4Dflow-VP-Net: A deep convolutional neural network for noninvasive estimation of relative pressures in stenotic flows from 4D flow MRI.

PURPOSE: To estimate relative transvalvular pressure gradient (TVPG) noninvasively from 4D flow MRI. METHODS: A novel deep learning-based approach is proposed to estimate pressure gradient across stenosis from four-dimensional flow MRI (4D flow MRI) velocities. A deep neural network 4D flow Velocity-to-Presure Network (4Dflow-VP-Net) was trained to learn the spatiotemporal relationship between velocities and pressure in stenotic vessels. Training data were simulated by computational fluid dynamics (CFD) for different pulsatile flow conditions under an aortic flow waveform. The network was tested to predict pressure from CFD-simulated velocity data, in vitro 4D flow MRI data, and in vivo 4D flow MRI data of patients with both moderate and severe aortic stenosis. TVPG derived from 4Dflow-VP-Net was compared to catheter-based pressure measurements for available flow rates, in vitro and Doppler echocardiography-based pressure measurement, in vivo. RESULTS: Relative pressures calculated by 4Dflow-VP-Net and in vitro pressure catheterization revealed strong correlation (r2 = 0.91). Correlations analysis of TVPG from reference CFD and 4Dflow-VP-Net for 450 simulated flow conditions showed strong correlation (r2 = 0.99). TVPG from in vitro MRI had a correlation coefficient of r2 = 0.98 with reference CFD. 4Dflow-VP-Net, applied to 4D flow MRI in 16 patients, showed comparable TVPG measurement with Doppler echocardiography (r2 = 0.85). Bland-Altman analysis of TVPG measurements showed mean bias and limits of agreement of -0.20 ± 2.07 mmHg and 0.19 ± 0.45 mmHg for CFD-simulated velocities and in vitro 4D flow velocities. In patients, overestimation of Doppler echocardiography relative to TVPG from 4Dflow-VP-Net (10.99 ± 6.77 mmHg) was observed. CONCLUSION: The proposed approach can predict relative pressure in both in vitro and in vivo 4D flow MRI of aortic stenotic patients with high fidelity.

Relative pressure estimation from 4D flow MRI using generalized Bernoulli equation in a phantom model of arterial stenosis.

OBJECTIVE: Arterial stenosis is a significant cardiovascular disease requiring accurate estimation of the pressure gradients for determining hemodynamic significance. In this paper, we propose Generalized Bernoulli Equation (GBE) utilizing interpolated-based method to estimate relative pressures using streamlines and pathlines from 4D Flow MRI. METHODS: 4D Flow MRI data in a stenotic phantom model and computational fluid dynamics simulated velocities generated under identical flow conditions were processed by Generalized Bernoulli Equation (GBE), Reduced Bernoulli Equations (RBE), as well as the Simple Bernoulli Equation (SBE) which is clinically prevalent. Pressures derived from 4D flow MRI and noise corrupted CFD velocities were compared with pressures generated directly with CFD as well as pressures obtained using Millar catheters under identical flow conditions. RESULTS: It was found that SBE and RBE methods underestimated the relative pressure for lower flow rates while overestimating the relative pressure at higher flow rates. Specifically, compared to the reference pressure, SBE underestimated the maximum relative pressure by 22[Formula: see text] for a pulsatile flow data with peak flow rate [Formula: see text] and overestimated by around 40[Formula: see text] when [Formula: see text]. In contrast, for GBE method the relative pressure values were overestimated by 15[Formula: see text] with [Formula: see text]and around 10[Formula: see text] with [Formula: see text]. CONCLUSION: GBE methods showed robust performance to additive image noise compared to other methods. Our findings indicate that GBE pressure estimation over pathlines attains the highest level of accuracy compared to GBE over streamlines, and the SBE and RBE methods.

Early Apixaban Use Following Stroke in Patients With Atrial Fibrillation: Results of the AREST Trial.

