Blauwet, Lori A.

Background: CP/R-CP may be associated with subtle features of ventricular dysfunction which are not easily detectable with the use of conventional echocardiographic modalities. The aim of this study was to evaluate myocardial mechanics by 2D-STE (2 Dimensional speckle-tracking echocardiography) between CP and R-CP. We hypothesized that strain/ strain rate (S/SR) would be worse in the R-CP patients due to radiation-induced myocardial injury. Methods: We analyzed 180 patients (62% male, age 62±13 years, 127 CP and 53 R-CP) with suitable echocardiographic images and normal left ventricular ejection fraction (LVEF>55%). The two groups were similar in terms of age, cardiovascular symptoms, risk factor profile and LVEF (Table). Selected images were analyzed off-line using Velocity Vector Imaging technology. The diagnosis of CP was based on clinical parameters as well as echocardiography and/or hemodynamic cardiac catheterization. Patients in whom radiation therapy was the primary etiology of CP were classified as R-CP. Global and segmental circumferential, radial, longitudinal, systolic and early diastolic strain and strain rate were analyzed in all patients. Results: Global and segmental radial (GRadS), global longitudinal (GLS), global basal (GBS), global mid-segment (GMS), septal wall (SWS), and anterior wall (AWS) strain was significantly reduced in the R-CP patients compared with the CP patients (Table). Antero-septal and anterior wall diastolic strain and strain rates (AS + AW Sre, SR) were reduced in the R-CP group. The best differentiators between the two groups were antero-septal (SAS), basal anterior (BAS) and mid anterior (MAS) segmental strain, based on receiver operating characteristic (ROC) and area under the curve (AUC) analysis. ROC calculations were AUC: SAS 0.67, SBA 0.69, and SMA 0.71. Conclusion: The study showed that compared with CP, R-CP is associated more with myocardial dysfunction, likely due to radiation-induced myocardial injury.

Peripartum cardiomyopathy (PPCM) is an idiopathic form of pregnancy-induced heart failure associated with preeclampsia. Circulating factors in late pregnancy are thought to contribute to both diseases, suggesting a common underlying pathophysiological process. However, what drives this process remains unclear. Using serum proteomics, we identified the senescence-associated secretory phenotype (SASP), a marker of cellular senescence associated with biological aging, as the most highly up-regulated pathway in young women with PPCM or preeclampsia. Placentas from women with preeclampsia displayed multiple markers of amplified senescence and tissue aging, as well as overall increased gene expression of 28 circulating proteins that contributed to SASP pathway enrichment in serum samples from patients with preeclampsia or PPCM. The most highly expressed placental SASP factor, activin A, was associated with cardiac dysfunction or heart failure severity in women with preeclampsia or PPCM. In a murine model of PPCM induced by cardiomyocyte-specific deletion of the gene encoding peroxisome proliferator–activated receptor γ coactivator-1α, inhibiting activin A signaling in the early postpartum period with a monoclonal antibody to the activin type II receptor improved heart function. In addition, attenuating placental senescence with the senolytic compound fisetin in late pregnancy improved cardiac function in these animals. These findings link senescence biology to cardiac dysfunction in pregnancy and help to elucidate the pathogenesis underlying cardiovascular diseases of pregnancy.

Abstract Aims Cardiovascular disease is a major threat to maternal health, with cardiomyopathy being among the most common acquired cardiovascular diseases during pregnancy and the postpartum period. The aim of our study was to evaluate the effectiveness of an electrocardiogram (ECG)-based deep learning model in identifying cardiomyopathy during pregnancy and the postpartum period. Methods and results We used an ECG-based deep learning model to detect cardiomyopathy in a cohort of women who were pregnant or in the postpartum period seen at Mayo Clinic. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. We compared the diagnostic probabilities of the deep learning model with natriuretic peptides and a multivariable model consisting of demographic and clinical parameters. The study cohort included 1807 women; 7%, 10%, and 13% had left ventricular ejection fraction (LVEF) of 35% or less, <45%, and <50%, respectively. The ECG-based deep learning model identified cardiomyopathy with AUCs of 0.92 (LVEF ≤ 35%), 0.89 (LVEF < 45%), and 0.87 (LVEF < 50%). For LVEF of 35% or less, AUC was higher in Black (0.95) and Hispanic (0.98) women compared to White (0.91). Natriuretic peptides and the multivariable model had AUCs of 0.85 to 0.86 and 0.72, respectively. Conclusions An ECG-based deep learning model effectively identifies cardiomyopathy during pregnancy and the postpartum period and outperforms natriuretic peptides and traditional clinical parameters with the potential to become a powerful initial screening tool for cardiomyopathy in the obstetric care setting.

