Clinical and Echocardiographic Diversity Associated With Physical Fitness in the Project Baseline Health Study: Implications for Heart Failure Staging.

BACKGROUND: Clinical and echocardiographic features may carry diverse information about the development of heart failure (HF). Therefore, we determined heterogeneity in clinical and echocardiographic phenotypes and its association with exercise capacity. METHODS: In 2036 community-dwelling individuals, we defined echocardiographic profiles of left and right heart remodeling and dysfunction. We subdivided the cohort based on presence (+) or absence (-) of HF risk factors (RFs) and echocardiographic abnormalities (RF-/Echo-, RF-/Echo+, RF+/Echo-, RF+/Echo+). Multivariable-adjusted associations between subgroups and physical performance metrics from 6-minute walk and treadmill exercise testing were assessed. RESULTS: The prevalence was 35.3% for RF-/Echo-, 4.7% for RF-/Echo+, 39.3% for RF+/Echo-, and 20.6% for RF+/Echo+. We observed large diversity in echocardiographic profiles in the Echo+ group. Participants with RF-/Echo+ (18.6% of Echo+) had predominantly echocardiographic abnormalities other than left ventricular (LV) diastolic dysfunction, hypertrophy and reduced ejection fraction, whereas their physical performance was similar to RF-/Echo-. In contrast, participants with RF+/Echo+ presented primarily with LV hypertrophy or dysfunction, features that related to lower 6-minute walking distance and lower exercise capacity. CONCLUSIONS: Subclinical echocardiographic abnormalities suggest HF pathogenesis, but the presence of HF risk factors and type of echo abnormality should be considered so as to distinguish adverse from benign adaptation and to stratify HF risk.

Multiparametric evaluation of right ventricular function in pulmonary arterial hypertension associated with congenital heart disease.

INTRODUCTION AND OBJECTIVES: Outcome in patients with congenital heart diseases and pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Two-dimensional echocardiographic parameters, such as strain imaging or RV end-systolic remodeling index (RVESRI) have emerged to quantify RV function. METHODS: We prospectively studied 30 patients aged 48±12 years with pretricuspid shunt and PAH and investigated the accuracy of multiple echocardiographic parameters of RV function (tricuspid annular plane systolic excursion, tricuspid annular peak systolic velocity, RV systolic-to-diastolic duration ratio, right atrial area, RV fractional area change, RV global longitudinal strain and RVESRI) to RV ejection fraction measured by cardiac magnetic resonance. RESULTS: RV ejection fraction <45% was observed in 13 patients (43.3%). RV global longitudinal strain (ρ [Spearman's correlation coefficient]=-0.75; P=.001; R2=0.58; P=.001), right atrium area (ρ=-0.74; P <.0001; R2=0.56; P <.0001), RVESRI (ρ=-0.64; P <.0001; R2=0.47; P <.0001), systolic-to-diastolic duration ratio (ρ=-0.62; P=.0004; R2=0.47; P <.0001) and RV fractional area change (ρ=0.48; P=.01; R2=0.37; P <.0001) were correlated with RV ejection fraction. RV global longitudinal strain, RVESRI and right atrium area predicted RV ejection fraction <45% with the greatest area under curve (0.88; 95%CI, 0.71-1.00; 0.88; 95%CI, 0.76-1.00, and 0.89; 95%CI, 0.77-1.00, respectively). RV global longitudinal strain >-16%, RVESRI ≥ 1.7 and right atrial area ≥ 22 cm2 predicted RV ejection fraction <45% with a sensitivity and specificity of 87.5% and 85.7%; 76.9% and 88.3%; 92.3% and 82.4%, respectively. CONCLUSIONS: RVESRI, right atrial area and RV global longitudinal strain are strong markers of RV dysfunction in patients with pretricuspid shunt and PAH.

