Cardiovascular Magnetic Resonance Imaging Phenotypes and Long-term Outcomes in Patients With Suspected Cardiac Sarcoidosis.

Importance: In patients with sarcoidosis with suspected cardiac involvement, late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging (CMR) identifies those with an increased risk of adverse outcomes. However, these outcomes are experienced by only a minority of patients with LGE, and identifying this subgroup may improve treatment and outcomes in these patients. Objective: To assess whether CMR phenotypes based on left ventricular ejection fraction (LVEF) and LGE in patients with suspected cardiac sarcoidosis (CS) are associated with adverse outcomes during follow-up. Design, Setting, and Participants: This cohort study included consecutive patients with histologically proven sarcoidosis who underwent CMR for the evaluation of suspected CS from 2004 to 2020 with a median follow-up of 4.3 years at an academic medical center in Minnesota. Demographic data, medical history, comorbidities, medications, and outcome data were collected blinded to CMR data. Exposures: CMR phenotypes were identified based on LVEF and LGE presence and features. LGE was classified as pathology-frequent or pathology-rare based on the frequency of cardiac damage features on gross pathology assessment of the hearts of patients with CS who had sudden cardiac death or cardiac transplant. Main Outcomes and Measures: Composite of ventricular arrhythmic events and composite of heart failure events. Results: Among 504 patients (mean [SD] age, 54.1 [12.5] years; 242 [48.0%] female and 262 [52.0%] male; 2 [0.4%] American Indian or Alaska Native, 6 [1.2%] Asian, 90 [17.9%] Black or African American, 399 [79.2%] White, 5 [1.0%] of 2 or more races (including the above-mentioned categories and Native Hawaiian or Other Pacific Islander), and 2 [0.4%] of unknown race; 4 [0.8%] Hispanic or Latino, 498 [98.8%] not Hispanic or Latino, and 2 [0.4%] of unknown ethnicity), 4 distinct CMR phenotypes were identified: normal LVEF and no LGE (n = 290; 57.5%), abnormal LVEF and no LGE (n = 53; 10.5%), pathology-frequent LGE (n = 103; 20.4%), and pathology-rare LGE (n = 58; 11.5%). The phenotype with pathology-frequent LGE was associated with a high risk of arrhythmic events (hazard ratio [HR], 12.12; 95% CI, 3.62-40.57; P < .001) independent of LVEF and extent of left ventricular late gadolinium enhancement (LVLGE). It was also associated with a high risk of heart failure events (HR, 2.49; 95% CI, 1.19-5.22; P = .02) independent of age, pulmonary hypertension, LVEF, right ventricular ejection fraction, and LVLGE extent. Risk of arrhythmic events was greater with an increasing number of pathology-frequent LGE features. The absence of the pathology-frequent LGE phenotype was associated with a low risk of arrhythmic events, even in the presence of LGE or abnormal LVEF. Conclusions and Relevance: This cohort study found that a CMR phenotype involving pathology-frequent LGE features was associated with a high risk of arrhythmic and heart failure events in patients with sarcoidosis. The findings indicate that CMR phenotypes could be used to optimize clinical decision-making for treatment options, such as implantable cardioverter-defibrillators.

Association between early ventricular arrhythmias and mortality in destination vs. bridge patients on continuous flow LVAD support.

The association between ventricular arrhythmias (VAs) and mortality in patients supported by continuous flow left ventricular assist devices (LVAD) remains controversial. To evaluate the association between pre-implantation, early (≤ 30 day) post-implantation VAs and mortality in bridge to transplant (BTT) and destination therapy (DT) LVAD patients, separately. The risk factors for post LVAD VAs were also investigated. In this observational cohort study, we included 341 patients who received a first time, continuous flow LVAD between January 1st 2010 and July 30th 2018. We used Kaplan-Meier curves and multivariable cox regression analyses to study the association between VAs and mortality in the BTT and DT populations. The mean age of the cohort was 58 ± 14 years, with 82% males, 53% had ischemic cardiomyopathy, and 45% were DT. The mean follow-up was 2.2 ± 2.1 years. In both BTT and DT cohorts, pre LVAD VAs were not associated with mortality after LVAD implantation (log-rank p = 0.95 and p = 0.089, respectively). In the BTT population, early post-LVAD VAs were not statistically associated with increased mortality (log rank p = 0.072). In the DT patients, early post LVAD VAs were associated with a 67% increase in the hazards rate of mortality on LVAD support (HR 1.67 [1.05-2.65], p = 0.029). The final model was adjusted for type of cardiomyopathy, INTERMACS profile, glomerular filtration rate, post LVAD atrial fibrillation, age and cerebrovascular events. Early post-LVAD VA is common after LVAD implantation and is an independent predictor of mortality in the DT LVAD population.

