Sarcoidosis

In a Nutshell

As in the lungs the the granulomatous nodules follow the lymphatics

Lymphatics of the heart

  • MRI LGE
    • Heart patchy mid  multifocal and epi
    • located predominantly in the subepicardial areas,
      • Also myocardial, and least common subendocardial
    • most characteristic free wall and basal septum (conduction)

Cardiac sarcoidosis (CS)detected in 20-30% of patients with sarcoidosis (up to 55% in Japanese population) and more than 20% of the cases of sarcoidosis are clinically silent. Complete heart block, bundle branch block, ventricular tachycardia (VT), congestive heart failure (HF), and sudden death are common presentations in CS

NORMAL LYMPHATIC DRAINAGE

Lymphatics run from the subendocardium through the myocardium  to the subendocardial layer where they accumulate in subendocardial plexuses

The subendocardial plexuses drain into lymphatics which accompany the coronary arteries which then drain into mediastinal nodes
LYMPHATIC DRAINAGE
The lymph drains from the subendocardium through the myocardium where it collects in subendocardial plexuses and then into lymphatic vessels which travel along with the LAD
Ashley Davidoff MD

 SARCOIDOSIS

25-30% cardiac involvement

No portion of the heart is immune to infiltration by sarcoid granulomas. The granulomas may involve the pericardium, myocardium, and endocardium, but of the three, the myocardium is, by far, the one most frequently involved. (sarcoid = meat – so myocardium most commonly involved)

  • Structures in the CV system affected by sarcoidosis
    • LV
    • RV
    • Conduction System
    • Pericardium
    • Pulmonary Artery

LV

The “S” of Sarcoidosis

 

“S” STARTING SUPERFICIALLY NEAR THE SURFACE OF THE HEART
The hallmark of cardiac sarcoidosis is LGE involving subepicardial regions of lateral free wall as well as medial basal septum but also mid myocardial with linear patchy and nodular forms.
Biventricular involvement is common
Ashley Davidoff MD

 

The most common involvement observed on MRI is the subepicardial layer
“S” STARTING SUPERFICIALLY NEAR THE SURFACE OF THE HEART
Ashley Davidoff MD

 

The pattern of LGE is typically patchy, mid-myocardial or epicardial and in a non-coronary distribution. LGE can be seen in both active disease (due to inflammation) and in scar.

NODULAR AND LINEAR SUBEPICARDIAL INVOLVEMENT
The hallmark of cardiac sarcoidosis is LGE involving subepicardial regions of lateral free wall as well as medial basal septum but also mid myocardial with linear patchy and nodular forms.
Biventricular involvement is common
Ashley Davidoff MD
NODULAR AND LINEAR MID MYOCARDIAL INVOLVEMENT
Ashley Davidoff MD

 

Clinical Examples

69 year old male presented with history of cardiomyopathy and atrial fibrillation  The findings on MRI are highly suggestive of sarcoidosis. There are multicentric foci of LGE in linear and nodular form in the mid myocardial and subepicardial layers and likely in the pericardium and myocardium of the right ventricle.

There was associated global hypokinesis of the LV with an EF of 40%, and increase in the LV mass of 120gms/ sq m

MULTICENTRIC SARCOIDOSIS WITH LGE IN RV AND LV INVOLVING MUSCULAR, SUBEPICARDIAL, AND PERICARDIAL REGIONS

In this series images on the right (b,,d,,f) are magnified views of images on the left (a,c,e)
There are multicentric foci of LGE nodular form in the mid myocardial region (white arrowheads) linear LGE in the subepicardial layers (red arrowheads, b and f) in the pericardium (teal blue arrowhead) and myocardium of the right ventricle (yellow arrowhead e).

