Emerging multimodality imaging techniques for the pulmonary circulation.

Pulmonary hypertension (PH) remains a challenging condition to diagnose, classify and treat. Current approaches to the assessment of PH include echocardiography, ventilation/perfusion scintigraphy, cross-sectional imaging using computed tomography and magnetic resonance imaging, and right heart catheterisation. However, these approaches only provide an indirect readout of the primary pathology of the disease: abnormal vascular remodelling in the pulmonary circulation. With the advent of newer imaging techniques, there is a shift toward increased utilisation of noninvasive high-resolution modalities that offer a more comprehensive cardiopulmonary assessment and improved visualisation of the different components of the pulmonary circulation. In this review, we explore advances in imaging of the pulmonary vasculature and their potential clinical translation. These include advances in diagnosis and assessing treatment response, as well as strategies that allow reduced radiation exposure and implementation of artificial intelligence technology. These emerging modalities hold the promise of developing a deeper understanding of pulmonary vascular disease and the impact of comorbidities. They also have the potential to improve patient outcomes by reducing time to diagnosis, refining classification, monitoring treatment response and improving our understanding of disease mechanisms.

3D Vortex-Energetics in the Left Pulmonary Artery for Differentiating Pulmonary Arterial Hypertension and Pulmonary Venous Hypertension Groups Using 4D Flow MRI.

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening. Differentiation pulmonary arterial hypertension (PAH) from pulmonary venous hypertension (PVH) is important due to distinct treatment protocols. Invasive right heart catheterization (RHC) remains the reference standard but noninvasive alternatives are needed. PURPOSE/HYPOTHESIS: To evaluate 4D Flow MRI-derived 3D vortex energetics in the left pulmonary artery (LPA) for distinguishing PAH from PVH. STUDY TYPE: Prospective case-control. POPULATION/SUBJECTS: Fourteen PAH patients (11 female) and 18 PVH patients (9 female) diagnosed from RHC, 23 healthy controls (9 female). FIELD STRENGTH/SEQUENCE: 1.5 T; gradient recalled echo 4D flow and balanced steady-state free precession (bSSFP) cardiac cine sequences. ASSESSMENT: LPA 3D vortex cores were identified using the lambda2 method. Peak vortex-contained kinetic energy (vortex-KE) and viscous energy loss (vortex-EL) were computed from 4D flow MRI. Left and right ventricular (LV, RV) stroke volume (LVSV, RVSV) and ejection fraction (LVEF, RVEF) were computed from bSSFP. In PH patients, mean pulmonary artery pressure (mPAP), pulmonary capillary wedge pressure (PCWR) and pulmonary vascular resistance (PVR) were determined from RHC. STATISTICAL TESTS: Mann-Whitney U test for group comparisons, Spearman's rho for correlations, logistic regression for identifying predictors of PAH vs. PVH and develop models, area under the receiver operating characteristic curve (AUC) for model performance. Significance was set at P < 0.05. RESULTS: PAH patients showed significantly lower vortex-KE (37.14 [14.68-78.52] vs. 76.48 [51.07-120.51]) and vortex-EL (9.93 [5.69-25.70] vs. 24.22 [12.20-32.01]) than PVH patients. The combined vortex-KE and LVEF model achieved an AUC of 0.89 for differentiating PAH from PVH. Vortex-EL showed significant negative correlations with mPAP (rho = -0.43), PCWP (rho = 0.37), PVR (rho = -0.64). In the PAH group, PVR was significantly negatively correlated with LPA vortex-KE (rho = -0.73) and vortex-EL (rho = -0.71), and vortex-KE significantly correlated with RVEF (rho = 0.69), RVSV, (rho = 0.70). In the PVH group, vortex-KE (rho = 0.52), vortex-EL significantly correlated with RVSV (rho = 0.58). DATA CONCLUSION: These preliminary findings suggest that 4D flow MRI-derived LPA vortex energetics have potential to noninvasively differentiate PAH from PVH and correlate with invasive hemodynamic parameters. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

Echocardiographic correlates of major adverse cardiac events at 1 year in patients with apical ballooning takotsubo syndrome.

