68. Case Report: WPW and HCM Phenotype – VCU

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CardioNerds (Amit Goyal & Daniel Ambinder) join Virginia Commonwealth University (VCU) cardiology fellows (Ajay Pillai, Amar Doshi, and Anna Tomdio) for a delicious skillet breakfast and amazing day in Richmond, VA! They discuss a fascinating case of a patient with Wolff-Parkinson-White (WPW) and hypertrophic cardiomyopathy (HCM). Dr. Keyur Shah provides the E-CPR and program director Dr. Gautham Kalahasty provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Colin Blumenthal with mentorship from University of Maryland cardiology fellow Karan Desai.

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CardioNerds (Amit Goyal & Daniel Ambinder) join Virginia Commonwealth University (VCU) cardiology fellows (Ajay Pillai, Amar Doshi, and Anna Tomdio) for a delicious skillet breakfast and amazing day in Richmond, VA! They discuss a fascinating case of a patient with Wolff-Parkinson-White (WPW) and hypertrophic cardiomyopathy (HCM). Dr. Keyur Shah provides the E-CPR and program director Dr. Gautham Kalahasty provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Colin Blumenthal with mentorship from University of Maryland cardiology fellow Karan Desai.
Episode graphic by Dr. Carine Hamo

The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus.

We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director.

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Patient Summary

A man in his mid-60s presented to the ED after an episode of unwitnessed syncope while drinking. Patient had suddenly passed out from a seated position with no prodrome or post-ictal state. He had episodes like this in the past, which were thought to be seizures, but otherwise PMHx only notable for alcohol use disorder. He denied any FH of SCD or syncope. In the ED, exam was unremarkable. Labs notable for mild thrombocytopenia, mild hyponatremia with AKI, 2:1 AST/ALT ratio, elevated NT-proBNP, and a very high lactate that rapidly corrected with fluids. EKG was notable for sinus tachycardia, short PR interval, wide QRS, and delta waves consistent with Wolff-Parkinson-White (WPW) pattern. Echo showed preserved LVEF, thickened LV septum (1.6 cm) and posterior wall (1.3 cm) concerning for hypertrophic cardiomyopathy (HCM). No outflow tract gradient was noted at rest or with stress, and the strain pattern demonstrated apical sparing. Evaluation for cardiac amyloid, including plasma cell dyscrasia and PYP scan, was negative. Cardiac MRI confirmed severely thickened LV inferior and inferolateral walls at 1.7 cm with no LVOT obstruction. 25% of the myocardium demonstrated patchy LGE.  

Due to concern for WPW syndrome, the patient underwent an EP study. This revealed a malignant septal accessory pathway that was successfully ablated with resolution of the WPW EKG features. Given large LGE burden in setting of HCM, patient underwent placement of primary prevention ICD. Genetic testing for PRKAG2 mutation is pending given comorbid WPW and HCM. 


Case Media

A. CXR: Slightly increased interstitial markings in the lung bases, an elevated right hemidiaphragm. No acute airspace disease or pulmonary edema
B. ECG: Sinus tachycardia rate 120bpm, PR interval 80ms, QRS 130ms, WPW pattern.  Arruda algorithm localizes to posterior septum.
C. CMR:  Myocardium nulls before blood pool.
D. CMR:  Delayed gadolinium enhancement
E. Follow up ECG: NSR 78, repolarization abnormalities.  T wave memory inferior leads.
F. CXR status post dual chamber ICD implantation

TTE: Apical 4 chamber
TTE: Apical 2 chamber
TTE: Apical 3 chamber
TTE: Strain imaging
CMR: 4 chamber cine
CMR: 2 chamber cine
CMR: 3 chamber cine
CMR: Short axis cine at base level
CMR: Short axis cine at mid-papillary level

