Race Comparisons in Patients with Cardiac Sarcoidosis: Insights from the Cardiac Sarcoidosis Consortium

Abstract

Background:

Differences in cardiac sarcoidosis (CS) between racial groups remain understudied. Therefore, this study aims to explore race differences in patients with CS.

Methods:

We analyzed data from the Cardiac Sarcoidosis Consortium, an international registry including over 25 centers. The primary clinical outcome was a composite endpoint of all-cause mortality, left ventricular assistant device (LVAD) implantation, heart transplantation, or implantable cardioverter-defibrillator (ICD) therapy.

Results:

A total of 619 patients were included in the study (362 White, 193 Black, 64 other races). Black patients were diagnosed with CS at a younger age (50.5±11.8 vs. 53.7±10.5 years old, p=0.010) compared to White patients. Left ventricular ejection fraction (LVEF) was significantly lower in Black patients (44.6±15.4 vs. 48.3±14.0, p=0.008). Additionally, extracardiac involvement in the lungs (80.3% vs. 72.7%, p=0.046), skin (22.8% vs 12.4%, p=0.002), and eyes (13.5% vs. 5.5%, p=0.001) was more prevalent in Black patients. patients had significantly higher rates of hypertension (69.9% vs. 50.6%, p<0.001), diabetes (37.8% vs. 21.0%, p<0.001), smoking (40.9% vs. 26.8%, p<0.001), COPD or emphysema (15.5% vs. 4.1%, p<0.001) and chronic kidney disease (25.9% vs. 12.4%, p<0.001). The treatment patterns including glucocorticoid (71% vs. 74.3%, p=0.4), glucocorticoid-sparing (53.4% vs. 59.9%, p=0.14), and ICD or cardiac resynchronization implantation (75.6% vs. 73.8%, p=0.63), were similar. No significant differences were found in the primary outcome (29.5% in Black vs. 28.5% in White, p=0.79). Subgroup analysis of the primary outcome also revealed no significant differences in both the LVEF > 35% group (24.1% in Black vs. 25.9% in White, p=0.72) and the LVEF ≤ 35% group (51% vs. 42.5%, p= 0.35).

Conclusions:

Black patients with CS exhibited significantly higher rates of lung, skin, and eye involvement and comorbidities, but had similar cardiac clinical outcomes and all cause mortality compared to White patients. Nonetheless, ascertainment bias cannot be excluded.

Graphical Abstract

Introduction

Sarcoidosis is a complex systemic inflammatory disease that can affect multiple organs and tissues by forming noncaseating granulomas—small clusters of immune cells. The incidence and prevalence of sarcoidosis differ based on region, sex, and race. The estimated prevalence of systemic sarcoidosis is 35.2 per 100,000 in the United State^1,2. Sarcoidosis is notably more prevalent in Black patients, who are approximately three times more likely to be affected than White patients. Furthermore, the condition is more common in women than in men^2–4.

Cardiac sarcoidosis (CS) is a relatively uncommon but potentially life-threatening manifestation of sarcoidosis. The clinical manifestations of cardiac sarcoidosis (CS) have been reported in approximately 5% of patients with systemic sarcoidosis, with up to 25% having asymptomatic cardiac involvement⁵. In CS, noncaseating granulomas infiltrate the heart tissue, leading to inflammation and scarring that can disrupt the heart’s normal electrical conduction system. This disruption can result in arrhythmias, including heart block and ventricular tachycardia, as well as other complications such as heart failure and, in severe cases, sudden cardiac death^1,6.

Black patients with systemic and pulmonary sarcoidosis have been reported to experience worse outcomes compared to Whites. This includes greater multiorgan involvement, more severe disease progression, higher mortality rates, and increased rates of hospitalization^7–9. Previous studies indicate that mortality rates among Black patients with sarcoidosis are 8 to 14 times higher than in White patients^7,10,11. Data from the Nationwide Inpatient Sample revealed significantly higher hospitalization rates among Black patients⁸, while the National Hospital Discharge Survey found that Black sarcoidosis patients had a ninefold increase in hospitalization rates¹². Moreover, Black patients faced a 2.1% increased risk of in-hospital mortality¹³.

