Comparison of Outcomes in Patients With Probable Versus Definite Cardiac Sarcoidosis

doi:10.1016/j.amjcard.2015.01.562

The American Journal of Cardiology

Volume 115, Issue 9, 1 May 2015, Pages 1293-1297

https://doi.org/10.1016/j.amjcard.2015.01.562 Get rights and content

Patients with probable cardiac sarcoidosis (CS) who satisfy only clinical cardiac findings for CS are not uncommon. The aim of this study was to compare outcomes between patients with probable CS and those with definite CS treated with steroids. The study population consisted of 101 consecutive patients who satisfied clinical cardiac findings for CS. Patients with definite CS were defined as having histologic or clinical confirmation of CS according to the guidelines and were treated with steroids. Patients with probable CS were defined as having only clinical cardiac findings but not definite CS because of no histologic confirmation or extracardiac sarcoidosis and were not treated with steroids. The end point was major adverse cardiac events. Forty-seven patients had definite CS, and the other 54 had probable CS. Except for serum angiotensin-converting enzyme levels and left ventricular dysfunction, clinical characteristics were similar between the 2 groups. Over a median follow-up period of 15 months, major adverse cardiac events occurred more frequently in patients with probable CS than in those with definite CS (74% vs 53%, p = 0.029). The event-free survival rate was worse in patients with probable CS than in those with definite CS (log-rank test, p = 0.006). Cox proportional-hazards analysis showed that probable CS was an independent predictor of major adverse cardiac events. In conclusion, outcomes were worse in patients with probable CS than in those with definite CS treated with steroids. The initiation of steroid treatment may be considered for patients who satisfy only clinical cardiac findings for CS.

Section snippets

Methods

We enrolled 109 consecutive patients who satisfied the CS diagnostic guidelines' clinical cardiac findings from December 1994 to April 2014. The guidelines for diagnosis of CS9, 10 are listed in Table 1. In brief, CS is diagnosed on the basis of histologic or clinical confirmation. Histologic diagnosis is confirmed when endomyocardial biopsy demonstrates noncaseating epithelioid cell granulomas. Clinical diagnosis is confirmed in the absence of endomyocardial biopsy when extracardiac

Results

Among the 47 patients with definite CS, 18 had histologic confirmation and 29 had clinical confirmation. All patients with definite CS were initiated on prednisone at doses of 30 or 40 mg/day. Thirty-eight patients had positive myocardial uptake on ⁶⁷Ga scintigraphy or FDG PET at baseline, and all of them showed the disappearance of myocardial uptake on repeat ⁶⁷Ga scintigraphy or FDG PET after steroid treatment. Among the 54 patients with probable CS, 44 satisfied >2 of 4 major findings, and

Discussion

The major findings of the present study are as follows: (1) clinical characteristics except for serum angiotensin-converting enzyme levels and left ventricular dysfunction were similar between patients with probable CS and those with definite CS, (2) outcomes were worse in patients with probable CS than in those with definite CS treated with steroids, and (3) probable CS was an independent predictor of MACEs.

There are 2 main scenarios for the manifestation of CS. In the first, patients with

Disclosures

The authors have no conflicts of interest to disclosure.

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Cited by (15)

