Blinded, randomized trial of sonographer versus AI cardiac function assessment.

Artificial intelligence (AI) has been developed for echocardiography1-3, although it has not yet been tested with blinding and randomization. Here we designed a blinded, randomized non-inferiority clinical trial (ClinicalTrials.gov ID: NCT05140642; no outside funding) of AI versus sonographer initial assessment of left ventricular ejection fraction (LVEF) to evaluate the impact of AI in the interpretation workflow. The primary end point was the change in the LVEF between initial AI or sonographer assessment and final cardiologist assessment, evaluated by the proportion of studies with substantial change (more than 5% change). From 3,769 echocardiographic studies screened, 274 studies were excluded owing to poor image quality. The proportion of studies substantially changed was 16.8% in the AI group and 27.2% in the sonographer group (difference of -10.4%, 95% confidence interval: -13.2% to -7.7%, P < 0.001 for non-inferiority, P < 0.001 for superiority). The mean absolute difference between final cardiologist assessment and independent previous cardiologist assessment was 6.29% in the AI group and 7.23% in the sonographer group (difference of -0.96%, 95% confidence interval: -1.34% to -0.54%, P < 0.001 for superiority). The AI-guided workflow saved time for both sonographers and cardiologists, and cardiologists were not able to distinguish between the initial assessments by AI versus the sonographer (blinding index of 0.088). For patients undergoing echocardiographic quantification of cardiac function, initial assessment of LVEF by AI was non-inferior to assessment by sonographers.

A new approach to improve the hemodynamic assessment of cardiac function independent of respiratory influence.

Cardiovascular and respiratory systems are anatomically and functionally linked; inspiration produces negative intrathoracic pressures that act on the heart and alter cardiac function. Inspiratory pressures increase with heart failure and can exceed the magnitude of ventricular pressure during diastole. Accordingly, respiratory pressures may be a confounding factor to assessing cardiac function. While the interaction between respiration and the heart is well characterized, the extent to which systolic and diastolic indices are affected by inspiration is unknown. Our objective was to understand how inspiratory pressure affects the hemodynamic assessment of cardiac function. To do this, we developed custom software to assess and separate indices of systolic and diastolic function into inspiratory, early expiratory, and late expiratory phases of respiration. We then compared cardiac parameters during normal breathing and with various respiratory loads. Variations in inspiratory pressure had a small impact on systolic pressure and function. Conversely, diastolic pressure strongly correlated with negative inspiratory pressure. Cardiac pressures were less affected by respiration during expiration; late expiration was the most stable respiratory phase. In conclusion, inspiration is a large confounding influence on diastolic pressure, but minimally affects systolic pressure. Performing cardiac hemodynamic analysis by accounting for respiratory phase yields more accuracy and analytic confidence to the assessment of diastolic function.

Relationship between extreme obesity and mortality in patients with reduced ejection fraction.

AIMS: Although obesity is associated with increased mortality, epidemiologic studies in heart failure have reported lower mortality in obese patients compared with matched nonobese patients (the 'obesity paradox'). However, the relationship between survival and extreme (morbid) obesity (BMI ≥ 40) is poorly understood. We evaluate survival in low ejection fraction patients across a range of BMI categories, including extreme obesity. METHODS: In a retrospective review, 12 181 consecutive patients receiving nuclear stress testing at a tertiary care center were stratified based on BMI and ejection fraction. Eight-year mortality data were collected using the social security death index. RESULTS: Normal ejection fraction patients (internal control, ejection fraction ≥50%) exhibited the J-shaped association between mortality and BMI that is observed in the general population. Among patients with reduced ejection fraction (<50%), survival improved as obesity increased (P < 0.0001). Those with extreme obesity had the lowest mortality (n = 1134, P < 0.05). CONCLUSION: In this cohort of reduced Ejection fraction patients, the obesity paradox was observed in all weight categories, with the highest survival of all observed in the extremely obese BMI category. This further supports hypotheses that an obesity-related physiologic phenomenon affects mortality in reduced ejection fraction patients.

Echocardiographic assessment of fetal cardiac function in the uterine artery ligation rat model of IUGR.

