Table 1.

Secondary Database Studies on Cardiovascular Mortality in Sarcoidosiss

Study	Journal	Inclusion criteria	Patient cohort	Years studied	Name of database	Cohort size	Follow‐up time	Outcomes
Tan et al 2024 ⁴	Journal of the American Heart Association	Age ≥25 y Cause of death: CVD (excluding IHD) with comorbid sarcoidosis	United States	1999–2020	Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research	3301 Cardiovascular deaths with comorbid sarcoidosis	22 y	AAMR increased from 0.53 (95% CI, 0.43–0.65) per 1 000 000 individuals in 1999 to 0.87 (95% CI, 0.75–0.98) per 1 000 000 individuals in 2020. AAMR was higher in women than men (0.77 [95% CI, 0.74–0.81] vs 0.58 [95% CI, 0.55–0.62]). AAMR was higher in Black ancestry than White ancestry (3.23 [95% CI, 3.07–3.39] vs 0.39 [95% CI, 0.37–0.41]). Highest percentage of mortality was observed in the 55–64 y age cohort in men (23.11%) and women (21.81%). South region had highest AAMR compared with other regions (0.78 [95% CI, 0.74–0.82]). AAMR was higher in urban regions than in rural areas (0.72 [95% CI, 0.69–0.74] vs 0.62 [95% CI, 0.56–0.68] per 1 000 000 individuals). Highest AAMR was seen in the large central metro region (0.90 [95% CI, 0.84–0.95] per 1 000 000 individuals). AAMR was highest in most vulnerable group vs least vulnerable group (social vulnerability index: 0.91 [95% CI, 0.79–1.03]) vs (0.61 [95% CI, 0.51–0.72]).
Casipit et al 2023 ⁵	International Journal of Cardiology. Heart & Vasculature	Hospitalized patients with sarcoidosis	United States	2018–2020	NIS database	36 864 Hospitalizations	Hospital admission	Concomitant heart failure was not an independent predictor of in‐hospital mortality or LOS. Age (aOR, 1.04 [95% CI, 1.03–1.06]; P≤0.001) and arrhythmia burden (aOR, 2.08 [95% CI, 1.47–2.95]; P≤0.001), specifically VT and VF, were independently associated with in‐hospital mortality among patients with sarcoidosis.
Dai et al 2022 ⁶	Cardiovascular Digital Health Journal	Patients with sarcoidosis admitted with acute HF	United States	2016–2019	NIS database	4659 Hospitalizations	Hospital admission	Comorbid arrhythmias, age, and fluid electrolyte disorders were the strongest factors in predicting in‐hospital mortality.
Tan et al 2022 ⁷	Journal of Cardiovascular Electrophysiology	Hospitalized patients with sarcoidosis ≥18 with VT	United States	2022–2018	NIS database	3220 Hospitalizations	Hospital admission	Patients who had catheter ablation were younger, predominantly male, and White. Although not significant, in‐hospital mortality was lower in catheter ablation (1.9% vs 6.6%, P=0.08). Catheter ablation procedure‐related complications occurred in 9.1%. Predictors of in‐hospital mortality in cohort with catheter ablation included congestive heart failure (OR, 13.2 [95% CI, 1.7–104.2]) and mild to moderate renal disease (OR, 3.9 [95% CI, 1.1–13.3]).
Taduru et al 2022 ⁸	Indian Heart Journal	Patients with CS	United States	2016–2017	NIS database	2420 Hospitalizations	Hospital admission	Most admissions occurred due to VT (12.8%), followed by myocarditis (9.9%) with a mean LOS of 7 d. The overall incidence of in‐hospital mortality was 2.5%.