Ashley Davidoff MD

MULTICENTRIC SARCOIDOSIS WITH LGE IN RV AND LV INVOLVING MID MYOCARDIAL AND  SUBEPICARDIAL,  REGIONS
There are multicentric foci of LGE in this short axis view taken closer to the apex with linear form in the mid myocardial region (pink arrowheads) and linear and nodular changes of LGE in the subepicardial layers (red arrowheads, a,b,c) Subepicardial changes are also notes in the RV in a (not marked)  Ashley Davidoff MD
MULTICENTRIC SARCOIDOSIS WITH LGE APICAL MID MYOCARDIAL LGE
69 year old male presented with history of cardiomyopathy and atrial fibrillation
In this series, the long axis 4 chambered view reveals intense continuous mid myocardial LGE
Ashley Davidoff MD
MULTICENTRIC SARCOIDOSIS WITH LGE APICAL MID MYOCARDIAL AND PERICARDIAL LGE
69-year-old male presented with history of cardiomyopathy and atrial fibrillation
In this series the long axis 3 chambered view reveals intense continuous sub epicardial disease (red arrowheads) and pericardial LE (teal blue arrowhead)
Ashley Davidoff MD
MULTICENTRIC SARCOIDOSIS WITH LGE APICAL MID MYOCARDIAL AND PERICARDIAL LGE
69-year-old male presented with history of cardiomyopathy and atrial fibrillation
In this series, the long axis 2 chambered view (c is magnified view of b) reveals intense continuous pericardial disease (teal blue arrowheads) and mid myocardial linear-nodular LGE (white arrowhead)
Ashley Davidoff MD
INVOLVEMENT OF THE CONDUCTION SYSTEM HEART BLOCK AND TACHYARRHYTHMIAS
Ashley Davidoff MD
SARCOID CARDIOMYOPATHY, HEART BLOCK
34-year-old male who was diagnosed with pulmonary sarcoidosis 1 year before, presents with progressive dyspnea over 6 months, previously able to run 5 miles per day and currently limited to walking short distances. Clinical evaluation revealed that he was in complete heart block with a heart rate of 35 /min. EKG showed a rate of 40 with AV dissociation with alternating junctional and ventricular escape rhythms.
CXR showed upper lobe predominance interstitial changes, slightly more prominent on the right side. There was evidence of CHF with enlargement of the LA (widening of the carinal angle) and cephalization of the vessels
An echocardiogram was normal with normal ejection fraction.
MRI revealed normal cardiac function, mild left atrial enlargement, and diffuse almost circumferential subendocardial enhancement of the LV, most prominent in the lateral wall. There was also a linear focus in the mid myocardium in the anterior region medially near the septum
A dual lead pacemaker was placed and follow up CXR showed improved CHF an persistent interstitial findings dominant in the upper lobes consistent with sarcoidosis.
Follow up CXR 7 years later showed a normal CXR. The pacemaker had been removed and the interstitial process had resolved
Ashley Davidoff MD
SARCOID CARDIOMYOPATHY, HEART BLOCK , PACEMAKER IMPROVED CHF
34-year-old male who was diagnosed with pulmonary sarcoidosis 1 year before, presents with progressive dyspnea over 6 months, previously able to run 5 miles per day and currently limited to walking short distances. Clinical evaluation revealed that he was in complete heart block with a heart rate of 35 /min. EKG showed a rate of 40 with AV dissociation with alternating junctional and ventricular escape rhythms.
CXR showed upper lobe predominance interstitial changes, slightly more prominent on the right side. There was evidence of CHF with enlargement of the LA (widening of the carinal angle) and cephalization of the vessels
An echocardiogram was normal with normal ejection fraction.
MRI revealed normal cardiac function, mild left atrial enlargement, and diffuse almost circumferential subendocardial enhancement of the LV, most prominent in the lateral wall. There was also a linear focus in the mid myocardium in the anterior region medially near the septum
A dual lead pacemaker was placed and follow up CXR showed improved CHF an persistent interstitial findings dominant in the upper lobes consistent with sarcoidosis.
Follow up CXR 7 years later showed a normal CXR. The pacemaker had been removed and the interstitial process had resolved
Ashley Davidoff MD
CONDUCTION DISTURBANCES IN SARCOIDOSIS OF THE HEART
The frontal CXR from a middle-aged female shows findings consistent with sarcoidosis (probably stage II) characterized by hilar adenopathy and mild interstitial disease noted abutting the minor fissure. Heart block and tachyarrhythmias are one of the more common manifestations of heart disease in patients with sarcoidosis of the heart. This patient required a dual lead pacemaker.
Ashley Davidoff MD
Pericardial Involvement

 