Incidence and Predictors of Relapse After Weaning Immune Suppressive Therapy in Cardiac Sarcoidosis
2023, American Journal of Cardiology
Cardiac sarcoidosis (CS) is a relapsing-remitting disease, and immune suppression (IS) is the mainstay of therapy. Predictors of relapse for patients with CS in remission are not well characterized. We assessed incidence of relapse in consecutive patients with CS treated with high-dose steroids and/or steroid-sparing agents (SSA) in our center from 2000 to 2020. Remission was defined as reaching maintenance therapy (no IS, SSA, and/or prednisone ≤5 mg/d) for ≥1 month. Relapse was defined as recurrence of CS syndrome requiring IS intensification: heart failure, ventricular arrhythmia, decrease in left ventricular ejection fraction, or increased disease burden on imaging. Among 68 patients, the mean age was 50.7±9.0 years; 25 (37%) were women, and 32 (47%) were Black. In total, 59 patients (87%) reached remission. Over a median follow-up of 39.5 months (interquartile range 17.6, 92.5), 28 (48%) relapsed. Greater percentage of late gadolinium enhancement (LGE) on pretreatment magnetic resonance imaging corresponded with increased likelihood of relapse (odds ratio 1.396 per 5% increase [95% confidence interval (CI) 1.04 to 1.88]; p = 0.028). LGE ≥11% predicted elevated risk of relapse (adjusted odds ratio 4.998 [1.34 to 18.64]; p = 0.017). Shorter time to relapse was observed with isolated CS (adjusted hazard ratio 4.084 [1.44,11.56]; p = 0.008) and LGE ≥11% (adjusted hazard ratio 3.007 [1.01, 8.98]; p = 0.049). Approximately 1 in 2 patients with CS in remission experienced relapse. Greater burden of LGE on cardiac magnetic resonance imaging and isolated CS are associated with greater risk of relapse. Future work is needed to refine risk stratification for relapse and to optimize surveillance strategies on the basis of the burden of disease.
Long-Term Outcome in Probable Versus Absolute Cardiac Sarcoidosis
2019, American Journal of Cardiology
Citation Excerpt :
This observation bears significantly on daily work as it supports the clinical equivalence of probable to absolute diagnosis of CS as long as the former adheres to the criteria specified in recent recommendations8,9 and used in our study. The only earlier study comparing diagnostic subgroups in CS found, unlike us, a worse outcome in probable than in definite CS.10 However, the subgroups were different from ours since patients with probable CS had neither clinical nor histologic evidence of sarcoidosis but only cardiac manifestations included in the Japanese diagnostic criteria11 (and seen in many other myocardial diseases as well).
Suspicion of cardiac sarcoidosis (CS) arises when a patient has clinical cardiac manifestations and findings on cardiac imaging suggestive of inflammatory cardiomyopathy with or without history of extracardiac sarcoidosis. The additional requirement for diagnosis is proof of sarcoidosis histology. Endomyocardial biopsy (EMB) showing granulomatous inflammation in absence of other explanations confirms an absolute diagnosis of CS while similar histology in an extracardiac biopsy gives a probable diagnosis of CS. Our aim was to study the equivalence of probable to absolute CS in terms of patients’ characteristics and outcome. We reviewed the available clinical information, diagnostic procedures, details of treatment and event-free survival of 149 consecutive patients (103 women, mean age 50 y) diagnosed with CS at our institution. The diagnosis was absolute in 68 patients and probable in 81 patients. There was no difference in age or sex distribution between the diagnostic subgroups but left ventricular dysfunction on echocardiography (ejection fraction <50%) was more common in absolute CS (60% vs 36%, p = 0.003) as was abnormal myocardial late gadolinium enhancement on magnetic resonance imaging (96% vs 78%, p = 0.006). Over a median of 54 months of follow-up, 19 of 68 patients with absolute CS versus 15 of 81 with probable CS either died, suffered an aborted sudden cardiac death or underwent cardiac transplantation (log rank p = 0.334). In conclusion, in terms of prognosis, clinical diagnosis of CS supported by extracardiac histology is equivalent to diagnosis confirmed by myocardial histology. No distinction should be made between probable and absolute CS as regards treatment and follow-up.
Cardiac sarcoidosis: Diagnosis, therapeutic management and prognostic factors
2017, Archives of Cardiovascular Diseases
Citation Excerpt :
CS is known to have a bad prognosis, with an estimated mortality rate of up to 50% [6,7]. We and others have shown that in patients who received steroids alone or combined with IST, the 5-year survival rate reached 60–90% [4,8,9,13], with a reduced risk of major adverse cardiac events [33]. To our knowledge, an analysis of CS relapses and their related factors has never been carried out.
Cardiac sarcoidosis (CS) is a severe localization, observed mostly in cardiology departments. Despite appropriate cardiological treatment, CS is a potentially life-threatening condition, and accounts for 13–85% of sarcoidosis-related deaths.
This retrospective study aimed to give an overview of CS in a non-cardiac unit, to analyse the effect of first-line immunosuppressive treatment on outcome and survival and to evaluate factors associated with relapses.
From 534 cases of sarcoidosis, we selected 59 patients with CS according to “2006 international criteria”. We performed an in-depth analysis regarding symptoms, physical signs and cardiac investigation results. Patients were followed for a median period of 60 months.