Although there is more established evidence of racial disparities in clinical presentations and clinical outcomes of systemic sarcoidosis, differences in cardiac sarcoidosis between racial groups remain understudied. Therefore, this cohort study aims to explore disparities in comorbidities, clinical presentations, treatment, and outcomes between Black and White patients with CS.

Methods

The data that support the findings of this study are available from the corresponding author upon reasonable request. We conducted a cross-sectional analysis of the cohort study including Black and White patients with CS by using the data from the Cardiac Sarcoidosis Consortium (CSC), which is an international collaborative registry with over 25 centers from the United States, India, Japan, the United Kingdom, Sweden, and the Netherlands from 2011 to 2024¹⁴. Demographic, clinical, imaging, and electrophysiologic data are collected annually through a web-based secure registry at the University of Michigan. All patients received treatment based on the protocols and guidelines followed at their local hospitals. Institutional Review Board (IRB) approval and informed consent were obtained from all patients. Patients were included in this analysis if they met at least one of the following four diagnostic criteria: the 1993 Japanese Ministry of Health & Welfare (JMHW), the 2006 joint committee of the Japan Society of Sarcoidosis and Other Granulomatous Disorders, the 2017 Japanese Society of Nuclear Cardiology Criteria^15–17, or the 2014 Heart Rhythm Society (HRS) Expert Consensus Statement Criteria¹⁸. In patients without implantable devices, sustained ventricular tachycardia (VT) was defined using standard criteria, including: (1) VT lasting at least 30 seconds; (2) VT associated with unstable vital signs; (3) VT resulting in cardiac arrest; (4) sustained VT documented on a monitor or event recorder.

The clinical outcomes included: 1) a composite endpoint of all-cause mortality, left ventricular assist device (LVAD) implantation, heart transplantation, or appropriate implantable cardioverter-defibrillator (ICD) therapy; 2) all-cause mortality; 3) LVAD implantation 4) heart transplant; and 5) appropriate ICD therapy. Appropriate ICD therapy was defined as antitachycardia pacing or shock for VT or ventricular fibrillation (VF).

Categorical variables are presented using percentages and frequencies, and continuous variables using means±standard deviations, medians and IQRs. Comparisons of baseline categorical variables were made using Chi-square tests and Fisher’s exact tests, while continuous variables were analyzed with t-tests and Wilcoxon rank-sum tests. Logistic regression was used to examine the relationship between race and outcomes in the LVEF groups. Statistical analysis was performed using using SAS 9.4 (SAS Institute, Inc, Cary, NC). Statistical significance was defined as p-value (p) <0.05.

Results

Demographics and Presentation

A total of 619 patients with known race in the CSC were included in this study. Of these, 362 (58.5%) were White, 193 (31.2%) were Black, and 64 (10.3%) identified as other races. Due to the small sample size of patients in the ‘other races’ category, meaningful comparisons could not be made, so our analysis focused solely on Black and White patients. However, we included an analysis of age and comorbidities for Hispanic (10) and Asian (35) patients in the Supplemental Table 1. Of 555 Black and White patients compared, 341 (61.4%) were male. The majority of the patients included were from the United States, the United Kingdom, and Sweden, as shown in Figure 1A. Among the U.S. patients, most were from Michigan, Illinois, Virginia, Ohio, Massachusetts, and Minnesota, as illustrated in Figure 1B. Most common symptoms at diagnosis were shortness of breath (39.7%), palpitations (27.2%), and syncope (17.1%) as detailed in Supplemental table 2.

Figure 1.

Distribution of cardiac sarcoidosis patients from the Cardiac Sarcoidosis Consortium. Contributing members to the Cardiac Sarcoidosis Consortium (CSC). The CSC countries include centers from the United States (US), United Kingdom (UK), the Netherlands, Sweden, India, and Japan. These countries are highlighted in purple with map pins indicating centers (A.); individual centers in the US are shown on a separate map (B.). The graphs at the right show the distribution of race for each country (A., either by center or overall), with the US distribution by center shown in detail in panel B. The map was created with BioRender.com, the graphs were created in GraphPad Prism, and compiled in PowerPoint.