INTRODUCTION: Takotsubo syndrome (TTS) is characterized by transient left ventricular dysfunction and associated with considerable morbidity and mortality. We sought to evaluate the association between change in cardiac mechanics after diagnosis of TTS with 1-year incidence of major adverse cardiovascular events (MACE). METHODS: We retrospectively identified 85 patients with apical TTS based on ICD 9/10 codes and chart adjudication, who had a follow-up echocardiogram within 6 months of diagnosis. Echocardiograms were analyzed for left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), GLS ratio, global circumferential strain (GCS), and global radial strain (GRS). Multivariable logistic regression was performed to identify parameters associated with MACE (all-cause mortality, heart failure, stroke, and coronary artery disease [CAD] requiring percutaneous coronary intervention [PCI]) at 1 year. Event-free survival was assessed in patients with GLS (≤-18% vs. >18%) and LVEF (≥53% vs. <53%). RESULTS: Within 1 year of diagnosis, MACE occurred in 15 (18%) patients. Between baseline and follow-up echocardiogram (median 15 [range 1-151] days), there were significant differences in change in LVEF and GLS in patients with versus without incident MACE. In multivariate analysis, change in LVEF (odds ratio [OR] = .93 [.87, .98], p = .013) and change in GLS (OR = 1.32 [1.04, 1.67], p = .022) were independently associated with MACE; however, the association with change in GLS was attenuated (odds ratio [OR] = 1.13 [.94, 1.36], p = .21) after adjustment for baseline and change in LVEF. Among patients with normalized LVEF at follow-up, there were five (14.7%) MACE; whereas, there were no events among patients with normalized GLS. CONCLUSIONS: In patients with apical TTS, recovery in GLS and LVEF at follow-up was associated with significantly lower MACE at 1 year. Normalization of GLS at follow-up was better able to discriminate event-free survival than normalization of LVEF.

Rapid reconstruction of highly undersampled, non-Cartesian real-time cine k-space data using a perceptual complex neural network (PCNN).

Highly accelerated real-time cine MRI using compressed sensing (CS) is a promising approach to achieve high spatio-temporal resolution and clinically acceptable image quality in patients with arrhythmia and/or dyspnea. However, its lengthy image reconstruction time may hinder its clinical translation. The purpose of this study was to develop a neural network for reconstruction of non-Cartesian real-time cine MRI k-space data faster (<1 min per slice with 80 frames) than graphics processing unit (GPU)-accelerated CS reconstruction, without significant loss in image quality or accuracy in left ventricular (LV) functional parameters. We introduce a perceptual complex neural network (PCNN) that trains on complex-valued MRI signal and incorporates a perceptual loss term to suppress incoherent image details. This PCNN was trained and tested with multi-slice, multi-phase, cine images from 40 patients (20 for training, 20 for testing), where the zero-filled images were used as input and the corresponding CS reconstructed images were used as practical ground truth. The resulting images were compared using quantitative metrics (structural similarity index (SSIM) and normalized root mean square error (NRMSE)) and visual scores (conspicuity, temporal fidelity, artifacts, and noise scores), individually graded on a five-point scale (1, worst; 3, acceptable; 5, best), and LV ejection fraction (LVEF). The mean processing time per slice with 80 frames for PCNN was 23.7 ± 1.9 s for pre-processing (Step 1, same as CS) and 0.822 ± 0.004 s for dealiasing (Step 2, 166 times faster than CS). Our PCNN produced higher data fidelity metrics (SSIM = 0.88 ± 0.02, NRMSE = 0.014 ± 0.004) compared with CS. While all the visual scores were significantly different (P < 0.05), the median scores were all 4.0 or higher for both CS and PCNN. LVEFs measured from CS and PCNN were strongly correlated (R2 = 0.92) and in good agreement (mean difference = -1.4% [2.3% of mean]; limit of agreement = 10.6% [17.6% of mean]). The proposed PCNN is capable of rapid reconstruction (25 s per slice with 80 frames) of non-Cartesian real-time cine MRI k-space data, without significant loss in image quality or accuracy in LV functional parameters.