AbstractObjectiveEndomyocardial biopsy (EMB) is a useful diagnostic tool though the yield may be limited in many myocardial diseases. Data on the diagnostic yield and prognostic significance of EMB guided by abnormal electrograms (EGM‐Bx) in suspected cardiac sarcoidosis (CS) are scarce.MethodsSeventy‐nine patients (mean age: 56 ± 12 years; 61% men) with suspected CS based on clinical and imaging features underwent right or left ventricular EGM‐Bx guided by electroanatomic mapping. Tissue samples were obtained from sites with abnormal EGMs and/or abnormal cardiac imaging. The diagnostic yield of EGM‐Bx was evaluated in reference to histopathologic analysis. Left ventricular assist device (LVAD) and transplantation‐free survival were compared between patients with positive and negative EGM‐Bx for CS.ResultsA total of 254 samples were obtained from abnormal EGM sites, and 126 samples from normal EGM sites guided by pre‐procedure imaging findings. Abnormal histopathology was noted in 65 (26%) and 10 (8%) samples from abnormal and normal EGM sites, respectively. Histopathology confirmed CS in 16 (20%) patients, while an alternative tissue diagnosis emerged in 10 (13%) patients. Abnormal EGMs at the biopsy site had sensitivity 89% and specificity 33% for a histopathologic diagnosis of CS. LVAD and transplantation‐free survival were not significantly associated with the EGM‐Bx result (log‐rank p = .91).ConclusionIn patients with suspected CS, abnormal EGM‐Bx has high sensitivity and low specificity for establishing a definite CS diagnosis. Consideration of substrate abnormalities apparent on preprocedural imaging as an adjunct for selection of biopsy sites may further improve EGM‐Bx yield.

Introduction: Pulmonary valve (PV) replacement is rare, so data regarding normal hemodynamics are limited. We sought to determine the normal Doppler-derived hemodynamic profiles of various PV prostheses (PVPs) in adults. Hypothesis: Doppler-derived hemodynamic profiles of normal PVPs will vary according to prosthesis type in adult patients. Methods: We performed a retrospective review of comprehensive two dimensional and Doppler echocardiographic examinations of 327 patients (median age, 35; range 18 -83 years) with normal PVPs performed early after implantation. Data were analyzed to determine mean±SD. Results: Parasternal short axis was the most commonly used window (96%) for assessment of PVPs. For the 327 PVPs, peak instantaneous gradient was 25±11 mmHg, mean systolic gradient was 13.1±6.1 mmHg, and mean right ventricular outflow tract velocity was 0.8±0.6 m/s. Results for selected variables analyzed by prosthesis type are listed in the Table. Pericardial prostheses had significantly lower peak gradient (21±10.1 mmHg; P=0.002) compared with porcine (25±9.7 mmHg), mechanical (26±16.6 mmHg), bovine venous (34±15.5 mmHg) and homograft PVPs (35±8.4 mm Hg). Conclusions: This is the largest series reporting normal Doppler-derived hemodynamic profiles of PVPs. This study establishes normative values for Doppler-derived variables for normal PVPs implanted in adults. Pericardial prostheses had the optimal hemodynamic profile in this patient population.

Abstract Background Sarcoidosis is an infiltrative inflammatory condition affecting multiple organs, with cardiac involvement designated as cardiac sarcoidosis (CS). It has been proposed that inflammatory conditions like sarcoid increase the risk of venous thromboembolism (VTE), defined as pulmonary embolism (PE) and deep vein thrombosis (DVT) due to the hypercoagulable environment created by inflammation. Purpose Although previous studies have demonstrated an association with sarcoidosis and VTE, these studies failed to account for steroid use (crucial for sarcoid treatment) as an important confounder. Also, no major studies have been done previously assessing the risk of VTE in CS specifically. The objective of this investigation is to determine the association between CS, steroid treatment for CS, and VTE. Methods Patients referred to our institution with concern for sarcoid/CS were retrospectively assessed. Specific variables of interest including general baseline characteristics and those specific to CS were analyzed for their association with VTE development. Results Using Heart Rhythm Society guidelines, 649 patients were split into three categories: 235 with no sarcoid (NS), 91 with extra-cardiac sarcoid (ECS) only, and 323 with CS. In univariate analysis, 39 (12%) CS patients developed a PE vs 9 (4%) NS patients (OR 3.44, p=0.0003) and 44 (14%) CS patients developed DVT vs 18 (8%) NS patients (OR 1.90, p=0.02). In multivariate regression analysis however, neither CS nor ECS was an independent risk factor for VTE (p>0.05) but steroid use was a strong predictor of VTE (HR 3.12, p=0.007 for PE, HR 6.17, p<0.0001 for DVT). Also, steroid dose was found to be an independent predictor for both PE (p=0.001) and DVT (p=0.007) in a Cox proportionate hazards model (significance appeared at >17.5 mg daily on a receiver operating characteristic curve). Conclusion Contrary to previous studies, the current study found that neither sarcoidosis nor CS is an independent risk factor for VTE. Rather, steroid therapy for CS treatment leads to an increased prevalence of VTE, specifically at a dose above 17.5 mg daily. More research is required to clarify this relationship and assess the importance of steroid-sparing immunosuppressive therapy and potentially VTE prophylaxis in CS management. Steroid use and time to PE/DVT Funding Acknowledgement Type of funding source: None