Black patients were diagnosed with CS at a significantly younger age compared to White patients (50.5±11.8 vs. 53.7±10.5 years, p=0.010). The majority of patients were male, with 52.3% of Black patients and 66.3% of White patients being male. The time from symptom onset to diagnosis was similar between Black (35.8±83.2 months) and White (32.4±64.2 months) patients (p=0.70). Left ventricular ejection fraction (LVEF) was significantly lower in Black patients compared to White patients (44.6±15.4 vs. 48.3±14.0, p=0.008). More Black patients had LVEF ≤ 35% (p=0.025). Lung involvement was the most extracardiac involvement in both Black and White CS patients. However, extracardiac involvement in lungs (80.3% vs. 72.7%, p=0.046), skin (22.8% vs 12.4%, p=0.002), and eyes (13.5% vs. 5.5%, p=0.001) were significantly more common in Black compared with White patients.

Comorbidities

Black CS patients had significantly higher rates of hypertension (69.9% vs. 50.6%, p<0.001), diabetes (37.8% vs. 21.0%, p<0.001), smoking (40.9% vs. 26.8%, p<0.001), chronic obstructive pulmonary disease (COPD) or emphysema (15.5% vs. 4.1%, p<0.001) and chronic kidney disease (CKD) (25.9% vs. 12.4%, p<0.001). The baseline characteristics of the 2 groups are presented in Table 1, and Figures 2 and 3.

Table 1:

Baseline Characteristics

Characteristics	White N=362	Black N=193	P-value
Age at diagnosis (mean ± SD, median, IQR)	53.7±10.5, 54.7, 14.2	50.5±11.8, 51.1, 17.4	0.010
Male	240 (66.3)	101 (52.3)	0.001
Female	122 (33.7)	92 (47.7)
Time from Earliest Symptom to Diagnosis in months (mean ± SD, median, IQR)	32.4±64.2, 7.3, 29.3	35.8±83.2, 3.8, 27.8	0.70
LVEF (mean±SD, median, IQR)	48.3±14.0, 53, 20	44.6±15.4, 45, 25	0.008
LVEF > 35%	259/332 (78.0)	112/163 (68.7)	0.025
LVEF ≤ 35%	73/332 (22.0)	51/163 (31.3)
Other organs with Clinical Manifestations of Sarcoidosis
Lung	263 (72.7)	155 (80.3)	0.046
Skin	45 (12.4)	44 (22.8)	0.002
Lymph Node	120 (33.1)	52 (26.9)	0.13
Eye	20 (5.5)	26 (13.5)	0.001
Liver	27 (7.5)	18 (9.3)	0.44
Spleen	15 (4.1)	9 (4.7)	0.77
Brain/Nervous System	19 (5.2)	9 (4.7)	0.76
Parotid (Salivary)	1 (0.3)	3 (1.6)	0.12
Bone Marrow	6 (1.7)	2 (1.0)	0.72
Renal	7 (1.9)	2 (1.0)	0.73
Bone/Joint	10 (2.8)	9 (4.7)	0.24
Muscle	4 (1.1)	1 (0.5)	0.66
ENT	3/256 (1.2)	4/120 (3.3)	0.22
Other	11/256 (4.3)	9/120 (7.5)	0.22
Comorbidities
Hypertension	183 (50.6)	135 (69.9)	<0.001
COPD/Emphysema	15 (4.1)	30 (15.5)	<0.001
Chronic Kidney Disease	45 (12.4)	50 (25.9)	<0.001
Hyperlipidemia	141 (39.0)	81 (42.0)	0.49
Coronary Artery Disease	65 (18.0)	34 (17.6)	0.92
Myocardial Infarction	28 (7.7)	16 (8.3)	0.82
Current or Former Smoker	97 (26.8)	79 (40.9)	<0.001
Diabetes Mellitus	76 (21.0)	73 (37.8)	<0.001
Immunosuppressant Use
Glucocorticoid	269 (74.3)	137 (71.0)	0.40
Glucocorticoid-sparing	217 (59.9)	103 (53.4)	0.14
Anti-arrhythmia Medication Use	119 (32.9)	64 (33.2)	0.95
ICD / Biv ICD Implantation	267 (73.8)	146 (75.6)	0.63
Pacemaker Implantation	104 (28.7)	33 (17.1)	0.002

Biv: biventricular, COPD: chronic obstructive pulmonary disease, ENT: ear/nose/throat, ICD: implantable cardioverter-defibrillator, LVEF: left ventricular ejection fraction, SD: standard deviation

Figure 2.