Echocardiographic parameters associated with in-hospital adverse outcomes in patients with Takotsubo syndrome.

INTRODUCTION: Takotsubo syndrome (TTS) is an acute heart failure syndrome that leads to significant morbidity and mortality. We sought to evaluate the association of cardiac mechanics on presentation with in-hospital adverse outcomes in patients with apical TTS. METHODS: We retrospectively identified 468 patients with TTS based on ICD-9/10 codes between 2006 and 2017. The association of echocardiographic parameters with a composite outcome of heart failure and all-cause mortality during the index hospitalization was analyzed. RESULTS: One hundred and forty one patients with the apical subtype and adequate imaging were included. 113 (80.1%) were female, left ventricular ejection fraction (LVEF) was 41.7% ± 12.4%, and global longitudinal strain was -10.1% ± 3.2%. The composite outcome occurred in 58 patients (41%), with heart failure occurring in 55 patients and death occurring in nine patients. Global longitudinal strain, global circumferential strain, global radial strain, right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular free wall strain were significantly worse in patients who experienced the composite outcome in univariate analyses. However, only LVEF was independently associated with the composite outcome in multivariable-adjusted analysis. CONCLUSIONS: In patients with apical TTS, the strain has limited prognostic utility in the acute setting compared to LVEF, which was the only echocardiographic parameter associated with in-hospital heart failure and all-cause mortality.

Rapid dealiasing of undersampled, non-Cartesian cardiac perfusion images using U-net.

Compressed sensing (CS) is a promising method for accelerating cardiac perfusion MRI to achieve clinically acceptable image quality with high spatial resolution (1.6 × 1.6 × 8 mm3 ) and extensive myocardial coverage (6-8 slices per heartbeat). A major disadvantage of CS is its relatively lengthy processing time (~8 min per slice with 64 frames using a graphics processing unit), thereby making it impractical for clinical translation. The purpose of this study was to implement and test whether an image reconstruction pipeline including a neural network is capable of reconstructing 6.4-fold accelerated, non-Cartesian (radial) cardiac perfusion k-space data at least 10 times faster than CS, without significant loss in image quality. We implemented a 3D (2D + time) U-Net and trained it with 132 2D + time datasets (coil combined, zero filled as input; CS reconstruction as reference) with 64 time frames from 28 patients (8448 2D images in total). For testing, we used 56 2D + time coil-combined, zero-filled datasets (3584 2D images in total) from 12 different patients as input to our trained U-Net, and compared the resulting images with CS reconstructed images using quantitative metrics of image quality and visual scores (conspicuity of wall enhancement, noise, artifacts; each score ranging from 1 (worst) to 5 (best), with 3 defined as clinically acceptable) evaluated by readers. Including pre- and post-processing steps, compared with CS, U-Net significantly reduced the reconstruction time by 14.4-fold (32.1 ± 1.4 s for U-Net versus 461.3 ± 16.9 s for CS, p < 0.001), while maintaining high data fidelity (structural similarity index = 0.914 ± 0.023, normalized root mean square error = 1.7 ± 0.3%, identical mean edge sharpness of 1.2 mm). The median visual summed score was not significantly different (p = 0.053) between CS (14; interquartile range (IQR) = 0.5) and U-Net (12; IQR = 0.5). This study shows that the proposed pipeline with a U-Net is capable of reconstructing 6.4-fold accelerated, non-Cartesian cardiac perfusion k-space data 14.4 times faster than CS, without significant loss in data fidelity or image quality.

Cardiac complications of systemic sclerosis and management: recent progress.