BACKGROUND: Intrauterine growth restriction (IUGR) leads to cardiac dysfunction and adverse remodeling of the fetal heart, as well as a higher risk of postnatal cardiovascular diseases. The rat model of IUGR, via uterine artery ligation, is a popular model but its cardiac sequelae is not well investigated. Here, we performed an echocardiographic evaluation of its cardiac function to determine how well it can represent the disease in humans. METHODS: Unilateral uterine artery ligation was performed at embryonic day 17 (E17) and echocardiography was performed at E19 and E20. RESULTS: Growth-restricted fetuses were significantly smaller and lighter, and had an higher placenta-to-fetus weight ratio. Growth-restricted fetal hearts had reduced wall thickness-to-diameter ratio, indicating left ventricular (LV) dilatation, and they had elevated trans-mitral and trans-tricuspid E/A ratios and reduced left and right ventricular fractional shortening (FS), suggesting systolic and diastolic dysfunction. These were similar to human IUGR fetuses. However, growth-restricted rat fetuses did not demonstrate head-sparing effect, displayed a lower LV myocardial performance index, and ventricular outflow velocities were not significantly reduced, which were dissimilar to human IUGR fetuses. CONCLUSIONS: Despite the differences, our results suggest that this IUGR model has significant cardiac dysfunction, and could be a suitable model for studying IUGR cardiovascular physiology. IMPACT: Animal models of IUGR are useful, but their fetal cardiac function is not well studied, and it is unclear if they can represent human IUGR fetuses. We performed an echocardiographic assessment of the heart function of a fetal rat model of IUGR, created via maternal uterine artery ligation. Similar to humans, the model displayed LV dilatation, elevated E/A ratios, and reduced FS. Different from humans, the model displayed reduced MPI, and no significant outflow velocity reduction. Despite differences with humans, this rat model still displayed cardiac dysfunction and is suitable for studying IUGR cardiovascular physiology.

The Role of Using HEART Score to Risk Stratify Chest Pain Among Emergency Department High Utilizers.

The HEART score is used to effectively risk stratify undifferentiated chest pain patients in the Emergency Department (ED). It is unclear whether such risk stratification can be applied among ED high utilizers. We aim to determine the efficacy and safety of using the HEART score to predict 30-day short-term major adverse cardiac events (MACE) in ED high utilizers. We conducted a retrospective, observational study in which ED high utilizers were defined as patients who had four or more ED visits within the past 12 months. ED high utilizers presenting at the study ED with chest pain were enrolled. Patients in which the HEART score was utilized were placed in the HEART group and patients with no HEART scores documented were placed to the usual care group. Hospital admissions and cardiac stress tests performed during the index hospitalizations, and 30-day MACE rates were analyzed and compared between the HEART and usual care groups. From January 1, 2017 to December 31, 2019, a total of 8,315 patient visits from ED high utilizers were enrolled. In the HEART group, 49% of ED visits were admitted with 20% receiving stress tests. A 30-day MACE outcome occurred among 1.4% of visits. In the usual care group, 44% of ED visits were admitted, with only 9% receiving index stress tests and a 1.5% of 30-day MACE occurrence (p=0.727). The study showed that similar short-term MACE outcomes occurred between patients using HEART scores and usual care to risk stratify chest pain among ED high utilizers.

Preoperative cardiac risk factors associated with in-hospital mortality in elderly patients without heart failure undergoing hip fracture surgery: a single-centre study.

INTRODUCTION: In the present study, our aim was to ascertain the preoperative cardiac risk factors related to the in-hospital mortality in the elderly patients (aged over 65 years) who required preoperative cardiology consultation for hip fracture surgery. MATERIAL AND METHODS: The present study was a retrospective, single-centre study, which enrolled consecutive elderly patients without heart failure scheduled for hip fracture surgery in our institution. In all patients, an anesthesiologist performed a detailed preoperative evaluation and decided the need for the cardiac consultation. Patients underwent preoperative cardiac evaluation by a trained cardiologist using the algorithms proposed in the recent preoperative guidelines. The in-hospital mortality was the main outcome of the study. RESULTS: In total, 277 elderly patients undergoing hip fracture surgery were enrolled in this analysis. The overall in-hospital mortality rate was 12.1% (n=30 cases). In a multivariate analysis, we found that insulin dependency, cancer, urea, presence of atrial fibrillation (AF) (OR: 3.906; 95% CI 1.470 to 10.381; p=0.006) and pulmonary artery systolic pressure (PASP) (OR: 1.057; 95% CI 1.016 to 1.100; p=0.006) were the predictors of in-hospital mortality. The receiver operating characteristic curve analysis revealed that the optimal value of PASP in predicting the in-hospital mortality was 35 mm Hg (area under the curve=0.71; 95% CI 0.60 to 0.81, p<0.001) with sensitivity of 87.7% and specificity of 59.5%. CONCLUSION: The present research found that the preoperative cardiac risk factors, namely AF and PASP, might be associated with increased in-hospital mortality in elderly patients without heart failure undergoing hip fracture surgery.