Higgins et al 2022 ⁹	American Heart Journal	Propensity‐matched patients with CS and NICM with ICD	United States	April 1, 2010 and December 31, 2015	National Cardiovascular Data Registry ICD Registry	1638 CS and 8190 NICM	2 y	Mortality following ICD implantation was similar in CS and NICM (9.0% vs 9.3%, P=0.72). Presence of heart failure (HR, 1.92 [95% CI, 1.44–3.22]), NYHA class III (HR, 1.68 [95% CI 1.16–2.45]), NYHA class IV (HR, 3.08 [95% CI, 1.49–6.39]), AF/flutter (HR, 1.66 [95% CI, 1.17–2.35]), chronic lung disease (HR, 1.64 [95% CI, 1.17–2.29]), creatinine >2.0 mg/dL (HR, 4.07 [95% CI, 2.63–6.30]), and paced rhythm (HR, 2.66 [95% CI, 1.07–6.59]) were predictors of increased 2‐year mortality among patients with CS with ICDs.
Jackson et al 2022 ¹⁰	Journal of Heart and Lung Transplantation	Patients with CS and and non‐CS undergoing OHT	United States	1987–2019	United Network for Organ Sharing Registry	63 947 Patients, which included 227 patients with CS	33 y	Patients with CS and non‐CS had similar post‐OHT survival (HR, 0.86 [95% CI, 0.59–1.3], P=0.446), odds of graft failure (HR, 0.849 [95% CI, 0.58–1.23], P=0.394), hospitalizations for infection, and posttransplant malignancy. Patients with CS had lower odds of rejection (OR, 0.558 [95% CI, 0.315–0.985], P=0.0444).
Gonen et al 2022 ¹¹	Journal of Clinical Medicine	Patients with sarcoidosis and matched nonsarcoidosis controls	Israel	2000–2016	Database of Clalit Health Services	3750 Patients with sarcoidosis and 18 139 controls	15 y	Patients with sarcoidosis were also at increased risk for all‐cause mortality compared with controls (multivariate model, adjusted HR, 1.93 [95% CI, 1.76–2.13]). Association between sarcoidosis and IHD was demonstrated by a multivariate analysis (aOR, 1.5 [95% CI, 1.36–1.66]).
Narasimhan et al 2021 ¹²	Journal of the American College of Cardiology. Clinical Electrophysiology	Patients with sarcoidosis ≥18 y and exclusion of IHD	United States	2005–2017	NIS database	803 557 Hospitalizations	Hospital admission	0.5% had SCA. Higher rates of SCA were noted in patients aged <40 y (OR, 1.012 [95% CI, 1.006–1.02]; P=0.001), Black individuals (OR, 1.63 [95% CI, 1.39–1.92]; P=0.001), and those with AF (OR, 1.69 [95% CI, 1.39–2.06]; P=0.001), heart failure, both HF with reserved ejection fraction (OR, 2.37[ 95% CI, 1.77–3.17]; P=0.001) and HF with preserved ejection fraction (OR, 1.88 [95% CI, 1.48–2.39]; P=0.001), Second‐degree atrioventricular block (OR, 3.22 [95% CI, 1.32–7.86]; P=0.001), third‐degree atrioventricular block (OR, 7.12 [95% CI, 4.38–10.57]; P=0.001), right BBB (OR, 2.59 [95% CI, 1.65–4.08]; P=0.001), left BBB (OR, 2.13 [95% CI, 1.13–4.02]; P=0.02), and fascicular blocks (OR, 2.75 [95% CI, 1.35–5.59]; P=0.005).
Larsson et al 2020 ¹³	Sarcoidosis, Vasculitis, and Diffuse Lung Diseases	Patients with sarcoidosis aged 20–65 y old with matched controls	Sweden	2007–2016	Swedish National Patient Register and Cause of Death Register	7828 Cases with sarcoidosis and 15 656 controls	Hospital admissions	Sarcoidosis was associated with increased mortality compared with controls (HR, 1.88 [95% CI, 1.56–2.26]) and the Swedish general population (standardized mortality ratio 1.75 [95% CI, 1.52–2.00]). Sarcoidosis was associated with increased hospital admissions for cardiomyopathy, heart failure, pulmonary embolism, and malignant neoplasm.