CMR: Short axis cine at apical level

Episode Schematics & Teaching


The CardioNerds 5! – 5 major takeaways from the #CNCR case

  1. Our patient was found to have Wolff-Parkinson-White (WPW) pattern. What are the diagnostic criteria for WPW pattern and how does it differ from WPW syndrome? How can you localize the accessory pathway using the EKG? 
    • WPW pattern refers to the presence of the below criteria on a patient’s surface EKG in the absence of symptomatic arrhythmias. If symptomatic arrhythmias related to the accessory pathway occur, then it is WPW syndrome. Symptoms may include palpitations, shortness of breath, presyncope, syncope, and sudden cardiac death (SCD).  
    • Not all patients with accessory pathways have EKG findings as only 60-75% of accessory pathways are “manifest” (meaning they conduct antegrade from atria to ventricles or are bidirectional). Conversely, a “concealed” accessory pathway only conducts retrograde (from ventricles to atria) and would not be apparent on resting sinus EKG; these patients can have WPW diagnosed after a ventricular premature beat, ventricular pacing, or an EP study that shows retrograde conduction through the accessory pathway.  
    • The WPW pattern is diagnosed by the following EKG criteria: 
      • Short PR interval < 120 ms 
      • Signs of pre-excitation: a delta wave (slurred upstroke of QRS complex) and QRS > 120 ms. The degree of pre-excitation on EKG depends on the position (how much of the ventricular myocardium is depolarized by the accessory pathway) and depolarization speed of the accessory pathway (more rapid conduction leading to earlier ventricular depolarization and wider delta wave).  
    • We can use EKG findings to localize accessory pathways using the Arruda Criteria, which has an overall sensitivity of 90% and specificity of 99%. Note, patients who have a left-lateral bypass tract as the antegrade limb may not have delta waves on surface EKG, as the atrial impulse can take longer to reach the bypass tract than the AV node.   
  2. What are the major mechanisms for WPW and how do they lead to early activation of the ventricles? How can this precipitate arrhythmias? 
    • Accessory pathways are abnormal congenital connections between the atria and ventricles when there is incomplete atrio-ventricular isolation during fetal development. They can be associated with congenital cardiac malformations like Ebstein anomaly. 
    • Depolarization of the ventricles occurs via the AV node and the accessory pathway simultaneously, leading to early depolarization of a portion of the ventricles and the characteristic delta wave. Depolarization through the His Purkinje system reaches the apex first and travels back up the ventricle, meeting the slower cell to cell conduction from the accessory pathway and causing termination of the impulses. The resulting QRS complex is essentially a “fusion beat” between the two sources. 
    • Accessory pathways often have more rapid conduction, but longer refractory periods than the AV node. If a PAC occurs when the accessory pathway is refractory, there will be antegrade conduction solely through the AV node. As the impulse travels through the ventricles it can conduct retrograde through the accessory pathway from V to A. This creates a reentrant pathway that results in atrioventricular reentrant tachycardia (AVRT), which accounts for up to 80% of SVT in WPW. Orthodromic AVRT (antegrade through AV node, retrograde through accessory pathway) accounts for 90-95% of AVRT in WPW.  
    • Other tachycardias can occur where the accessory pathway is a bystander and not required for initiation and maintenance of the arrhythmia like in AVRT. This includes atrial arrhythmias (e.g., atrial fibrillation, atrial flutter), ventricular tachycardia, and ventricular fibrillation. Atrial fibrillation is relatively common (~20%) in WPW syndrome patients. Atrial fibrillation with an accessory pathway can produce rapid ventricular rates due to unencumbered conduction via the accessory pathway. In these situations, QRS width and morphology may vary due to variable conduction via the AV node vs accessory pathway. Depending on the rate of conduction, the patient can degenerate into VF. A shorter refractory period places patients at the highest risk for VF.  
  3. How do we risk stratify patients with WPW pattern? When would an EP study (EPS) be beneficial? What features are high risk on EPS and would warrant treatment? 
    • Patients who are asymptomatic are typically at low risk of sudden cardiac death. Those who do have SCD typically have symptoms at some point prior to arrest. Patients with intermittent loss of the delta wave on a beat-to-beat basis are likely at lower risk, as it suggests the accessory pathway lacks the ability for rapid AV conduction. However, persistent delta wave in asymptomatic patients may still be at low risk.  
    • The risk for SCD is thought to be due to rapid conduction of Afib down the accessory pathway leading to VF. Accessory pathways with shorter refractory periods are able to conduct at higher rates (shorter R to R intervals). Delta waves disappear when R to R interval is less than the refractory period, at which point the atrial impulse only conducts through AV node. Thus, the lower the HR that delta waves become intermittent, the lower the risk of SCD. 
    • We can start risk stratification in most patients noninvasively with a resting EKG and exercise EKG stress test, unless we clearly demonstrate intermittent delta wave at rest. If preexcitation persists even with maximal sinus heart rates, then an EPS is recommended.  
    • High risk features on EPS include multiple accessory pathways, inducible AVRT or Afib, shortest pre-excited RR interval (SPERRI) < 250 ms, and accessory pathway refractory period < 240 ms 
  1. How are high risk WPW pattern and WPW syndrome treated? 
    • For the chronic prevention of arrhythmia: 
      • In patients with high risk WPW pattern, we typically refer for catheter ablation (typically radiofrequency ablation though cryoablation can be utilized) of the accessory pathway to help prevent SCD. Successful ablation is curative.  
      • In patients with WPW syndrome, we can still risk stratify with the above algorithm, but symptomatic patients should receive treatment. Ablation is first line for all patients who are candidates and willing given success rates of 90-95%.  In terms of medical therapy for patients who are not ablation candidates, flecainide and propafenone are reasonable options in the absence of structural heart disease. Dofetilide or sotalol are options in patients with structural heart disease. AV nodal blocking agents can be considered in the setting of orthodromic AVRT. 
    • For WPW patients presenting with an acute arrhythmia and who are hemodynamically unstable, synchronized cardioversion is first line therapy. Pharmacologic therapy in the hemodynamically stable patient depends on the suspected level of involvement of the accessory pathway and type of arrhythmia. For arrhythmias not dependent on the accessory pathway for initiation and maintenance (e.g., atrial fibrillation), AV nodal blocking agents can induce rapid antegrade conduction down the accessory pathway which could degenerate into ventricular fibrillation. In the setting of rapid pre-excited atrial fibrillation, procainamide or ibutilide are the agents of choice.  
    • AVRT requires the accessory pathway for initiation and maintenance of the arrhythmia. Orthodromic AVRT will typically be a narrow complex tachycardia (unless there is aberrancy) and can be managed similarly to other regular narrow complex tachycardias (e.g., use of adenosine). If there is any doubt about the diagnosis, procainamide should be utilized.   
  2. Where do the diagnostic schema for WPW and HCM overlap and what syndrome should you think of in patients where they coexist? 
    • Familial WPW is rare and characterized by the autosomal dominant inheritance of the combination of WPW syndrome and non-sarcomeric HCM. It is caused by mutations in the PRKAG2 gene, which encodes a portion of 5’AMP-activated protein kinase (AMPK). This mutation leads to cardiac glycogen overload, resulting in ventricular hypertrophy (HCM phenocopy), WPW-like syndrome, AV block, and progressive conduction system disease.  
    • Cardiac myocyte glycogen accumulation is thought to decrease the myocardial activation threshold and so overcomes the insulating properties of the AV annulus fibrosus, resulting in electrical leak between the atria and ventricles. This gives the clinical appearance of an accessory pathway. Given the typical absence of a distinct accessory pathway, EPS with ablation is often not effective.  
    • Other glycogen storage disorders may cause a similar overlap between an HCM phenocopy and WPW mimic like Pompe disease and Danon disease. 