Sex Differences in Patients With Suspected Cardiac Sarcoidosis Assessed by Cardiovascular Magnetic Resonance Imaging.

Background: There are few data on sex differences in suspected cardiac sarcoidosis. Methods: Consecutive patients with histologically proven sarcoidosis and suspected cardiac involvement were studied. We investigated sex differences in presenting features, cardiac involvement, and the long-term incidence of a primary composite end point of all-cause death or significant ventricular arrhythmia and secondary end points of all-cause death and significant ventricular arrhythmia. Results: Among 324 patients, 163 (50.3%) were female and 161 (49.7%) were male patients. Female patients had a greater prevalence of chest pain (37.4% versus 23.6%; P=0.010) and palpitations (39.3% versus 26.1%; P=0.016) than male patients but not dyspnea, presyncope, syncope, or arrhythmias at presentation. Female patients had a lower prevalence of late gadolinium enhancement on cardiovascular magnetic resonance imaging (20.2% versus 35.4%; P=0.003) and less often met criteria for a clinical diagnosis of cardiac sarcoidosis (Heart Rhythm Society consensus criteria, 22.7% versus 36.0%; P=0.012 and 2016 Japanese Circulation Society guideline criteria, 8.0% versus 19.3%; P=0.005), indicating lesser cardiac involvement. However, the long-term incidence of all-cause death or significant ventricular arrhythmia was not different between female and male patients (23.2% versus 23.2%; P=0.46). Among the secondary end points, the incidence of all-cause death was not different between female and male patients (20.7% versus 14.3%; P=0.51), while female patients had a lower incidence of significant ventricular arrhythmia compared with male patients (4.3% versus 13.0%; P=0.022). On multivariable analyses, sex was not associated with the primary end point (hazard ratio for female patients, 1.36 [95% CI, 0.77­2.43]; P=0.29). Conclusions: We observed distinct sex differences in patients with suspected cardiac sarcoidosis. A paradox was identified wherein female patients had a greater prevalence of chest pain and palpitations than male patients, but lesser cardiac involvement, and a similar long-term incidence of all-cause death or significant ventricular arrhythmia.

Thinking inside the box: Custom pacemaker improves device longevity in a congenital heart patient.

Patients with congenital heart disease have unique pacing challenges and often require epicardial systems. High pacing threshold is one of the major factors that decrease these systems' durability. Sometimes surgical reintervention or lead replacement is difficult or prohibitive in these patients due to repeated surgeries and extensive epicardial scar. We present a case report of a patient with Fontan physiology and chronically high epicardial lead pacing thresholds requiring frequent generator changes and a unique solution focusing on improving generator longevity.

Right Ventricular Abnormalities on Cardiovascular Magnetic Resonance Imaging in Patients With Sarcoidosis.

OBJECTIVES: This study aimed to determine the prevalence on cardiac magnetic resonance (CMR) of right ventricular (RV) systolic dysfunction and RV late gadolinium enhancement (LGE), their determinants, and their influences on long-term adverse outcomes in patients with sarcoidosis. BACKGROUND: In patients with sarcoidosis, RV abnormalities have been described on many imaging modalities. On CMR, RV abnormalities include RV systolic dysfunction quantified as an abnormal right ventricular ejection fraction (RVEF), and RV LGE. METHODS: Consecutive patients with biopsy-proven sarcoidosis who underwent CMR for suspected cardiac involvement were studied. They were followed for 2 endpoints: all-cause death, and a composite arrhythmic endpoint of sudden cardiac death or significant ventricular arrhythmia. RESULTS: Among 290 patients, RV systolic dysfunction (RVEF <40% in men and <45% in women) and RV LGE were present in 35 (12.1%) and 16 (5.5%), respectively. The median follow-up time was 3.2 years (interquartile range [IQR]: 1.6 to 5.7 years) for all-cause death and 3.0 years (IQR: 1.4 to 5.5 years) for the arrhythmic endpoint. On Cox proportional hazards regression multivariable analyses, only RVEF was independently associated with all-cause death (hazard ratio [HR]: 1.05 for every 1% decrease; 95% confidence interval [CI]: 1.01 to 1.09; p = 0.022) after adjustment for left ventricular EF, left ventricular LGE extent, and the presence of RV LGE. RVEF was not associated with the arrhythmic endpoint (HR: 1.01; 95% CI: 0.96 to 1.06; p = 0.67). Conversely, RV LGE was not associated with all-cause death (HR: 2.78; 95% CI: 0.36 to 21.66; p = 0.33), while it was independently associated with the arrhythmic endpoint (HR: 5.43; 95% CI: 1.25 to 23.47; p = 0.024). CONCLUSIONS: In this study of patients with sarcoidosis, RV systolic dysfunction and RV LGE had distinct prognostic associations; RV systolic dysfunction but not RV LGE was independently associated with all-cause death, whereas RV LGE but not RV systolic dysfunction was independently associated with sudden cardiac death or significant ventricular arrhythmia. These findings may indicate distinct implications for the management of RV abnormalities in sarcoidosis.