Comorbidity Presentations Based on Race

Figure 3.

Comorbidity Presentations Based on Race and Sex

Medication and device therapy

Glucocorticoids were the most commonly used immunosuppressant in both groups. Immunosuppressant use rates including both glucocorticoid (71% vs. 74.3%, p=0.4) and glucocorticoid-sparing (53.4% vs. 59.9%, p=0.14), were comparable between 2 groups, as shown in Figure 4. In addition, the rates of antiarrhythmic medication use were not different between the Black and White groups (33.2% vs. 32.9%, p=0.95). Implantable cardioverter defibrillator (ICD) or cardiac resynchronization (CRT) rates were similar among Blacks and Whites (75.6% vs. 73.8%, p=0.63), but Black CS patients had significantly lower rates of pacemaker implantation (17.1% vs. 28.7%, p=0.002), as shown in Table 1. Rates of biventricular defibrillator implants were similar in both groups (23.8% vs 26.5% in Black vs. White, p=0.49).

Figure 4.

Immunosuppressant use Based on Race

Clinical outcomes

The median follow-up time was 3 years [Q1–Q3: 1–5 years]. The composite endpoint of all-cause mortality, LVAD implantation, heart transplantation, or appropriate ICD therapy was similar between 2 groups (29.5% in Black vs. 28.5% in White, p=0.79). All-cause mortality (10.4% vs. 7.2%, p=0.2), LVAD (2.6% vs. 1.9%, p=0.76), heart transplant (3.1% vs 3.9%, p=0.65), and appropriate ICD therapy (25.3% vs. 26.6%, p=0.78), showed no significant differences between Black and White groups. The clinical outcomes are shown in Table 2 and Figure 5.

Table 2:

Outcomes Based on Race

Outcomes	White N=362	Black N=193	P-value
Composite Endpoint	103 (28.5)	57 (29.5)	0.79
All-cause Mortality	26 (7.2)	20 (10.4)	0.20
LVAD	7 (1.9)	5 (2.6)	0.76
Heart Transplant	14 (3.9)	6 (3.1)	0.65
Appropriate ICD Therapy (of patients who had ICD/Biv ICD implantation)	71/267 (26.6)	37/146 (25.3)	0.78
ATP	211/267 (79.0)	114/146 (78.1)	0.82
1 Shock	31/267 11.6)	14/146 (9.6)	0.53
2–5 Shocks	21/267 (7.9)	16/146 (11.0)	0.29
>5 Shocks	4/267 (1.5)	2/146 (1.4)	1.0

ATP: antitachycardia pacing, Biv: biventricular, ICD: implantable cardioverter-defibrillator, LVAD: left ventricular assistant device

Figure 5.

Clinical Outcomes

Clinical outcomes based on race and LVEF

Amoung 495 patients with echoes recorded, those with baseline LVEF ≤ 35% experienced a significantly higher composite endpoint of all-cause mortality, LVAD implantation, heart transplantation, or appropriate ICD therapy compared to those with LVEF > 35%. All-cause mortality (15.3% vs. 6.7%, p=0.004), LVAD (5.6% vs. 1.3%, p=0.013), and heart transplant (9.7% vs 2.2%, p<0.001) were higher in the group with LVEF ≤ 35%. However, appropriate ICD therapy was similar between the 2 groups (31.3% in LVEF ≤ 35% vs. 23.8% in LVEF > 35%, p=0.13).