PURPOSE OF REVIEW: Cardiac complications in systemic sclerosis (SSc) continue to be a leading cause of death in this patient population. Early recognition and treatment of the cardiac diseases commonly associated with SSc is essential. RECENT FINDINGS: Recent studies have confirmed the significant increase in mortality in SSc patients with cardiac involvement. Electrocardiography and echocardiography (2DE) continue to play a major role in screening and diagnosing cardiac manifestations such as arrhythmias or biventricular dysfunction, respectively. Novel techniques such as myocardial strain imaging on 2DE and T1 mapping on cardiovascular magnetic resonance are useful for detecting subclinical cardiac abnormalities, but the clinical relevance of these findings is still not known. An expert consensus was recently published to help establish best practice guidelines on management of cardiac complications in SSc, but data supporting these recommendations remain limited. SUMMARY: Recent studies continue to enhance our understanding of SSc cardiac disease. Although the results of these studies help lessen the ambiguity of managing and treating these patients, there is still much more research to be done.

Physicians' professional identities: a roadmap to understanding "value" in cardiovascular imaging.

BACKGROUND: Quality improvement efforts in cardiovascular imaging have been challenged by limited adoption of initiatives and policies. In order to better understand this limitation and inform future efforts, the range clinical values related to cardiovascular imaging at a large academic hospital was characterized. MATERIALS AND METHODS: 15 Northwestern Medicine physicians from internal medicine, cardiology, emergency medicine, cardiac/vascular surgery, and radiology were interviewed about their use of cardiovascular imaging and imaging guidelines. Interview transcripts were systemically analyzed according to constructivist grounded theory and combined with 56 previous interviews with interventional radiologists, interventional cardiologists, gynecologists, and vascular surgeons to develop a model describing specialty-specific values. This model was applied to the 15 pilot interviews focused on cardiovascular imaging, highlighting specialty specific differences in values and practice patterns. Transcripts were also reviewed independently by a cardiologist and 2 radiologists followed by a group discussion to assess reproducibility and achieve a consensus regarding the results. RESULTS: Differences in perceived value of cardiovascular imaging and use of guidelines among physicians were well explained by three value-associated identity categories (managers, diagnosticians, and fixers) that were further differentiated along three axes (broad v. focused-thinkers, complex v. definitive-answer-seekers, and public visibility). CONCLUSIONS: Quality improvement in cardiovascular imaging may be limited by a lack of understanding and incorporation of the complexity of medical culture into ongoing initiatives. Both individually and during policy development, it is important to first understand the complexity of stakeholders' diverse perceptions of "value," "quality," and "appropriateness."

Right ventricular strain in pulmonary arterial hypertension: a 2D echocardiography and cardiac magnetic resonance study.

BACKGROUND: Right ventricular (RV) strain is a potentially useful prognostic marker in patients with pulmonary arterial hypertension (PAH). However, published reports regarding the accuracy of two-dimensional echocardiography (2DE)-derived RV strain against an independent reference in this patient population are limited. The aims of this study were: (1) to study the relationship between 2DE RV longitudinal strain and cardiovascular magnetic resonance (CMR)-derived RV ejection fraction (RVEF) in patients with PAH; (2) to compare 2DE-derived and CMR-derived RV longitudinal strain in these patients; and (3) to determine the reproducibility of these measurements. METHODS: Thirty patients with PAH underwent 2DE and CMR imaging within a 2-hour time period. 2DE RV longitudinal strain was measured from a focused RV apical four-chamber view using speckle tracking software. CMR RV longitudinal strain was measured from short-axis slices acquired using fast-strain-encoded sequence. Global peak systolic RV longitudinal strain was calculated for both 2DE and CMR. RESULTS: RV longitudinal strain using 2DE software correlated well with CMR-derived RVEF (R = 0.69, P = 0.0006). There was moderate agreement when comparing 2DE to CMR RV longitudinal strain (R = 0.74, P = 0.0002; bias -1%, limits of agreement -9 to 7%). Inter-observer variability and intra-observer variability for RV longitudinal strain were lower for 2DE than CMR. CONCLUSIONS: RV longitudinal strain by 2DE provides a good alternative for CMR-derived RVEF in patients with PAH. The moderate agreement in strain measurements between 2DE and CMR suggests that further software improvements are needed before these measurements can be used interchangeably in clinical practice.