Temporal Trends in Prevalence and Prognostic Implications of Comorbidities Among Patients With Acute Decompensated Heart Failure: The ARIC Study Community Surveillance.

BACKGROUND: Patients with heart failure (HF) have multiple coexisting comorbidities. The temporal trends in the burden of comorbidities and associated risk of mortality among patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not well established. METHODS: HF-related hospitalizations were sampled by stratified design from 4 US areas in 2005 to 2014 by the community surveillance component of the ARIC study (Atherosclerosis Risk in Communities). Acute decompensated HF was classified by standardized physician review and a previously validated algorithm. An ejection fraction <50% was considered HFrEF. A total of 15 comorbidities were abstracted from the medical record. Mortality outcomes were ascertained for up to 1-year postadmission by linking hospital records with death files. RESULTS: A total of 5460 hospitalizations (24 937 weighted hospitalizations) classified as acute decompensated HF had available ejection fraction data (53% female, 68% white, 53% HFrEF, 47% HFpEF). The average number of comorbidities was higher for patients with HFpEF versus HFrEF, both for women (5.53 versus 4.94; P<0.0001) and men (5.20 versus 4.82; P<0.0001). There was a significant temporal increase in the overall burden of comorbidities, both for patients with HFpEF (women: 5.17 in 2005-2009 to 5.87 in 2010-2013; men: 4.94 in 2005-2009 and 5.45 in 2010-2013) and HFrEF (women: 4.78 in 2005-2009 to 5.14 in 2010-2013; men: 4.62 in 2005-2009 and 5.06 in 2010-2013; P-trend<0.0001 for all). Higher comorbidity burden was significantly associated with higher adjusted risk of 1-year mortality, with a stronger association noted for HFpEF (hazard ratio [HR] per 1 higher comorbidity, 1.19 [95% CI, 1.14-1.25] versus HFrEF (HR, 1.10 [95% CI, 1.05-1.14]; P for interaction by HF type=0.02). The associated mortality risk per 1 higher comorbidity also increased significantly over time for patients with HFpEF and HFrEF, as well (P for interaction with time=0.002 and 0.02, respectively) Conclusions: The burden of comorbidities among hospitalized patients with acute decompensated HFpEF and HFrEF has increased over time, as has its associated mortality risk. Higher burden of comorbidities is associated with higher risk of mortality, with a stronger association noted among patients with HFpEF versus HFrEF.

Unsupervised hidden semi-Markov model for automatic beat onset detection in 1D Doppler ultrasound.

OBJECTIVE: One dimensional (1D) Doppler ultrasound (DUS) is commonly used for fetal health assessment, during both regular prenatal visits and labor. It is used in preference to ECG and other modalities because of its simplicity and cost. To date, all analysis of such data has been confined to a smoothed, windowed heart rate estimation derived from the 1D DUS signal, reducing the potential of short-term variability information. A first step in improving the assessment of short-term variability of the fetal heart rate (FHR) is through implementing an accurate beat detector for 1D DUS signals. APPROACH: This work presents an unsupervised probabilistic segmentation method enabled by a hidden semi-Markov model (HSMM). The proposed method employs envelope and spectral features for an online segmentation of fetal 1D DUS signal. The beat onsets and fetal cardiac beat-to-beat intervals are then estimated from the segmentations. For this work, two data sets were used, including 1D DUS recordings from five fetuses recorded in Germany, comprising 6521 beats and 45.06 minutes of data (dataset 1). Simultaneous fetal ECG (fECG) was used as the reference for beat timing. Dataset 2, comprising 4044 beats captured from 17 subjects in the UK was hand scored for beat location and was used as an independent held-out test set. Leave-one-out subject cross-validation was used for parameter tuning on dataset 1. No retraining was performed for dataset 2. To assess the performance of the beat onset detection, the root mean square error (RMSE), F1 score, sensitivity, positive predictivity (PPV) and the error in several standard common heart rate variability metrics were used. These metrics were evaluated on three fiducial points: (1) beat onset, (2) beat offset, and (3) middle of beat interval. MAIN RESULTS: In dataset 1, the proposed method provided an RMSE of 20 ms, F1 score of 97.5 %, a Se of 97.6%, and a PPV of 97.3%. In dataset 2, the proposed method achieved an RMSE of 26 ms, an F1 score of 98.5 %, a Se of 98.0 % and a PPV of 98.9 %. It was also determined that the best beat-to-beat interval was derived from the onset of each beat. For the dataset 2, significant correlations were found in all short term heart rate variability metrics tested, both in the time and frequency domain. Only the proportion of successive normal-to-normal interval differences greater than 20 ms (pNN20) exhibited a significant absolute difference. SIGNIFICANCE: This work presents the first-ever description of an algorithm to identify cardiac beats with 1D DUS, closely matching the fetal ECG-derived beats, to enable short-term heart rate variability analysis. The novel algorithm proposed requires no human labeling of data, and could have applicability beyond 1D DUS to other similar highly variable time series.