BACKGROUND AND PURPOSE: It is unknown when to start anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF). Early anticoagulation may prevent recurrent infarctions but may provoke hemorrhagic transformation as AF strokes are typically larger and hemorrhagic transformation-prone. Later anticoagulation may prevent hemorrhagic transformation but increases risk of secondary stroke in this time frame. Our aim was to compare early anticoagulation with apixaban in AF patients with stroke or transient ischemic attack (TIA) versus warfarin administration at later intervals. METHODS: AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was an open-label, randomized controlled trial comparing the safety of early use of apixaban at day 0 to 3 for TIA, day 3 to 5 for small-sized AIS (<1.5 cm), and day 7 to 9 for medium-sized AIS (≥1.5 cm, excluding full cortical territory), to warfarin, in a 1:1 ratio at 1 week post-TIA, or 2 weeks post-AIS. RESULTS: Although AREST ended prematurely after a national guideline focused update recommended direct oral anticoagulants over warfarin for AF, it revealed that apixaban had statistically similar yet generally numerically lower rates of recurrent strokes/TIA (14.6% versus 19.2%, P=0.78), death (4.9% versus 8.5%, P=0.68), fatal strokes (2.4% versus 8.5%, P=0.37), symptomatic hemorrhages (0% versus 2.1%), and the primary composite outcome of fatal stroke, recurrent ischemic stroke, or TIA (17.1% versus 25.5%, P=0.44). One symptomatic intracerebral hemorrhage occurred on warfarin, none on apixaban. Five asymptomatic hemorrhagic transformation occurred in each arm. CONCLUSIONS: Early initiation of anticoagulation after TIA, small-, or medium-sized AIS from AF does not appear to compromise patient safety. Potential efficacy of early initiation of anticoagulation remains to be determined from larger pivotal trials. Registration: URL: https://www.clinicaltrials.gov/; Unique identifier: NCT02283294.

Childhood cancer survivors: The integral role of the cardiologist and cardiovascular imaging.

IMPORTANCE: With 80% of childhood cancer survivors (CCS) alive 30 years after diagnosis, preventable causes of death, such as cardiovascular disease resulting from initial cancer therapy, becomes an important metric. This leads to a more pronounced role for cardiologists in the care of CCS. OBSERVATIONS: While routine cardiovascular screening has been traditionally performed by the hematologist/oncologist or primary care provider, our understanding of cardiovascular disease in CCS has advanced. The measurement of left ventricular ejection fraction (LVEF) can now be complemented with additional assessments of strain, LV mass, right ventricular function, diastolic function, valve function, the pericardium, coronary perfusion, and biomarkers. Risk factor modification, prophylaxis, and timing of treatment are also critical. CONCLUSIONS AND RELEVANCE: Early cardiovascular screening and treatment in asymptomatic CCS can be nuanced and complex. As a result, there is a renewed opportunity for the cardiologist to play an integral role in the care of CCS. KEY POINTS: Question/Purpose: Review cardiovascular disease and the role of the cardiologist in the care of asymptomatic childhood cancer survivors (CCS). FINDINGS: Cardiovascular care in CCS benefits from a multi-faceted approach that does not overly rely on LVEF. Meaning: Adequate screening and treatment of cardiovascular disease in asymptomatic CCS may often be optimized by the involvement of a cardiologist.

Dual-Venc acquisition for 4D flow MRI in aortic stenosis with spiral readouts.

BACKGROUND: Single Venc 4D flow MRI with Cartesian readout is hampered by poor velocity resolution and noise when imaging during diastole. Dual Venc acquisitions typically require the acquisition of two distinct datasets, which leads to longer scan times. PURPOSE/HYPOTHESIS: To design and develop a 4D Spiral Dual Venc sequence. The sequence allows for separate systolic and diastolic Venc s as part of a single acquisition with a prescribed switch time. The implemented sequence was hypothesized to be comparable to Cartesian 4D flow, but with increased velocity resolution in the diastolic phase and with better scan efficiency and reduced noise. STUDY TYPE: Prospective. POPULATION: The studied populations were two phantoms-a straight pipe with a stenotic narrowing and a phantom of the aortic arch which included a calcific polymeric valve-under both steady and pulsatile flows, six healthy volunteers, and eight patients with severe aortic stenosis (AS). FIELD STRENGTH/SEQUENCE: 1.5T, Dual Venc 4D flow with spiral readouts. ASSESSMENT: Data from the proposed sequence were compared with data from 4D Cartesian Dual Venc and Single Venc acquisitions. Noise was assessed from the acquired velocity data with the pump turned off and by varying Venc . Steady acquisitions were compared to the proximal slice of the lowest Single Venc acquisition. STATISTICAL TESTS: Steady flows were compared using relative-root-mean-squared-error (RRMSE). For in vivo flows and pulsatile in vitro flows, net flow for corresponding timepoints were compared with the Pearson correlation test (P < 0.01). RESULTS: For steady flows, RRMSEs for Single Venc s ranged from 17.6% to 19.4%, and 9.6% to 16.5% for Dual Venc s. The net flow correlation coefficient for the aortic arch phantom was 0.975, and 0.995 for the stenotic phantom. Normal volunteer and patient comparisons yielded a correlation of 0.970 and 0.952, respectively. in vitro and in vivo pulsatile flow waveforms closely matched. DATA CONCLUSION: The Dual Venc offers improved noise properties and velocity resolution, while the spiral trajectory offers a scan efficient acquisition with short echo time yielding reduced flow artifacts. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;52:117-128.