We didn’t find race to have a significant effect on both the composite endpoint and the individual outcomes in either the LVEF > 35% group or the LVEF ≤ 35% group (Table 3). Among patients with LVEF > 35%, the event rates were comparable between Black (24.1%) and White (25.9%) patients (p=0.72), including all-cause mortality (8% vs. 6.2%, p=0.51), LVAD implantation (1.8% vs. 1.2%, p=0.63), heart transplantation (3.6% vs. 1.5%, p=0.23), and appropriate ICD therapy (18.6% vs. 26.2%, p=0.17). Similarly, in the LVEF ≤ 35% group, outcome event rates were not significantly different between Black (51%) and White (42.5%) patients (p=0.35). This included all-cause mortality (19.6% vs. 12.3%, p=0.27), LVAD implantation (5.9% vs. 5.5%, p=0.92), heart transplantation (3.9% vs. 13.7%, p=0.089), and appropriate ICD therapy (38.6% vs. 26.5%, p=0.18).

Table 3:

Outcomes Based on Race and LVEF

Outcomes	LVEF > 35%			LVEF ≤ 35%			p-value
	1 Total N = 371	1 (A) White N = 259	1 (B) Black N = 112	2 Total N = 124	2 (A) White N = 73	2 (B) Black N = 51	1 vs. 2	1 (A) vs. 1 (B)	2 (A) vs. 2 (B)
Composite Endpoint	94 (25.3)	67 (25.9)	27 (24.1)	57 (46.0)	31 (42.5)	26 (51.0)	<0.001	0.72	0.35
All-cause Mortality	25 (6.7)	16 (6.2)	9 (8.0)	19 (15.3)	9 (12.3)	10 (19.6)	0.004	0.51	0.27
LVAD	5 (1.3)	3 (1.2)	2 (1.8)	7 (5.6)	4 (5.5)	3 (5.9)	0.013	0.63	0.92
Heart Transplant	8 (2.2)	4 (1.5)	4 (3.6)	12 (9.7)	10 (13.7)	2 (3.9)	<0.001	0.23	0.089
Appropriate ICD Shock/Pacing (of patients who had ICD/Biv ICD implantation)	64/269 (23.8)	48/183 (26.2)	16/86 (18.6)	35/112 (31.3)	18/68 (26.5)	17/44 (38.6)	0.13	0.17	0.18

Biv: biventricular, ICD: implantable cardioverter-defibrillator, LVAD: left ventricular assistant device, LVEF: left ventricular ejection fraction, SD: standard deviation

Discussion

The Cardiac Sarcoidosis Consortium is the largest international multi-center registry for cardiac sarcoidosis (CS) with annual data collection since 2011. This study aimed to evaluate disparities in comorbidities, clinical presentations, treatment, and outcomes between Black and White CS patients. The key findings of our study were: 1) Black CS patients presented at a younger age compared to White CS patients; 2) Black patients were more likely to have lung, skin, and eye involvement; 3) Black patients with CS had significantly higher rates of comorbidities; 4) Black patients had a lower baseline LVEF; and 5) Despite higher comorbidity rates, lower LVEF, and greater lung involvement among Black CS patients, clinical outcomes attributable to CS were similar between the two groups.

Research indicates that Black patients with systemic sarcoidosis tend to experience worse clinical outcomes, including significantly higher mortality rates, compared to White patients, with lung involvement being more common among Black patients^7,10,11,19. However, in our study, we observed no significant differences in clinical outcomes between Black and White patients with CS, despite a higher prevalence of lung involvement in Black patients. Similarly, a single-center study by Duvall et al., which included 252 patients with CS, found no differences in the composite outcomes of mortality, LVAD implantation, and heart transplant between Black and White patients²⁰. Interestingly, lung involvement rates were also not significantly different between the two groups. The study by Mirsaeidi et al. reported that pulmonary hypertension (PHT) was twice as common in Black patients with sarcoidosis and may be linked to their higher mortality⁷. However, we lacked data on PHT rates between Black and White patients. Further research focused on PHT is necessary to determine if Black patients with CS have different PHT rates compared to White CS patients.

Socioeconomic status may contribute to the worse outcomes in Black patients with sarcoidosis. Poverty can negatively affect health through various pathways, such as limited access to healthcare and specialized services^21,22. Studies showed that Black patients with sarcoidosis often had significantly lower incomes and lack of insurance, associated with more severe disease, increased morbidity, higher hospitalization rates, and greater mortality^21,23,24. In our study, however, both groups had comparable rates of immunosuppressant use, antiarrhythmic therapy, and ICD or CRT implantations. The similar outcomes observed between the two racial groups may be explained by the standardized treatment pathways used in subspecialty clinics, as the data from the CSC registry was collected from large specialty centers. An analogous study by Tang et al. which compared prostate cancer patients in multidisciplinary clinics to national trends, found that patients in specialized clinics received more appropriate treatment, potentially minimizing the influence of sociodemographic factors on outcomes²⁵. The current study findings may not apply to sarcoidosis patients treated outside of sarcoidosis specialty centers.

