Download DR Sarcoid 30.4.15

Themes
● Case which presented a diagnostic challenge
o when to suspect sarcoid?
● Demonstrates sequelae of the disease when untreated
o decline in ejection fraction and ventricular arrhythmias
● Highlights severe manifestations of underlying disease process
o refractory ventricular tachycardia
● Provides an example of how these are complications are managed
o multiple antiarrhythmics, AICD, RFA and transplantation
Overview
Multisystem disorder of unknown etiology
Characterized by noncaseating granulomas in
involved tissues composed of T lymphocytes and
monocytes
The lungs are affected in approximately 90 percent
of patients, other tissues commonly involved
include the skin, eyes, heart and lymph nodes
Baughman RP et al. Sarcoidosis Lancet 2003 361(9363):1111
Fig. 1 multisystem involvement in sarcoidosis
Eitiology
Thought to be an immunological response to an
unidentified antigenic trigger or triggers
Disease prevalence follows geographical,
seasonal, and occupational clustering suggesting
possible infectious, environmental or occupational
eitiologies
Baughman RP et al. Sarcoidosis Lancet 2003 361(9363):1111
Fig. 2 – process of granuloma formation in sarocidosis
Source: Broos et al. Granuloma formation in pulmonary sarcoidosis Frontiers in
Immunology 2013
Prevalence
•Autopsy studies estimate the prevalence of
cardiac involvement in at least 25% of patients
with sarcoidosis
•Imaging studies have found asymptomatic
cardiac involvement in 3.7%–54.9% of the
patients with extra-cardiac sarcoidosis
•Cardiac sarcoidosis accounts for 13% to 25%
of deaths from the disease
•Perry A, Vuitch F. Causes of death in patients with sarcoidosis. A morphologic study of 38 autopsies with clinicopathologic correlations.Arch Pathol Lab Med 1995;119:167-72.
•Silverman KJ, Hutchins GM, Bulkley BH. Cardiac sarcoid: a clinicopathologic study of 84 unselected patients with systemic sarcoidosis. Circulation 1978;58:1204-11.
Clinical Presentation
The typical presentation of cardiac sarcoid
is initial conduction block then progressing
to ventricular tachycardia and heart failure
However very heterogeneous with a
significant proportion presenting with
sudden cardiac death
Kim et al. Cardiac Sarcoidosis. Am Heart J, 01/2009, Volume 157,
Issue 1
Arrhythmia
•Supraventricular arrhythmias are less common
than ventricular arrhythmias
•Thought to be related to atrial dilatation
secondary to left ventricular dysfunction
•Ventricular arrhythmias more common and
caused by direct granulomatous involvement of
the myocardium
Roberts WC, McAllister HA, Ferrans VJ. Sarcoidosis of the heart: a clinicopathologic study of 35
necropsy patients and review of 78 previously described necropsy patients. Am J Med 1977;63:86108.
Heart Failure
Congestive heart failure is common and due to
direct granulomatous involvement of the
myocardium or valvular regurgitation
Ventricular dysfunction is systolic or diastolic or
both
•Does not follow coronary artery distribution
•Mitral valve regurgitation is the most common
valvular lesion due to papillary muscle dysfunction
Kim et al. Cardiac Sarcoidosis. Am Heart J, 01/2009, Volume 157,
Issue 1
Effusions
Pericardial effusions detected by echocardiography have been reported in up to 19% of
patients with cardiac sarcoid
Although the effusions are usually small, cases of very large effusions with associated
tamponade have been reported
Kinney E, Murthy R, Ascunce G, et al. Pericardial effusions in sarcoidosis. Chest 1979;76:476-8.
Zelcer AA, LeJemtel TH, Jones J, et al. Pericardial tamponade in sarcoidosis. Can J Cardiol 1987;3:12-3.
Diagnosis
Because of the potential life-threatening complications and potential benefit of
treatment, all patients diagnosed with sarcoidosis should be screened for
cardiac involvement
Kim et al. Cardiac Sarcoidosis.
