CardioNerds (Amit Goyal & Daniel Ambinder) join join Mayo Clinic cardiology fellows (Mays Ali, Charlie Jain, Korosh Sharain) for a scenic walk through gorgeous Rochester, Minnesota! They discuss a fascinating case of constrictive pericarditis and severe mitral regurgitation. Dr. Rick Nishimura provides the E-CPR and program director Dr. Frank Brozovich provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Bibin Varghese with mentorship from University of Maryland cardiology fellow Karan Desai.  

Jump to: Patient summary – Case figures & media – Case teaching – References – Production team

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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A woman in her late 40s with a history of lupus and hypertension presented with worsening dyspnea on exertion and orthopnea over a year. She reported intermittent pleuritic chest discomfort that had persisted since an episode of acute pericarditis years prior. A TTE suggested severe mitral regurgitation, and she was referred to the Mayo Clinic for mitral valve intervention.   

The official TTE report from the OSH suggested non-dilated LV, EF 55-60%, normal RV function, severe MR with thickened leaflets and sub-valvular apparatus, moderate to severe TR and a dilated IVC. Furthermore, the CXR showed pericardial calcifications. Upon evaluation by the Mayo Clinic fellows, the JVP was elevated to about 10-12 cm with rapid x and y descents, a positive Kussmaul’s sign, and the murmurs of MR and TR. Her lungs were clear to auscultation and extremities did not demonstrate edema. Re-review of the TTE images revealed posterior pericardial thickening, no septal shift on respiration, but suggestion of annulus reversus where medial mitral annulus tissue doppler (9 cm/s) was greater than lateral (8 cm/s). Further, there was evidence of expiratory hepatic vein diastolic flow reversal. 

For the team, there was discordance between the apparent severity of her MR reported by echocardiogram and her clinical symptoms. In addition, the echocardiogram was suggestive of specific signs of constrictive pericarditis. Thus, simultaneous RHC/LHC was obtained. There was equalization of RV/LV pressures during diastole, demonstration of a “square root sign” and importantly discordance between LV and RV pressures with respiration. Thus, discordant clinical findings led to a suspicion for constrictive pericarditis and was corroborated by discordance on invasive hemodynamics! Further, the V-waves were not prominent on wedge pressure tracing and to investigate the mitral regurgitation further, an LV ventriculogram was done. This demonstrated 3+ to 4+ MR.  Based on all the findings, the patient was diagnosed with constrictive pericarditis, severe MR and moderate to severe TR. She underwent pericardiectomy, mitral valve replacement (given that repair was not feasible due to the sub-valvular thickening) and given that TR has been shown to worsen after pericardiectomy and is a poor prognostic factor, she additionally underwent tricuspid valve repair. Her symptoms improved markedly following intervention. 

• A
• B
• C
• D
• E
• F
• G
• H

A. CXR: Heart size was borderline enlarged with biatrial enlargement.  LV does not appear very enlarged.
B. Mitral Regurgitation by CW Doppler
C. Tricuspid regurgitation by CW Doppler. TR Max 2.43
D. Tissue Doppler of the mitral valve annulus: Medial e’ = 9 cm/s, Lateral e’ 8 cm/s
E. Hepatic Vein PW Doppler
F. Right atrial pressure tracing
G. RV and LV simultaneous pressure tracings
H. Wedge pressure and LV simultaneous pressure tracings

1. One of the early clues to the etiology of this patient’s dyspnea was a positive Kussmaul’s sign. What is the mechanism and differential of Kussmaul’s Sign?  

• Typically the JVP decreases with inspiration as the negative intrathoracic pressure “sucks in” blood from the vena cavae. When there is a lack of decrease or an increase in JVP with inspiration, this finding is called Kussmaul’s sign. Kussmaul’s sign reflects conditions where there is right ventricular dysfunction, impaired RV filling and elevated right atrial pressure   
• Kussmaul’s sign is classically associated with constrictive pericarditis. Remember, during normal inspiration, the diaphragm contracts and increases abdominal pressure with variable effect on venous return. However, in constriction, the rise in abdominal pressure increases venous return from the congested hepato-splanchnic vasculature. And since RV filling is constrained by a non-compliant pericardium, there is a rise in JVP during inspiration.   
• Other conditions where we may see a positive Kussmaul’s sign include restrictive cardiomyopathy, RV predominant infarction, massive pulmonary embolism, tricuspid stenosis, and severe tricuspid regurgitation. 

2. A decision was made to pursue invasive hemodynamic evaluation to differentiate between restrictive and constrictive physiology. How do we differentiate between the two on echocardiogram?  

• Differentiating between the two diagnoses requires an understanding of the pathophysiologic differences between constriction and restriction.  Enjoy Ep #58 and CN5 for understanding constrictive physiology and echocardiographic findings! In restriction we do not have intrathoracic-intracardiac disassociation as intrathoracic pressures are transmitted normally to the cardiac chambers during respiration. Further, there is no exaggerated interventricular dependence.   
• We may see increased myocardial thickness in restriction (secondary to infiltrative or storage disorders – enjoy Ep #50 – restrictive cardiomyopathy) and increased pericardial thickness/calcification in constriction.   
• Unlike constrictive pericarditis, restrictive cardiomyopathies should not demonstrate respirophasic septal shift or variation across the atrioventricular valves. Both conditions will demonstrate hepatic vein diastolic flow reversal. However, in constriction, the exaggerated ventricular interdependence and greater LV filling during expiration causes septal bowing into the RV and results in greater hepatic vein diastolic flow reversal during expiration. In restriction, hepatic vein flow reversal is more prominent in inspiration as the stiff myocardium is unable to tolerate the increased RV preload that occurs during inspiration.   
• The estimated pulmonary artery systolic pressures tend to be elevated (>55-60 mmHg) in restrictive cardiomyopathy and are often normal in constriction. In constriction, the annular tissue velocity is preserved except at the lateral annulus, where tethering of the lateral wall results in decreased velocities and annulus reversus (See Ep#58 and CN5). Meanwhile, annular tissue velocity (e’) is significantly reduced in restrictive cardiomyopathy.   
• Enjoy Ep #58 and CN5 for differences on invasive hemodynamics! 

