Risk of Adverse Outcomes Associated With Cardiac Sarcoidosis Diagnostic Schemes.

BACKGROUND: Multiple cardiac sarcoidosis (CS) diagnostic schemes have been published. OBJECTIVES: This study aims to evaluate the association of different CS diagnostic schemes with adverse outcomes. The diagnostic schemes evaluated were 1993, 2006, and 2017 Japanese criteria and the 2014 Heart Rhythm Society criteria. METHODS: Data were collected from the Cardiac Sarcoidosis Consortium, an international registry of CS patients. Outcome events were any of the following: all-cause mortality, left ventricular assist device placement, heart transplantation, and appropriate implantable cardioverter-defibrillator therapy. Logistic regression analysis evaluated the association of outcomes with each CS diagnostic scheme. RESULTS: A total of 587 subjects met the following criteria: 1993 Japanese (n = 310, 52.8%), 2006 Japanese (n = 312, 53.2%), 2014 Heart Rhythm Society (n = 480, 81.8%), and 2017 Japanese (n = 112, 19.1%). Patients who met the 1993 criteria were more likely to experience an event than patients who did not (n = 109 of 310, 35.2% vs n = 59 of 277, 21.3%; OR: 2.00; 95% CI: 1.38-2.90; P < 0.001). Similarly, patients who met the 2006 criteria were more likely to have an event than patients who did not (n = 116 of 312, 37.2% vs n = 52 of 275, 18.9%; OR: 2.54; 95% CI: 1.74-3.71; P < 0.001). There was no statistically significant association between the occurrence of an event and whether a patient met the 2014 or the 2017 criteria (OR: 1.39; 95% CI: 0.85-2.27; P = 0.18 or OR: 1.51; 95% CI: 0.97-2.33; P = 0.067, respectively). CONCLUSIONS: CS patients who met the 1993 and the 2006 criteria had higher odds of adverse clinical outcomes. Future research is needed to prospectively evaluate existing diagnostic schemes and develop new risk models for this complex disease.

Acute Effects of Coffee Consumption on Health among Ambulatory Adults.

BACKGROUND: Coffee is one of the most commonly consumed beverages in the world, but the acute health effects of coffee consumption remain uncertain. METHODS: We conducted a prospective, randomized, case-crossover trial to examine the effects of caffeinated coffee on cardiac ectopy and arrhythmias, daily step counts, sleep minutes, and serum glucose levels. A total of 100 adults were fitted with a continuously recording electrocardiogram device, a wrist-worn accelerometer, and a continuous glucose monitor. Participants downloaded a smartphone application to collect geolocation data. We used daily text messages, sent over a period of 14 days, to randomly instruct participants to consume caffeinated coffee or avoid caffeine. The primary outcome was the mean number of daily premature atrial contractions. Adherence to the randomization assignment was assessed with the use of real-time indicators recorded by the participants, daily surveys, reimbursements for date-stamped receipts for coffee purchases, and virtual monitoring (geofencing) of coffee-shop visits. RESULTS: The mean (±SD) age of the participants was 39±13 years; 51% were women, and 51% were non-Hispanic White. Adherence to the random assignments was assessed to be high. The consumption of caffeinated coffee was associated with 58 daily premature atrial contractions as compared with 53 daily events on days when caffeine was avoided (rate ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). The consumption of caffeinated coffee as compared with no caffeine consumption was associated with 154 and 102 daily premature ventricular contractions, respectively (rate ratio, 1.51; 95% CI, 1.18 to 1.94); 10,646 and 9665 daily steps (mean difference, 1058; 95% CI, 441 to 1675); 397 and 432 minutes of nightly sleep (mean difference, 36; 95% CI, 25 to 47); and serum glucose levels of 95 mg per deciliter and 96 mg per deciliter (mean difference, -0.41; 95% CI, -5.42 to 4.60). CONCLUSIONS: In this randomized trial, the consumption of caffeinated coffee did not result in significantly more daily premature atrial contractions than the avoidance of caffeine. (Funded by the University of California, San Francisco, and the National Institutes of Health; CRAVE ClinicalTrials.gov number, NCT03671759.).