Am Heart J, 01/2009, Volume 157, Issue 1
Gold Standard
The diagnostic approach has not been standardized, and the most commonly accepted guidelines written in 1993 by the
Japanese Ministry Of Health and Welfare are now outdated
Positive biopsy or
BBB, AV block or VT
+ 1 or more of
RWMAs, decreased LVEF, non specific inflammatory
biopsy, MPS perfusion defect
Hiraga H et al. Guideline for diagnosis of cardiac sarcoidosis: study
report on diffuse pulmonary diseases from the Japanese Ministry of
Health and Welfare. Tokyo: Japanese Ministry of Health and Welfare;
1993. pp. 23Q4.
Heart Rhythm Society Consensus
Latest expert consensus guidelines
Heart Rhythm Society in 2014
A. Histological diagnosis of cardiac
sarcoid
Or
B. Histological diagnosis of extra cardiac
sarcoid
+
Conduction abnormality, reduced EF,
increased uptake on PET, late Gd
enhancement on MRI
Bimie et al. HRS Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated With Cardiac Sarcoidosis 2014
Heart Rhythm Society
Endomyocardial Biopsy
• Gold Standard for diagnosis
• Prognostic indicator - a positive biopsy is
associated with a shorter median survival
time
• Limitations:
• Not sensitive as may not capture parts of
the heart with sarcoid
• Risks of invasive procedure – tamponade
Fig 2. Non caseating granulomas seen on RV biopsy
Ardehali H, Howard DL, Hariri A, et al. A positive endomyocardial biopsy result for sarcoid is associated with poor prognosis in patients
with initially unexplained cardiomyopathy. Am Heart J 2005;150:459-63
ECHO
• Although characteristic findings on imaging are known, there is no
pathognomonic for diagnosis
• Echocardiographic abnormalities have been reported in 14-56% of
patients with sarcoidosis
• Regional wall motion abnormalities, ventricular systolic or diastolic
dysfunction, valvular abnormalities or abnormal ventricular wall
thickness (thick or thin)
Lewin RF, Mor R, Spitzer S, et al. Echocardiographic evaluation of patients with systemic sarcoidosis. Am Heart J 1985;110: 116-22.
Burstow DJ, Tajik J, Baily KR, et al. Two-dimensional echocardiographic findings in systemic sarcoidosis. Am J Cardiol 1989;63: 478-82.
Dilated LV
Thinned akinetic basal inferolateral wall and papillary muscle
Burstow DJ, Tajik J, Baily KR, et al. Two-dimensional echocardiographic findings in systemic sarcoidosis. Am J Cardiol 1989;63: 478-82.
FDG-PET
• FDG PET may provide both a measure of disease activity via FDG uptake,
as well as a measure of fibrogranulomatous replacement of the myocardium
using perfusion imaging
• Essentially get an overlap of areas of reduced perfusion (scar) with areas of
inflammation
Kaminaga T, Takeshita T, Yamauchi T, et al. The role of iodine-123– labeled 15-(p-iodophenyl)-3R, S-methylpentadecanoic acid scintigraphy in the detection of local
myocardial involvement of sarcoidosis. Int J Cardiol 2004;94:99-103
Early in disease process normal
perfusion with high FDG uptake
secondary to inflammation
Late in the disease after scarring low
perfusion with high FDG uptake
FDG-PET
•Increased FDG uptake is assumed to be associated with areas of inflammation and is postulated to identify
patients at higher risk of sudden cardiac death given increased disease activity and risk of progression
•Blankstein et al. found the
presence of both a
perfusion defect and an
abnormal FDG uptake was
associated with death or
sustained VT, even after
adjusting for LVEF
Blankstein R et al. Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis. J Am Coll
Cardiol 2013;October 1.
MRI
•
MRI has the advantage of superior spatial resolution
•
Areas of inflammation are seen with increased
signal intensity on T2-weighted images and early
gadolinium-DTPA (Gd)-enhanced images
•
Sarcoid granulomas may also be seen in the
myocardium, appearing as nodules on T2-weighted
and Gd-enhanced images
Matsuki M, Matsuo M. MR findings of myocardial sarcoidosis. Clin Radiol 2000;55:323-5.