The evolution of apical hypertrophic cardiomyopathy: Development of mid-ventricular obstruction and apical aneurysm 11 years after initial diagnosis.

Asian hypertrophic cardiomyopathy (AHCM) is a rare variant of hypertrophic cardiomyopathy (HCM) that is more prevalent in the Asian population. There is significant overlap between AHCM, mid-cavitary obstruction, and apical aneurysms. Although more benign compared to HCM, the course of AHCM is not clearly defined. We present an interesting case of an African American male with known AHCM who develops symptomatic mid-cavitary obstruction and apical aneurysm 11 years after initial diagnosis.

Two-dimensional strain echocardiography-derived left ventricular ejection fraction, volumes, and global systolic dyssynchrony index: Comparison with three-dimensional echocardiography.

BACKGROUND: Three-dimensional (3D) echocardiography is the most accurate echocardiographic method for ventricular chamber quantification. It is unclear how two-dimensional (2D) techniques perform against 3D technology and whether 2D methods can be extrapolated to obtain 3D data. METHODS: Retrospective review of transthoracic echocardiography was performed, with comparison of ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), and 2D strain-derived global longitudinal strain (GLS) and synchrony index. RESULTS: One-hundred patients were identified. Using 3D echocardiography as reference standard, good correlation was noted with 2D strain-derived EF (r = 0.89, P < 0.01) and with 2D standard biplane EF (r = 0.90, P < 0.01) and similarly for EDV (r = 0.84 and r = 0.81, respectively, both P < 0.01). Two-dimensional strain-derived EDV by 8% and 2D biplane-derived EDV underestimated by 8% (P < 0.01). In relation to 3D EF, 2D strain underestimated by 2% and 2D standard biplane overestimated by 2% (P < 0.01). There was a negative correlation between GLS and 3D EF (r = 0.84, P = 0.001). On multivariate analysis, 3D EF could be derived from 2D strain [3D EF = 34.345 + (0.125 * EDV) + (-0.289 * ESV) + (-1.141 * GLS)]. Three-dimensional echocardiography-derived synchrony parameter (ie, standard deviation from mean time to minimum systolic volume from 16 subvolumes) did not correlate with 2D strain-derived synchrony index (r = 0.171). CONCLUSIONS: Two-dimensional standard biplane and 2D strain EF and EDV strongly correlate with 3D EF and EDV. Although 2D methods are predictive of 3D findings, over- and underestimations may occur. Three-dimensional echocardiography should be used when available.

Frequent premature atrial contractions impair left atrial contractile function and promote adverse left atrial remodeling.

OBJECTIVES: This study assessed if frequent premature atrial contractions (PACs) were associated with decreased left atrial (LA) strain and adverse remodeling. BACKGROUND: Left atrial dysfunction and enlargement increases risk of stroke. If frequent PACs cause LA dysfunction and remodeling, PAC suppressive therapy may be beneficial. METHODS: Inclusion criteria were age ≥18 years and sinus rhythm. Exclusion criteria were atrial fibrillation or any etiology for LA enlargement. Hundred and thirty-two patients with frequent PACs (≥100/24 hours) by Holter were matched to controls. Speckle tracking strain of the left atrium was performed from the 4-chamber view. Strain measurements were LA peak contractile, reservoir and conduit strain and strain rates. RESULTS: In the frequent PAC vs control group, PACs were more frequent (1959 ± 3796 vs 28 ± 25/24 hours, P < .0001). LA peak contractile strain was reduced in the group with frequent PACs vs controls (-7.85 ± 4.12% vs -9.33 ± 4.45%, P = .006). LA peak late negative contractile strain rate was less negative in the frequent PAC vs control group (-0.63 ± 0.27 s-1 vs -0.69 ± 0.32 s-1 , P = .051). LA reservoir and conduit strain and strain rates did not differ. LA volume index (LAVI) was larger in the frequent PAC vs control group (26.6 ± 7.8 vs 24.6 ± 8.8 mL/m2 , P < .05). Frequent PACs were an independent predictor of reduced LA peak contractile strain and reduced LA peak late negative contractile strain rate. CONCLUSIONS: Patients with frequent PACs have reduced LA peak contractile strain and strain rates and larger LAVI compared to controls. Frequent PACs are an independent predictor of reduced LA peak contractile strain and strain rate. These findings support the hypothesis that frequent PACs impair LA contractile function and promote adverse LA remodeling.

