Jump to: Case media – Case schematic & teaching – References

• 

---

Case Media

---

Episode Teaching

Pearls

1. The etiology of wide-complex tachycardias (WCT) of ventricular origin can be broken down by structurally normal versus structurally abnormal hearts. WCT in structurally normal hearts can be further broken down into idiopathic or primary arrhythmia syndromes. WCT in structurally abnormal hearts can be broken down into ischemic and non-ischemic etiologies.
   
2. In patients with an unexplained non-ischemic cardiomyopathy, conduction abnormalities and/or ventricular arrhythmias should raise suspicion for cardiac sarcoidosis. Additional manifestations include atrial arrhythmias and  pulmonary hypertension.
   
3. Accurate diagnosis and treatment of cardiac sarcoidosis often requires multimodality cardiovascular imaging. Check out these terrific videos from Cardiac Imaging Agora: 1) PET for inflammation/sarcoidosis and 2) Echo and CMR for sarcoidosis.
   
4. While a pathological tissue diagnosis is the gold-standard, endomyocardial biopsy has a low sensitivity, weven when paired with image guidance. Remember to consider extra-cardiac sites for biopsy.
   
5. Decisions regarding ablation of ventricular arrhythmia or ICD placement should be done individually with careful assessment of active inflammation secondary to cardiac sarcoidosis and possible response to immunosuppressive medications.
   
6. Management of cardiac sarcoidosis has two basic principles: 1) Treat the underlying process with immunosuppression and 2) Treat the cardiac sequelae: heart failure, conduction abnormalities, ventricular arrhythmias, atrial arrhythmias, and pulmonary hypertension.

Notes

1. The patient in this case was found to be in VT storm. Taking a step back, when we suspect a wide complex tachycardia (WCT) is VT, what are some etiologies we should keep in mind?

• Differentiating between a supraventricular vs. ventricular origin of a WCT will be a topic for a future episode! But after you have determined that the origin of WCT is ventricular, considerations for the underlying etiology should include ischemia-related, non-ischemic cardiomyopathy-associated, primary arrhythmia syndromes and idiopathic (in addition to common considerations such as medications and electrolyte abnormalities)
• Chronic ischemia-related WCT is typically scar-mediated, a result of re-entrant mechanism and more commonly presenting as monomorphic VT. WCT in the setting of acute ischemia is likely a result of combination increased automaticity and re-entry, typically manifesting as polymorphic VT.  In fact, acute ischemia is the most common cause of polymorphic VT, not Torsades de Pointes, and should be our first consideration. Torsades de Pointes specifically occurs due to an early afterdepolarization in a patient with an acquired or congenital prolonged QT interval.
• Non-ischemic related WCT etiologies in structurally abnormal hearts include (but not limited to) cardiac sarcoidosis, myocarditis (specifically giant-cell myocarditis), hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left dominant arrhythmogenic cardiomyopathy and Chagas disease. Especially in patients with dilated CM, if your initial evaluation does not reveal an etiology, then genetic testing should be considered to identify genetic sources of arrhythmogenic cardiomyopathies, such as laminin and desmoplakin mutations (See Episode 56: CNCR with Northwestern University!)
• Primary arrhythmia syndromes include, but are not limited to, Brugada, Long QT, Short QT, and catecholaminergic polymorphic VT (CPVT).
•  Idiopathic WCT includes outflow tract, fascicular, or papillary muscle ventricular tachycardias (VT).

2. What is the underlying pathophysiology for the cardiac manifestations of sarcoidosis?

• Typically, the clinical manifestations of cardiac sarcoidosis depend on the extent and location of the inflammatory process and subsequent fibrosis. Granulomas can be found anywhere in the heart, though more commonly involve the interventricular septum and left ventricle.
• The most common presentations include conduction abnormalities (e.g., atrioventricular block, right bundle branch block), atrial and ventricular arrhythmias, and less commonly clinical heart failure. Of note, AV blocks and ventricular arrhythmia increase the risk of sudden cardiac death, which may be the first manifestation of cardiac sarcoid.
• Furthermore, RV involvement is common in cardiac sarcoid – whether it be from the hemodynamic consequences of extensive LV involvement, pulmonary hypertension (pre- and post-capillary mechanisms) or direct RV involvement. However, isolated RV involvement is rare.
• Sarcoidosis-associated pulmonary hypertension may be present in 5-20% of patients with sarcoidosis and is multifactorial with FIVE major etiologic categories:
  1. Cardiac: Group 2 (post-capillary) PH from elevated left-sided filling pressures related to heart failure.
  2. Parenchymal: Group 3 PH related to pulmonary parenchymal fibrosis.
  3. Vascular: vasculitis, arteritis, pulmonary embolism, pulmonary venoocclusive disease
  4. Anatomic: adenopathy compressing arteries, vascular distortion from pulmonary fibrosis, fibrosing mediastinitis
  5. Comorbidities: portopulmonary hypertension (if there is hepatic involvement), anemia, OSA.