Vignaux O. Cardiac sarcoidosis: spectrum of MRI features. AJR Am J Roentgenol 2005;184:249-54.
MRI vs PET
• Ideal imaging modality is contentious
• MRI benefit of greater sensitivity in subclinical disease while FDG-PET
provides better information on inflammation/acitivity
• Whether MRI or PET scanning should be performed as initial screening
tests in this asymptomatic population is unknown
• Unknown whether treating such asymptomatic patients is of benefit
Kim et al. Cardiac Sarcoidosis. Am Heart J, 01/2009, Volume 157, Issue
Patel et al. 2009
•Followed 81 patients with biopsy-proven
extracardiac sarcoidosis.
•Followed for major adverse events (death,
defibrillator shock, or pacemaker
requirement)
•At 5 years, 6 of 8 patients in the group with
LGE had ventricular arrhythmia or died
compared with 1 death in the group without
LGE
Patel etal.Detection of myocardialdamage in patients with sarcoidosis.Circulation2009;120:1969–1977
Contrast ECHO
•Contrast ECHO not been studied extensively in
this setting
•Potential to be used to track disease progression
in patients with non-MRI compatible devices
•Can also be used to target areas for biopsy to
increase diagnostic yield
Prognosis
The data on prognosis is quite variable, with 5-year survival ranging from 60% to
90% in patients with treatment and preserved systolic function, to 10% in autopsy
subjects
LVEF involvement and response to steroids appear to be two most significant
prognostic indicators
Yazaki Y, Isobe M, Hiroe M, et al. Prognostic determinants of longterm survival in Japanese patients with cardiac sarcoidosis treated with prednisone. Am J
Cardiol 2001;88:1006-10.
Yazaki et al. 2001
Retrospective study of 95 patients diagnosed with
cardiac sarcoidosis at a Japanese hospital 19841996
A - Overall, patients had survival rates of 50% at 10
years
C – (top) Steroid treated patients with LVEF>50%
89% survival rate at 10 years, LVEF <50% had 27%
at 10 years, those diagnosed at autopsy (aka no
cardiac treatment) had survival rate 10% at 5 years
Yazaki Y, Isobe M, Hiroe M, et al. Prognostic determinants of longterm survival in Japanese patients with cardiac sarcoidosis treated with prednisone. Am J
Cardiol 2001;88:1006-10.
Greulich et al. 2013
•
155 consecutive patients with systemic sarcoid underwent cMRI for evaluation of cardiac
sarcoid
•
Median follow up time 2.6 years
•
Primary endpoints: death, aborted sudden cardiac death, appropriate ICD discharge
The present of LGE yields a hazard ratio
of 31.9 for primary outcome
Superior to parameters including LVEF,
presentation with heart failure
No patient without LGE experienced any
event or died in the follow up even if the
LV was enlarged or reduced EF
Corticosteroids
•
Corticosteroid therapy is the mainstay of treatment for cardiac sarcoidosis
•
The effects of corticosteroid treatment on the clinical course have not been studied in large,
randomized, prospective trials.
•
To date, no study has prospectively compared different corticosteroid dosing regimens and no
study has compared corticosteroids to alternative immunosuppressants such as methotrexate or
azathioprine.