Assessment of the 2017 AHA/ACC/HRS Guideline Recommendations for Implantable Cardioverter-Defibrillator Implantation in Cardiac Sarcoidosis.

BACKGROUND: Implantable cardioverter-defibrillators are used to prevent sudden cardiac death in patients with cardiac sarcoidosis. The most recent recommendations for implantable cardioverter-defibrillator implantation in these patients are in the 2017 American Heart Association/American College of Cardiology/Heart Rhythm Society Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. These recommendations, based on observational studies or expert opinion, have not been assessed. We aimed to assess them. METHODS: We performed a large retrospective cohort study of patients with biopsy-proven sarcoidosis and known or suspected cardiac sarcoidosis that underwent cardiovascular magnetic resonance imaging. Patients were followed for a composite end point of significant ventricular arrhythmia or sudden cardiac death. The discriminatory performance of the Guideline recommendations was tested using time-dependent receiver operating characteristic analyses. The optimal cutoff for the extent of late gadolinium enhancement predictive of the composite end point was determined using the Youden index. RESULTS: In 290 patients, the class I and IIa recommendations identified all patients who experienced the composite end point during a median follow-up of 3.0 years. Patients meeting class I recommendations had a significantly higher incidence of the composite end point than those meeting class IIa recommendations. Left ventricular ejection fraction (LVEF) >35% with >5.7% late gadolinium enhancement on cardiovascular magnetic resonance imaging was as sensitive as and significantly more specific than LVEF >35% with any late gadolinium enhancement. Patients meeting 2 class IIa recommendations, LVEF >35% with the need for a permanent pacemaker and LVEF >35% with late gadolinium enhancement >5.7%, had high annualized event rates. Excluding 2 class IIa recommendations, LVEF >35% with syncope and LVEF >35% with inducible ventricular arrhythmia, resulted in improved discrimination for the composite end point. CONCLUSIONS: We assessed the Guideline recommendations for implantable cardioverter-defibrillator implantation in patients with known or suspected cardiac sarcoidosis and identified topics for future research.

Usefulness of Atrial Fibrillation as a Marker for Adverse Cardiovascular Outcomes in Both Primary and Secondary Prevention in Patients With Implantable Cardioverter-Defibrillators.

Whether the risk factors for cardiovascular (CV) outcomes are different in primary versus secondary prevention implantable cardioverter-defibrillator (ICD) patients is unclear. We sought to identify predictors of CV outcomes in ICD recipients for primary (G1) versus secondary prevention (G2). Consecutive patients who had ICD implanted during August 2005 to December 2009 were included. The primary outcome was a composite of appropriate shock, acute coronary syndrome, ischemic stroke, coronary revascularization, heart failure exacerbation, CV hospitalization, or all-cause death. We used Cox proportional hazards model and a stepwise selection method to fit the most parsimonious model to predict the primary outcome in all patients and separately for G1 and G2 patients. We followed 223 (184 G1 and 39 G2, mean age 61 years) patients through December 31, 2012; 141 (63.2%) developed the primary outcome. In all patients, atrial fibrillation (AF; hazard ratio 6.72, 95% CI 4.20 to 10.75; p <0.001), use of antiarrhythmic drug (1.55, 1.02 to 2.36; p = 0.04), and lower estimated glomerular filtration rate (0.99, 0.98 to 0.997; p = 0.01) were associated with increased risk of the primary outcome; the attributable risks were 21.6%, 16.0%, and 15.9%, respectively. In G1, AF, hypertension, and lower estimated glomerular filtration rate were associated with increased risk, whereas in G2, AF, use of antiarrhythmic drug, and nonischemic cardiomyopathy were associated with increased risk. In conclusion, although risk factors are different for primary and secondary prevention patients, AF is a strong and consistent risk factor for adverse outcomes in both populations.