A curious case of an absent left atrial appendage.

The left atrial appendage (LAA) in the setting of non-valvular atrial fibrillation (NVAF) is the predominant location for intracardiac thrombus formation. An absent LAA is a very rare congenital cardiac anomaly. We present a case of a 79-year-old female with NVAF, high CHADS2VASC2 score, and high bleeding risk who presented for elective Watchman™ left atrial appendage closure device implant. A pre-procedural transesophageal echocardiography showed an absent LAA. This finding was confirmed with cardiac computed tomography and a left atrial angiogram. The patient was discharged on medical therapy with close outpatient follow-up.

4D spiral imaging of flows in stenotic phantoms and subjects with aortic stenosis.

PURPOSE: The utility of four-dimensional (4D) spiral flow in imaging of stenotic flows in both phantoms and human subjects with aortic stenosis is investigated. METHODS: The method performs 4D flow acquisitions through a stack of interleaved spiral k-space readouts. Relative to conventional 4D flow, which performs Cartesian readout, the method has reduced echo time. Thus, reduced flow artifacts are observed when imaging high-speed stenotic flows. Four-dimensional spiral flow also provides significant savings in scan times relative to conventional 4D flow. RESULTS: In vitro experiments were performed under both steady and pulsatile flows in a phantom model of severe stenosis (one inch diameter at the inlet, with 87% area reduction at the throat of the stenosis) while imaging a 6-cm axial extent of the phantom, which included the Gaussian-shaped stenotic narrowing. In all cases, gradient strength and slew rate for standard clinical acquisitions, and identical field of view and resolution were used. For low steady flow rates, quantitative and qualitative results showed a similar level of accuracy between 4D spiral flow (echo time [TE] = 2 ms, scan time = 40 s) and conventional 4D flow (TE = 3.6 ms, scan time = 1:01 min). However, in the case of high steady flow rates, 4D spiral flow (TE = 1.57 ms, scan time = 38 s) showed better visualization and accuracy as compared to conventional 4D flow (TE = 3.2 ms, scan time = 51 s). At low pulsatile flow rates, a good agreement was observed between 4D spiral flow (TE = 2 ms, scan time = 10:26 min) and conventional 4D flow (TE = 3.6 ms, scan time = 14:20 min). However, in the case of high flow-rate pulsatile flows, 4D spiral flow (TE = 1.57 ms, scan time = 10:26 min) demonstrated better visualization as compared to conventional 4D flow (TE = 3.2 ms, scan time = 14:20 min). The feasibility of 4D spiral flow was also investigated in five normal volunteers and four subjects with mild-to-moderate aortic stenosis. The approach achieved TE = 1.68 ms and scan time = 3:44 min. The conventional sequence achieved TE = 2.9 ms and scan time = 5:23 min. In subjects with aortic stenosis, we also compared both MRI methods with Doppler ultrasound (US) in the measurement of peak velocity, time to peak systolic velocity, and eject time. Bland-Altman analysis revealed that, when comparing peak velocities, the discrepancy between Doppler US and 4D spiral flow was significantly less than the discrepancy between Doppler and 4D Cartesian flow (2.75 cm/s vs. 10.25 cm/s), whereas the two MR methods were comparable (-5.75 s vs. -6 s) for time to peak. However, for the estimation of eject time, relative to Doppler US, the discrepancy for 4D conventional flow was smaller than that of 4D spiral flow (-16.25 s vs. -20 s). CONCLUSION: Relative to conventional 4D flow, 4D spiral flow achieves substantial reductions in both the TE and scan times; therefore, utility for it should be sought in a variety of in vivo and complex flow imaging applications.