4D flow cardiovascular magnetic resonance recovery profiles following pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) allows comprehensive assessment of pulmonary artery (PA) flow dynamics. Few studies have characterized longitudinal changes in pulmonary flow dynamics and right ventricular (RV) recovery following a pulmonary endarterectomy (PEA) for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This can provide novel insights of RV and PA dynamics during recovery. We investigated the longitudinal trajectory of 4D flow metrics following a PEA including velocity, vorticity, helicity, and PA vessel wall stiffness. METHODS: Twenty patients with CTEPH underwent pre-PEA and > 6 months post-PEA CMR imaging including 4D flow CMR; right heart catheter measurements were performed in 18 of these patients. We developed a semi-automated pipeline to extract integrated 4D flow-derived main, left, and right PA (MPA, LPA, RPA) volumes, velocity flow profiles, and secondary flow profiles. We focused on secondary flow metrics of vorticity, volume fraction of positive helicity (clockwise rotation), and the helical flow index (HFI) that measures helicity intensity. RESULTS: Mean PA pressures (mPAP), total pulmonary resistance (TPR), and normalized RV end-systolic volume (RVESV) decreased significantly post-PEA (P < 0.002). 4D flow-derived PA volumes decreased (P < 0.001) and stiffness, velocity, and vorticity increased (P < 0.01) post-PEA. Longitudinal improvements from pre- to post-PEA in mPAP were associated with longitudinal decreases in MPA area (r = 0.68, P = 0.002). Longitudinal improvements in TPR were associated with longitudinal increases in the maximum RPA HFI (r=-0.85, P < 0.001). Longitudinal improvements in RVESV were associated with longitudinal decreases in MPA fraction of positive helicity (r = 0.75, P = 0.003) and minimum MPA HFI (r=-0.72, P = 0.005). CONCLUSION: We developed a semi-automated pipeline for analyzing 4D flow metrics of vessel stiffness and flow profiles. PEA was associated with changes in 4D flow metrics of PA flow profiles and vessel stiffness. Longitudinal analysis revealed that PA helicity was associated with pulmonary remodeling and RV reverse remodeling following a PEA.

Elucidating tricuspid Doppler signal interpolation and its implication for assessing pulmonary hypertension.

Doppler echocardiography plays a central role in the assessment of pulmonary hypertension (PAH). We aim to improve quality assessment of systolic pulmonary arterial pressure (SPAP) by applying a cubic polynomial interpolation to digitized tricuspid regurgitation (TR) waveforms. Patients with PAH and advanced lung disease were divided into three cohorts: a derivation cohort (n = 44), a validation cohort (n = 71), an outlier cohort (n = 26), and a non-PAH cohort (n = 44). We digitized TR waveforms and analyzed normalized duration, skewness, kurtosis, and first and second derivatives of pressure. Cubic polynomial interpolation was applied to three physiology-driven phases: the isovolumic phase, ejection phase, and "shoulder" point phase. Coefficients of determination and a Bland-Altman analysis was used to assess bias between methods. The cubic polynomial interpolation of the TR waveform correlated strongly with expert read right ventricular systolic pressure (RVSP) with R 2 > 0.910 in the validation cohort. The biases when compared to invasive SPAP measured within 24 h were 6.03 [4.33; 7.73], -2.94 [1.47; 4.41], and -3.11 [-4.52; -1.71] mmHg, for isovolumic, ejection, and shoulder point interpolations, respectively. In the outlier cohort with more than 30% difference between echocardiographic estimates and invasive SPAP, cubic polynomial interpolation significantly reduced underestimation of RVSP. Cubic polynomial interpolation of the TR waveform based on isovolumic or early ejection phase may improve RVSP estimates.

Association of left ventricular diastolic function with coronary artery calcium score: A Project Baseline Health Study.