Reference Values for Indexed Echocardiographic Chamber Sizes in Older Adults: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Normalization of echocardiographic chamber measurements for body surface area may result in misclassification of individuals with obesity or sarcopenia. Normalization for alternative measures of body size may be preferable, but there remains a dearth of information on their normative values and association with cardiovascular function metrics. METHODS AND RESULTS: A total of 3032 individuals underwent comprehensive 2-dimensional echocardiography at Exam 6 in MESA (Multi-Ethnic Study of Atherosclerosis). In the subgroup of 608 individuals free of cardiopulmonary disease (69.5±7.0 years, 46% male, 48% White, 17% Chinese, 15% Black, 21% Hispanic), normative values were derived for left and right cardiac chamber measurements across a variety of ratiometric (body surface area, body mass index, height) and allometric (height1.6, height2.7) scaling parameters. Normative upper and lower reference values were provided for each scaling parameter stratified across age groups, sex, and race or ethnicity. Among scaling parameters, body surface area and height were associated with the least variability across race and ethnicity categories and height2.7 was associated with the least variability across sex categories. CONCLUSIONS: In this diverse cohort of community-dwelling older adults, we provide normative values for common echocardiographic parameters across a variety of indexation methods.

Optimal Method for Assessing Right Ventricular to Pulmonary Arterial Coupling in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis.

Right ventricular (RV) to pulmonary arterial (PA) coupling describes the ability of the RV to augment contractility in response to increased afterload. Several echocardiographic indexes of RV-PA coupling have been defined; however, the optimal numerator in the coupling ratio is unclear. We sought to establish which of these ratios is best for assessing RV-PA coupling based on their relations with 6-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the Kansas City Cardiomyopathy Questionnaire (KCCQ) in aging adults. In this study of 1,611 Multi-Ethnic Study of Atherosclerosis participants who underwent echocardiography at Exam 6, we evaluated the association between different numerators, including tricuspid annular planar systolic excursion (TAPSE), fractional area change (FAC), RV free wall strain, and tissue Doppler imaging S' velocity to pulmonary artery systolic pressure (PASP) with 6MWD, NT-proBNP, and KCCQ score, adjusted for socioeconomic and cardiovascular disease risk factors. Our cohort had a mean age of 73 ± 8 years, 54% female, 17% Chinese American, 22% African American, 22% Hispanic, and 39% White participants. The mean ( ± SD) TAPSE/PASP, FAC/PASP, tissue Doppler imaging S' velocity/PASP, and RV free wall strain:PASP ratios were 0.7 ± 0.2, 1.3 ± 0.3, 0.5 ± 0.1, and 0.8 ± 0.2, respectively. All RV-PA coupling indices decreased with age (p <0.0001 for all). TAPSE:PASP ratio was lower in older (³85 years) female (0.59 ± 0.14) versus male (0.65 ± 0.17) participants (p = 0.01), whereas FAC/PASP ratio was higher in the same female versus male participants (p <0.01). TAPSE/PASP and FAC/PASP ratios were significantly and strongly associated with all NT-proBNP, 6MWD, and KCCQ scores in fully adjusted and receiver operating characteristic analysis. In older community-dwelling adults free of heart failure and pulmonary hypertension, both FAC/PASP and TAPSE:PASP ratios are optimal for assessment of RV-PA coupling based on its association with 6MWD, NT-proBNP, and KCCQ score. FAC/PASP ratio has the additional benefit of reflecting age and gender-related geometric and functional changes.

Multi-Ethnic Study of Atherosclerosis Early Heart Failure Study: Rationale, Design, and Baseline Characteristics.