SARCOIDOSIS –
RECURRENT PERICARDIAL EFFUSION CXR,CT CORRELATION
54-year-old female with peripheral adenopathy who had an inguinal node biopsied 6 years prior showing sarcoidosis. Who chest examinations at the time showed little evidence of sarcoid except for a few small nodules. She has a history of hypertension COPD; sleep apnea, on CPAP; diabetes mellitus, on metformin; lumpectomy x2; GERD; and vertigo
4 years ago she presented with SOB and was noted to have a pericardial effusion by echo without tamponade
The pericardial effusion was drained with negative cytology and negative for TB . CT at the time following the drainage showed a thickened pericardium with pericardial drain in place
She represented 1 year later with symptoms of worsening intermittent chest pain, and shortness of breath exacerbated with exertion. An echocardiogram, showed recurrent increasing pericardial effusion confirmed by CT. She was placed on steroids but did not tolerate the steroids.
Later in that year she underwent surgery for pericardial window and VATS biopsy of her left lower lobe. Her pericardium was noted to be thickened
Pathology revealed Non-necrotizing granulomatous inflammation involving pulmonary interstitium and occasional airways; AFB, GMS, and PAS stains were negative for micro-organisms.
The left pericardial biopsy showed diffuse and extensive non-necrotizing granulomatous inflammation and AFB, GMS, and PAS stains were negative for micro-organisms.
CT scan at the end of that year (131555) showed thickened pericardium.
An MRI at the time showed diffuse thickening of the pericardium with enhancement as well as nodular mid myocardial changes at the hinge points and the inferolateral aspects. Subendocardial changes were also noted.
Repeat MRI the next year showed similar findings
Ashley Davidoff MD
SARCOIDOSIS –
RECURRENT PERICARDIAL EFFUSION CXR,CT CORRELATION
The lateral examination soft pericardial effusion layering dependently and posteriorly.

Ashley Davidoff MD

SARCOIDOSIS – LGE of the MYOCARDIUM and PERICARDIUM
The short axis LGE sequence starting at the base of the heart (a, b) progressing through the body © and apex (d) shows focal LGE in the RVOT(a, green arrowhead) and in the LV (b green arrowhead) extensive pericardial enhancement (a,b,c,d – red arrowheads, and in the septum (white arrowhead c).
54-year-old female with peripheral adenopathy who had an inguinal node biopsied 6 years prior showing sarcoidosis. Who chest examinations at the time showed little evidence of sarcoid except for a few small nodules. She has a history of hypertension COPD; sleep apnea, on CPAP; diabetes mellitus, on metformin; lumpectomy x2; GERD; and vertigo
4 years ago she presented with SOB and was noted to have a pericardial effusion by echo without tamponade
The pericardial effusion was drained with negative cytology and negative for TB. CT at the time following the drainage showed a thickened pericardium with pericardial drain in place
She represented 1 year later with symptoms of worsening intermittent chest pain, and shortness of breath exacerbated with exertion. An echocardiogram, showed recurrent increasing pericardial effusion confirmed by CT. She was placed on steroids but did not tolerate the steroids.
Later in that year she underwent surgery for pericardial window and VATS biopsy of her left lower lobe. Her pericardium was noted to be thickened
Pathology revealed Non-necrotizing granulomatous inflammation involving pulmonary interstitium and occasional airways; AFB, GMS, and PAS stains were negative for micro-organisms.
The left pericardial biopsy showed diffuse and extensive non-necrotizing granulomatous inflammation and AFB, GMS, and PAS stains were negative for micro-organisms.
CT scan at the end of that year (131555) showed thickened pericardium.
An MRI at the time showed diffuse thickening of the pericardium with enhancement as well as nodular mid myocardial changes at the hinge points and the inferolateral aspects. Subendocardial changes were also noted.
Repeat MRI the next year showed similar findings
Ashley Davidoff MD
BIVENTRICULAR INFILTRATION
Sarcoidosis involves both ventricles and may cause bi-ventricular thickening
Ashley Davidoff MD
Cardiac Enlargement
CXR – LVE –
SARCOID CARDIOMYOPATHY with LIVER and LYMPH NODE INVOLVEMENT
57-year-old male with pathology findings consistent with granulomatous hepatitis and non-necrotizing granulomas in inguinal lymphadenitis both consistent with sarcoidosis but without pulmonary findings. Lymphadenopathy is present in the axillae and groins without involvement of the mediastinum
Associated cardiovascular findings include findings consistent with hypertrophic cardiomyopathy with:
o Diabetes and Hypertension
o CXR showing LVE
o Abnormal stress test with concerning regions in RCA territory inferiorly
o Moderate LVH on echo with normal EF (68%) normal LA, RA PAP and RV function. LV mass was 127g/sq. m
o Focal nodular LGE in the anterior apical region in mid myocardial/subendocardial region and in the inferior mid myocardial wall medially
o Subsequently developed episodes of paroxysmal ventricular tachycardia with EP ablation and placement of a defibrillator (ICD)
o LH and RH catheterization performed 6 years after initial studies showed elevation of PC WP of 25 mmHg, mean RA pressure of 16 mmHg, mean PAP of 34 mmHg no CAD
o Subsequent CT showed mildly enlarged LA and RA with mild TR
o 6 years after initial presentation he had symptoms of biventricular failure with increasing dyspnea and pedal edema culminating in an acute episode of monomorphic VT episode, ectopic atrial flutter/fibrillation, and left bundle branch aberrancy requiring amiodarone and cardioversion. Underwent upgrade to biventricular upgrade ICD
Ashley Davidoff MD
LV THICKENING – MRI AXIAL
Ashley Davidoff MD