References

  1. Aggarwal, V., Dobrolet, N., Fishberger, S., Zablah, J., Jayakar, P., & Ammous, Z. (2015). PRKAG2 mutation: An easily missed cardiac specific non-lysosomal glycogenosis. Annals of Pediatric Cardiology8(2), 153. 
  2. Arruda, M. S., McCLELLAND, J. H., Wang, X., Beckman, K. J., Widman, L. E., Gonzalez, M. D., Nakagawa, H., Lazzara, R., & Jackman, W. M. (1998). Development and Validation of an ECG Algorithm for Identifying Accessory Pathway Ablation Site in Wolff-Parkinson-White Syndrome. Journal of Cardiovascular Electrophysiology9(1), 2–12. 
  3. Calkins Hugh, Yong Patrick, Miller John M., Olshansky Brian, Carlson Mark, Saul J. Philip, Huang Shoei K. Stephen, Liem L. Bing, Klein Lawrence S., Moser Suzan A., Bloch Daniel A., Gillette Paul, & Prystowsky Eric. (1999). Catheter Ablation of Accessory Pathways, Atrioventricular Nodal Reentrant Tachycardia, and the Atrioventricular Junction. Circulation99(2), 262–270. 
  4. Chhabra, L., Goyal, A., & Benham, M. D. (2020). Wolff Parkinson White Syndrome (WPW). In StatPearls. StatPearls Publishing. 
  5. Gollob, M. H., Green, M. S., Tang, A. S.-L., Gollob, T., Karibe, A., Hassan, A.-S., Ahmad, F., Lozado, R., Shah, G., Fananapazir, L., Bachinski, L. L., Tapscott, T., Gonzales, O., Begley, D., Mohiddin, S., & Roberts, R. (2001). Identification of a Gene Responsible for Familial Wolff–Parkinson–White Syndrome. New England Journal of Medicine344(24), 1823–1831. 
  6. Gollob Michael H., Seger John J., Gollob Tanya N., Tapscott Terry, Gonzales Oscar, Bachinski Linda, & Roberts Robert. (2001). Novel PRKAG2 Mutation Responsible for the Genetic Syndrome of Ventricular Preexcitation and Conduction System Disease With Childhood Onset and Absence of Cardiac Hypertrophy. Circulation104(25), 3030–3033. 
  7. Miyamoto, L. (2018). Molecular Pathogenesis of Familial Wolff-Parkinson-White Syndrome. The Journal of Medical Investigation: JMI65(1.2), 1–8. 
  8. Page, R. L., Joglar, J. A., Caldwell, M. A., Calkins, H., Conti, J. B., Deal, B. J., Estes III, N. A. M., Field, M. E., Goldberger, Z. D., Hammill, S. C., Indik, J. H., Lindsay, B. D., Olshansky, B., Russo, A. M., Shen, W.-K., Tracy, C. M., & Al-Khatib, S. M. (2016). 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia. Heart Rhythm13(4), e136–e221. 
  9. Spector, P., Reynolds, M. R., Calkins, H., Sondhi, M., Xu, Y., Martin, A., Williams, C. J., & Sledge, I. (2009). Meta-Analysis of Ablation of Atrial Flutter and Supraventricular Tachycardia†. American Journal of Cardiology104(5), 671–677.
  10. Talle, M. A., Buba, F., Bonny, A., & Baba, M. M. (2019). Hypertrophic Cardiomyopathy and Wolff-Parkinson-White Syndrome in a Young African Soldier with Recurrent Syncope. Case Reports in Cardiology2019

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68. Case Report: WPW and HCM Phenotype – VCU