BACKGROUND: Current prevalence estimates of heart failure (HF) are primarily based on self-report or HF hospitalizations. There is an unmet need to define the prevalence and pathogenesis of early symptomatic HF, which may be undiagnosed and precedes HF hospitalization. METHODS: The MESA (Multi-Ethnic Study of Atherosclerosis) Early HF study was conducted during MESA exam 6 to determine the prevalence of early HF and investigate the transition from risk factors to early HF in a diverse population-based cohort of older adults. Between 2016 and 2018, 3285 MESA participants from 6 field centers underwent comprehensive speckle-tracking echocardiography with passive leg raise maneuver, Kansas City Cardiomyopathy Questionnaire, 6-minute walk test, arterial stiffness assessment, and proteomics (including NT-proBNP [N-terminal pro-B-type natriuretic peptide]). RESULTS: Median age was 73 (25th-75th percentile 67-81) years, 53.2% were female, 25.6% were Black, 12.8% were Chinese, and 40.0% were White. The prevalence of HF risk factors was high: hypertension, 61.9%; former or current smoking, 53.7%; obesity 34.8%; diabetes; 24.7%; and chronic kidney disease; 22%. Overt cardiovascular disease, which ranged from 2.1% (HF) to 13.6% (atrial fibrillation), was less common. Of the 3285 participants, 96% underwent proteomics, 94% Kansas City Cardiomyopathy Questionnaire, 93% speckle-tracking echocardiography with passive leg raise, 82% arterial stiffness exam, and 77% 6-minute walk test. Feasibility of resting speckle-tracking echocardiography (87%-99% across cardiac chambers) and passive leg raise Doppler/speckle-tracking echocardiography (>84%) measurements was high. A total of 120 unique echocardiographic indices were measured. CONCLUSIONS: The MESA Early HF study is a key resource for cardiovascular researchers who are interested in improving the epidemiological and phenotypic characterization of early HF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005487.

Normative Values of Echocardiographic Chamber Size and Function in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Echocardiographic (2-dimensional echocardiography) thresholds indicating disease or impaired functional status compared with normal physiological aging in individuals aged ≥65 years are not clearly defined. In the present study, we sought to establish standard values for 2-dimensional echocardiography parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions. METHODS: In this cross-sectional study of 3032 individuals who underwent 2-dimensional echocardiography at exam 6 in the MESA (Multi-Ethnic Study of Atherosclerosis), 608 participants fulfilled our inclusion criteria of healthy aging, with normative values defined as the mean ± 1.96 standard deviation and compared across sex and race and ethnicity. Functional status measures included NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, and Kansas City Cardiomyopathy Questionnaire. Prognostic performance using MESA cutoffs was compared with established guideline cutoffs using time-to-event analysis. RESULTS: The normative aging cohort (69.5±7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6-minute walk distance, and higher (better) Kansas City Cardiomyopathy Questionnaire summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, whereas Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities. CONCLUSIONS: Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function by sex and race/ethnicity, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.

Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction.

Metabolic comorbidities, such as obesity and diabetes, are associated with subclinical alterations in both cardiac structure/function and natriuretic peptides prior to the onset of heart failure (HF). Despite this, the exact metabolic pathways of cardiac dysfunction which precede HF are not well-defined. Among older individuals without HF in the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated the associations of 47 circulating metabolites measured by 1H-NMR with echocardiographic measures of cardiac structure and function. We then evaluated associations of significant metabolites with circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a separate cohort, we evaluated differences between top metabolites in patients with HF with preserved ejection fraction (HFpEF) and comorbidity-matched controls. Genetic variants associated with top metabolites (mQTLs) were then related to echocardiographic measures and NT-proBNP. Among 3440 individuals with metabolic and echocardiographic data in MESA (62 ± 10 years, 52% female, 38% White), 10 metabolites broadly reflective of glucose and amino acid metabolism were associated with at least 1 measure of cardiac structure or function. Of these 10 metabolites, 4 (myo-inositol, glucose, dimethylsulfone, carnitine) were associated with higher NT-proBNP and 2 (d-mannose, acetone) were associated with lower NT-proBNP. In a separate cohort, patients with HFpEF had higher circulating myo-inositol levels compared with comorbidity-matched controls. Genetic analyses revealed that 1 of 6 known myo-inositol mQTLs conferred risk of higher NT-proBNP. In conclusion, metabolomic profiling identifies several novel metabolites associated with cardiac dysfunction in a cohort at high risk for HF, revealing pathways potentially relevant to future HF risk.