BACKGROUND: Coronary artery calcium (CAC) and left ventricular diastolic dysfunction (LVDD) are strong predictors of cardiovascular events and share common risk factors. However, their independent association remains unclear. METHODS: In the Project Baseline Health Study (PBHS), 2082 participants underwent cardiac-gated, non-contrast chest computed tomography (CT) and echocardiography. The association between left ventricular (LV) diastolic function and CAC was assessed using multidimensional network and multivariable-adjusted regression analyses. Multivariable analysis was conducted on continuous LV diastolic parameters and categorical classification of LVDD and adjusted for traditional cardiometabolic risk factors. LVDD was defined using reference limits from a low-risk reference group without established cardiovascular disease, cardiovascular risk factors or evidence of CAC, (n â€‹= â€‹560). We also classified LVDD using the American Society of Echocardiography recommendations. RESULTS: The mean age of the participants was 51 â€‹± â€‹17 years with 56.6% female and 62.6% non-Hispanic White. Overall, 38.1% had hypertension; 13.7% had diabetes; and 39.9% had CAC >0. An intertwined network was observed between diastolic parameters, CAC score, age, LV mass index, and pulse pressure. In the multivariable-adjusted analysis, e', E/e', and LV mass index were independently associated with CAC after adjustment for traditional risk factors. For both e' and E/e', the effect size and statistical significance were higher across increasing CAC tertiles. Other independent correlates of e' and E/e' included age, female sex, Black race, height, weight, pulse pressure, hemoglobin A1C, and HDL cholesterol. The independent association with CAC was confirmed using categorical analysis of LVDD, which occurred in 554 participants (26.6%) using population-derived thresholds. CONCLUSION: In the PBHS study, the subclinical coronary atherosclerotic disease burden detected using CAC scoring was independently associated with diastolic function. GOV IDENTIFIER: NCT03154346.

Induction and Phenotyping of Acute Right Heart Failure in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension.

The development of acute right heart failure (ARHF) in the context of chronic pulmonary hypertension (PH) is associated with poor short-term outcomes. The morphological and functional phenotyping of the right ventricle is of particular importance in the context of hemodynamic compromise in patients with ARHF. Here, we describe a method to induce ARHF in a previously described large animal model of chronic PH, and to phenotype, dynamically, right ventricular function using the gold standard method (i.e., pressure-volume PV loops) and with a non-invasive clinically available method (i.e., echocardiography). Chronic PH is first induced in pigs by left pulmonary artery ligation and right lower lobe embolism with biological glue once a week for 5 weeks. After 16 weeks, ARHF is induced by successive volume loading using saline followed by iterative pulmonary embolism until the ratio of the systolic pulmonary pressure over systemic pressure reaches 0.9 or until the systolic systemic pressure decreases below 90 mmHg. Hemodynamics are restored with dobutamine infusion (from 2.5 µg/kg/min to 7.5 µg/kg/min). PV-loops and echocardiography are performed during each condition. Each condition requires around 40 minutes for induction, hemodynamic stabilization and data acquisition. Out of 9 animals, 2 died immediately after pulmonary embolism and 7 completed the protocol, which illustrates the learning curve of the model. The model induced a 3-fold increase in mean pulmonary artery pressure. The PV-loop analysis showed that ventriculo-arterial coupling was preserved after volume loading, decreased after acute pulmonary embolism and was restored with dobutamine. Echocardiographic acquisitions allowed to quantify right ventricular parameters of morphology and function with good quality. We identified right ventricular ischemic lesions in the model. The model can be used to compare different treatments or to validate non-invasive parameters of right ventricular morphology and function in the context of ARHF.

Insulin Growth Factor Phenotypes in Heart Failure With Preserved Ejection Fraction, an INSPIRE Registry and CATHGEN Study.

BACKGROUND: The insulin-like growth factor (IGF) axis emerged as an important pathway in heart failure with preserved ejection (HFpEF). We aimed to identify IGF phenotypes associated with HFpEF in the context of high-dimensional proteomic profiling. METHODS: From the INtermountain Healthcare Biological Samples Collection Project and Investigational REgistry for the On-going Study of Disease Origin, Progression and Treatment (Intermountain INSPIRE Registry), we identified 96 patients with HFpEF and matched controls. We performed targeted proteomics, including IGF-1,2, IGF binding proteins (IGFBP) 1-7 and 111 other proteins (EMD Millipore and ELISA). We used partial least square discriminant analysis (PLS-DA) to identify a set of proteins associated with prevalent HFpEF, pulmonary hypertension and 5-year all-cause mortality. K-mean clustering was used to identify IGF phenotypes. RESULTS: Patients with HFpEF had a high prevalence of systemic hypertension (95%) and coronary artery disease (74%). Using PLS-DA, we identified a set of biomarkers, including IGF1,2 and IGFBP 1,2,7, that provided a strong discrimination of HFpEF, pulmonary hypertension and mortality with an area under the curve of 0.91, 0.77 and 0.83, respectively. Using K mean clustering, we identified 3 IGF phenotypes that were independently associated with all-cause 5-year mortality after adjustment for age, NT-proBNP and kidney disease (P = 0.004). Multivariable analysis validated the prognostic value of IGFBP-1 and 2 in the CATHeterization GENetics (CATHGEN) biorepository. CONCLUSION: IGF phenotypes were associated with pulmonary hypertension and mortality in HFpEF.