Outcomes Associated With Catheter Ablation of Ventricular Tachycardia in Patients With Cardiac Sarcoidosis.

Importance: Ventricular tachycardia (VT) is associated with high mortality in patients with cardiac sarcoidosis (CS), and medical management of CS-associated VT is limited by high failure rates. The role of catheter ablation has been investigated in small, single-center studies. Objective: To investigate outcomes associated with VT ablation in patients with CS. Design, Setting, and Participants: This cohort study from the Cardiac Sarcoidosis Consortium registry (2003-2019) included 16 tertiary referral centers in the US, Europe, and Asia. A total of 158 consecutive patients with CS and VT were included (33% female; mean [SD] age, 52 [11] years; 53% with ejection fraction [EF] <50%). Exposures: Catheter ablation of CS-associated VT and, as appropriate, medical treatment. Main Outcomes and Measures: Immediate and short-term outcomes included procedural success, elimination of VT storm, and reduction in defibrillator shocks. The primary long-term outcome was the composite of VT recurrence, heart transplant (HT), or death. Results: Complete procedural success (no inducible VT postablation) was achieved in 85 patients (54%). Sixty-five patients (41%) had preablation VT storm that did not recur postablation in 53 (82%). Defibrillator shocks were significantly reduced from a median (IQR) of 2 (1-5) to 0 (0-0) in the 30 days before and after ablation (P < .001). During median (IQR) follow-up of 2.5 (1.1-4.9) years, 73 patients (46%) experienced VT recurrence and 81 (51%) experienced the composite primary outcome. One- and 2-year rates of survival free of VT recurrence, HT, or death were 60% and 52%, respectively. EF less than 50% and myocardial inflammation on preprocedural 18F-fluorodeoxyglucose positron emission tomography were significantly associated with adverse prognosis in multivariable analysis for the primary outcome (HR, 2.24; 95% CI, 1.37-3.64; P = .001 and HR, 2.93; 95% CI, 1.31-6.55; P = .009, respectively). History of hypertension was associated with a favorable long-term outcome (adjusted HR, 0.51; 95% CI, 0.28-0.92; P = .02). Conclusions and Relevance: In this observational study of selected patients with CS and VT, catheter ablation was associated with reductions in defibrillator shocks and recurrent VT storm. Preablation LV dysfunction and myocardial inflammation were associated with adverse long-term prognosis. These data support the role of catheter ablation in conjunction with medical therapy in the management of CS-associated VT.

Heart Failure, Atrioventricular Block, and Ventricular Tachycardia in Sarcoidosis.

Background Sarcoidosis is a granulomatous disease usually affecting the lungs, although cardiac morbidity may be common. The risk of these outcomes and the characteristics that predict them remain largely unknown. This study investigates the epidemiology of heart failure, atrioventricular block, and ventricular tachycardia among patients with and without sarcoidosis. Methods and Results We identified California residents aged ≥21 years using the Office of Statewide Health Planning and Development ambulatory surgery, emergency, or inpatient databases from 2005 to 2015. The risk of sarcoidosis on incident heart failure, atrioventricular block, and ventricular tachycardia were each determined. Linkage to the Social Security Death Index was used to ascertain overall mortality. Among 22 527 964 California residents, 19 762 patients with sarcoidosis (0.09%) were identified. Sarcoidosis was the strongest predictor of heart failure (hazard ratio [HR], 11.2; 95% CI, 10.7-11.7), atrioventricular block (HR, 117.7; 95% CI, 103.3-134.0), and ventricular tachycardia (HR, 26.1; 95% CI, 24.2-28.1) identified among all risk factors. The presence of any cardiac involvement best predicted each outcome. Approximately 22% (95% CI, 18%-26%) of the relationship between sarcoidosis and increased mortality was explained by the presence of at least 1 of these cardiovascular outcomes. Conclusions The magnitude of risk associated with sarcoidosis as a predictor of heart failure, atrioventricular block, and ventricular tachycardia, exceeds all established risk factors. Surveillance for and anticipation of these outcomes among patients with sarcoidosis is indicated, and consideration of a sarcoidosis diagnosis may be prudent among patients with heart failure, atrioventricular block, or ventricular tachycardia.