 

BiVentricular Thickening/Infiltration
LV MAss of 120g/sq m with extensive Myocardial Involvement
BIVENTICULAR INFILTRATION WITH THICKENING
69 year old male presented with history of cardiomyopathy and atrial fibrillation
The LGE on the short axis shows biventricular thickening of the RV and LV
There are other findings on the MRI that are highly suggestive of sarcoidosis. There are multicentric foci of LGE in linear and nodular form in the mid myocardial and subepicardial layers and likely in the pericardium and myocardium of the right ventricle.
There was associated global hypokinesis of the LV with an EF of 40%, and increase in the LV mass of 120gms/ sq m
Ashley Davidoff MD
MULTICENTRIC SARCOIDOSIS WITH LGE APICAL MID MYOCARDIAL REGION
69 year old male presented with history of cardiomyopathy and atrial fibrillation
In this series the long axis 4 chambered view reveals intense continuous mid myocardial LGE
Ashley Davidoff MD

Cardiac sarcoidosis is an inflammatory disorder of the heart characterized by non-caseating granulomas in the myocardium  The heart is involved in about  25% of patients with systemic sarcoidosis

Etiology

unknown

Structurally

The disease is patchy and multifocal.  Te=he endocardium is spared.

Clinically

Most patient are asymptomatic but may present with conduction abnormalities and less frequently CHF

 

Diagnosis

Clinically if a patient has  systemic sarcoidosis and cardiac symptoms are present there is a 50 % likelihood that card

Imaging

MRI and FDG -PET

MRI Typical LGE patterns in patients with cardiac sarcoidosis include patchy multifocal subepicardial and midwall LGE  along the basal septum, sometimes with extension into the right ventricular insertion points as well as the infero-lateral wall.

53 year old male with a clinical history of sarcoidosis and right bundle branch block. Echocardiography showed left ventricular hypertrophy and normal ejection fraction
MRI shows multifocal regions of LGE in the mid myocardium involving the inferobasal portion and inferolateral portion of the of the LV

 

Nonetheless, no specific pattern of LGE on CMR is diagnostic for cardiac sarcoidosis.

The presence of LGE in a non-infarct pattern may also be associated with fibrosis from prior myocarditis or idiopathic cardiomyopathy; rarely, cardiac sarcoidosis may mimic an infarct pattern.

CMR and FDG-PET evaluate different pathological processes, LGE evaluates  fibrosis and FDG PEt evaluates acute inflammation by activated macrophages. Neither technique is specific cardiac sarcoidosis. These tests therefore provide complementary information

CMR images demonstrating 3-dimensional LGE imaging (top row), also fused with FDG-PET signal (bottom row), suggestive of active inflammation surrounding regions of scar (arrows) in a patient with unexplained cardiomyopathy and suspected cardiac sarcoidosis. Images are shown in the 4-chamber, short-axis, and 2-chamber orientations, respectively. Reproduced with permission from White et al.
Courtesy https://www.acc.org/latest-in-cardiology/articles/2017/04/10/08/43/cardiac-mri-vs-pet

Both techniques provided high sensitivity of >75% for detection of cardiac sarcoidosis

Biopsy 30%

Prognosis

The extent of myocardial LGE is  an important prognostic marker. Patients with cardiac sarcoidosis involving ≥20% of left ventricular mass have higher risk of cardiac death, hospitalization for heart failure and life-threatening arrhythmias.  Additionally they were less likely to demonstrate functional recovery of the left ventricle following steroid therapy.

 

References and Links

Ipek, E et al  Sarcoidosis and the heart: A review of the literature . 2015 Nov; 4(4): 170–180.

Citations: 17

Paco E. Bravo, MDViviany R Taqueti, MD, MPH, FACC Cardiac MRI vs. PET for the Evaluation of Cardiac Sarcoidosis: Consider MRI First

Shimada,T et al  Structure and distribution of lymphatic capillaries and fenestrated blood capillaries in the conduction system of the rabbit heart  Heart and Vessels volume 4pages123–127(1988)

Cardiac Sarcoidosis   Society of Thoracic Radiology