To our knowledge, natural history has not been reported for cardiac sarcoidosis (CS) diagnosed by pathologic evaluation of the apical core at left ventricular assist device (LVAD) implantation or cardiac transplantation. We retrospectively identified 232 consecutive patients meeting CS criteria. Of these patients, 54 were diagnosed by pathologic confirmation of CS, 10 after evaluation of the apical core (LVAD implant) or explanted heart (transplant). We compared clinical characteristics at initial evaluation and outcomes for these 10 patients with those of 10 patients with known CS before LVAD implant/transplant. In the study group, five patients (50%) had confirmed extracardiac sarcoidosis before LVAD implant/transplant; five had not been diagnosed with sarcoidosis. Mean (standard deviation) left ventricular ejection fraction at initial evaluation was 23% (16%), and left ventricular end-diastolic dimension was 61 (10) mm. Four patients died during follow-up; however, no survival difference was found for the 10 patients diagnosed incidentally and the group with a previous diagnosis or institutional LVAD/transplant cohorts. Patients diagnosed with CS on pathological examination of the apical core/explanted heart may have severe dilated cardiomyopathy as the initial presentation. Outcomes for patients with CS after advanced heart failure therapies may be comparable with those of non-CS patients.

Abstract Background: Sarcoidosis is a systemic granulomatous disease that may affect the myocardium. This study evaluated the diagnostic and prognostic value of 2-dimensional speckle tracking echocardiography in cardiac sarcoidosis (CS). Methods: Eighty-three patients with extracardiac, biopsy-proven sarcoidosis and definite/probable diagnosis of cardiac involvement diagnosed from January 2005 through December 2016 were included. Strain parameters in early stages of CS, in a subgroup of 23 CS patients with left ventricular ejection fraction (LVEF) within normal limits (LVEF>52% for men: >54% for women, mean value: 57.3%±3.8%) and no wall motion abnormalities was compared with 97 controls (1:4) without cardiac disease. LV and right ventricular (RV) global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain and strain rate (SR) analyses were performed with TomTec software and correlated with cardiac outcomes (including heart failure and arrhythmias). This study was approved by the Mayo Clinic Institutional Review Board, and all patients gave informed written consent to participate. Results: Mean age of CS patients was 53.6±10.8 years, and 34.9% were women. Mean LVEF was 43.2%±12.4%; LV GLS, -12.4%±3.7%; LV GCS, -17.1%±6.5%; LV GRS, 29.3%±12.8%; and RV wall GLS, 14.6%±6.3%. In the 23 patients with early stage CS with normal LVEF and RV systolic function, strain parameters were significantly reduced when compared with controls (respectively: LV GLS, -15.9%±2.5% vs -18.2%±2.7% [ P =.001]; RV GLS, -16.9%±4.5% vs -24.1%±4.0% [ P <.001]). A LV GLS value of -16.3% provided 82.2% sensitivity and 81.2% specificity for the diagnosis of CS (AUC 0.91), while a RV value of -19.9% provided 88.1% sensitivity and 86.7% specificity (AUC 0.93). Hospital admission and heart failure significantly correlated to impaired LV GLS (> -14%). Conclusion: Reduced strain values in the LV GLS and RV GLS can be used in the diagnostic algorithm in patients with suspicion of cardiac sarcoidosis. These values also correlate with adverse cardiovascular events.