•
The optimal dose, when to begin treatment, and the duration of treatment all remain undetermined
Kim et al. Cardiac Sarcoidosis. Am Heart J, 01/2009, Volume 157, Issue 1
Corticosteroids
Review article 2013 Canadian Journal of
Cardiology which evaluated corticosteroid
therapy in cardiac sarcoidosis
•10 publications identified
•None randomised control trials
•Doses ranged from 20mg alternate days – to
60mg daily
•Duration ranged from 3 to 168 months
•No definite conclusions were able to be drawn
due to heterogeneity between studies
Corticosteroids
•
One study showed no significant difference in prognosis in those patients treated with greater than
40 mg or prednisone per day compared to those treated with 30 mg of prednisone or less
•
One study suggested that patients with severe left ventricular dysfunction should be offered a
corticosteroid trial for one to three months (30 to 40 mg/day of prednisone equivalent) then taper
over 12 months, with or without a steroid sparing agent
•
Immunosuppressive agents such as infliximab, methotrexate, azathioprine and cyclophosphamide
have been used with reported success in the treatment of sarcoidosis
Yazaki Y, Isobe M, Hiroe M, et al. Prognostic determinants of longterm survival in Japanese patients with cardiac sarcoidosis treated with
prednisone. Am J Cardiol 2001;88:1006-10
Arrythmia - ?ICD
•
ICD recommended for patients with cardiac sarcoid and spontaneous
sustained ventricular tachycardia or ventricular fibrillation
•
Unknown whether patients without functional impairment and without
spontaneous significant arrhythmias should be considered for ICD therapy
or at least some risk-stratification strategy
Epstein AE, Dimarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities.
Circulation 2008;117:2820-40.
ACCF/AHA/HRS
• 2012 Focussed update still did not
make any firm recommendation
regarding device therapy in
sarcoidosis
• Sufficient data is not available to
stratify risk of sudden cardiac
death among patients with
sarcoidosis
Tracy et al. 2012 ACCF/AHA/HRS Focused Update of the 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities
J Am Coll Cardiol. 2012;60(14):1297-1313.
ICD
Heart Rhythm Society Consensus 2014
indicated
EF<35% or sustained VT = ICD
EF>40% no late Gd enhancement = do
not put in an ICD
Everything in between it can be
considered but no strong
recommendation made
Bimie et al. HRS Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated With Cardiac
Sarcoidosis 2014 Heart Rhythm Society
Ventricular Arrhythmias
Class IIa recommendation from HRS 2014
Immunosuppression, can be useful – evidence of inflammation
Antiarrhythmic medication can be useful – if refractory to immunosuppression
Catheter ablation can be useful – if refractory to both of the above
Bimie et al. HRS Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated With Cardiac Sarcoidosis 2014 Heart
Rhythm Society
VT Ablation
Kumar et al. Ventricular tachycardia in cardiac sarcoidosis Characterization of Ventricular Substrate and Outcomes of Catheter Ablation
Circ Arrhythm Electrophysiol. 2015;8:87-93.
VT Ablation
21 patients with cardiac sarcoidosis
EPS confirmed scar mediated re-entry
Catheter ablation is effective in eliminating VT storm and >=1 inducible VT in the majority of
patients but recurrences
are common
Heart Failure & Transplantation
Heart failure due to cardiac sarcoidosis should be treated in the same manner as heart failure due to
other causes
Including: angiotensin converting enzyme inhibitors, diuretics and β-blockers
•Studies report that patients with sarcoidosis undergoing heart transplant have better mean short- and
intermediate-term survival than patients undergoing transplant due to other causes
•Recurrence of sarcoidosis in the transplanted heart has been documented
•All recurrences can be treated with steroids usually with good outcome
Kim et al. Cardiac Sarcoidosis. Am Heart J, 01/2009, Volume 157, Issue 1
Zaidi et al. 2007
•Analysed 65 patients over an 18 year period who
underwent orthotopic heart transplantation for
cardiac sarcoid
•One year post transplant survival was
significantly better in sarcoid patients versus
patients receiving transplants for all other
diagnosis
•No difference in baseline characteristics
•No difference in incidence of rejection
Zaidi AR, Zaidi A, Vaitkus PT. Outcome of heart transplantation in patients with sarcoid cardiomyopathy. J Heart Lung Transplant
2007;26:714-7.
Themes
●
Case which presented a diagnostic challenge
o
●
Demonstrates sequelae of the disease when untreated
o
●
?any predictors of who will decline vs respond to therapy
Highlights severe manifestations of underlying disease process
o
●
when to suspect sarcoid?
Optimal treatment regime unknown
Example of how these are complications are managed
o
multiple antiarrhythmics, AICD, RFA and transplantation
Thank You