Citations

Background Sarcoidosis is an inflammatory, noncaseating, granulomatous disorder of unknown cause that can affect any body system and is associated with cardiovascular disease including sudden cardiac death (SCD). Cardiac involvement in sarcoidosis is associated with higher risk of SCD, but the SCD risk in the general sarcoidosis population is unknown. We aimed to determine the risk of SCD in people with sarcoidosis versus the matched general population. Methods and Results A population‐based cohort of sarcoidosis and age‐ and sex‐matched comparators from January 1, 1976 to December 31, 2013 was used; presence of other comorbidities in the comparator group was not an exclusion criterion. Mortality, including time, place, and cause of death were measured and manually adjudicated for SCD events. Incidence rates are reported per 100 000 person‐years, and Cox models were used for group comparisons. Of the 345 incident cases of sarcoidosis (171 men; 50%) there were 58 reported deaths; 10 were definite/probable SCD versus 57 all‐cause and 9 SCDs in comparators. Median follow‐up was 12.9 years (interquartile range, 6.0–23.4 years) . Incidence rate of SCD in sarcoidosis was 192 (95% CI, 92–352) versus 155 (95% CI, 71–294) in comparators (hazard ratio [HR], 1.28 (95% CI, 0.52–3.17). Nocturnal deaths were more frequent in sarcoidosis 57 (95% CI, 12–168) versus 17 (95% CI, 0.4–95) (HR, 3.76 [95% CI, 0.39–36.47]). No significant differences were detected between the groups by sex, age, calendar year of diagnosis, or disease duration. Conclusions In a population‐based cohort of patients with sarcoidosis, the risk for SCD compared with matched comparators was not increased. There were more nocturnal deaths among patients with sarcoidosis, yet this was statistically insignificant.

Abstract Aims Obesity is a risk factor for heart failure with preserved ejection fraction (HFpEF), particularly in women, but the mechanisms remain unclear. The present study aimed to investigate the impact of central adiposity in patients with HFpEF and explore potential sex differences. Methods and results A total of 124 women and 105 men with HFpEF underwent invasive haemodynamic exercise testing and rest echocardiography. Central obesity was defined as a waist circumference (WC) ≥88 cm for women and ≥102 cm for men. Exercise‐normalized pulmonary capillary wedge pressure (PCWP) responses were evaluated by the ratio of PCWP to workload (PCWP/W) and after normalizing to body weight (PCWL). The prevalence of central obesity (77%) exceeded that of general obesity (62%) defined by body mass index ≥30 kg/m 2 . Compared to patients without central adiposity, patients with HFpEF and central obesity displayed greater prevalence of diabetes and dyslipidaemia, higher right and left heart filling pressures and pulmonary artery pressures during exertion, and more severely reduced aerobic capacity. Associations between WC and fasting glucose, low‐density lipoprotein (LDL) cholesterol, peak workload, and pulmonary artery pressures were observed in women but not in men with HFpEF. Although increased WC was associated with elevated PCWP in both sexes, the association with PCWP/W was observed in women but not in men. The strength of correlation between PCWP/W and WC was more robust in women with HFpEF as compared to men (Meng's test p = 0.0008), and a significant sex interaction was observed in the relationship between PCWL and WC ( p for interaction = 0.02). Conclusions Central obesity is even more common than general obesity in HFpEF, and there appear to be important sexual dimorphisms in its relationships with metabolic abnormalities and haemodynamic perturbations, with greater impact in women.

Abstract Funding Acknowledgements Type of funding sources: None. Background Pulmonary hypertension (PH) is a progressive pulmonary vascular disorder with an elevated mortality risk due to right ventricular failure. Pulmonary arterial pulsatility index (PAPi) based on invasively acquired parameters has emerged as a potentially valuable hemodynamic risk predictor. Whether non-invasively derived PAPi (PA pulse pressure/ RA pressure) is valuable is unclear. Purpose To assess whether PAPi measured non-invasively by transthoracic echocardiography acts as a prognostic hemodynamic biomarker of patient risk. Methods Consecutive patients undergoing transthoracic echocardiography for known or suspected PH over a one year period were included. PA systolic and diastolic pressure were estimated in standard fashion from peak tricuspid and end-pulmonary regurgitant Doppler profiles. Right atrial pressure was estimated based on 2D & Doppler assessment of the inferior vena cava hepatic vein. In those patients with PH (mean PA pressure > 20 mm Hg), PAPi was divided into 3 groups based on prior publications with invasive data as <1.5, 1.5 to 3 and >3. Mortality was assessed over 5 years. Results Of 1,045 patients enrolled 64% had PH. Patients with the lowest PAPi (table) had higher NT-proBNP levels, larger right ventricles, worse right heart systolic function (cardiac output, TAPSE, systolic annular velocity, free wall systolic strain) and greater degrees of tricuspid regurgitation (Table). In patients with PH, PAPi was inversely associated with death (figure, p < 0.0001) with each group of PAPi correlating with incrementally worse survival. Patients with a PAPi of <1.5 had worst right heart size and dysfunction on echo (table) and worst survival (figure). Conclusions In patients with PH, low PAPi derived non-invasively by transthoracic echocardiography is associated with markers of right heart failure, right ventricular dysfunction and worse survival. PAPi could be incorporated into the conventional echo parameters reported in patients with known or suspected PH and maybe a useful predictor of outcome. Abstract Table Abstract Figure