Jeon et al 2020 ¹⁴	Sarcoidosis, V asculitis, and D iffuse L ung Diseases	Patients with sarcoidosis	Korea	2008–2015	National Health Insurance database	3259 New patients with sarcoidosis	8 y	The average annual incidence of sarcoidosis was 0.81 per 100 000. The annual mortality rate was 9.26 per 1000 person‐years. Mortality rate was significantly higher than those of the general population (standardized mortality rate, 1.91 [95% CI, 1.62–2.25]). The most common cause of death was cancer (41.7%), followed by respiratory disease (13.1%), sarcoidosis (13.1%), and heart disease (8.3%).
Yafasova et al 2020 ¹⁵	Journal of the American College of Cardiology	Patients with sarcoidosis ≥18 y and matched controls	Denmark	1996–2016	Danish nationwide registries	11 834 Patients with sarcoidosis and 47 336 controls	Median 8.2 y	All‐cause mortality was higher in patients with sarcoidosis vs controls (10.88% [95% CI, 10.23%–11.55%] vs 7.43% [95% CI, 7.15%–7.72%]). Cardiac outcomes were higher in patients with sarcoidosis vs controls (HF, 3.18% [95% CI, 2.83%–3.57%] vs 1.72% [95% CI, 1.58%–1.86%]; composite of ICD implantation, ventricular arrhythmias, and cardiac arrest: 0.96% [95% CI, 0.77%–1.18%] vs 0.45% [95% CI, 0.38%–0.53%]; composite of pacemaker implantation, atrioventricular block, and sinoatrial dysfunction: 0.94% [95% CI, 0.75%–1.16%] vs 0.51% [95% CI, 0.44%–0.59%]; AF or flutter: 3.44% [95% CI, 3.06%–3.84%] vs 2.66% [95% CI, 2.49%–2.84%]).
Durugu et al 2020 ¹⁶	Cureus	Patients with sarcoidosis age ≥18 y without IHD	United States	2010–2014	NIS database	308 064 Hospitalizations	Hospital admission	In‐hospital mortality was higher in women (64% vs 36%; P<0.001). Women had higher rates of AF (59% vs 41%; P<0.001). Men had a higher burden of VT (55% vs 45%; P<0.001), more ICD (56% vs 44%; P<0.001), and cardiac resynchronization therapy defibrillator implantations (58% vs 42%; P=0.025) , and more endomyocardial biopsies (55% vs 45%; P<0.001).
Salama et al 2020 ¹⁷	Cardiology Journal	Hospitalizations with and without concomitant sarcoidosis	United States	2012–2014	NIS database	18 013 878 Hospitalizations (0.26% had sarcoidosis)	Hospital admission	Patients with sarcoidosis had more prevalent VT, VF, and SCA (VT: 2.29% vs 1.22%; P<0.001, VF: 0.25% vs 0.21%; P<0.001 and SCA: 0.72% vs 0.6% [P<0.001]). In unadjusted analysis, comorbidities were more common in sarcoidosis (diabetes: 31.6% vs 21.25%; P<0.001; hypertension: 65.2% vs 51.74%; P<0.001; chronic kidney disease: 21.09% vs 14.02%; P<0.001; HF: 24.87% vs 15%; P<0.001; acute coronary syndrome: 4.32% vs 3.35%; P<0.001)
Desai et al 2018 ¹⁸	Annals of Translational Medicine	Patients with sarcoidosis with and without arrhythmias	United States	2010–2014	NIS database	369 285 Hospitalizations	Hospital admission	19.9% had arrythmias, which included a male preponderance. AF (10.97%) and VT (1.97%) were most common. The group with sarcoid‐arrhythmia had significantly higher mortality (3.7% vs 1.5%; aOR, 2.06), mean hospital LOS (6.4 vs 5.2 d) and hospital charges ($64 118 vs $41 565) compared with the group without arrhythmia (P<0.001).