Prognostic value of normal regadenoson stress perfusion cardiovascular magnetic resonance.

BACKGROUND: Regadenoson is a vasodilator stress agent that selectively activates the A2A receptor. Compared to adenosine, regadenoson is easier to administer and results in fewer side effects. Although extensively studied in patients undergoing nuclear perfusion imaging (MPI), its use for perfusion cardiovascular magnetic resonance (CMR) is not well described. The aim of this study was to determine the prognostic value of a normal regadenoson perfusion CMR in patients with known or suspected coronary artery disease. METHODS: Patients with known or suspected coronary artery disease were prospectively enrolled to receive perfusion CMR (Philips 1.5 T) with regadenoson. Three short-axis slices of the left ventricle (LV) were obtained during first pass of contrast using a hybrid GRE-EPI pulse sequence (0.075 mmol/kg Gadolinium-DTPA-BMA at 4 ml/sec). Imaging was performed 1 minute after injection of regadenoson (0.4 mg) and repeated 15 minutes after reversal of hyperemia with aminophylline (125 mg). Perfusion defects were documented if they persisted for ≥ 2 frames after peak enhancement of the LV cavity. CMR was considered abnormal if there was a resting wall motion abnormality, decreased LVEF (<40%), presence of LGE, or the presence of a perfusion defect during hyperemia. All patients were followed for a minimum of 1 year for major adverse cardiovascular event (MACE) defined as coronary revascularization, non-fatal myocardial infarction, and cardiovascular death. RESULTS: 149 patients were included in the final analysis. Perfusion defects were noted in 43/149 (29%) patients; 59/149 (40%) had any abnormality on CMR. During the mean follow-up period of 24 ± 9 months, 17/149 (11.4%) patients experienced MACE. The separation in the survival distributions for those with perfusion defects and those without perfusion defects was highly significant (log-rank p = 0.0001). When the absence of perfusion defects was added to the absence of other resting CMR abnormalities, the negative predictive value improved from 96% to 99%. CONCLUSION: Regadenoson perfusion CMR provides high confidence for excellent prognosis in patients with normal perfusion.

Characteristics of Right Ventricular to Pulmonary Arterial Coupling and Association With Functional Status Among Older Aged Adults from the Multi-Ethnic Study of Atherosclerosis.

Although the echocardiographic:derived ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) is an important prognostic tool in heart failure (HF), the relation with 6-minute walk distance (6MWD) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) is less established. We sought to establish the normative values of TAPSE:PASP among older adults without cardiovascular disease (CVD) and evaluate the relation with NT-proBNP and 6MWD. Among 1,542 participants of the Multi-Ethnic Study of Atherosclerosis-HF ancillary study, the cross-sectional association of TAPSE:PASP with the outcomes of 6MWD and NT-proBNP was analyzed using multivariable linear regression, with progressive adjustment for sociodemographic and CVD risk factors. Our cohort had a mean age (SD) of 73 ± 8 years, 55% women, and a mean TAPSE:PASP ratio of 0.68 ± 0.16. In the unadjusted analysis, increasing tertiles of TAPSE:PASP were associated with younger age, less diabetes, higher estimated glomerular filtration rate, and less antihypertensive medication use. The TAPSE:PASP ratio significantly correlated with both 6MWD and NT-proBNP in the fully adjusted models. A 1-unit increment in TAPSE:PASP was associated with an adjusted 9.9% (4.8% to 15.2%) higher 6MWD, whereas a 1-unit increment in TAPSE:PASP was associated with an adjusted 38.0% (16.0% to 54.2%) lower NT-proBNP. There was a significant gender interaction of the association of TAPSE:PASP ratio and 6MWD, with stronger association seen in women. Among multiethnic older adults free of clinical CVD, the TAPSE:PASP ratio decreased with age, especially in women and was associated with decreased 6MWD and increasing NT-proBNP, the markers of subclinical HF.