AbstractInflammatory pseudotumor (IPT), also known as plasma cell granuloma, is a rare lesion of unknown etiology that occurs in many organs, especially in the lung. Here we report five cases of IPT arising in pulmonary artery mimicking chronic thromboembolic disease, not previously documented in the literature. Those cases were identified at our institute among over 2500 pulmonary endarterectomy (PEA) specimens acquired from 2000 to 2017. The cohort included three men and two women with a median age of 41 years (range: 23–54). All patients presented with dyspnea and radiologic findings of pulmonary artery thromboembolism, some concerning for intimal sarcoma. The duration between disease onset and PEA ranged from 6 months to approximately 3 years. Histologically, all cases showed proliferation of spindle cells with marked inflammatory infiltrates composed predominantly of plasma cells, histiocytes, and small lymphocytes. Ancillary studies were performed in each case and ruled out other possibilities, such as sarcoma, lymphoma, plasmacytoma, IgG4‐related disease, and infection. IPT arising in pulmonary artery presenting clinically as acute or chronic thromboembolic disease is very unusual, in which clinical data, radiographic findings, and histopathologic features have to be integrated for reaching the proper diagnosis.

Objective Mild aortic valve stenosis (AS) and aortic valve (AV) sclerosis are associated with diastolic dysfunction and increased mortality in the general population. This study specifically investigated the impact of mild AV disease in heart failure with preserved ejection fraction (HFpEF). Methods Consecutive patients hospitalised with HFpEF (n=370) underwent assessment of cardiac structure and function and long-term clinical follow-up. Results In the study cohort, 111 had mild AS (30%), 104 AV sclerosis (28%) and 155 a non-calcified AV (42%). Mild-to-moderate AV regurgitation (AR) was present in 64 (17%). Compared with patients with a normal AV, those with AV disease were older, with worse renal function and more atrial fibrillation. E/e′ increased from non-calcified AV to AV sclerosis to mild AS (13.8 (10.8–16.8) vs 15.0 (10.9–20.0) vs 18.0 (12.7–23.3), respectively; p<0.001)). Left ventricular diastolic pressure–volume relationships were shifted leftwards in patients with AS and AV sclerosis, but not influenced by AR. The left ventricular end-diastolic volume normalised at 20 mm Hg was 117±34 mL, 106±30 mL and 112±30 mL in non-calcified AV, AV sclerosis and mild AS, respectively (p=0.023), while 112±32 mL in mild-to-moderate AR. Over 30 months (IQR, 8–61 months), 247 patients died (67%). The presence of mild AV disease was associated with increased mortality, but this was no longer significant after adjusting for age and sex. Conclusions Low-grade AV disease is common among patients hospitalised for HFpEF and is associated with older age, atrial arrhythmia, renal dysfunction, higher left heart filling pressures and increased left ventricular chamber stiffness.