A Multiparametric Assay Platform for Simultaneous In Vivo Assessment of Pronephric Morphology, Renal Function and Heart Rate in Larval Zebrafish.

Automated high-throughput workflows allow for chemical toxicity testing and drug discovery in zebrafish disease models. Due to its conserved structural and functional properties, the zebrafish pronephros offers a unique model to study renal development and disease at larger scale. Ideally, scoring of pronephric phenotypes includes morphological and functional assessments within the same larva. However, to efficiently upscale such assays, refinement of existing methods is required. Here, we describe the development of a multiparametric in vivo screening pipeline for parallel assessment of pronephric morphology, kidney function and heart rate within the same larva on a single imaging platform. To this end, we developed a novel 3D-printed orientation tool enabling multiple consistent orientations of larvae in agarose-filled microplates. Dorsal pronephros imaging was followed by assessing renal clearance and heart rates upon fluorescein isothiocyanate (FITC)-inulin microinjection using automated time-lapse imaging of laterally positioned larvae. The pipeline was benchmarked using a set of drugs known to induce developmental nephrotoxicity in humans and zebrafish. Drug-induced reductions in renal clearance and heart rate alterations were detected even in larvae exhibiting minor pronephric phenotypes. In conclusion, the developed workflow enables rapid and semi-automated in vivo assessment of multiple morphological and functional parameters.

Comparison of NICE and ESC proposed strategies on new onset chest pain and the contemporary clinical utility of pretest probability risk score.

AIMS: Patients with de novo chest pain are usually investigated non-invasively. The new UK-National Institute for Health and Care Excellence (NICE) guidelines recommend CT coronary angiography (CTCA) for all patients, while European Society of Cardiology (ESC) recommends functional tests. We sought to compare the clinical utility and perform a cost analysis of these recommendations in two UK centres with different primary investigative strategies. METHODSRESULTS: We compared two groups of patients, group A (n=667) and group B (n=654), with new onset chest pain in two neighbouring National Health Service hospitals, each primarily following either ESC (group A) or NICE (group B) guidance. We assessed the clinical utility of each strategy, including progression to invasive coronary angiography (ICA) and revascularisation. We present a retrospective cost analysis in the context of UK tariff for stress echo (£176), CTCA (£220) and ICA (£1001). Finally, we sought to identify predictors of revascularisation in the whole population.Baseline characteristics in both groups were similar. The progression to ICA was comparable (9.9% vs 12.0%, p=0.377), with similar requirement for revascularisation (4.0% vs 5.0%.; p=0.532). The average cost of investigations per investigated patient was lower in group A (£279.66 vs £325.77), saving £46.11 per patient. The ESC recommended risk score (RS) was found to be the only predictor of revascularisation (OR 1.05, 95% CI 1.04 to 1.06; p<0.001). CONCLUSION: Both NICE and ESC-proposed strategies led to similar rates of ICA and need for revascularisation in discrete, but similar groups of patients. The SE-first approach had a lower overall cost by £46.11 per patient, and the ESC RS was the only variable correlated to revascularisation.

Preoperative cardiac assessment in liver transplant candidates.