Donor and Recipient Size Matching in Heart Transplantation With Predicted Heart and Lean Body Mass.

Donor and recipient size matching during heart transplant can be assessed using weight or predicted heart mass (PHM) ratios. We developed sex-specific allomteric equations for PHM and predicted lean body mass (PLBM) using the United Kingdom Biobank (UKB) and evaluated their predictive value in the United Network of Organ Sharing database. Donor and recipient size matching was based on weight, PHM and PLBM ratios. PHM was calculated using the Multiethnic Study of Atherosclerosis and UKB equations. PLBM was calculated using the UKB and National Health and Nutrition Examination Survey equations. Relative prognostic utility was compared using multivariable Cox analysis, adjusted for predictors of 1-year survival in the Scientific Registry of Transplant Recipients model. Of 53,648 adult patients in the United Network of Organ Sharing database between 1996 and 2016, 6528 (12.2%) died within the first year. In multivariable analysis, undersized matches by any metric were associated with increased 1-year mortality (all P < 0.01). Oversized matches were at increased risk using PHM or PLBM (all P < 0.01), but not weight ratio. There were significant differences in classification of size matching by weight or PHM in sex-mismatched donor-recipient pairs. A significant interaction was observed between pulmonary hypertension and donor undersizing (hazard ratio 1.15, P = 0.026) suggesting increased risk of undersizing in pulmonary hypertension. Donor and recipient size matching with simplified PHM and PLBM offered an advantage over total body weight and may be more important for sex-mismatched donor-recipient pairs. Donor undersizing is associated with worse outcomes in patients with pulmonary hypertension.

The Right Heart Network and Risk Stratification in Pulmonary Arterial Hypertension.

BACKGROUND: Prognosis in pulmonary arterial hypertension (PAH) is closely related to indexes of right ventricular function. A better understanding of their relationship may provide important implications for risk stratification in PAH. RESEARCH QUESTION: Can clinical network graphs inform risk stratification in PAH? STUDY DESIGN AND METHODS: The study cohort consisted of 231 patients with PAH followed up for a median of 7.1 years. An undirected, correlation network was used to visualize the relationship between clinical features in PAH. This network was enriched for right heart parameters and included N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP), comprehensive echocardiographic parameters, and hemodynamics, as well as 6-min walk distance (6MWD), vital signs, laboratory data, and diffusing capacity for carbon monoxide (Dlco). Connectivity was assessed by using eigenvector and betweenness centrality to reflect global and regional connectivity, respectively. Cox proportional hazards regression was used to model event-free survival for the combined end point of death or lung transplantation. RESULTS: A network of closely intertwined features centered around NT-proBNP with 6MWD emerging as a secondary hub were identified. Less connected nodes included Dlco, systolic BP, albumin, and sodium. Over the follow-up period, death or transplantation occurred in 92 patients (39.8%). A strong prognostic model was achieved with a Harrell's C-index of 0.81 (0.77-0.85) when combining central right heart features (NT-proBNP and right ventricular end-systolic remodeling index) with 6MWD and less connected nodes (Dlco, systolic BP, albumin, sodium, sex, connective tissue disease etiology, and prostanoid therapy). When added to the baseline risk model, serial change in NT-proBNP significantly improved outcome prediction at 5 years (increase in C-statistic of 0.071 ± 0.024; P = .003). INTERPRETATION: NT-proBNP emerged as a central hub in the intertwined PAH network. Connectivity analysis provides explainability for feature selection and combination in outcome models.