The median age at cardiac signs was 42 years. Echocardiography abnormalities, isotopic defects and abnormal magnetic resonance imaging findings were observed in 81%, 84% and 92% of patients, respectively. First-line treatment included steroids alone in 24 patients and steroids plus immunosuppressive therapy in 35 patients. Forty-seven (80%) patients recovered; 12 stabilized or worsened. The recovery rate was 75% in the steroids alone group versus 83% in the steroids plus immunosuppressive therapy group. Five (9%) patients died during follow-up, with two deaths attributed to CS. The overall 1- and 5-year survival rates were 98% and 92%, respectively.
Our series of patients with CS who received steroids alone or combined with immunosuppressive therapy had a good prognosis, with an overall 5-year survival rate of 92%. The recovery rate was 85%, with no significant difference between patients treated with steroids alone or plus immunosuppressive therapy.
La sarcoïdose cardiaque est une localisation sévère, le plus souvent prise en change en cardiologie. Malgré un traitement cardiologique approprié, le pronostic est sombre avec un taux de mortalité de 13 à 85 %.
Étude rétrospective permettant de : (1) présenter les sarcoïdoses cardiaques en médecine interne ; (2) analyser l’impact des immunosuppresseurs sur le pronostic et la survie.
Dans une cohorte de 534 sarcoïdoses, 59 patients répondaient aux critères internationaux de 2006. L’analyse a porté sur les signes cliniques et les investigations cardiologiques. Ils ont été suivis pendant une période médiane de 60 mois.
L’âge médian lors des signes cardiaques est de 42 ans. L’échocardiographie, les examens isotopiques, et l’IRM ont été anormaux respectivement dans 81 %, 84 % et 92 % des cas. De première intention, ils ont reçu soit de la prednisone dans 24 cas, soit de la prednisone associée à un immunosuppresseur dans 35 cas. Quatre-vingt pour cent ont évolué favorablement, 12 se sont stabilisés ou aggravés. Le taux de guérison a été de 75 % dans le groupe prednisone seule contre 83 % dans le groupe prednisone plus immunosuppresseur. Cinq patients sont décédés, deux sont en rapport avec la sarcoïdose cardiaque. L’espérance de vie à 1 et 5 ans est respectivement de 98 et 92 %.
Dans cette série, les patients traités par prednisone seule ou associée à un autre immunosuppresseur ont un bon pronostic avec une espérance de vie à 5 ans de 92 %. Le taux de guérison ne diffère pas entre les deux groupes de traitement.
Early and frequent defibrillator discharge in patients with cardiac sarcoidosis compared with patients with idiopathic dilated cardiomyopathy
2017, International Journal of Cardiology
Citation Excerpt :
Therefore, in the clinical setting, some patients are considered as suspected CS that satisfies the guideline-established clinical cardiac findings of CS [8,9], but they are not determined definite CS because of the absence of histological confirmation or extracardiac sarcoidosis. In our previous study, the clinical characteristics of patients with suspected CS were similar to those of patients with definite CS, and the outcome in patients with suspected CS was worse than that in patients with definite CS [10]. These findings might indicate the need to recognize suspected CS as CS and treat with the same therapeutic strategy.
Little is known about the suitability of implantable cardioverter defibrillator (ICD) implantation in patients with cardiac sarcoidosis (CS). We evaluated the efficacy of ICD implantation in patients with CS, including suspected CS, compared with those with idiopathic dilated cardiomyopathy (DCM).
A total of 102 consecutive patients with definite CS, suspected CS, or DCM who underwent ICD implantation were enrolled. The endpoint was the first documentation of appropriate ICD therapy for ventricular tachyarrhythmias. The follow-up started after ICD implantation.
Appropriate ICD therapies occurred in 15 (56%) of 27 patients with definite CS, 17 (68%) of 25 with suspected CS, and 16 (32%) of 50 with DCM. The rate of appropriate ICD therapies was higher in patients with definite CS and those with suspected CS than in those with DCM (log-rank test, p = 0.010). After ICD implantation, five or more appropriate ICD therapies occurred in 5 (19%) patients with definite CS and 10 (40%) with suspected CS, but in only 1 (2%) with DCM. Cox proportional hazard analysis showed that CS, including suspected CS, was independently associated with appropriate ICD therapies. For primary prevention, the rate of appropriate ICD therapies was higher in patients with CS than in those with DCM (log-rank test, p = 0.034). More than half of patients with CS received appropriate ICD therapies.
Patients with CS receive appropriate ICD therapies for ventricular tachyarrhythmias at a higher rate, compared with those with DCM, suggesting that ICD implantation should be performed in patients with CS.
Long-Term Outcomes of Cardiac Sarcoid: Prognostic Implications of Isolated Cardiac Involvement and Impact of Diagnostic Delays
2023, Journal of the American Heart Association
Cardiac sarcoidosis: Systematic review of the literature on corticosteroid and immunosuppressive therapies
2022, European Respiratory Journal

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CardiomyopathyComparison of Outcomes in Patients With Probable Versus Definite Cardiac Sarcoidosis

Section snippets

Methods

Results

Discussion

Disclosures

Am J Med

Am J Cardiol

Am Heart J

Heart Rhythm

Am J Cardiol

Chest

Sarcoidosis

N Engl J Med

Cardiac sarcoidosis: a clinicopathologic study of 84 unselected patients with systemic sarcoidosis

Circulation

The prognosis of sarcoid heart disease in the United Kingdom

Ann N Y Acad Sci

Cardiac sarcoidosis: a comprehensive review

Arch Med Sci

Detection of myocardial damage in patients with sarcoidosis

Circulation

Cardiomyopathy
Comparison of Outcomes in Patients With Probable Versus Definite Cardiac Sarcoidosis