Abstract Background Wild type transthyretin cardiac amyloidosis (wtATTR-CA) is increasingly recognized as a cause of heart failure with preserved ejection fraction (HFpEF) but prognosis is often limited due to late or misdiagnosis.Longitudinal left ventricular strain and biomarkers are established as markers of disease severity, but the role of RV free wall strain, reflecting RV contractility, is less well understood. Purpose We sought to determine whether RV free wall strain might add incremental prognostic value in wtATTR-CA. Methods Consecutive patients diagnosed with wtATTR-CA with tissue confirmation at Mayo clinic between 2013 and 2015 were included. Patients with TTR gene mutations were excluded. Baseline characteristics and transthoracic echocardiography measurements were obtained from the medical records. Speckle tracking RV free wall longitudinal 2D strain and peak LA longitudinal 2D strain were measured using Tom Tec Imaging System. Survival was determined using Kaplan Meier estimates and using the cox proportional hazard ratio, univariate and multivariable analysis were performed to identify predictors of mortality in patients with wtATTR. Results The study group comprised 139 patients (mean age 74.9±8.6, 92.8% male), of which 102 had adequate image quality for RV strain, and 99 for LA strain. Amongst these, 102 (73.3%) had AF and 118 patients (84.8%) had HF. During 3.23±2.0 years of follow up, 66 patients died. Both mean RV and LA strain were impaired at baseline: RV free wall strain was −14.7±4.9, and peak atrial longitudinal strain (PALS) was 13.2±8.8%. Using ROC analysis, RV strain of −16.8% was an independent predictor of all-cause mortality. In univariate modeling, higher levels of NT-proBNP (HR: 1.1 per 1000 pg.ml; 95%, CI 1.05–1.15, p&lt;0.001) and Troponin T (HR: 2.0 per 0.1ng/ml; 95% CI 1.49–2.61, p&lt;0.001) were associated with increased all-cause mortality. In addition, LV GLS (HR: 1.13 per 1%; 95% CI1.04–1.24, p=0.003), RV free wall LS (HR: 2.16 per 5%; 95%, CI 1.57–3.03, p&lt;0.0001), and PALS (HR: 0.91 per1%; 95% CI 0.85–0.96, p&lt;0.0001) were univariate predictors of all-cause mortality. In multivariate analysis using a stepwise regression model, RV free wall longitudinal strain (HR: 1.81; 95% CI 1.29–2.62, p&lt;0.001) and Troponin T (HR: 1.7; 95% CI 1.25–2.26, p=0.001) remained independent predictors. Kaplan-Meier survival analysis demonstrated a higher mortality rate above −16.8 RV strain cut-off (Wilcoxon &lt;0.0001). All stages were divided into two groups by −16.8% RV strain, and survival in individual stages analyzed. Stage 1 and 2 with &lt;−16.8 RV free wall strain value had higher mortality than ≤-16.8% RV strain (Stage 1: Wilcoxon = 0.0041 and Stage 2: Wilcoxon = 0.023). However, there was not a survival difference between two RV strain groups in stage3 (Wilcoxon = 0.34) Conclusion RV free wall strain is an independent predictor of survival in wtATTR patients and may add incremental prognostic value to NT-proBNP and Troponin. Funding Acknowledgement Type of funding sources: None. Kaplan-Meier curve of all patientsKaplan-Meier curve of stages

The aim of this study was to identify the optimal echocardiographic measurement of aortic regurgitation (AR) in continuous flow left ventricular assist devices (LVAD) and determine risk factors and clinical implications of de novo AR. Echocardiographic images from consecutive patients who underwent LVAD implantation from February 2007 to March 2017 were reviewed. Severity of de novo AR was determined by vena contracta (VC). Preimplant clinical characteristics, LVAD settings at discharge, and outcomes including heart failure hospitalizations, all-cause mortality, and ventricular arrhythmias of patients with greater than or equal to moderate de novo AR were compared with those with mild or no AR. Among 219 patients, greater than or equal to moderate de novo AR occurred in 65 (29.7%). Left ventricular assist devices support duration was longer with greater than or equal to moderate AR than no or mild AR. In multivariable analysis, preimplant trivial AR and persistent aortic valve (AV) closure were independently associated with de novo AR. By time-varying covariate analysis, survival and freedom from cardiovascular events in greater than or equal to moderate AR were significantly worse (hazard ratio [HR] = 3.947, p < 0.001 and HR = 4.666, p < 0.001). In conclusion, de novo greater than or equal to moderate AR measured by VC increases risk of adverse events. Longer LVAD support duration, preimplant trivial AR, and a closed AV are associated with occurrence of greater than or equal to moderate de novo AR.

Objective Graves’ disease (GD) can both aggravate pre-existing cardiac disease and cause de novo heart failure (HF), but large-scale studies are lacking. We aimed to investigate the incidence, risk factors and outcomes of incident GD-related HF. Methods Patients with GD (2009–2019) were retrospectively included. HF with reduced ejection fraction (HFrEF) was defined by left ventricular ejection fraction <50% and Framingham criteria, while HF with preserved ejection fraction (HFpEF) was defined according to the HFA-PEFF criteria. HF due to ischaemia, valve disorder or other structural heart disease was excluded. Proportional hazards regression was used to analyse risk factors and outcomes. Results Of 1371 patients with GD, HF occurred in 74 (5.4%) patients (31 (2.3%) HFrEF; 43 (3.1%) HFpEF). In HFrEF, atrial fibrillation (AF) (HR 10.5 (3.0–37.3), p<0.001) and thyrotropin receptor antibody (TRAb) level (HR 1.05 (1.01–1.09) per unit, p=0.007) were independent risk factors. In HFpEF, the independent risk factors were chronic obstructive pulmonary disease (HR 7.2 (3.5–14.6), p<0.001), older age (HR 1.5 (1.2–2.0) per 10 years, p=0.001), overt hyperthyroidism (HR 6.4 (1.5–27.1), p=0.01), higher body mass index (BMI) (HR 1.07 (1.03–1.10) per unit, p=0.001) and hypertension (HR 3.1 (1.3–7.2), p=0.008). The risk of cardiovascular hospitalisations was higher in both HFrEF (HR 10.3 (5.5–19.4), p<0.001) and HFpEF (HR 6.7 (3.7–12.2), p<0.001). However, only HFrEF was associated with an increased risk of all-cause mortality (HR 5.17 (1.3–19.9), p=0.02) and ventricular tachycardia/fibrillation (HR 64.3 (15.9–259.7), p<0.001). Conclusion De novo HF occurs in 5.4% of patients with GD and is associated with increased risk of cardiovascular hospitalisations and mortality. Risk factors include AF, higher TRAb, higher BMI and overt hyperthyroidism.