Predicting post-operative right ventricular failure using video-based deep learning.

Despite progressive improvements over the decades, the rich temporally resolved data in an echocardiogram remain underutilized. Human assessments reduce the complex patterns of cardiac wall motion, to a small list of measurements of heart function. All modern echocardiography artificial intelligence (AI) systems are similarly limited by design - automating measurements of the same reductionist metrics rather than utilizing the embedded wealth of data. This underutilization is most evident where clinical decision making is guided by subjective assessments of disease acuity. Predicting the likelihood of developing post-operative right ventricular failure (RV failure) in the setting of mechanical circulatory support is one such example. Here we describe a video AI system trained to predict post-operative RV failure using the full spatiotemporal density of information in pre-operative echocardiography. We achieve an AUC of 0.729, and show that this ML system significantly outperforms a team of human experts at the same task on independent evaluation.

Optimal Tricuspid Regurgitation Velocity to Screen for Pulmonary Hypertension in Tertiary Referral Centers.

BACKGROUND: A mean pulmonary artery pressure >20 mm Hg now defines pulmonary hypertension. We hypothesize that echocardiographic thresholds must be adjusted. RESEARCH QUESTION: Should tricuspid regurgitation velocity thresholds to screen for pulmonary hypertension be revised, given the new hemodynamic definition? STUDY DESIGN AND METHODS: This multicenter retrospective study included 1,608 patients who underwent both echocardiography and right heart catherization within 4 weeks. The discovery cohort consisted of 1,081 individuals; the validation cohort included 527. Screening criteria for pulmonary hypertension were derived with the use of receiver operating characteristic analysis and the Youden index, assuming equal cost for false-positive and -negative classification. A lower threshold was calculated with the use of a predefined sensitivity: 95%. RESULTS: In the discovery cohort, echocardiographic tricuspid regurgitation velocity had a good discrimination for pulmonary hypertension: area under the curve, 88.4 (95% CI, 85.3-91.5). A 3.4-m/s threshold provided a 78% sensitivity, 87% specificity, and 6.13 positive likelihood ratio to detect pulmonary hypertension; 2.7 m/s had a 95% sensitivity and 0.12 negative likelihood ratio to exclude pulmonary hypertension. In the validation cohort, the discovery threshold of 2.7 m/s provided sensitivity and negative likelihood ratios of 80% and 0.31, respectively. Right cardiac size improved detection of pulmonary hypertension in the lower tricuspid regurgitation velocity groups. INTERPRETATION: Our data support a lower tricuspid regurgitation velocity of approximately 2.7 m/s for screening pulmonary hypertension, with a high sensitivity in tertiary referral centers. Right heart chamber measurements improve the diagnostic yield of echocardiography.

CTA pulmonary artery enlargement in patients with severe aortic stenosis: Prognostic impact after TAVR.

BACKGROUND: Identifying high-risk patients who will not derive substantial survival benefit from TAVR remains challenging. Pulmonary hypertension is a known predictor of poor outcome in patients undergoing TAVR and correlates strongly with pulmonary artery (PA) enlargement on CTA. We sought to evaluate whether PA enlargement, measured on pre-procedural computed tomography angiography (CTA), is associated with 1-year mortality in patients undergoing TAVR. METHODS: We retrospectively included 402 patients undergoing TAVR between July 2012 and March 2016. Clinical parameters, including Society of Thoracic Surgeons (STS) score and right ventricular systolic pressure (RVSP) estimated by transthoracic echocardiography were reviewed. PA dimensions were measured on pre-procedural CTAs. Association between PA enlargement and 1-year mortality was analyzed. Kaplan-Meier and Cox proportional hazards regression analyses were performed. RESULTS: The median follow-up time was 433 (interquartiles 339-797) days. A total of 56/402 (14%) patients died within 1 year after TAVR. Main PA area (area-MPA) was independently associated with 1-year mortality (hazard ratio per standard deviation equal to 2.04 [95%-confidence interval (CI) 1.48-2.76], p â€‹< â€‹0.001). Area under the curve (95%-CI) of the clinical multivariable model including STS-score and RVSP increased slightly from 0.67 (0.59-0.75) to 0.72 (0.72-0.89), p â€‹= â€‹0.346 by adding area-MPA. Although the AUC increased, differences were not significant (p â€‹= â€‹0.346). Kaplan-Meier analysis showed that mortality was significantly higher in patients with a pre-procedural non-indexed area-MPA of ≥7.40 â€‹cm2 compared to patients with a smaller area-MPA (mortality 23% vs. 9%; p â€‹< â€‹0.001). CONCLUSIONS: Enlargement of MPA on pre-procedural CTA is independently associated with 1-year mortality after TAVR.

