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The aim was to test the hypothesis that left ventricular (LV) and right ventricular (RV) activation from body surface electrical mapping (CardioInsight 252-electrode vest, Medtronic) identifies optimal cardiac resynchronization therapy (CRT) pacing strategies and outcomes in 30 patients. The LV80, RV80, and BIV80 were defined as the times to 80% LV, RV, or biventricular electrical activation. Smaller differences in the LV80 and RV80 (|LV80-RV80|) with synchronized LV pacing predicted better LV function post-CRT (p = 0.0004) than the LV-paced QRS duration (p = 0.32). Likewise, a lower RV80 was associated with a better pre-CRT RV ejection fraction by CMR (r =  - 0.40, p = 0.04) and predicted post-CRT improvements in myocardial oxygen uptake (p = 0.01) better than the biventricular-paced QRS (p = 0.38), while a lower LV80 with BIV pacing predicted lower post-CRT B-type natriuretic peptide (BNP) (p = 0.02). RV pacing improved LV function with smaller |LV80-RV80| (p = 0.009). In conclusion, 3-D electrical mapping predicted favorable post-CRT outcomes and informed effective pacing strategies.

As the mechanism for worse prognosis after cardiac resynchronization therapy (CRT) upgrades in heart failure patients with RVP dependence (RVP-HF) has clinical implications for patient selection and CRT implementation approaches, this study's objective was to evaluate prognostic implications of cardiac magnetic resonance (CMR) findings and clinical factors in 102 HF patients (23.5% female, median age 66.5 years old, median follow-up 4.8 years) with and without RVP dependence undergoing upgrade and de novo CRT implants. Compared with other CRT groups, RVP-HF patients had decreased survival (p = 0.02), more anterior late-activated LV pacing sites (p = 0.002) by CMR, more atrial fibrillation (p = 0.0006), and higher creatinine (0.002). CMR activation timing at the LV pacing site predicted post-CRT LV functional improvement (p < 0.05), and mechanical activation onset < 34 ms by CMR at the LVP site was associated with decreased post-CRT survival in a model with higher pre-CRT creatinine and B-type natriuretic peptide (AUC 0.89; p < 0.0001); however, only the higher pre-CRT creatinine partially mediated (37%) the decreased survival in RVP-HF patients. In conclusion, RVP-HF had a distinct CMR phenotype, which has important implications for the selection of LV pacing sites in CRT upgrades, and only chronic kidney disease mediated the decreased survival after CRT in RVP-HF.

BACKGROUND: Cardiac resynchronization therapy (CRT) response is complex, and better approaches are required to predict survival and need for advanced therapies. OBJECTIVE: The objective was to use machine learning to characterize multidimensional CRT response and its relationship with long-term survival. METHODS: Associations of 39 baseline features (including cardiac magnetic resonance [CMR] findings and clinical parameters such as glomerular filtration rate [GFR]) with a multidimensional CRT response vector (consisting of post-CRT left ventricular end-systolic volume index [LVESVI] fractional change, post-CRT B-type natriuretic peptide, and change in peak VO2) were evaluated. Machine learning generated response clusters, and cross-validation assessed associations of clusters with 4-year survival. RESULTS: Among 200 patients (median age 67.4 years, 27.0% women) with CRT and CMR, associations with more than 1 response parameter were noted for the CMR CURE-SVD dyssynchrony parameter (associated with post-CRT brain natriuretic peptide [BNP] and LVESVI fractional change) and GFR (associated with peak VO2 and post-CRT BNP). Machine learning defined 3 response clusters: cluster 1 (n = 123, 90.2% survival [best]), cluster 2 (n = 45, 60.0% survival [intermediate]), and cluster 3 (n = 32, 34.4% survival [worst]). Adding the 6-month response cluster to baseline features improved the area under the receiver operating characteristic curve for 4-year survival from 0.78 to 0.86 (P = .02). A web-based application was developed for cluster determination in future patients. CONCLUSION: Machine learning characterizes distinct CRT response clusters influenced by CMR features, kidney function, and other factors. These clusters have a strong and additive influence on long-term survival relative to baseline features.