Risk of Recurrent Neurologic Stroke or Transient Ischemic Attack in Patients with Cryptogenic Stroke and Intrapulmonary Shunt.

BACKGROUND AND PURPOSE: Cardio-embolic phenomenon is believed to underlie a significant proportion of cryptogenic strokes. We recently showed that intrapulmonary shunt (IPS) was associated with cryptogenic stroke and transient ischemic attack (TIA). We hypothesized that patients with prior cryptogenic stroke or TIA that had an IPS were at a higher risk for recurrent ischemic events. METHODS: The population included subjects with cryptogenic cerebrovascular accident (CVA) or TIA. Inclusion criteria were age ≥18 years, sinus rhythm, and clinically indicated transesophageal echocardiography (TEE). Exclusion criteria were hemorrhagic CVA, septal defect, and patent foramen. Patients were followed from index TEE. RESULTS: Of 71 patients, 8 were lost to follow-up. A total of 23 patients had and 40 were without IPS. Average follow-up duration was 38.3 ± 19.2 months. Groups were similar at baseline. There was no significant difference in the recurrence of ischemic CVA or TIA in the IPS versus non-IPS groups (0% vs. 7.5%; P = NS). There was no difference between the incidence of hemorrhagic CVA in the IPS and non-IPS groups (4.3% vs. 5.0%; P = NS). The proportion of patients on warfarin in the IPS group was significantly higher compared to the non-IPS group (17.4% vs. 0%; P < 0.05). CONCLUSIONS: Patients with IPS and cryptogenic stroke or TIA did not have a higher recurrence of ischemic cerebral events. Warfarin was significantly higher at follow-up in the IPS compared to the non-IPS group, which may explain these findings. A study randomizing patients with IPS and cryptogenic stroke or TIA to warfarin or no warfarin would be of great interest.

Echocardiographic Assessment of Cardiotoxic Effects of Cancer Therapy.

Patients with cancer can present with difficult management issues, as the medicine can sometimes cause sequelae destructive to healthy tissue. As this population lives longer, cardiotoxic effects are beginning to emerge, but the early recognition of this signal can prove difficult, with too late a recognition leading to lifelong cardiac impairment and dysfunction. Cardio-oncology can bridge this difficulty, and echocardiography and its newer imaging abilities are proving efficacious in this population. This article will address common sequelae of cardiotoxic treatment regimens and offer recommendations for echocardiographic surveillance. We recommend echocardiography, preferably three-dimensional and strain imaging, to monitor for cardiotoxic myocardial effects before, during, and after chemotherapy with cardiotoxic drug regimens, particularly anthracycline derivatives. A reduction in left ventricular (LV) global longitudinal strain in all patients, or reduction in LV global circumferential strain or global radial strain in patients at intermediate to high risk for cardiotoxicity, despite normal LV ejection fraction warrants a clinical assessment on the benefits of continuing cardiotoxic chemotherapeutic agents. Lifelong surveillance using echocardiography for cardiotoxicity and radiation-related valvular, pericardial, and coronary artery disease is prudent.

4D UTE flow: a phase-contrast MRI technique for assessment and visualization of stenotic flows.

PURPOSE: Inaccuracy of conventional four-dimensional (4D) flow MR imaging in the presence of random unsteady and turbulent blood flow distal to a narrowing has been an important challenge. Previous investigations have revealed that shorter echo times (TE) decrease the errors, leading to more accurate flow assessments. METHODS: In this study, as part of a 4D flow acquisition, an Ultra-Short TE (UTE) method was adopted. UTE works based on a center-out radial k-space trajectory that inherently has a short TE. By employing free induction decay sampling starting from read-out gradient ramp-up, and by combining the refocusing lobe of the slice select gradient with the bipolar flow encoding gradient, TEs of ≈1 msec may be achieved. RESULTS: Both steady and pulsatile flow regimes, and in each case a range of Reynolds numbers, were studied in an in-vitro model. Flow assessment at low and medium flow rates demonstrated a good agreement between 4D UTE and conventional 4D flow techniques. However, 4D UTE flow significantly outperformed conventional 4D flow, at high flow rates for both steady and pulsatile flow regimes. Feasibility of the method in one patient with Aortic Stenosis was also demonstrated. CONCLUSION: For both steady and pulsatile high flow rates, the measured flow distal to the stenotic narrowing using conventional 4D flow revealed more than 20% error compared to the ground-truth flow. This error was reduced to less than 5% using the 4D UTE flow technique.