Retraction notice to ICAM-1 PROMOTES THE ABNORMAL ENDOTHELIAL CELL PHENOTYPE IN CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Authors. This request follows an examination by The Editors of the uncut gels provided by the authors, which led the Editors to conclude that data were compromised in the following western blot images: Figure 3C, Figure 5B and Figure 6B. Duplicated data for the beta actin images were found in Figures 5 and 6. Examination of the raw data used for the western blot quantification also revealed frequent duplicated data. The microscopy data in Figure 5A also has features compatible with compromised data although the raw data were not available to the Editors due to the regrettable death of Dr. Saadia Eddahibi. All of the remaining authors agree with the retraction and apologize to the Editors and the readers of The Journal for difficulties this issue has caused.

Targeted proteomics of right heart adaptation to pulmonary arterial hypertension.

No prior proteomic screening study has centred on the right ventricle (RV) in pulmonary arterial hypertension (PAH). This study investigates the circulating proteomic profile associated with right heart maladaptive phenotype (RHMP) in PAH.Plasma proteomic profiling was performed using multiplex immunoassay in 121 (discovery cohort) and 76 (validation cohort) PAH patients. The association between proteomic markers and RHMP, defined by the Mayo right heart score (combining RV strain, New York Heart Association (NYHA) class and N-terminal pro-brain natriuretic peptide (NT-proBNP)) and Stanford score (RV end-systolic remodelling index, NYHA class and NT-proBNP), was assessed by partial least squares regression. Biomarker expression was measured in RV samples from PAH patients and controls, and pulmonary artery banding (PAB) mice.High levels of hepatocyte growth factor (HGF), stem cell growth factor-ß, nerve growth factor and stromal derived factor-1 were associated with worse Mayo and Stanford scores independently from pulmonary resistance or pressure in both cohorts (the validation cohort had more severe disease features: lower cardiac index and higher NT-proBNP). In both cohorts, HGF added value to the REVEAL score in the prediction of death, transplant or hospitalisation at 3 years. RV expression levels of HGF and its receptor c-Met were higher in end-stage PAH patients than controls, and in PAB mice than shams.High plasma HGF levels are associated with RHMP and predictive of 3-year clinical worsening. Both HGF and c-Met RV expression levels are increased in PAH. Assessing plasma HGF levels might identify patients at risk of heart failure who warrant closer follow-up and intensified therapy.

Preoperative C-reactive protein predicts early postoperative outcomes after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension.