Schistosomiasis is a major cause of pulmonary arterial hypertension (PAH) worldwide, but the prevalence and risk factors for schistosomiasis-associated PAH (SchPAH) development are not well understood. Schistosomiasis-associated hepatosplenic disease (SchHSD) is thought to be a major risk factor for PAH development. Herein, we describe our plans for prospectively screening SchHSD subjects for clinical evidence of PAH at two major academic medical centers and national referral hospitals in Addis Ababa, Ethiopia and Lusaka, Zambia. The screening study will primarily be conducted by echocardiography, in addition to clinical assessments. Plasma samples will be drawn and banked for subsequent analysis based on preclinical animal model rationale. If successful, this study will demonstrate feasibility of conducting prospective cohort studies of SchPAH screening in schistosomiasis-endemic regions of Africa, and provide initial data on clinic-based disease prevalence and potential mechanistic biomarkers underlying disease pathogenesis.

BACKGROUND: Mechanisms of sex-based differences in outcomes following cardiac resynchronization therapy (CRT) are poorly understood. OBJECTIVE: To use cardiac magnetic resonance (CMR) to define mechanisms of sex-based differences in outcomes after CRT and describe distinct CMR-based phenotypes of CRT candidates based on sex and non-ischemic/ischemic cardiomyopathy type. MATERIALS AND METHODS: In a prospective study, sex-based differences in three short-term CRT response measures [fractional change in left ventricular end-systolic volume index 6 months after CRT (LVESVI-FC), B-type natriuretic peptide (BNP) 6 months after CRT, change in peak VO2 6 months after CRT], and long-term survival were evaluated with respect to 39 baseline parameters from CMR, exercise testing, laboratory testing, electrocardiograms, comorbid conditions, and other sources. CMR was also used to quantify the degree of left-ventricular mechanical dyssynchrony by deriving the circumferential uniformity ratio estimate (CURE-SVD) parameter from displacement encoding with stimulated echoes (DENSE) strain imaging. Statistical methods included multivariable linear regression with evaluation of interaction effects associated with sex and cardiomyopathy type (ischemic and non-ischemic cardiomyopathy) and survival analysis. RESULTS: Among 200 patients, the 54 female patients (27%) pre-CRT had a smaller CMR-based LVEDVI (p = 0.04), more mechanical dyssynchrony based on the validated CMR CURE-SVD parameter (p = 0.04), a lower frequency of both late gadolinium enhancement (LGE) and ischemic cardiomyopathy (p < 0.0001), a greater RVEF (p = 0.02), and a greater frequency of LBBB (p = 0.01). After categorization of patients into four groups based on cardiomyopathy type (ischemic/non-ischemic cardiomyopathy) and sex, female patients with non-ischemic cardiomyopathy had the lowest CURE-SVD (p = 0.003), the lowest pre-CRT BNP levels (p = 0.01), the lowest post-CRT BNP levels (p = 0.05), and the most favorable LVESVI-FC (p = 0.001). Overall, female patients had better 3-year survival before adjustment for cardiomyopathy type (p = 0.007, HR = 0.45) and after adjustment for cardiomyopathy type (p = 0.009, HR = 0.67). CONCLUSION: CMR identifies distinct phenotypes of female CRT patients with non-ischemic and ischemic cardiomyopathy relative to male patients stratified by cardiomyopathy type. The more favorable short-term response and long-term survival outcomes in female heart failure patients with CRT were associated with lower indexed CMR-based LV volumes, decreased presence of scar associated with prior myocardial infarction and ICM, and greater CMR-based dyssynchrony with the CURE-SVD.