Determination of the optimum number of cardiac cycles to differentiate intra-pulmonary shunt and patent foramen ovale by saline contrast two- and three-dimensional echocardiography.

INTRODUCTION: Patent foramen ovale (PFO) and intra-pulmonary shunt (IPS) are potential causes of stroke. The most optimum cardiac cycle cutoff for bubbles to appear in the left heart on saline contrast transthoracic echocardiography (TTE) as criteria to differentiate the 2 entities is unknown. METHODS: Ninety-five adult patients had saline contrast transesophageal echocardiography (TEE), two-dimensional (2D) and 3DTTE. Sensitivity and specificity of each cardiac cycle as cutoff to differentiate a PFO and IPS were obtained. RESULTS: Transesophageal echocardiography showed IPS in 28 and PFO in 15 patients. If bubbles appeared in the left heart within the first 4 cardiac cycles (the 4th cardiac cycle rule) as compared to alternate cutoffs, a PFO was most accurately diagnosed by both 2D and 3DTTE. Bubbles appearing at or after the 5th cardiac cycle most accurately determined an IPS. 3D versus 2DTTE had a trend for a higher sensitivity (61% vs. 36%, P = 0.06), but similar specificity (94% vs. 91%) for IPS. Accuracy of 3DTTE was 84% and 2DTTE was 75% (P = 0.08) for IPS. For PFO, 2DTTE sensitivity (87%) and specificity (98%) did not differ (P = NS) from that of 3DTTE sensitivity (73%) and specificity (100%). CONCLUSIONS: This study demonstrates for the first time that the 4th cardiac cycle rule differentiates PFO and IPS most optimally by 2D and 3DTTE. 3DTTE appears to have higher sensitivity for diagnosing IPS. These data suggest that 3DTTE is preferable when IPS is to be diagnosed. Both methods are similar for diagnosing PFO.

Administration of cardiac stem cells in patients with ischemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance.

BACKGROUND: SCIPIO is a first-in-human, phase 1, randomized, open-label trial of autologous c-kit(+) cardiac stem cells (CSCs) in patients with heart failure of ischemic etiology undergoing coronary artery bypass grafting (CABG). In the present study, we report the surgical aspects and interim cardiac magnetic resonance (CMR) results. METHODS AND RESULTS: A total of 33 patients (20 CSC-treated and 13 control subjects) met final eligibility criteria and were enrolled in SCIPIO. CSCs were isolated from the right atrial appendage harvested and processed during surgery. Harvesting did not affect cardiopulmonary bypass, cross-clamp, or surgical times. In CSC-treated patients, CMR showed a marked increase in both LVEF (from 27.5 ± 1.6% to 35.1 ± 2.4% [P=0.004, n=8] and 41.2 ± 4.5% [P=0.013, n=5] at 4 and 12 months after CSC infusion, respectively) and regional EF in the CSC-infused territory. Infarct size (late gadolinium enhancement) decreased after CSC infusion (by manual delineation: -6.9 ± 1.5 g [-22.7%] at 4 months [P=0.002, n=9] and -9.8 ± 3.5 g [-30.2%] at 12 months [P=0.039, n=6]). LV nonviable mass decreased even more (-11.9 ± 2.5 g [-49.7%] at 4 months [P=0.001] and -14.7 ± 3.9 g [-58.6%] at 12 months [P=0.013]), whereas LV viable mass increased (+11.6 ± 5.1 g at 4 months after CSC infusion [P=0.055] and +31.5 ± 11.0 g at 12 months [P=0.035]). CONCLUSIONS: Isolation of CSCs from cardiac tissue obtained in the operating room is feasible and does not alter practices during CABG surgery. CMR shows that CSC infusion produces a striking improvement in both global and regional LV function, a reduction in infarct size, and an increase in viable tissue that persist at least 1 year and are consistent with cardiac regeneration. CLINICAL TRIAL REGISTRATION: This study is registered with clinicaltrials.gov, trial number NCT00474461.

Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial.

BACKGROUND: c-kit-positive, lineage-negative cardiac stem cells (CSCs) improve post-infarction left ventricular (LV) dysfunction when administered to animals. We undertook a phase 1 trial (Stem Cell Infusion in Patients with Ischemic cardiOmyopathy [SCIPIO]) of autologous CSCs for the treatment of heart failure resulting from ischaemic heart disease. METHODS: In stage A of the SCIPIO trial, patients with post-infarction LV dysfunction (ejection fraction [EF] ≤40%) before coronary artery bypass grafting were consecutively enrolled in the treatment and control groups. In stage B, patients were randomly assigned to the treatment or control group in a 2:3 ratio by use of a computer-generated block randomisation scheme. 1 million autologous CSCs were administered by intracoronary infusion at a mean of 113 days (SE 4) after surgery; controls were not given any treatment. Although the study was open label, the echocardiographic analyses were masked to group assignment. The primary endpoint was short-term safety of CSCs and the secondary endpoint was efficacy. A per-protocol analysis was used. This study is registered with ClinicalTrials.gov, number NCT00474461. FINDINGS: This study is still in progress. 16 patients were assigned to the treatment group and seven to the control group; no CSC-related adverse effects were reported. In 14 CSC-treated patients who were analysed, LVEF increased from 30·3% (SE 1·9) before CSC infusion to 38·5% (2·8) at 4 months after infusion (p=0·001). By contrast, in seven control patients, during the corresponding time interval, LVEF did not change (30·1% [2·4] at 4 months after CABG vs 30·2% [2·5] at 8 months after CABG). Importantly, the salubrious effects of CSCs were even more pronounced at 1 year in eight patients (eg, LVEF increased by 12·3 ejection fraction units [2·1] vs baseline, p=0·0007). In the seven treated patients in whom cardiac MRI could be done, infarct size decreased from 32·6 g (6·3) by 7·8 g (1·7; 24%) at 4 months (p=0·004) and 9·8 g (3·5; 30%) at 1 year (p=0·04). INTERPRETATION: These initial results in patients are very encouraging. They suggest that intracoronary infusion of autologous CSCs is effective in improving LV systolic function and reducing infarct size in patients with heart failure after myocardial infarction, and warrant further, larger, phase 2 studies. FUNDING: University of Louisville Research Foundation and National Institutes of Health.

Coronary artery fistula: 64-slice computed tomographic delineation and correlation with multiplane transesophageal echocardiography and surgical findings.

A 49-year-old female who presented with 3 weeks of exertional chest pain had an abnormal mediastinal finding at chest x-ray imaging. Conventional, nongated computed tomography of the chest revealed a "mass" in proximity to the right atrium. 64-slice, cardiac gated computed tomographic coronary angiography, and transesophageal echocardiography delineated the "mass" as a coronary artery fistula structure. The fistula originated from the left main as a tubular vessel that continued into an aneurysmal sac-like cavity that emptied into the superior vena cava near the right atrium. Computed tomographic coronary angiography showed otherwise normal coronary arteries. Findings were ultimately confirmed at cardiac catheterization. Coronary steal was clinically diagnosed and she underwent surgical ligation and resection of the fistula and aneurysm. Her subsequent course was uncomplicated.

FlowRAU-Net: Accelerated 4D Flow MRI of Aortic Valvular Flows With a Deep 2D Residual Attention Network.

In this work, we propose a novel deep learning reconstruction framework for rapid and accurate reconstruction of 4D flow MRI data. Reconstruction is performed on a slice-by-slice basis by reducing artifacts in zero-filled reconstructed complex images obtained from undersampled k-space. A deep residual attention network FlowRAU-Net is proposed, trained separately for each encoding direction with 2D complex image slices extracted from complex 4D images at each temporal frame and slice position. The network was trained and tested on 4D flow MRI data of aortic valvular flow in 18 human subjects. Performance of the reconstructions was measured in terms of image quality, 3-D velocity vector accuracy, and accuracy in hemodynamic parameters. Reconstruction performance was measured for three different k-space undersamplings and compared with one state of the art compressed sensing reconstruction method and three deep learning-based reconstruction methods. The proposed method outperforms state of the art methods in all performance measures for all three different k-space undersamplings. Hemodynamic parameters such as blood flow rate and peak velocity from the proposed technique show good agreement with reference flow parameters. Visualization of the reconstructed image and velocity magnitude also shows excellent agreement with the fully sampled reference dataset. Moreover, the proposed method is computationally fast. Total 4D flow data (including all slices in space and time) for a subject can be reconstructed in 69 seconds on a single GPU. Although the proposed method has been applied to 4D flow MRI of aortic valvular flows, given a sufficient number of training samples, it should be applicable to other arterial flows.