OBJECTIVE: To determine whether preoperative systemic inflammation (defined by C-reactive protein [CRP] levels ≥10 mg/L) is associated with worse functional and hemodynamic status and poor early outcomes postendarterectomy in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: This study included 159 patients who underwent pulmonary endarterectomy from 2009 to 2013 (derivation cohort) and 238 patients from 2015 to 2016 (validation cohort) with CRP data from the national CTEPH registry. The correlations between proinflammatory markers (CRP, interleukins 1 and 6, fibrinogen, and leukocytes) and hemodynamics were assessed in the derivation cohort. Pre-, perioperative characteristics, and 30-day outcomes (ie, death or lung transplant or extracorporeal membrane oxygenation need or inotropic or vasopressor need ≥3 days) of patients with CRP levels ≥ or <10 mg/L were compared. RESULTS: Median age of the derivation cohort was 63 [52-73] years with 48% female, 80% in New York Heart Association class III/IV. The validation cohort had similar demographics and disease severity. Patients with CRP ≥10 mg/L had greater resistance levels and lower cardiac index than those with CRP <10 mg/L in both cohorts. The primary endpoint was reached in 38% (derivation) and 42% (validation) of patients. In multivariable logistic regression analysis, CRP ≥10 mg/L was associated with the primary endpoint in both the derivation cohort (odd ratio, 2.49 [1.11-5.61], independently of New York Heart class class IV and aortic clamping duration) and the validation cohort (odd ratio, 1.89 [1.09-3.61], independently of age and aortic clamping duration). CONCLUSIONS: Preoperative CRP ≥10 mg/L is independently associated with adverse early outcomes postendarterectomy.

Hemodynamic trajectories and outcomes in patients with pulmonary arterial hypertension.

The relative pulmonary to systemic pressure ratio (mean pulmonary arterial pressure/mean arterial pressure) has been proven to be valuable in cardiac surgery. Little is known on the prognostic value of baseline and trajectory of mean pulmonary arterial pressure/mean arterial pressure in pulmonary arterial hypertension. Patients with confirmed idiopathic, familial, drug and toxins, or connective tissue disease-related pulmonary arterial hypertension and at least one complete right heart catheterization were included and prospectively followed-up for 5.9 ± 4.03 years. Correlates of the primary end point (i.e. death or lung transplant need) during follow-up were determined using Cox regression modeling. Results showed that among the 308 patients included, 187 had at least one follow-up catheterization (median time between catheterizations: 2.16 (1.16-3.19) years). In the total cohort (mean age 47.3 ± 14.9 years, 82.8% of female and 58.1% in New York Heart Association class 3 or 4), mean pulmonary arterial pressure/mean arterial pressure (1.38 (1.07-1.77)) was associated with outcome (p = 0.01). Mean pulmonary arterial pressure/mean arterial pressure was incremental to a basic model (including right atrial pressure, systolic blood pressure, New York Heart Association class 3 or 4, and connective tissue disease) for outcome prediction, while mean pulmonary arterial pressure was not. In the 187 patients with a follow-up catheterization, both delta mean pulmonary arterial pressure and delta mean pulmonary arterial pressure/mean arterial pressure were associated with outcome (1.32 (1.11-1.58) and 1.31 (1.1-1.57) respectively, p < 0.01). Mean pulmonary arterial pressure and mean pulmonary arterial pressure/mean arterial pressure were both incremental to the basic model, while worsening in mean pulmonary arterial pressure or mean pulmonary arterial pressure/mean arterial pressure did not reach significance. In conclusion, mean pulmonary arterial pressure/mean arterial pressure at baseline prognosticates long-term outcome with a significant, albeit modest, incremental value to basic variables.

Mechanics of right ventricular dysfunction in pulmonary arterial hypertension and heart failure with preserved ejection fraction.

Right ventricular (RV) dysfunction is the most important determinant of survival in patients with pulmonary hypertension (PH). The manifestations of RV dysfunction not only include changes in global RV systolic function but also abnormalities in the pattern of contraction and synchrony. The effects of PH on the right ventricle have been mainly studied in patients with pulmonary arterial hypertension (PAH). However, with the demographic shift towards an aging population, heart failure with preserved ejection fraction (HFpEF) has become an important etiology of PH in recent years. There are significant differences in RV mechanics, function and adaptation between patients with PAH and HFpEF (with or without PH), which are related to different patterns of remodeling and dysfunction. Due to the unique features of the RV chamber, its connection with the main pulmonary artery and the pulmonary circulation, an understanding of the mechanics of RV function and its clinical significance is mandatory for both entities. In this review, we describe the mechanics of the pressure overloaded right ventricle. We review the different mechanical components of RV dysfunction and ventricular dyssynchrony, followed by insights via analysis of pressure-volume loop, energetics and novel blood flow patterns, such as vortex imaging. We conduct an in-depth comparison of prevalence and characteristics of RV dysfunction in HFpEF and PAH, and summarize key outcome studies. Finally, we provide a perspective on needed and expected future work in the field of RV mechanics.