New and extended indications, older age, higher cardiovascular risk, and the long-standing cirrhosis-associated complications mandate specific skills for an appropriate preoperative assessment of the liver transplant (LT) candidate. The incidence of cardiac diseases (dysrhythmias, cardiomyopathies, coronary artery disease, valvular heart disease) are increasing among LT recipients: however, no consensus exists among clinical practice guidelines for cardiovascular screening and risk stratification. In spite of different "transplant center-centered protocols", basic "pillars" are common (electrocardiography, baseline echocardiography, functional assessment). Owing to intrinsic limitations, yields and relevance of noninvasive stress tests, under constant scrutiny even if used, are discussed, focusing the definition of the "high risk" candidate and exploring noninvasive imaging and new forms of stress imaging. The aim is to find an appropriate and rational stepwise algorithm. The final commitment is to select the right candidate for a finite resource, the graft, able to save (and change) lives.

Hemodynamic assessment of diastolic function for experimental models.

Traditionally, the evaluation of cardiac function has focused on systolic function; however, there is a growing appreciation for the contribution of diastolic function to overall cardiac health. Given the emerging interest in evaluating diastolic function in all models of heart failure, there is a need for sensitivity, accuracy, and precision in the hemodynamic assessment of diastolic function. Hemodynamics measure cardiac pressures in vivo, offering a direct assessment of diastolic function. In this review, we summarize the underlying principles of diastolic function, dividing diastole into two phases: 1) relaxation and 2) filling. We identify parameters used to comprehensively evaluate diastolic function by hemodynamics, clarify how each parameter is obtained, and consider the advantages and limitations associated with each measure. We provide a summary of the sensitivity of each diastolic parameter to loading conditions. Furthermore, we discuss differences that can occur in the accuracy of diastolic and systolic indices when generated by automated software compared with custom software analysis and the magnitude each parameter is influenced during inspiration with healthy breathing and a mild breathing load, commonly expected in heart failure. Finally, we identify key variables to control (e.g., body temperature, anesthetic, sampling rate) when collecting hemodynamic data. This review provides fundamental knowledge for users to succeed in troubleshooting and guidelines for evaluating diastolic function by hemodynamics in experimental models of heart failure.

A novel index equivalent to the myocardial performance index for right ventricular functional assessment in children and adolescent patients.

The aims of the present study were to develop and check the utility and feasibility of a novel right ventricular (RV) functional index (RV angular velocity; RVω, s-1) derived from the angular velocity in harmonic oscillator kinematics obtained from the RV pressure waveform. We hypothesized that RVω reflects the myocardial performance index (MPI), which represents global RV function. A total of 132 consecutive patients, ranging in age from 3 months to 34 years with various cardiac diseases were included in this prospective study. RVω was defined as the difference between the peak derivative of pressure (dP/dt_max - dP/dt_min) divided by the difference between the maximum and minimum pressure (Pmax - Pmin). RVω showed significant negative correlations with the pulsed-wave Doppler-derived myocardial performance index (PWD-MPI) and the tissue Doppler imaging-derived MPI (TDI-MPI) (r = -0.52 and -0.51, respectively; both p < 0.0001). RVω also showed significant positive correlations with RV fractional area change (RVFAC) and RV ejection fraction (RVEF) (r = 0.41 and 0.39, respectively; both p < 0.0001), as well as a significant negative correlation with tricuspid E/e' (r = -0.19, p = 0.0283). The clinical feasibility and utility of RVω for assessing global RV performance, incorporating both systolic and diastolic function, were demonstrated.

Cardiac safety assessment with motion field imaging analysis of human iPS cell-derived cardiomyocytes is improved by an integrated evaluation with cardiac ion channel profiling.

We validated a motion field imaging (MFI) assay with human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) as a model to assess multiple cardiac liabilities by comparing the guinea-pig Langendorff heart with hiPS-CMs using 4 reference compounds and 9 internal compounds. We investigated repolarization duration, beating rate (BR), conduction speed, contractility, and inhibitory profile of three cardiac ion channels: hERG, Cav1.2, and Nav1.5. For repolarization, the contraction-relaxation duration (CRDc) of hiPS-CMs was generally consistent with the QTc interval of Langendorff heart. However, 2 internal compounds shortened CRDc despite QTc prolongation in Langendorff heart. Cardiac ion channel profiling revealed that hiPS-CMs could not be used to detect QTc prolongation when the value of Cav1.2 IC50 / hERG IC50 for a compound was between 1 and 10, whereas hiPS-CMs showed responses largely consistent with Langendorff heart when Cav1.2 IC50 / hERG IC50 was below 1 or above 10. The accuracy of hiPS-CMs for the BR was not high, mainly because the BR of hiPS-CMs was increased by an inhibition of Cav1.2. The hiPS-CMs were highly sensitive to conduction speed and contractility, able to detect QRS widening caused by Nav1.5-inhibition, as well as decreased LVdP/dtmax caused by the inhibition of Cav1.2 and/or Nav1.5. In conclusion, the MFI assay with hiPS-CMs would be useful for evaluating multiple cardiac liabilities. The ion channel profile helps to interpret the results of MFI assay and correctly evaluate cardiac risks. Therefore, an integrated cardiac safety assessment with MFI and ion channel profiling is recommended.