While we found no race disparities in clinical outcomes, our study found that Black CS patients were diagnosed at a younger age and had significantly higher rates of comorbidities including higher rates of hypertension, diabetes, and chronic kidney disease. Additionally, Black patients exhibited more extracardiac involvement. Similar findings have been reported in studies on pulmonary and systemic sarcoidosis. Rybicki et al. found that Black patients were diagnosed at the younger age¹⁹. The ACCESS study indicated that Black patients with sarcoidosis tended to have more extrapulmonary sarcoidosis and develop new organ involvement over time²⁶. Zhou et al. also noted that Black sarcoidosis had more multiorgan involvement than White sarcoidosis²⁷. However, few studies have specifically focused on comorbidities in these patients. Our findings underscore the importance of addressing comorbidities and extracardiac symptoms alongside the treatment of CS, particularly in Black patients with CS. In this cohort, the higher rates of diabetes and hypertension cannot be ascribed to more frequent treatment with glucocorticoids, although we did not compare the average steroid doses over time or the duration of treatment, which could affect the prevalence of diabetes. Nonetheless, prioritizing careful management of extracardiac sarcoidosis and comorbidities is critical in CS patients.

Limitations

As this is an observational study, there is a potential risk for selection bias. Higher rates of extracardiac involvement and comorbilities in black CS patients may reflect biases in how Black patients were initially diagnosed with CS. Importantly, disadvantaged Black patients may not be referred to or evaluated by a specialty center, which may result in underrepresentation of this population in our cohort. This referral bias may partially explain why no significant differences in outcomes between Black and White patients in our study. Similarly, higher proportion of men with CS compared to women may be influenced by referral bias specific to each center. Additionally, the data were collected from large specialty centers, which may not reflect outcomes seen in community centers. This limitation could affect the applicability and generalizability of our findings to CS in community-based populations. Furthermore, the CSC registry predominantly included patients from the United States and the United Kingdom, potentially limiting the applicability of the findings to patients in other regions of the world. Our analysis focused on Black and White patients; other races including Hispanics and Asians were not represented enough to draw conclusions. Nonetheless, to our knowledge, this in one of the largest analyses of Black CS patients.

Conclusion

This large cohort study revealed that Black patients with cardiac sarcoidosis had significantly higher rates of comorbidities but exhibited similar outcomes to White patients with the condition. These findings emphasize the critical role of managing comorbidities in Black patients with cardiac sarcoidosis. However, the potential influence of ascertainment bias cannot be excluded.

Supplementary Material

Tables S1-S2

What Is Known?

• Black patients with systemic sarcoidosis are more likely to have multiorgan involvement at diagnosis and face worse outcomes including more severe disease progression, higher mortality rates, and increased rates of hospitalization compared to White patients.

What the Study Adds?

• The Cardiac Sarcoidosis Consortium is the largest international multi-center registry for cardiac sarcoidosis and has diverse patient representation.

• Our study revealed that, despite Black patients with cardiac sarcoidosis being diagnosed at a younger age, experiencing more comorbidities, having a lower baseline left ventricular ejection fraction, and having increased involvement of the lungs, skin, and eyes, their clinical cardiac sarcoidosis outcomes are similar to those of White patients with cardiac sarcoidosis. Nonetheless, we cannot exclude he role of ascertainment bias of these findings.

Nonstandard Abbreviations and Acronyms

CKD

Chronic kidney disease

COPD

chronic obstructive pulmonary disease

CS

cardiac sarcoidosis

ICD

Implantable cardioverter-defibrillator

PHT

Pulmonary hypertension

LVAD

left ventricular assistant device

LVEF

left ventricylar ejection fraction

VT

ventricular tachycardia

VF

ventricular fibrillation