The overestimation of concentric hypertrophy in patients with HFpEF as determined by 2D-echocardiography.

Background: Heart failure with preserved ejection fraction continues to pose multiple challenges in terms of accurate diagnosis, treatment, and associated morbidity. Accurate left ventricular (LV) mass calculation yields essential prognostic information relating to structural heart disease. Two-dimensional (2D) echocardiography-based calculations are solely limited to LV geometric assumptions of symmetry, whereas three-dimensional (3D) echocardiography could overcome these limitations. This study aims to compare the performance of 2D and 3D LV mass calculations. Methods: A prospective review of echocardiography findings at the University of Louisville, Kentucky, was conducted and assessed. Normal ejection fraction (EF) was defined as >=52% in males and >=54% in females. The following calculations were performed: relative wall thickness (RWT) = 2x posterior wall thickness/LV internal diastolic dimension (LVIDd) and 2D LV mass = 0.8{1.04([LVIDd + IVSd +PWd]3 - LVIDd3)} + 0.6. Concentric hypertrophy was RWT >0.42 and LV mass >95 kg/m2 in females or >115 kg/m2 in males. The same cut-offs were used for 2D and 3D echocardiography. Results: Echocardiographic findings for a total number of 154 patients in the study were investigated. There was a weak positive correlation between 2D and 3D LV mass indices (R = 0.534, r2 = 0.286, p = 0.001). Seventy patients had 3D EF >=45% with clinical heart failure (HFpEF). Among HFpEF patients, LV hypertrophy (LVH) was present in 74% of patients by 2D echocardiography and 30% by 3D echocardiography (McNemar test p = 0.001). Using 3D echocardiography as the reference, 68% of normal patients were misdiagnosed with LV hypertrophy by 2D echocardiography. Two-thirds of the patients with concentric remodeling by 3D echocardiography were misclassified as having concentric hypertrophy by 2D echocardiography (p = 0.001). Conclusion: Adapting necropsy-proven LV mass index cutoffs, 2D over-diagnosed LV hypertrophy through overestimation of the mass, compared to 3D echocardiography. In turn, the majority of HFpEF patients showed no structural hypertrophy of the LV on 3D imaging. This suggests that the majority of patients with HFpEF may qualify for pharmacological prevention to prevent further progression to LV remodeling or LVH.

Calculation of Mitral Valve Area by Continuity Equation Using Velocity-Time Integral From Mitral Valve Orifices After Mitral Clip.

BACKGROUND: This study investigates the hemodynamics of a dual-orifice mitral valve after mitral valve clip closure (MVCC) in patients with functional and nonfunctional mitral regurgitation (MR). If inflow velocity-time integral (VTi) of both orifices is equal, then the standard continuity equation can be applied to calculate the total mitral valve area (MVA). METHODS AND RESULTS: Adults undergoing MVCC placement were prospectively enrolled. With transesophageal echocardiography (TEE), the vena contracta (VC) of the medial and lateral mitral valve (MV) orifices were determined using color-flow Doppler and dual MV orifice areas were calculated. Valve orifices were classified as large vs small based on VC diameters. Continuous-wave Doppler measurements from both orifices were obtained. Forty-nine patients with severe MR (functional, n = 18) were enrolled. The VTi, mean gradient, peak gradient, and mean velocity of the larger vs smaller orifice were not significantly different, irrespective of MR etiology (P=nonsignificant). There was no difference in these parameters between large and small orifice regardless of MR mechanism (P=nonsignificant). There were no differences in the means of MVA as derived from either large or small VTi-derived and VC-derived areas (P=nonsignificant). CONCLUSIONS: Mitral valve inflow hemodynamics were the same regardless of the size differences between the large and small orifices. Therefore, total MVA can be calculated using the continuity equation in patients irrespective of MR mechanism. This allows for a derivation of total MVA at the time of MVCC placement to evaluate for mitral stenosis.