initial non-invasive risk stratification tool, where abrupt, complete loss of pre-excitation at higher heart rates suggests a low-risk accessory pathway 1
• Intermittent pre-excitation during sinus rhythm on resting ECG is consistent with a low-risk pathway and may obviate the need for exercise testing, though recent data suggest even intermittent pre-excitation may not be entirely benign 1, 6
• If non-invasive testing cannot confirm a low-risk pathway or is inconclusive, electrophysiological study should be performed to determine the shortest pre-excited RR interval during induced atrial fibrillation 1
• If the shortest pre-excited RR interval is ≤250 ms (≥240 beats/min), the accessory pathway is deemed high-risk and transcatheter ablation is recommended 1

Definitive Management Algorithm

For Confirmed WPW Pattern (Delta Wave Present):

Immediate Actions:

• Refer urgently to cardiac electrophysiology for comprehensive evaluation, as sudden death can occur without warning even in asymptomatic patients 2, 5
• Do not dismiss WPW pattern as benign even if the patient is currently asymptomatic, because sudden cardiac death risk ranges from 0.15% to 0.39% over 3-10 years 2
• Avoid Class Ic antiarrhythmics (flecainide, propafenone) if any structural heart disease is present due to substantial pro-arrhythmic risk 5

Definitive Treatment:

• Catheter ablation is the definitive treatment for WPW pattern given the sudden death risk, with >95% acute success rate for AVNRT, <5% recurrence, and <1% risk of complete heart block 1, 2, 5
• For competitive athletes or high-intensity sport participants, some physicians recommend electrophysiological studies irrespective of exercise test results, on the premise that high catecholamine concentrations during intensive exercise may modify the refractory period unpredictably 1

For Isolated Short PR Without Delta Wave:

• A short PR interval in isolation without widened QRS or delta wave in an asymptomatic patient should not trigger further cardiac assessment according to international athletic guidelines 1
• However, the presence of a gallop rhythm elevates concern and mandates echocardiography to exclude structural disease that could explain both findings 2, 5

Management of Concurrent Ventricular Dysfunction

If echocardiography confirms systolic dysfunction or significant hypertrophy:

• Tachycardia-induced cardiomyopathy from unrecognized recurrent SVT episodes must be considered, particularly if the patient has had palpitations that were dismissed or undiagnosed 5
• Beta-blockers are the preferred initial agent for rate control and symptomatic benefit, but must be used with extreme caution in WPW with atrial fibrillation because they can paradoxically accelerate ventricular response over the accessory pathway 1
• Definitive ablation of the accessory pathway may allow recovery of ventricular function if tachycardia-induced cardiomyopathy is the underlying mechanism 5

Critical Pitfalls to Avoid

• Never attribute the short PR interval to enhanced AV nodal conduction or athletic heart without first excluding WPW pattern with careful delta wave assessment 1, 2
• Do not use adenosine in patients with pre-excitation and irregular tachycardia (atrial fibrillation), as it may precipitate rapid ventricular rates and degeneration to ventricular fibrillation 1
• Avoid AV nodal blocking agents (beta-blockers, calcium channel blockers, digoxin) in WPW with atrial fibrillation, as they preferentially block the AV node and force conduction down the accessory pathway, potentially causing hemodynamic collapse 1, 7
• Do not reassure the patient based solely on absence of symptoms, because sudden death can be the first manifestation in WPW syndrome 2, 6
• Proper ECG calibration is crucial when QRS voltage is extremely high, as in metabolic storage diseases like Pompe disease that can also present with short PR 2

Alternative Diagnoses to Consider

Fabry Disease

• Fabry disease is an X-linked lysosomal storage disorder characterized by short PR interval, sinus bradycardia, and left ventricular hypertrophy, with an incidence of approximately 1 in 40,000 to 60,000 males 2
• Consider Fabry disease in patients with short PR and LVH, especially with multisystem symptoms such as angiokeratomas, acroparesthesias, or renal dysfunction 2

Pompe Disease

• Pompe disease can present with short PR interval, extremely tall QRS complexes, and cardiomegaly, particularly in infantile cases 2

Lown-Ganong-Levine Syndrome

• This is a controversial entity characterized by short PR without delta wave or QRS widening, thought to represent enhanced AV nodal conduction, but its clinical significance remains uncertain 2

Follow-Up Protocol

Immediate (within 1 week):

• Complete 12-lead ECG with manual interpretation
• Transthoracic echocardiography
• Cardiology consultation with electrophysiology referral if WPW confirmed

Short-term (within 1 month):

• Exercise stress testing for risk stratification
• 24-48 hour Holter monitoring to detect asymptomatic arrhythmias
• Electrophysiology study if non-invasive testing is inconclusive

Long-term:

• If ablation is performed, follow-up ECG at 3 months to confirm absence of pre-excitation
• If conservative management is chosen (low-risk pathway), annual ECG and symptom assessment
• Patient education on recognizing palpitations, syncope, or presyncope requiring immediate evaluation