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

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.

Long-Term Corticosteroid-Sparing Immunosuppression for Cardiac Sarcoidosis.

Background Long-term corticosteroid therapy is the standard of care for treatment of cardiac sarcoidosis (CS). The efficacy of long-term corticosteroid-sparing immunosuppression in CS is unknown. The goal of this study was to assess the efficacy of methotrexate with or without adalimumab for long-term disease suppression in CS, and to assess recurrence and adverse event rates after immunosuppression discontinuation. Methods and Results Retrospective chart review identified treatment-naive CS patients at a single academic medical center who received corticosteroid-sparing maintenance therapy. Demographics, cardiac uptake of 18-fluorodeoxyglucose, and adverse cardiac events were compared before and during treatment and between those with persistent or interrupted immunosuppression. Twenty-eight CS patients were followed for a mean 4.1 (SD 1.5) years. Twenty-five patients received 4 to 8 weeks of high-dose prednisone (>30 mg/day), followed by taper and maintenance therapy with methotrexate±low-dose prednisone (low-dose prednisone, <10 mg/day). Adalimumab was added in 19 patients with persistently active CS or in those with intolerance to methotrexate. Methotrexate±low-dose prednisone resulted in initial reduction (88%) or elimination (60%) of 18-fluorodeoxyglucose uptake, and patients receiving adalimumab-containing regimens experienced improved (84%) or resolved (63%) 18-fluorodeoxyglucose uptake. Radiologic relapse occurred in 8 of 9 patients after immunosuppression cessation, 4 patients on methotrexate-containing regimens, and in no patients on adalimumab-containing regimens. Conclusions Corticosteroid-sparing regimens containing methotrexate with or without adalimumab is an effective maintenance therapy in patients after an initial response is confirmed. Disease recurrence in patients on and off immunosuppression support need for ongoing radiologic surveillance regardless of immunosuppression regimen.

Cardiac sarcoidosis: Diagnosis confirmation by bronchoalveolar lavage and lung biopsy.

INTRODUCTION: The diagnosis of cardiac sarcoidosis (CS) is difficult to ascertain due to the insensitivity of endomyocardial biopsy. Current diagnostic criteria require a positive endomyocardial biopsy or extra-cardiac biopsy with clinical features suggestive of CS. Common tests for diagnosis of pulmonary sarcoidosis include bronchoalveolar lavage (BAL), lung and mediastinal lymph node (MLN) biopsies. Our objective was to determine the diagnostic utility of these tests in patients with suspected CS and without prior history of pulmonary involvement. METHODS: This retrospective cohort study included 37 patients without history of extra-cardiac sarcoidosis referred for suspected CS. All patients underwent chest computed tomography (CT) staged using the modified Scadding criteria, and had BAL, and/or lung or MLN biopsy. BAL cellular analyses with lymphocytes>15% and/or CD4/CD8 ratio≥ 4 were considered suggestive of sarcoidosis. The number of positive biopsies and BALs were compared between normal CT (Scadding stage 0) and abnormal CT (Scadding stage 1-4) groups. RESULTS: A definitive diagnosis of sarcoidosis was ascertained in 18/31 (58%) patients undergoing lung or lymph node biopsy, and a potential diagnosis in 18/27 (67%) patients with BAL CD4/CD8>4 or lymphocytes>15%. Of the 12 patients in the normal CT group, 4/10 (40%) had positive lung biopsies, and 9/12 (75%) patients had either positive biopsy or BAL criteria. CONCLUSIONS: In suspected cardiac sarcoidosis, a diagnosis of extra-cardiac sarcoidosis was ascertained in a majority of patients irrespective of degree of lung involvement on chest CT. Our results support referral for pulmonary biopsy/bronchoalveolar lavage in suspected CS to confirm the diagnosis of sarcoidosis.