Patel et al 2018 ¹⁹	Journal of the American Heart Association	Patients with sarcoidosis without IHD	United States	2005–2014	NIS database	609 051 Sarcoidosis hospitalizations	Hospital admission	The number of sarcoidosis hospitalizations increased from 2005 through 2014 (138 vs 175 per 100 000; P _trend<0.001). Unadjusted in‐hospital mortality decreased (6.5 to 4.9 per 100 sarcoidosis hospitalizations; P _trend<0.001). Black race was associated with increased risk of in‐hospital mortality (OR, 1.21 [95% CI, 1.16–1.27]; P<0.001). HF (≈16%) and arrhythmias (≈15%) were the most common presentations. ICD placement was low (≈7.5 per 1000 sarcoidosis hospitalizations)
Guo et al 2017 ²⁰	Cardiology Journal	Patients with CS	United States	2005–2011	NIS database	13 045 Hospitalizations	Hospital admission	The annual admissions of CS increased from 1108 in 2005 to 2182 in 2011. The proportions of patients with CS with severe comorbidities, VT, VF, and HF all increased from 2005 to 2011. However, the in‐hospital mortality rate declined (P=0.0462). Overall, in‐hospital mortality was 2.3%.
Te et al 2017 ²¹	International Journal of Cardiology	Patients with sarcoidosis matched with controls (without structural heart disease)	Taiwan	2000–2004	National Health Insurance Research Database	2237 Patients with sarcoidosis and 2237 controls	Mean 11.4 y	Cohort with sarcoidosis had higher VT incidence (0.94% [85 per 100 000 person‐years] vs 0.09% [8 per 100 000 person‐years], HR, 12.7 [95% CI, 2.82–56.9]; P<0.001). Mortality and ICD implantation was similar between the 2 groups.
Jamilloux et al 2016 ²²	European R espiratory Journal	Death certificates mentioning sarcoidosis	France	2002–2011	French Epidemiological Centre for the Medical Causes of Death	1662	10 y	AAMR was 3.6 per million and significantly increased over the study period (P=0.006). The in‐hospital deaths were higher for sarcoidosis than general population (66.5% vs 49%). Sarcoidosis was most common underlying cause of death with main other mentions being chronic respiratory and CVDs. The overall observed/expected ratio was >1 for infectious disease, tuberculosis, and chronic respiratory disease, and <1 for neoplasms. There was a north–south gradient in AAMR at the country level. The mean age at death was 70.4 y (vs 76.2 y for the general population). The ratio (range) of women to men was 1.3 (0.9–1.8). Compared with the general population, sarcoidosis‐related death before the age of 65 y was statistically more frequent among men (P=0.002) and was statistically more frequent for women aged ≥65 y (P<0.001).
Swigris et al 2011 ²³	American Journal of Respiratory and Critical Care Medicine	Death certificates mentioning sarcoidosis	United States	1988–2007	National Center for Health Statistics	46 450 489 Deaths including 23 679 with sarcoidosis	20 y	AAMR was 4.32 per 1 000 000 population. AAMR for sarcoidosis increased 50.5% in women and 30.1% in men, with greatest increase in non‐Hispanic Black patients. For any year, mortality rate was nearly 10‐fold higher for non‐Hispanic Black than White patients. Mortality rates rose most in decedents 55 y or older. Most common cause of death was sarcoidosis itself. Younger decedents with sarcoidosis and pulmonary fibrosis were more likely to be Black (P=0.001), and younger decedents with sarcoidosis (25–44y) were more likely than similarly aged decedents in the general population to have a cardiac cause (coded as ischemia or myocardial infarction, sudden cardiac death or arrhythmia, congestive HF, or cardiomyopathy) contributing to death. However, for most other age strata, sarcoidosis was protective against having a cardiac cause contribute to death.

AAMR indicates age‐adjusted mortality rate; AF, atrial fibrillation; aOR, adjusted odds ratio; BBB, bundle‐branch block; CS, cardiac sarcoidosis; CVD, cardiovascular disease; HF, heart failure; HR, hazard ratio; ICD, implantable cardioverter defibrillator; IHD, ischemic heart disease; LOS, length of stay; NICM, nonischemic cardiomyopathy; NIS, National Inpatient Sample Database; NYHA, New York Heart Association; OHT, orthotopic heart transplantation; OR, odds ratio; SCA, sudden cardiac arrest; VF, ventricular fibrillation; and VT, ventricular tachycardia.