3. Given that the patient had subvavlular thickening, the patient was not a candidate for mitral valve repair and the patient underwent mitral valve replacement. What are the indications for mitral valve surgery in patients with severe chronic MR? Why is mitral valve repair preferred for primary MR?  

• Class I indications for mitral valve surgery include (1) symptomatic patients in the absence of severe LV dysfunction (defined as EF <30%; Stage D MR); (2) asymptomatic patients with chronic severe MR and mild to moderate LV dysfunction (EF 30% to 60% and/or LV end-systolic dimension ≥ 40 mm; Stage C); (3) patients with chronic severe primary MR undergoing cardiac surgery for other indications. 
• Class IIa indications include (1) asymptomatic patients with LVEF > 60% and LVESD < 40 mm (Stage C1) in whom the likelihood of successful repair is >95% and expected mortality is <1%; (2) asymptomatic patients with new-onset atrial fibrillation and preserved LVEF (Stage C1); (3) asymptomatic patients with pulmonary hypertension (defined as PASP > 50 mmHg) and preserved LVEF. 
• For primary mitral regurgitation involving an abnormality of the valve apparatus (e.g., leaflets, chordae, annulus, papillary muscles) – MV repair is preferred over MV replacement in most patients as it is associated with lower operative mortality and improved long term survival. Feasibility of valve repair will generally depend on valve anatomy and surgical experience. Class I indications for MV repair over mitral valve replacement (MVR) include chronic severe primary MR limited to the posterior leaflet and chronic severe primary MR involving the anterior leaflet or both leaflets when a successful and durable repair appears feasible. 

4. The patient underwent TV repair. What is the reason to potentially pursue TV intervention in patients undergoing pericardiectomy?  

• Tricuspid regurgitation (TR) is often a co-morbid condition in patients with constrictive pericarditis. After pericardiectomy, TR can worsen after a thickened, calcified pericardium is removed allowing RV dilation and subsequent dilation of the TV annulus leading to worsening functional TR. Tricuspid regurgitation is associated with increased short and long-term mortality following pericardiectomy, and the Mayo Clinic in particular has been integral in demonstrating that even mild TR is a marker of increased operative and long-term mortality and worsening symptoms. Thus, in patients with moderate to severe TR at the time of pericardiectomy, consideration should be given for tricuspid valve repair (if feasible). Of note, most data to date suggests that this approach provides symptomatic improvement but no clear mortality benefit has been demonstrated. 

5. Finally, the Mayo CardioNerds taught us to think about our thinking! What are some cognitive errors to be aware of when evaluating patients?  

• The team at the Mayo Clinic masterfully demonstrated how to avoid the common cognitive errors of the anchoring heuristic and premature closure while diagnosing a case of constrictive pericarditis and severe mitral regurgitation. 
• Anchoring heuristic is the tendency to rely on selected signs or simple investigations, often fixating on early data and not incorporating new information. In other words, one “anchors” onto the initial data and impressions. Ways to avoid anchoring include: attention to base rates of disease, knowledge of test characteristics of diagnostics, deliberately seeking more information to support or refute the initial impression, and following data-driven diagnostic algorithms.  
• Premature closure is the acceptance of a diagnosis before it has been fully verified. To avoid this, consider alternative diagnoses and search for data that challenge the provisional diagnosis. 

References for episode 59: Constrictive Pericarditis & Severe Mitral Regurgitation

1. Geske, J. B., Anavekar, N. S., Nishimura, R. A., Oh, J. K. & Gersh, B. J. Differentiation of Constriction and Restriction: Complex Cardiovascular Hemodynamics. J. Am. Coll. Cardiol. 68, 2329–2347 (2016). 
2. Garcia, M. J. Constrictive Pericarditis Versus Restrictive Cardiomyopathy? J. Am. Coll. Cardiol. 67, 2061–2076 (2016). 
3. Chiabrando, J. G. et al. Management of Acute and Recurrent Pericarditis: JACC State-of-the-Art Review. J. Am. Coll. Cardiol. 75, 76–92 (2020). 
4. Scott, I. A. Errors in clinical reasoning: causes and remedial strategies. BMJ 338, (2009). 
5. Nishimura, R. A. et al. 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J. Am. Coll. Cardiol. 70, 252–289 (2017). 
6. Bilchick, K. C. & Wise, R. A. Paradoxical physical findings described by Kussmaul: pulsus paradoxus and Kussmaul’s sign. Lancet Lond. Engl. 359, 1940–1942 (2002). 
7. Tariq, M. U., Aman, W., Karwa, A., Benatti, R. & Klein, A. Right Ventricular Dilatation Post Pericardiectomy Causes Tricuspid Regurgitation. J. Am. Coll. Cardiol. 65, A1315 (2015). 
8. Lazam, S. et al. Twenty-Year Outcome After Mitral Repair Versus Replacement for Severe Degenerative Mitral Regurgitation: Analysis of a Large, Prospective, Multicenter, International Registry. Circulation 135, 410–422 (2017). 

• Bibin Varghese, MD
• Rick Ferraro, MD
• Tommy Das, MD
• Eunice Dugan, MD
• Evelyn Song, MD
• Colin Blumenthal, MD
• Karan Desai, MD
• Amit Goyal, MD
• Daniel Ambinder, MD