Abstract Background: Sarcoidosis is a systemic granulomatous disease that may affect the myocardium. This study evaluated the diagnostic and prognostic value of 2-dimensional speckle tracking echocardiography in cardiac sarcoidosis (CS). Methods: Eighty-three patients with extracardiac, biopsy-proven sarcoidosis and definite/probable diagnosis of cardiac involvement diagnosed from January 2005 through December 2016 were included. Strain parameters in early stages of CS, in a subgroup of 23 CS patients with left ventricular ejection fraction (LVEF) within normal limits (LVEF>52% for men: >54% for women, mean value: 57.3%±3.8%) and no wall motion abnormalities was compared with 97 controls (1:4) without cardiac disease. LV and right ventricular (RV) global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain and strain rate (SR) analyses were performed with TomTec software and correlated with cardiac outcomes (including heart failure and arrhythmias). This study was approved by the Mayo Clinic Institutional Review Board, and all patients gave informed written consent to participate. Results: Mean age of CS patients was 53.6±10.8 years, and 34.9% were women. Mean LVEF was 43.2%±12.4%; LV GLS, -12.4%±3.7%; LV GCS, -17.1%±6.5%; LV GRS, 29.3%±12.8%; and RV wall GLS, 14.6%±6.3%. In the 23 patients with early stage CS with normal LVEF and RV systolic function, strain parameters were significantly reduced when compared with controls (respectively: LV GLS, -15.9%±2.5% vs -18.2%±2.7% [P=.001]; RV GLS, -16.9%±4.5% vs -24.1%±4.0% [P<.001]). A LV GLS value of -16.3% provided 82.2% sensitivity and 81.2% specificity for the diagnosis of CS (AUC 0.91), while a RV value of -19.9% provided 88.1% sensitivity and 86.7% specificity (AUC 0.93). Hospital admission and heart failure significantly correlated to impaired LV GLS (> -14%). Conclusion: Reduced strain values in the LV GLS and RV GLS can be used in the diagnostic algorithm in patients with suspicion of cardiac sarcoidosis. These values also correlate with adverse cardiovascular events.

Abstract Background Cardiac sarcoidosis (CS) is an infiltrative inflammatory condition defined by infiltration of noncaseating granulomas into the heart. Based on the location of sarcoid lesion involvement, patients can present with symptoms of congestive heart failure, arrhythmias, and even sudden cardiac death. Purpose Diagnosis of CS has been somewhat challenging, with the Heart Rhythm Society (HRS) and Japanese Ministry of Health and Welfare (JMHW) being the 2 widely accepted diagnostic guidelines. Endomyocardial biopsy is the gold standard to prove definite CS but has a low sensitivity. Imaging studies have been helpful as non-invasive methods to diagnose probable CS but these can be logistically difficult and expensive. Thus, investigating for laboratory biomarkers that can act as both diagnostic and prognostic can be crucial in how we diagnose and manage CS in the future. Methods Patients meeting HRS for CS were evaluated at a single institution (n=217). Biomarkers of interest included angiotensin-converting enzyme (ACE), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin-T, 1,25 dihydroxyvitamin D (1,25-OHVit-D), and creatinine. Biomarkers were stratified by clinical variables of interest and their association with prognosis was examined. The primary endpoint was LVAD implantation, transplantation, or death. Results Mean values on presentation were: ACE 32.9±28, ESR 12±13, CRP 7.4±19, NT-proBNP 1630±2923, Troponin-T 0.03±0.1, 1,25-OHVit-D 55.5±20, and creatinine 1.12±0.3. None of the biomarkers differed by sex, definite or probable CS, or a history of immunosuppression. ACE levels were associated with the presence of cardiac fibrosis on cardiac MRI (mean difference 14.7, p=0.032). Troponin-T (p=0.006; HR 1.06 per 0.01 ng/mL), NT-proBNP (p=0.0003; HR 1.31 per 1,000 pg/mL), and creatinine (p=0.01; HR 4.02 per mg/dL) were each associated with the primary endpoint (52/217 patients). Biomarkers associated with long term outcomes in patients with cardiac sarcoidosis Biomarker Hazard ratio P value Troponin-T 1.06 (1.02–1.11)* 0.006 NT-pro BNP 1.31 (1.15–1.48)** 0.0003 Creatinine 4.02 (1.41–9.94)*** 0.01 *Per 0.01 ng/mL change; 99th percentile upper reference limit <0.01 ng/mL; **per 1,000 pg/mL change; ***per 1 mg/dL change. Conclusion Troponin-T, NT-proBNP, and creatinine at presentation predict outcomes in patients with CS. Further investigation on the utility of biomarkers for assessment of disease activity and treatment response is warranted.