Percutaneous coronary intervention for ventricular fibrillation in the setting of an anomalous right coronary artery.

We present a case of a quadriplegic male who developed ventricular fibrillation associated with an anomalous aortic origin of the right coronary artery. Successful revascularization was achieved with percutaneous coronary intervention. This case highlights the application of an unconventional approach to resolve ischemia in a patient with prohibitive surgical risk.

Normative Values of Echocardiographic Chamber Size and Function in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis.

Background: Echocardiographic (2DE) thresholds indicating disease or impaired functional status compared to normal physiologic aging in individuals ≥ 65 years are not clearly defined. In the present study, we sought to establish standard values for 2DE parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions. Methods: In this cross-sectional study of 3032 individuals who underwent 2DE at Exam 6 in the Multi-Ethnic Study of Atherosclerosis (MESA), 608 participants fulfilled our inclusion criteria, with normative values defined as the mean value ± 1.96 standard deviations and compared across sex and race/ethnicity. Functional status measures included NT-proBNP, 6-minute walk distance [6MWD], and Kansas City Cardiomyopathy Questionnaire [KCCQ]. Prognostic performance using MESA cutoffs was compared to established guideline cutoffs using time-to-event analysis. Results: Participants meeting our inclusion criteria (69.5 ± 7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6MWD, and higher (better) KCCQ summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, while Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities. Conclusions: Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function across sexes and races/ethnicities, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.

Considerations when measuring myocardial perfusion reserve by cardiovascular magnetic resonance using regadenoson.

BACKGROUND: Adenosine cardiovascular magnetic resonance (CMR) can accurately quantify myocardial perfusion reserve. While regadenoson is increasingly employed due to ease of use, imaging protocols have not been standardized. We sought to determine the optimal regadenoson CMR protocol for quantifying myocardial perfusion reserve index (MPRi) - more specifically, whether regadenoson stress imaging should be performed before or after rest imaging. METHODS: Twenty healthy subjects underwent CMR perfusion imaging during resting conditions, during regadenoson-induced hyperemia (0.4 mg), and after 15 min of recovery. In 10/20 subjects, recovery was facilitated with aminophylline (125 mg). Myocardial time-intensity curves were used to obtain left ventricular cavity-normalized myocardial up-slopes. MPRi was calculated in two different ways: as the up-slope ratio of stress to rest (MPRi-rest), and the up-slope ratio of stress to recovery (MPRi-recov). RESULTS: In all 20 subjects, MPRi-rest was 1.78 ± 0.60. Recovery up-slope did not return to resting levels, regardless of aminophylline use. Among patients not receiving aminophylline, MPRi-recov was 36 ± 16% lower than MPRi-rest (1.13 ± 0.38 vs. 1.82 ± 0.73, P = 0.001). In the 10 patients whose recovery was facilitated with aminophylline, MPRi-recov was 20 ± 24% lower than MPRi-rest (1.40 ± 0.35 vs. 1.73 ± 0.43, P = 0.04), indicating incomplete reversal. In 3 subjects not receiving aminophylline and 4 subjects receiving aminophylline, up-slope at recovery was greater than at stress, suggesting delayed maximal hyperemia. CONCLUSIONS: MPRi measurements from regadenoson CMR are underestimated if recovery perfusion is used as a substitute for resting perfusion, even when recovery is facilitated with aminophylline. True resting images should be used to allow accurate MPRi quantification. The delayed maximal hyperemia observed in some subjects deserves further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT00871260.