Biomechanical assessment of remote and postinfarction scar remodeling following myocardial infarction.

The importance of collagen remodeling following myocardial infarction (MI) is extensively investigated, but little is known on the biomechanical impact of fibrillar collagen on left ventricle post-MI. We aim to identify the significant effects of the biomechanics of types I, III, and V collagen on physio-pathological changes of murine hearts leading to heart failure. Immediately post-MI, heart reduces its function (EF = 40.94 ± 2.12%) while sarcomeres' dimensions are unchanged. Strikingly, as determined by immunohistochemistry staining, type V collagen fraction significantly grows in remote and scar for sustaining de novo-types I and III collagen fibers' assembly while hindering their enzymatic degradation. Thereafter, the compensatory heart function (EF = 63.04 ± 3.16%) associates with steady development of types I and III collagen in a stiff remote (12.79 ± 1.09 MPa) and scar (22.40 ± 1.08 MPa). In remote, the soft de novo-type III collagen uncoils preventing further expansion of elongated sarcomeres (2.7 ± 0.3 mm). Once the compensatory mechanisms are surpassed, the increased turnover of stiff type I collagen (>50%) lead to a pseudo-stable biomechanical regime of the heart (≅9 MPa) with reduced EF (50.55 ± 3.25%). These end-characteristics represent the common scenario evidenced in patients suffering from heart failure after MI. Our pre-clinical data advances the understanding of the cause of heart failure induced in patients with extended MI.

Trends in High- and Low-Value Cardiovascular Diagnostic Testing in Fee-for-Service Medicare, 2000-2016.

Importance: Owing to a rapid increase in rates of diagnostic cardiovascular testing in the 1990s and early 2000s, the Centers for Medicare & Medicaid Services implemented a series of payment changes intended to reduce overall spending on fee-for-service testing. Whether guideline-concordant testing has been subsequently affected is unknown to date. Objective: To determine whether changes in overall rates of use of diagnostic cardiovascular tests were associated with changes in high-value testing recommended by guidelines and low-value testing that is expected to provide minimal benefits. Design, Setting, and Participants: This retrospective cohort study assessed a national 5% random sample of Medicare fee-for-service beneficiaries aged 65 to 95 years from January 1, 1999, through December 31, 2016. Data were analyzed from February 15, 2018, through August 15, 2019. Exposures: Eligibility to receive high-value testing (assessment of left ventricular systolic function among patients hospitalized with acute myocardial infarction or heart failure) and low-value testing (stress testing before low-risk noncardiac surgery and routine stress testing within 2 years of coronary revascularization not associated with acute care visits). Main Outcomes and Measures: Age- and sex-adjusted annual rates of overall, high-value, and low-value diagnostic cardiovascular testing. Results: Mean (SD) age was similar over time (75.57 [7.32] years in 2000-2003; 74.82 [7.79] years in 2012-2016); the proportion of women slightly declined over time (63.23% in 2000 to 2003; 57.27% in 2012 to 2016). The rate of overall diagnostic cardiovascular testing per 1000 patient-years among the 5% sample of Medicare beneficiaries increased from 275 in 2000 to 359 in 2008 (P < .001) and then declined to 316 in 2016 (P < .001). High-value testing increased steadily over the entire study period for patients with acute myocardial infarction (85.7% to 89.5%; P < .001) and heart failure (72.6% to 80.1%; P < .001). Low-value testing among patients undergoing low-risk surgery increased from 2.4% in 2000 to 3.8% in 2008 (P < .001) but then declined to 2.5% in 2016 (P < .001). Low-value testing within 2 years of coronary revascularization slightly increased from 47.4% in 2000 to 49.2% in 2003 (P = .03) but then declined to 30.8% in 2014 (P < .001). Conclusions and Relevance: Rates of overall and low-value diagnostic cardiovascular testing appear to have declined considerably and rates of high-value testing have increased slightly. Payment changes intended to reduce spending on overall testing may not have adversely affected testing recommended by guidelines.