Invasive Hemodynamics and Rejection Rates in Patients With Cardiac Sarcoidosis After Heart Transplantation.

BACKGROUND: Orthotopic heart transplant (OHT) is increasingly used for end-stage heart failure due to cardiac sarcoidosis (CS). However, concern regarding long-term outcomes in patients with CS after OHT persists because of multiorgan involvement. METHODS: Baseline demographics and invasive hemodynamics were measured in 12 patients with CS and 28 patients with nonischemic cardiomyopathy requiring OHT at the time of transplantation, 1 week after OHT, and in routine follow-up. Primary endpoints included changes in pulmonary artery pressure, right ventricular stroke work index, and pulmonary compliance. Secondary endpoints included degree of allograft rejection and death. RESULTS: During a mean follow-up of 73.8 months, no differences in pulmonary artery pressures, right ventricular stroke work index, or cardiac index were observed in patient with CS (n = 12) compared with those without CS (n = 28) between 1 week after OHT and the most recent follow-up. Long-term follow-up showed that pulmonary hemodynamics remained normal in the CS group. International Society for Heart and Lung Transplantation (ISHLT) 1990 grade ≥ 1a rejection occurred less frequently in the CS group (17% vs 68%, P = 0.006), and 0 of 12 patients in the CS group experienced histologic or clinical recurrence of sarcoidosis or ≥2 rejection. Patients with CS had excellent survival after OHT, with 0 deaths or significant rejection. CONCLUSIONS: Patients with CS have similar post-transplant hemodynamics as patients without CS, without evidence of right ventricular dysfunction or pulmonary hypertension. Neither significant rejection nor recurrence of sarcoid in the allograft was observed in this cohort of patients with CS. Survival is similar between patients with CS and those without CS. Heart transplant is a viable strategy in selected patients with CS with excellent outcomes.

Risk assessment of patients with clinical manifestations of cardiac sarcoidosis with positron emission tomography and magnetic resonance imaging.

BACKGROUND: Prior studies have shown that late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) and fluorodeoxyglucose (FDG) positron emission tomography (PET) confer incremental risk assessment in patients with cardiac sarcoidosis (CS). However, the incremental prognostic value of the combined use of LGE and FDG compared to either test alone has not been investigated, and this is the aim of the present study. METHODS: Retrospective observational study of 56 symptomatic patients with high clinical suspicion for CS who underwent LGE-CMR and FDG-PET and were followed for the occurrence of death and/or malignant ventricular arrhythmias (VA). RESULTS: The combination of PET and CMR yielded the following groups: 1) LGE-negative/normal-PET (n=20), 2) LGE-positive/abnormal-FDG (n=20), and 3) LGE-positive/normal FDG (n=16). After a median follow-up of 2.6years (IQR 1.2-4.1), 16 patients had events (7 deaths, 10 VA). All, but 1, events occurred in patients with LGE. LGE-positive/abnormal-FDG (7 events, HR 10.1 [95% CI 1.2-84]; P=0.03) and LGE-positive/normal-FDG (8 events, HR 13.3 [1.7-107]; P=0.015) patients had comparable risk of events compared to the reference LGE-negative/normal-PET group. In adjusted Cox-regression analysis, presence of LGE (HR 18.1 [1.8-178]; P=0.013) was the only independent predictor of events. CONCLUSION: CS patients with LGE alone or in association with FDG were at similar risk of future events, which suggests that outcomes may be driven by the presence of LGE (myocardial fibrosis) and not FDG (inflammation).

