Atrial Arrhythmias in Clinically Manifest Cardiac Sarcoidosis: Incidence, Burden, Predictors, and Outcomes.

Background Recent data have suggested a substantial incidence of atrial arrhythmias (AAs) in cardiac sarcoidosis (CS). Our study aims were to first assess how often AAs are the presenting feature of previously undiagnosed CS. Second, we used prospective follow-up data from implanted devices to investigate AA incidence, burden, predictors, and response to immunosuppression. Methods and Results This project is a substudy of the CHASM-CS (Cardiac Sarcoidosis Multicenter Prospective Cohort Study; NCT01477359). Inclusion criteria were presentation with clinically manifest cardiac sarcoidosis, treatment-naive status, and implanted with a device that reported accurate AA burden. Data were collected at each device interrogation visit for all patients and all potential episodes of AA were adjudicated. For each intervisit period, the total AA burden was obtained. A total of 33 patients met the inclusion criteria (aged 56.1±7.7 years, 45.5% women). Only 1 patient had important AAs as a part of the initial CS presentation. During a median follow-up of 49.1 months, 11 of 33 patients (33.3%) had device-detected AAs, and only 2 (6.1%) had a clinically significant AA burden. Both patients had reduced burden after CS was successfully treated and there was no residual fluorodeoxyglucose uptake on positron emission tomography scan. Conclusions First, we found that AAs are a rare presenting feature of clinically manifest cardiac sarcoidosis. Second, AAs occurred in a minority of patients at follow-up; the burden was very low in most patients. Only 2 patients had clinically significant AA burden, and both had a reduction after CS was treated. Registration URL: https://www.clini​caltr​ials.gov; unique identifier NCT01477359.

Treatment with corticosteroids is associated with an increase in ventricular arrhythmia burden in patients with clinically manifest cardiac sarcoidosis: Insights from implantable cardioverter-defibrillator diagnostics.

INTRODUCTION: We sought to explore the relationship between ventricular tachycardia (VT) and premature ventricular complex (PVC) burden (from implantable cardioverter-defibrillator diagnostics), before and during corticosteroid use in patients with newly diagnosed clinically manifest cardiac sarcoidosis (CS). METHODS: A single-centre, prospective cohort study was performed in consecutive patients who met all of the following criteria: (1) presentation with clinically manifest CS, (2) abnormal myocardial fluoro-deoxyglucose (FDG) uptake on positron emission tomography scan, (3) plan for implantation with implantable cardioverter-defibrillator device that reports accurate PVC count, (4) plan to initiate corticosteroids after the device healing period. Data were collected during each device interrogation visit for all patients in the study. For each inter-visit period the total number of episodes of VT-sustained and nonsustained, and the number of PVCs was obtained. Each inter-visit period was classified into one of the following three periods: (1) New diagnosis of treatment-naive active disease without corticosteroids during the period. (2) Known treatment-naive active disease with corticosteroids initiated during the inter-visit period. (3) On corticosteroid therapy during the entire period. RESULTS: A total of 20 patients with a mean age of 59.7 ± 7.7 years were recruited and 82 inter-visit periods were analyzed. All patients were corticosteroid responders based on FDG uptake. The maximum left ventricular standardized uptake value was 11.14 ± 5.19 before corticosteroid initiation and 4.07 ± 0.88 after (p < .001). Patients with active untreated CS had an average of 496.4 ± 879.1 PVCs per day. After treatment with corticosteroids, the average PVC count increased to 1332.4 ± 1865.7/day during Period 2 (p = .036) and to 1590.1 ± 2362.2 per day during Period 3 (p = .008). There was also a statistically significant increase in episodes of nonsustained ventricular tachycardia (NSVT) before and after treatment with corticosteroids (p = .017). There were too few episodes of sustained ventricular arrhythmia to analyze. Overall, 18 out of 20 patients (90%) had an increase in PVC burden after corticosteroid initiation. CONCLUSION: This study demonstrated, on average, a threefold increase in daily PVC count in clinically manifest CS patients during treatment with corticosteroids compared to pretreatment. There was also a significant increase in episodes of NSVT. Clinicians and patients with active manifest CS should be aware that corticosteroids are unlikely to lead to a reduction in the burdens of PVC and NSVT.

Is there an association between clinical presentation and the location and extent of myocardial involvement of cardiac sarcoidosis as assessed by ¹8F- fluorodoexyglucose positron emission tomography?

BACKGROUND: Positron emission tomography using (18)F-Fluorodeoxyglucose (FDG) is an emerging modality for diagnosis of cardiac sarcoidosis (CS). We compared the location and degree of FDG uptake in CS patients presenting with either advanced atrioventricular block (AVB) or ventricular tachycardia (VT). METHODS AND RESULTS: We included consecutive patients who presented with either AVB or VT with a diagnosis of CS. A cohort of patients with clinically silent CS was included as controls. FDG activity was quantified as standardized uptake values (SUV) and both the overall mean left ventricular (LV) SUV as well as the Maximum Mean Segmental SUV was recorded for each patient. Receiver operator characteristic (ROC) analysis was performed to identify cutoff SUV values that best identified patients with VT. A total of 27 patients with CS were included (13 females; mean age, 56 ± 8 years; 8 VT, 12 AVB, and 7 controls). Both mean LV SUV and Max SUV in CS patients presenting with VT were significantly higher compared with those with AVB (mean SUV: VT median 5.33, range 4.7-9.35 versus AVB median 2.48, range 0.86-8.59, P=0.016; max SUV: VT median 11.07, range 9.24-14.4 versus AVB median 5.63, range 3.42-15.71, P=0.005) and compared with controls. There was no significant difference in SUV values between AVB patients and controls. ROC analysis for identification of patients with VT showed AUCs of 0.93 and 0.895 for a mean LV SUV of >3.42 and a max SUV >8.56, respectively (P<0.001). CONCLUSIONS: CS patients with VT displayed significantly higher FDG uptake when compared with those with AVB and asymptomatic controls. Further prospective studies are required to evaluate this finding.

