Risk of Adverse Cardiovascular Events in Cardiac Sarcoidosis Independent of Left Ventricular Function

doi:10.1016/j.amjcard.2020.04.025

The American Journal of Cardiology

Volume 127, 15 July 2020, Pages 142-148

https://doi.org/10.1016/j.amjcard.2020.04.025 Get rights and content

This study investigated the association between left ventricular ejection fraction (LVEF) and the risk of ventricular arrhythmias (VA), heart transplantation, and death in cardiac sarcoidosis (CS). We identified 110 CS patients meeting 2014 Heart Rhythm Society (HRS) diagnostic criteria with baseline LVEF <35% (n = 32) or ≥35% (n = 78). The primary end point was sustained VA or sudden cardiac death (SCD), and secondary end points included risk of heart transplantation, death, or a composite. Logistic regression determined risk factors for VA/SCD, and Cox proportional hazards regression analysis was performed for secondary end points. Receiver operating curve analysis determined the best discrimination point of LVEF for each end point; sensitivity analyses evaluated the effects of higher LVEF on each end point. Over a follow-up of 2.6 (range 1.0 to 5.8) years, 49 (44.5%) CS patients experienced VA/SCD, including 19 of 32 (59.4%) with LVEF <35%, and 30 of 78 (38.5%) with LVEF ≥35%. After adjustment, LVEF <35% was not significantly associated with an increased risk of VA/SCD compared with LVEF ≥35% (odds ratio 1.3, 95% confidence intervals 0.5 to 3.7). Although LVEF <35% was associated with an increased risk of heart transplantation and death (28.1% vs 12.8%, p = 0.05), this was not significant after adjustment (hazard ratio 1.7, 95% confidence intervals 0.5 to 9.0, p = 0.53). In conclusion, patients with CS experience high rates of VA, SCD, and heart transplantation, even when LVEF is mildly impaired or normal. Patients with LVEF <35% are at particularly elevated risk of VA/SCD. Our findings highlight the imperative to investigate arrhythmia risk in all patients with CS, even in the setting of an otherwise reassuring LVEF.

Section snippets

Methods

We performed a retrospective chart review of patients with CS who were cared for at the University of Washington Medical Center from January 1, 2006 to December 31, 2016. Patients were diagnosed with CS using 2014 Heart Rhythm Society (HRS) diagnostic criteria¹; those with high clinical suspicion of CS based on abnormal 18F-fluoro-2-deoxyglucose positron emission tomography or cardiac magnetic resonance imaging without histologic confirmation of sarcoidosis were excluded.

Baseline

Results

A total of 110 patients meeting 2014 HRS diagnostic criteria for CS were identified. Baseline demographics, medical co-morbidities, and initial New York Heart Association class are shown in Table 1. The mean age in the cohort was 52.9 years, 64.6% of subjects were women, and the mean baseline LVEF was 45.6%. Median follow-up time was 2.6 years (interquartile range 25 to 75: 0.96 to 5.8 years). Patients with baseline LVEF <35% had a higher prevalence of chronic kidney disease, diabetes, and

Discussion

In this single-center observational cohort of patients with CS, we found a very high risk of both arrhythmic and heart failure events, independent of baseline LVEF. Overall, 45% of CS patients suffered a life-threatening arrhythmic event, 15% underwent heart transplantation, and 3.6% died over a median follow-up of 2.6 years. Among CS patients with baseline LVEF ≥35%, over 38% of patients experienced significant VA and 12.8% underwent heart transplantation or died during follow-up. The ROC

Disclosures

The authors have no conflicts of interest to disclose.

Acknowledgment

None.

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Cited by (11)