Hemophagocytic Lymphohistiocytosis Secondary to Human Immunodeficiency Virus-Associated Histoplasmosis.

Hemophagocytic lymphohistiocytosis (HLH) in immunocompromised hosts is a fulminant syndrome of immune activation with high rates of mortality that may be triggered by infections or immunodeficiency. Rapid diagnosis and treatment of the underlying disorder is necessary to prevent progression to multiorgan failure and death. We report a case of HLH in a patient with human immunodeficiency virus, disseminated histoplasmosis, Mycobacterium avium complex, and Escherichia coli bacteremia. We discuss management of acutely ill patients with HLH and treatment of the underlying infection versus initiation of HLH-specific chemotherapy.

Management of Arrhythmias in Cardiac Sarcoidosis.

The prevalence of cardiac involvement in sarcoidosis is under-recognized and is associated with multiple complications, including conduction block, arrhythmias, and sudden death. The comparative roles of common therapies have been inadequately studied. The purpose of this review is to examine the literature regarding treatments utilized to manage arrhythmias associated with cardiac sarcoidosis.

Physical, behavioral, and cognitive effects of prenatal tobacco and postnatal secondhand smoke exposure.

The purpose of this review is to examine the rapidly expanding literature regarding the effects of prenatal tobacco and postnatal secondhand smoke (SHS) exposure on child health and development. Mechanisms of SHS exposure are reviewed, including critical periods during which exposure to tobacco products appears to be particularly harmful to the developing fetus and child. The biological, biochemical, and neurologic effects of the small fraction of identified components of SHS are described. Research describing these adverse effects of both in utero and childhood exposure is reviewed, including findings from both animal models and humans. The following adverse physical outcomes are discussed: sudden infant death syndrome, low birth weight, decreased head circumference, respiratory infections, otitis media, asthma, childhood cancer, hearing loss, dental caries, and the metabolic syndrome. In addition, the association between the following adverse cognitive and behavioral outcomes and such exposures is described: conduct disorder, attention-deficit/hyperactivity disorder, poor academic achievement, and cognitive impairment. The evidence supporting the adverse effects of SHS exposure is extensive yet rapidly expanding due to improving technology and increased awareness of this profound public health problem. The growing use of alternative tobacco products, such as hookahs (a.k.a. waterpipes), and the scant literature on possible effects from prenatal and secondhand smoke exposure from these products are also discussed. A review of the current knowledge of this important subject has implications for future research as well as public policy and clinical practice.

Dual-standard reference values of left ventricular volumetric parameters by multidetector CT angiography.

BACKGROUND: The papillary and trabecular muscles constitute a significant percentage of left ventricular mass and volume. The influence of the papillary and trabecular muscles on left ventricular parameters has not been described with multidetector CT angiography. OBJECTIVE: The aims of this study are (1) to derive reference values for left ventricular volumetric parameters both including and excluding the papillary and trabecular muscles and (2) to establish the optimal segmentation method for measuring these values. METHODS: A total of 179 subjects (mean age, 55.4 ± 9 years; 102 women) without heart disease and at low risk of cardiovascular disease who underwent CT angiography were selected. Left ventricular volumes, myocardial volume, and ejection fraction were measured with epicardial and 2 endocardial trace methods, including and excluding trace for the papillary and trabecular muscles. Values of all parameters obtained by both endocardial trace methods were compared. RESULTS: Significant difference between both trace groups for all parameters on both sexes was found (P < .001). Significant differences in precision error of remeasurement were found in the including trace (3.6%) compared with the excluding trace (4.7%; P < .05) and in the epicardial trace (2.2%) compared with both endocardial traces (P < .001). CONCLUSION: The left ventricular parameters measured by CT angiography were influenced significantly by the trace method by including or excluding the papillary and trabecular muscles. The dual-standard reference values of left ventricular parameters were established, and the optimal segmentation methods were definite in considering the heart size and image quality studied with retrospective and prospective CT angiography.