OBJECTIVES: The objective was to determine the feasibility and effectiveness of cardiac magnetic resonance (CMR) cine and strain imaging before and after cardiac resynchronization therapy (CRT) for assessment of response and the optimal resynchronization pacing strategy. BACKGROUND: CMR with cardiac implantable electronic devices can safely provide high-quality right ventricular/left ventricular (LV) ejection fraction (RVEF/LVEF) assessments and strain. METHODS: CMR with cine imaging, displacement encoding with stimulated echoes for the circumferential uniformity ratio estimate with singular value decomposition (CURE-SVD) dyssynchrony parameter, and scar assessment was performed before and after CRT. Whereas the pre-CRT scan constituted a single imaging set with complete volumetric, strain, and scar imaging, multiple imaging sets with complete strain and volumetric data were obtained during the post-CRT scan for biventricular pacing (BIVP), LV pacing (LVP), and asynchronous atrial pacing modes by reprogramming the device outside the scanner between imaging sets. RESULTS: 100 CMRs with a total of 162 imaging sets were performed in 50 patients (median age 70 years [IQR: 50-86 years]; 48% female). Reduction in LV end-diastolic volumes (P = 0.002) independent of CRT pacing were more prominent than corresponding reductions in right ventricular end-diastolic volumes (P = 0.16). A clear dependence of the optimal CRT pacing mode (BIVP vs LVP) on the PR interval (P = 0.0006) was demonstrated. The LVEF and RVEF improved more with BIVP than LVP with PR intervals ≥240 milliseconds (P = 0.025 and P = 0.002, respectively); the optimal mode (BIVP vs LVP) was variable with PR intervals

RationaleObesity is associated with pulmonary arterial hypertension (PAH), but its impact on outcomes such as health-related quality of life (HRQoL), hospitalizations and survival is not well understood.ObjectivesTo assess the effect of obesity on health-related quality of life (HRQoL), hospitalizations and survival in patients with PAH.MethodsWe performed a cohort study of adults with PAH from the Pulmonary Hypertension Association Registry, a prospective multicenter registry. Multivariate linear mixed effects regression was used to examine the relationship between weight categories and HRQoL using the Short Form-12 (SF-12) and emPHasis-10 (e10). We used multivariable negative binomial regression to estimate hospitalization incidence rate ratios (IRRs) and Cox regression to estimate hazard ratios (HRs) for transplant-free survival by weight status.Results767 subjects were included: mean age of 57 years, 74% female, 33% overweight and 40% obese, with median follow-up duration of 527 days. Overweight and obese patients had higher baseline e10 scores (worse HRQoL), which persisted over time (p

Pulmonary arterial hypertension (PAH) is a disease of the lung blood vessels that results in right heart failure. PAH is thought to occur in about 5% to 10% of patients with hepatosplenic schistosomiasis, particularly due to S. mansoni. The lung blood vessel injury may result from a combination of embolization of eggs through portocaval shunts into the lungs causing localized Type 2 inflammatory response and vessel remodeling, triggering of autonomous pathology that becomes independent of the antigen, and high cardiac output as seen in portopulmonary hypertension. The condition is likely underdiagnosed as there is little systematic screening, and risk factors for developing PAH are not known. Screening is done by echocardiography, and formal diagnosis requires invasive right heart catheterization. Patients with Schistosoma-associated PAH show reduced functional capacity and can be treated with pulmonary vasodilators, which improves symptoms and may improve survival. There are animal models of this disease that might help in understanding disease pathogenesis and identify novel targets to screen and treatment. Pathogenic mechanisms include Type 2 immunity and activation and signaling in the TGF-β pathway. There are still major uncertainties regarding Schistosoma-associated PAH development, course and treatment.