The role of ICDs in patients with sarcoidosis–A comprehensive review
2024, Current Problems in Cardiology
Implantable cardioverter defibrillator (ICD) use in cardiac sarcoidosis (CS) to prevent sudden cardiac death (SCD) is a potentially life-saving intervention. However, the factors that determine outcome in this cohort remains largely unknown. This review analyses CS patients with an ICD and highlights determinants of poor outcome.
Analysis of studies which used the 2014 HRS Consensus, 2017 AHA/ACC/HRS Guideline and 2022 ESC Guidelines showed that those with class I recommendations have higher incidences of ventricular arrhythmia (VA) than those with class II recommendations. Additionally, even those with normal left ventricular ejection fraction (LVEF) and CS are at high risk of VA and SCD.
Compounding research emphasises the importance of cardiac imaging in those with sarcoidosis, with evidence to suggest a possible need for revision of the guidelines. Other variables such as demographics and ventricular characteristics may prove useful in predicting those to benefit most from ICD insertion.
Fatal Arrhythmic Risks in Cardiac Sarcoidosis With Mildly Impaired Cardiac Function
2023, JACC: Asia
The prognosis and later fatal arrhythmia in cardiac sarcoidosis (CS) with relatively preserved cardiac function were unclear.
This study aimed to evaluate the prognosis and arrhythmic events in patients with CS and mildly impaired cardiac function.
Data were collected from a nationwide Japanese cohort survey conducted in 57 hospitals (n = 420); 322 patients with CS with left ventricular ejection fraction (LVEF) >35% were investigated.
Ventricular tachycardia (VT) manifestation was present in 50 patients (16%) and absent in 272 (84%), of whom 36 (72%) and 46 (17%), respectively, had an implantable cardioverter-defibrillator (ICD). Over a median of 5 years, 23 all-cause deaths and 31 appropriate ICD discharges were observed. In Kaplan-Meier analysis, all-cause death did not differ between patients with and without VT manifestation (P = 0.660), although appropriate ICD therapy was significantly less used in patients without VT manifestation than in those with VT manifestation (P < 0.001). Of the 272 patients without VT manifestation, 18 had ventricular arrhythmic events (VAEs), including 3 sudden cardiac deaths and 15 appropriate ICD discharges. In multivariate analysis, concomitant nonsustained ventricular tachycardia (NSVT) with atrioventricular block (AVB), lower LVEF, abnormal gallium-67 scintigraphy or ¹⁸F-fluorodeoxyglucose positron emission tomography of the heart (Ga/PET), and concomitant NSVT with abnormal Ga/PET at CS diagnosis were independent predictors of VAEs (P = 0.008, P = 0.021, P = 0.049, and P = 0.024, respectively).
If concomitant NSVT with AVB, concomitant NSVT with abnormal Ga/PET, or abnormal Ga/PET is observed in patients with CS and mildly impaired cardiac function (LVEF >35%), ICD should be considered as primary prevention.
Long-term monitoring of arrhythmias with cardiovascular implantable electronic devices in patients with cardiac sarcoidosis
2022, Heart Rhythm
Citation Excerpt :
An implantable cardioverter-defibrillator (ICD) is recommended for patients with VA, third-degree AVB, or left ventricular ejection fraction (LVEF) <35%.2,6 Also, scar detected by cardiac magnetic resonance imaging (CMR) is strongly related to the occurrence of VA and SCD.7–9 However, less is known about patients with a preserved ejection fraction, a small amount of scar tissue and no or mild cardiac symptoms.2,6
Risk stratification for sudden cardiac death (SCD) in cardiac sarcoidosis (CS) is challenging in patients without overt cardiac symptoms.
The purpose of this study was to determine the incidence of ventricular arrhythmias (VAs) and mortality after long-term monitoring with a cardiovascular implantable electronic device (CIED) in CS patients identified after systematic screening of patients with extracardiac sarcoidosis (ECS).
A retrospective study was performed in 547 predominantly Caucasian patients with ECS screened for cardiac involvement. If CS was diagnosed, risk stratification (high vs low risk) for SCD was performed by a multidisciplinary team. The primary endpoint was defined as sustained VA, appropriate implantable cardioverter-defibrillator (ICD) therapy, or cardiac death.
In total, 105 patients were included (mean follow-up 33 ± 16 months). An ICD was implanted in 17 high-risk patients (16.2%), whereas 80 low-risk patients (76.1%) received an implantable loop recorder (ILR). Eight low-risk patients (7.6%) did not receive a device. The primary endpoint occurred in 4.8% (n = 5), with an overall annualized event rate of 1.7%. The annualized event rate was 9.8% in high-risk patients and 0.4% in low-risk patients. Nine low-risk patients received an ICD during follow-up, in 7 patients as a result of the ILR recordings. None of these patients required ICD therapy.
In CS patients without overt cardiac symptoms at initial presentation the annualized overall event rate was 1.7%; 10% in high-risk patients, but only 0.4% in low-risk patients. In low-risk patients long-term arrhythmia monitoring with an ILR enabled early detection of clinically important arrhythmias without showing impact on prognosis.
Sarcoidosis-Related Cardiomyopathy: Current Knowledge, Challenges, and Future Perspectives State-of-the-Art Review
2022, Journal of Cardiac Failure
Citation Excerpt :
Identifying patients with CS who are at increased risk of arrhythmic sudden cardiac death is a clinical challenge. Patients with CS and a normal LVEF may be at increased risk for VA.82,83 Among those with preserved ventricular function, there is an association with LGE and FDG with VA.76,83 However, in 1 cohort of patients that underwent both CMR and PET, only those who had LGE on CMR had an arrhythmic event in follow-up, and no patients with FDG uptake alone had VA.84 Given the high prevalence of LGE in CS and significant association with outcomes, an electrophysiology study with programmed electrical stimulation may provide prognostic information, with an excellent negative predictive value.83,85 CS has a predilection for involving the intraventricular septum and thus conduction system disease, to include bundle branch blocks and second- or third-degree AVB, is common.
The prevalence of sarcoidosis-related cardiomyopathy is increasing. Sarcoidosis impacts cardiac function through granulomatous infiltration of the heart, resulting in conduction disease, arrhythmia, and/or heart failure. The diagnosis of cardiac sarcoidosis (CS) can be challenging and requires clinician awareness as well as differentiation from overlapping diagnostic phenotypes, such as other forms of myocarditis and arrhythmogenic cardiomyopathy. Clinical manifestations, extracardiac involvement, histopathology, and advanced cardiac imaging can all lend support to a diagnosis of CS. The mainstay of therapy for CS is immunosuppression; however, no prospective clinical trials exist to guide management. Patients may progress to developing advanced heart failure or ventricular arrhythmia, for which ventricular assist device therapies or heart transplantation may be considered. The existing knowledge gaps in CS call for an interdisciplinary approach to both patient care and future investigation to improve mechanistic understanding and therapeutic strategies.
Predictors of outcome in a contemporary cardiac sarcoidosis population: Role of brain natriuretic peptide, left ventricular function and myocardial inflammation
2023, European Journal of Heart Failure
Cardiac Sarcoidosis: Current Approaches to Diagnosis and Management
2022, Current Allergy and Asthma Reports

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: This work was funded by grants from the Catherine Holmes Wilkins Charitable Foundation to Dr. Patton, and the American Medical Association Foundation to Dr. Rosenthal.

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Risk of Adverse Cardiovascular Events in Cardiac Sarcoidosis Independent of Left Ventricular Function

Section snippets

Methods

Results

Discussion

Disclosures

Acknowledgment

Am J Cardiol

Heart Rhythm

Respir Med

Heart Rhythm

J Am Coll Cardiol

J Cardiol

HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis

Heart Rhythm

Cardiac sarcoidosis: epidemiology, characteristics, and outcome over 25 years in a nationwide study

Circulation