Reduced septal glucose metabolism predicts response to cardiac resynchronization therapy.

BACKGROUND: Up to 50% of patients do not respond to Cardiac Resynchronization Therapy (CRT). Recent work has focused on quantifying mechanical dyssynchrony and left ventricular scar. Septal reverse-mismatch (R-MM) (reduced FDG uptake vs perfusion) has been observed in patients with cardiomyopathy and prolonged QRS duration. We hypothesized that a greater quantity of septal R-MM would indicate a greater potential for reversibility of the cardiomyopathy, when the dyssynchrony is improved with CRT. Therefore, this study's objective was to assess whether greater septal R-MM pattern predicts response to CRT. METHODS AND RESULTS: Forty-nine patients had pre-implant Rubidium-82 and Fluorine-18-fluorodeoxyglucose PET scanning. Total and regional left ventricular scar size and extent of R-MM were calculated. Response to CRT was defined as ≥10% improvement in left ventricular end-systolic volume or ≥5% absolute ejection fraction improvement. In the non-ischemic cardiomyopathy subset non-responders had significantly less septal R-MM than responders (13.1% compared to 27.1%, P = .012). There were correlations between the extent of septal R-MM and the increase in ejection fraction (r = 0.692, P = .0004) and reduction in left ventricular end-systolic volume (r = -0.579, P = .004). For each 5% absolute increase in extent of septal R-MM the odds ratio of being a responder was 2.17 (95% CI 1.15, 4.11, P = .017). Extent of septal R-MM displayed high sensitivity and specificity (area under curve = 0.855, P = .017) to predict response. CONCLUSIONS: In patients with non-ischemic cardiomyopathy, greater extent of septal glucose metabolic R-MM pattern, predicted response to CRT. This parameter may be useful for identifying patients who benefit from CRT.

Acute and chronic effects of continuous positive airway pressure therapy on left ventricular systolic and diastolic function in patients with obstructive sleep apnea and congestive heart failure.

BACKGROUND: Obstructive sleep apnea (OSA) may contribute to the pathogenesis of congestive heart failure (CHF). Nocturnal continuous positive airway pressure (CPAP) therapy can alleviate OSA and may have a role in the treatment of CHF patients. OBJECTIVES: To investigate the acute and chronic effects of CPAP therapy on left ventricular systolic function, diastolic function and filling pressures in CHF patients with OSA. METHODS: Twelve patients with stable CHF (New York Heart Association II or III, radionuclide ejection fraction lower than 40%) underwent overnight polysomnography to detect OSA. In patients with OSA (n=7), echocardiography was performed at baseline (awake, before and during acute CPAP administration) and after 6.9+/-3.3 weeks of nocturnal CPAP therapy. Patients without OSA (n=5) did not receive CPAP therapy, but underwent a baseline and follow-up echocardiogram. RESULTS: In CHF patients with OSA, acute CPAP administration resulted in a decrease in stroke volume (44+/-15 mL versus 50+/-14 mL, P=0.002) and left ventricular ejection fraction ([LVEF] 34.8+/-5.0% versus 38.4+/-3.3%, P=0.006) compared with baseline, but no change in diastolic function or filling pressures (peak early diastolic mitral annular velocity [Ea]: 6.0+/-1.6 cm/s versus 6.3+/-1.6 cm/s, P not significant; peak early filling velocity to peak late filling velocity [E/A] ratio: 1.05+/-0.74 versus 1.00+/-0.67, P not significant; E/Ea ratio: 10.9+/-4.1 versus 11.3+/-4.1, P not significant). In contrast, chronic CPAP therapy resulted in a trend to an increase in stroke volume (59+/-19 mL versus 50+/-14 mL, P=0.07) and a significant increase in LVEF (43.4+/-4.8% versus 38.4+/-3.3%, P=0.01) compared with baseline, but no change in diastolic function or filling pressures (Ea: 6.2+/-1.2 cm/s versus 6.3+/-1.6 cm/s, P not significant; E/A ratio: 1.13+/-0.61 versus 1.00+/-0.67, P not significant; E/Ea ratio: 12.1+/-2.7 versus 11.3+/-4.1, P not significant). There was no change in left ventricular systolic function, diastolic function or filling pressures at follow-up in CHF patients without OSA. CONCLUSIONS: Acute CPAP administration decreased stroke volume and LVEF in stable CHF patients with OSA. In contrast, chronic CPAP therapy for seven weeks improved left ventricular systolic function, but did not affect diastolic function or filling pressures. The potential clinical implications of the discrepant effects of CPAP therapy on left ventricular systolic and diastolic function in CHF patients with OSA warrant further study.

Positron emission tomography: a study of PET test-related anxiety.

The objective of this study was to determine whether sending an information pamphlet to patients scheduled for a PET test two weeks prior to the appointment date significantly reduced patient anxiety and increased patient knowledge about the test. This study was conducted as a randomized controlled trial in which patients were randomly allocated to receive a mailed information pamphlet (intervention) or no mailed pamphlet two weeks prior to the appointment (usual care). The results of this study suggested that sending information pamphlets to patients scheduled for PET scans did not decrease pre-test levels of patient anxiety or result in increased patient knowledge about test preparation and procedures.