Assessment of patients with hereditary transthyretin amyloidosis - understanding the impact of management and disease progression.

Timely diagnosis of hereditary variant transthyretin (ATTRv) amyloidosis is critical for appropriate treatment and optimal outcomes. Significant differences are seen between patients receiving treatment and those who are not, though disease progression may continue despite treatment in some patients. Healthcare professionals caring for patients with ATTRv amyloidosis therefore need reliable ongoing assessments to understand the continuing course of disease and make appropriate treatment choices on an individual basis. Various signs and symptoms experienced by patients may be evaluated as indicators of disease progression, though there is currently no validated score that can be used for such ongoing assessment. Recognizing this situation, a group of clinicians highly experienced in ATTR amyloidosis developed an approach to understand and define disease progression in diagnosed and treated patients with ATTRv amyloidosis. The suggested approach is based on the recognition of distinct phenotypes which may usefully inform the particular tools, tests and investigations that are most likely to be appropriate for individual patients. It is aimed at implementing appropriate and ongoing assessment of patients being treated for ATTRv amyloidosis, such that the effectiveness of management can be usefully assessed throughout the course of disease and management can be tailored according to the patient's requirements.

Assessment of Pharmacology, Safety, and Metabolic activity of Capsaicin Feeding in Mice.

Capsaicin (CAP) activates transient receptor potential vanilloid subfamily 1 (TRPV1) to counter high-fat diet (HFD)-induced obesity. Several studies suggest that CAP induces the browning of white adipocytes in vitro or inguinal white adipose tissue (iWAT) in vivo. However, there is a lack of data on the dose-response for CAP to inhibit HFD-induced obesity. Therefore, we first performed experiments to correlate the effect of various doses of CAP to prevent HFD-induced weight gain in wild-type (WT) mice. Next, we performed a subchronic safety study in WT mice fed a normal chow diet (NCD ± CAP, 0.01% in NCD) or HFD ± CAP (0.01% in HFD) for eight months. We analyzed the expression of adipogenic and thermogenic genes and proteins in the iWAT from these mice, conducted histological studies of vital organs, measured the inflammatory cytokines in plasma and iWAT, and evaluated liver and kidney functions. The dose-response study showed that CAP, at doses above 0.001% in HFD, countered HFD-induced obesity in mice. However, no difference in the anti-obesity effect of CAP was observed at doses above 0.003% in HFD. Also, CAP, above 0.001%, enhanced the expression of sirtuin-1 and thermogenic uncoupling protein 1 (UCP-1) in the iWAT. Safety analyses suggest that CAP did not cause inflammation. However, HFD elevated plasma alanine aminotransferase and creatinine, caused iWAT hypertrophy and hepatic steatosis, and CAP reversed these. Our data suggest that CAP antagonizes HFD-induced metabolic stress and inflammation, while it does not cause any systemic toxicities and is well tolerated by mice.

The role of ventricular-arterial coupling in cardiac disease and heart failure: assessment, clinical implications and therapeutic interventions. A consensus document of the European Society of Cardiology Working Group on Aorta & Peripheral Vascular Diseases, European Association of Cardiovascular Imaging, and Heart Failure Association.

Ventricular-arterial coupling (VAC) plays a major role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac disease. VAC assessment possesses independent diagnostic and prognostic value and may be used to refine riskstratification and monitor therapeutic interventions. Traditionally, VAC is assessed by the non-invasive measurement of the ratio of arterial (Ea) to ventricular end-systolic elastance (Ees). With disease progression, both Ea and Ees may become abnormal and the Ea/Ees ratio may approximate its normal values. Therefore, the measurement of each component of this ratio or of novel more sensitive markers of myocardial (e.g. global longitudinal strain) and arterial function (e.g. pulse wave velocity) may better characterize VAC. In valvular heart disease, systemic arterial compliance and valvulo-arterial impedance have an established diagnostic and prognostic value and may monitor the effects of valve replacement on vascular and cardiac function. Treatment guided to improve VAC through improvement of both or each one of its components may delay incidence of heart failure and possibly improve prognosis in heart failure. In this consensus document, we describe the pathophysiology, the methods of assessment as well as the clinical implications of VAC in cardiac diseases and heart failure. Finally, we focus on interventions that may improve VAC and thus modify prognosis.