Contemporary anticancer therapies frequently have different efficacy and side effects in men and women. Yet, whether women are well‐represented in pivotal trials supporting contemporary anticancer drugs is unknown. Leveraging the Drugs@FDA database, clinicaltrials.gov, MEDLINE, and publicly available FDA‐drug‐reviews, we identified all pivotal (phase II and III) non‐sex specific trials supporting FDA‐approval of anticancer drugs (1998–2018). Observed‐enrollment‐rates were compared to expected‐population‐rates derived from concurrent US‐National‐Cancer‐Institute's Surveillance‐Epidemiology‐and‐End‐Results (SEER) reported rates and US‐Census databases. Primary outcome was the proportional representation of women across trials, evaluated by a participation‐to‐prevalence ratio (PPR), according to cancer type. Secondary outcome was the report of any sex‐specific analysis of efficacy and/or safety, irrespective of treatment‐arm. Overall, there were 148 trials, enrolling 60,216 participants (60.5 ± 4.0 years, 40.7% female, 79.1% biologic, targeted, or immune‐based therapies) evaluating 99 drugs. Sex was reported in 146 (98.6%) trials, wherein 40.7% (24,538) were women, compared to 59.3% (35,678) men (p <.01). Altogether, women were under‐represented in 66.9% trials compared to the proportional incidence of cancers by respective disease type; weight‐average PPR of 0.91 (relative difference: ‐9.1%, p <.01). Women were most under‐represented in gastric (PPR = 0.63), liver (PPR = 0.71), and lung (PPR =.81) cancer trials. Sex‐based safety data was reported in 4.0% trials. There was no association between adequate female enrollment and drug efficacy (HR: 0.616 vs. 0.613, p =.96). Over time, there was no difference in the percentage of women recruited into clinical trials. Among pivotal clinical trials supporting contemporary FDA‐approved cancer drugs, women were frequently under‐represented and sex‐specific‐efficacy and safety‐outcomes were commonly not reported. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis affecting the spine, presenting a considerable morbidity risk. Although evidence consistently indicates an elevated risk of ischemic heart disease among AS patients, debates persist regarding the likelihood of these patients developing left ventricular dysfunction (LVD). Our investigation aimed to determine whether individuals with AS face a greater risk of LVD compared to the general population. To accomplish this, we identified studies exploring LVD in AS patients across five major databases and Google Scholar. Initially, 431 studies were identified, of which 30 met the inclusion criteria, collectively involving 2933 participants. Results show that AS patients had: (1) poorer Ejection Fraction (EF) [mean difference (MD): −0.92% (95% CI: −1.25 to −0.59)], (2) impaired Early (E) and Late (atrial—A) ventricular filling velocity (E/A) ratio [MD: −0.10 m/s (95% CI: −0.13 to −0.08)], (3) prolonged deceleration time (DT) [MD: 12.30 ms (95% CI: 9.23–15.36)] and, (4) a longer mean isovolumetric relaxation time (IVRT) [MD: 8.14 ms (95% CI: 6.58–9.70)] compared to controls. Though AS patients show increased risks of both systolic and diastolic LVD, we found no significant differences were observed in systolic blood pressure [MD: 0.32 mmHg (95% Confidence Interval (CI): −2.09 to 2.73)] or diastolic blood pressure [MD: 0.30 mmHg (95% CI: −0.40 to 1.01)] compared to the general population. This study reinforces AS patients' susceptibility to LVD without a notable difference in HTN risk. [ABSTRACT FROM AUTHOR]

Background: Heart Failure (HF) is associated with increased morbidity and mortality. Identification of patients at risk for adverse events could lead to improved outcomes. Few studies address the association of echocardiographic-derived PAWP with exercise capacity, readmissions, and mortality in HF. Methods: HF-ACTION enrolled 2331 outpatients with HF with reduced ejection fraction (HFrEF) who were randomized to aerobic exercise training versus usual care. All patients underwent baseline echocardiography. Echocardiographic-derived PAWP (ePAWP) was assessed using the Nagueh formula. We evaluated the relationship between ePAWP to clinical outcomes. Results: Among the 2331 patients in the HF-ACTION trial, 2125 patients consented and completed follow-up with available data. 807 of these patients had complete echocardiographic data that allowed the calculation of ePAWP. Of this cohort, mean age (SD) was 58 years (12.7), and 255 (31.6%) were female. The median ePAWP was 14.06 mmHg. ePAWP was significantly associated with cardiovascular death or HF hospitalization (Hazard ratio [HR] 1.02, coefficient 0.016, CI 1.002–1.030, p = 0.022) and all-cause death or HF hospitalization (HR 1.01, coefficient 0.010, CI 1.001–1.020, p = 0.04). Increased ePAWP was also associated with decreased exercise capacity leading to lower peak VO2 (p = < 0.001), high Ve/VCO2 slope (p = < 0.001), lower exercise duration (p = < 0.001), oxygen uptake efficiency (p = < 0.001), and shorter 6-MWT distance (p = < 0.001). Conclusions: Among HFrEF patients, echocardiographic-derived PAWP was associated with increased mortality, reduced functional capacity and heart failure hospitalization. ePAWP may be a viable noninvasive marker to risk stratify HFrEF patients. [ABSTRACT FROM AUTHOR]