3. How do we utilize multi-modality imaging in the diagnosis of cardiac sarcoidosis?

• Multi-modality imaging aids in the diagnosis of cardiac sarcoidosis in two primary ways: (1) evaluating the extent and pattern of myocardial scar/fibrosis and (2) assessing for active inflammation.
• Cardiac magnetic resonance imaging (CMR) is utilized to delineate the pattern of scar if present. As discussed in EP #33, CMR is a powerful tool in the evaluation of cardiomyopathy, allowing quantification of RV/LV size, mass, global/regional function, and identification of myocardial scar by late gadolinium enhancement (LGE). Characteristic scar patterns of cardiac sarcoid include patchy, multifocal LGE typically in the mid-myocardium and sub-epicardium. While a positive CMR scan in the setting of biopsy-proven extracardiac sarcoid is indicative of probable cardiac sarcoid, a negative CMR scan does not exclude subclinical disease.
• PET/CT is also used for the evaluation of cardiac sarcoid, typically to identify the extent of active inflammation, guide immunosuppression therapy and/or if CMR is not available. 18-fluorodeoxyglucose (FDG)-PET/CT requires proper dietary preparation. Macrophages present in inflamed tissues will avidly take up ¹⁸F-FDG. But to avoid a false positive we need to suppress physiologic myocardial uptake of glucose to identify only pathologic WBC uptake. One way to suppress physiologic ¹⁸F-FDG is to give patients a high fat, ultra-low carb diet (instead of a prolonged fasting state alone), so myocytes preferentially rely on free fatty acids for fuel. PET imaging should be accompanied by an evaluation of myocardial perfusion, similar to the resting portion of a nuclear stress test, to evaluate for defects corresponding to areas of inflammation.
• Note, if 18F-FDG-PET scan reveals diffuse FDG uptake with no perfusion defect this can commonly indicate a false positive result from inadequate suppression of physiologic FDG uptake, as extensively inflamed myocardial should also lead to decreased perfusion in the involved region. See our upcoming Nuclear and Multi-Modality Imaging Series for more on imaging in Cardiac Sarcoid!

4. What is the role of endomyocardial biopsy in the diagnosis of cardiac sarcoidosis?

• Endomyocardial biopsy (EMB) historically has only a 25% success rate due to the patchiness of cardiac sarcoidosis. There are improved chances of success if EMB is done via an image-guided or electro-anatomical guided method, but sensitivity remains insufficient to rule out cardiac sarcoidosis even with guided biopsies.
• Importantly, to confirm the diagnosis of cardiac sarcoidosis, per the 2014 Heart Rhythm Society (HRS) Expert Consensus Recommendation, pathological tissue of non-caseating granulomas is needed. This can either be directly from the myocardium, via EMB, or from an extra-cardiac source when  paired with at least one cardiac manifestation. Common places to biopsy include mediastinal lymph nodes via bronchoscopy or lymph nodes near the skin surface. Extra-cardiac sites can be identified on whole-body PET scans by FDG-uptake, as described above.

5. What is the role of VT ablation and ICD placement in cardiac sarcoid?

Ventricular arrhythmia ablation is considered on an individual patient basis in cardiac sarcoidosis. Patients should be assessed for active inflammation, and if present, they should typically first be treated with immunosuppression as this may suppress the arrhythmias without ablation. Antiarrhythmic medications may be added to help prevent additional VT episodes. If ventricular arrhythmias persist despite adequate immunosuppressive and anti-arrhythmic treatment, then ablation may be considered.

According to the HRS guidelines, ICD implantation in cardiac sarcoid is given a Class I indication if the patient has sustained VT (including prior cardiac arrest) and/or LVEF <35% despite optimizing immunosuppression. EP study, CMR and/or PET can be used to guide ICD implantation on an individual basis in patients not meeting a Class I indication. ICD implantation is not recommended (Class III) in patients with no history of syncope, normal LVEF/RVEF, no LGE on CMR, negative EP study, no indication for permanent pacing, incessant VT, or severe NYHA Class IV heart failure.

6. What are common immunosuppressive regimens in cardiac sarcoid?

• Immunosuppression regimens vary institution to institution, and often physician to physician. Prednisone is the most common first line agent. It has been shown to improve atrioventricular conduction, mild-moderate left ventricular dysfunction, and burden of ventricular arrhythmias. Most often patients are started on higher doses of prednisone, and then subsequently weaned off with the goal of fully stopping, or reducing to as low a dose as possible, so as to avoid the chronic side effects of prednisone. Common steroid-sparing agent include methotrexate, azathioprine, and mycophenolate. In refractory cases, biologic therapies such as infliximab or rituximab can be used.
• Repeat cardiac PET scans can be done to assess for improvement in inflammation, often two to three months after starting treatment. The timing and frequency of this repeat imaging is not well delineated and may vary between institutions and physicians. Finally, aside from immunosuppression, there are limited data on use of standard heart failure guideline-directed medical therapy (GDMT) in these patients. Overall, it is recommended that patients with reduced ejection fraction (EF) are put on the same GDMT as the standard patient with a reduced EF, as they may have beneficial effects in regard to EF improvement and heart failure-related outcomes.

References

1. Birnie DH, Sauer WH, Bogun F et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm 2014;11:1305-23.
2. Birnie DH, Nery PB, Ha AC, Beanlands RS. Cardiac Sarcoidosis. J Am Coll Cardiol 2016;68:411-21.
3. Trivieri MG, Spagnolo P, Birnie D,  et al. Challenges in Cardiac and Pulmonary Sarcoidosis: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Oct 20;76(16):1878-1901. doi: 10.1016/j.jacc.2020.08.042.
4. Shlobin OA, Baughman RP. Sarcoidosis-Associated Pulmonary Hypertension. Semin Respir Crit Care Med. 2017. doi:10.1055/s-0037-1603767

---

CardioNerds Case Report Production Team