Circulating whole genome miRNA expression corresponds to progressive right ventricle enlargement and systolic dysfunction in adults with tetralogy of Fallot.

INTRODUCTION: The adult congenital heart disease population with repaired tetralogy of Fallot (TOF) is subject to chronic volume and pressure loading leading to a 40% probability of right ventricular (RV) failure by the 3rd decade of life. We sought to identify a non-invasive signature of adverse RV remodeling using peripheral blood microRNA (miRNA) profiling to better understand the mechanisms of RV failure. METHODS: Demographic, clinical data, and blood samples were collected from adults with repaired TOF (N = 20). RNA was isolated from the buffy coat of peripheral blood and whole genome miRNA expression was profiled using Agilent's global miRNA microarray platform. Fold change, pathway analysis, and unbiased hierarchical clustering of miRNA expression was performed and correlated to RV size and function assessed by echocardiography performed at or near the time of blood collection. RESULTS: MiRNA expression was profiled in the following groups: 1. normal RV size (N = 4), 2. mild/moderate RV enlargement (N = 11) and 3. severe RV enlargement (N = 5). 267 miRNAs were downregulated, and 66 were upregulated across the three groups (fold change >2.0, FDR corrected p<0.05) as RV enlargement increased and systolic function decreased. qPCR validation of a subset of these miRNAs identified increasing expression of miRNA 28-3p, 433-3p, and 371b-3p to be associated with increasing RV size and decreasing RV systolic function. Unbiased hierarchical clustering of all patients based on miRNA expression demonstrates three distinct patient clusters that largely coincide with progressive RV enlargement. Pathway analysis of dysregulated miRNAs demonstrates up and downregulation of cell cycle pathways, extracellular matrix proteins and fatty acid synthesis. HIF 1α signaling was downregulated while p53 signaling was predicted to be upregulated. CONCLUSION: Adults with TOF have a distinct miRNA profile with progressive RV enlargement and dysfunction implicating cell cycle dysregulation and upregulation in extracellular matrix and fatty acid metabolism. These data suggest peripheral blood miRNA can provide insight into the mechanisms of RV failure and can potentially be used for monitoring disease progression and to develop RV specific therapeutics to prevent RV failure in TOF.

Speckle tracking echocardiography can predict subclinical myocardial involvement in patients with sarcoidosis: A meta-analysis.

BACKGROUND: This meta-analysis aims to evaluate the utility of speckle tracking echocardiography (STE) as a tool to evaluate for cardiac sarcoidosis (CS) early in its course. Electrocardiography and echocardiography have limited sensitivity in this role, while advanced imaging modalities such as cardiac magnetic resonance (CMR) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) are limited by cost and availability. METHODS: We compiled English language articles that reported left ventricular global longitudinal strain (LVGLS) or global circumferential strain (GCS) in patients with confirmed extra-cardiac sarcoidosis versus healthy controls. Studies that exclusively included patients with probable or definite CS were excluded. Continuous data were pooled as a standard mean difference (SMD), comparing sarcoidosis group with healthy controls. A random-effect model was adopted in all analyses. Heterogeneity was assessed using Q and I2 statistics. RESULTS: Nine studies were included in our final analysis with an aggregate of 967 patients. LVGLS was significantly lower in the extra-cardiac sarcoidosis group as compared with controls, SMD -3.98, 95% confidence interval (CI): -5.32, -2.64, P < .001, also was significantly lower in patients who suffered major cardiac events (MCE), -3.89, 95% CI -6.14, -1.64, P < .001. GCS was significantly lower in the extra-cardiac sarcoidosis group as compared with controls, SMD: -3.33, 95% CI -4.71, -1.95, P < .001. CONCLUSION: LVGLS and GCS were significantly lower in extra-cardiac sarcoidosis patients despite not exhibiting any cardiac symptoms. LVGLS correlates with MCEs in CS. Further studies are required to investigate the role of STE in the early screening of CS.