Introduction: The T peak - T end interval (Tpe) is a measure of transmural dispersion of repolarisation with prolongation of this interval linked to an increased risk of ventricular arrhythmias and sudden death. Patients with cardiac amyloid experience a high rate of sudden cardiac death. Objective: To determine the prognostic utility of the Tpeak-Tend interval in patients with transthyretin (TTR) cardiac amyloidosis. Methods: Of the 240 patients who underwent evaluation for TTR amyloidosis at our tertiary referral center from 1966 to 2010, 39 met inclusion criteria (65 excluded for AF, 66 BBB/Paced Rhythm, 25 CAD, 21 other). Inclusion criteria were presence of histological diagnosis of TTR amyloid and confirmed cardiac involvement by echocardiogram or biopsy and absence of atrial fibrillation (AF) or bundle branch block/paced rhythm on the index surface ECG, or history of coronary heart disease (CAD). Tpe was measured in leads V3 and V5. Cox proportional hazards model were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Kaplan-Meier curves were used to estimate overall survival and differences between curves were estimated using log rank. Primary endpoints were death or heart transplantation. Results: Of the 39 patients, 85% were male, and 69% were mTTR. Mean age 66.4 ± 13.9 years. Mean follow up period of 4.2 ± 3.2 years, 25 died and 5 received heart transplants. Median survival was 3.8 years, with 5 year survival 34%. On univariate analysis, Tpe in lead V3 was predictive of adverse outcome, HR per 10msec, 1.195 (1.051-1.370). Further multivariate analysis, in a model accounting for age, gender, Lead V3 Tpe was independently associated with survival, HR per 10msec, 1.207, (1.094-1.411, p=0.009). Conclusions: The Tpe interval in Lead V3 at diagnosis is a novel, noninvasive independent predictor of survival in transthyretin cardiac amyloidosis patients in sinus rhythm.

Introduction: Appropriate selection of patients (pts) with heart failure (HF) who may benefit from cardiac resynchronization therapy (CRT) is difficult. We sought to identify a clinical risk score to better risk stratify patients prior to CRT implantation. Methods: Pts undergoing CRT at Mayo Clinic from 2000 –2005 were included. Multiple clinical variables (age, gender, anemia (Hgb <10g/dL), RF (creatinine clearance ≤ 60ml/min/1.73m 2 ), hyponatremia (Na ≤130mEq/L), elevated BNP level (>500pg/ml), etiology, EF ≤20%, and advanced HF (NYHA functional class III–IV) were assessed with outcomes following CRT. Multivariate analysis was used to determine a clinical risk score. Results: A total of 496 patients (80% males) age 68 ± 12 years (62% ischemic cardiomyopathy, EF 22% ± 8%) were included. In univariate analysis relative risk (RR) was > 1 for RF (RR 1.8, CI 1.3–2.8; p = 0.002), anemia (RR 3.3, CI 1.8 –5.5; p = 0.001), hyponatremia (RR 3.4, CI 1.4 – 6.9; p = 0.008), elevated BNP (RR 2.9, CI 1.6 –5.7; p < 0.001), ischemic cardiomyopathy (ICM) (RR 1.8, CI 1.2–2.7; p < 0.002), EF ≤ 20% (RR 1.5, CI 1.0 –2.1; p = 0.033), and advanced HF (RR 2.5, CI 1.5– 4.9; p < 0.001). Following multivariate analysis RF, anemia, ICM, and advanced HF remained significant predictors of poor outcome (p >0.01 for all). Survival with 3 or more of these clinical risk factors was significantly worse than with less risk factors (p <0.01, Figure ). Conclusions: Pre-implant clinical risk factors including anemia, RF, ICM and advanced HF predict worse outcome following CRT with ≥3 variables predicting >2-fold increased risk of death or heart transplantation. These factors should be considered when selecting pts prior to CRT.