Efficacy and Safety of Aficamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4.

BACKGROUND: This open-label phase 2 trial evaluated the safety and efficacy of aficamten in patients with nonobstructive hypertrophic cardiomyopathy (nHCM). METHODS: Patients with symptomatic nHCM (left ventricular outflow tract obstruction gradient ≤ 30 mmHg, left ventricular ejection fraction [LVEF] ≥ 60%, N-terminal pro-B-type natriuretic peptide [NT-proBNP] > 300 pg/mL) received aficamten 5-15 mg once daily (doses adjusted according to echocardiographic LVEF) for 10 weeks. RESULTS: We enrolled 41 patients (mean ± SD age 56 ± 16 years; 59% female). At Week 10, 22 (55%) patients experienced an improvement of ≥ 1 New York Heart Association class; 11 (29%) became asymptomatic. Clinically relevant improvements in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores occurred in 22 (55%) patients. Symptom relief was paralleled by reductions in NT-proBNP levels (56%; P < 0.001) and high-sensitivity cardiac troponin I (22%; P < 0.005). Modest reductions in LVEF (mean ± SD) of -5.4% ± 10 to 64.6% ± 9.1 were observed. Three (8%) patients had asymptomatic reduction in LVEF < 50% (range: 41%-48%), all returning to normal after 2 weeks of washout. One patient with prior history of aborted sudden cardiac death experienced a fatal arrhythmia during the study. CONCLUSIONS: Aficamten administration for symptomatic nHCM was generally safe and was associated with improvements in heart failure symptoms and cardiac biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04219826.

High-resolution spiral real-time cardiac cine imaging with deep learning-based rapid image reconstruction and quantification.

The objective of the current study was to develop and evaluate a DEep learning-based rapid Spiral Image REconstruction (DESIRE) and deep learning (DL)-based segmentation approach to quantify the left ventricular ejection fraction (LVEF) for high-resolution spiral real-time cine imaging, including 2D balanced steady-state free precession imaging at 1.5 T and gradient echo (GRE) imaging at 1.5 and 3 T. A 3D U-Net-based image reconstruction network and 2D U-Net-based image segmentation network were proposed and evaluated. Low-rank plus sparse (L+S) served as the reference for the image reconstruction network and manual contouring of the left ventricle was the reference of the segmentation network. To assess the image reconstruction quality, structural similarity index, peak signal-to-noise ratio, normalized root-mean-square error, and blind grading by two experienced cardiologists (5: excellent; 1: poor) were performed. To assess the segmentation performance, quantification of the LVEF on GRE imaging at 3 T was compared with the quantification from manual contouring. Excellent performance was demonstrated by the proposed technique. In terms of image quality, there was no difference between L+S and the proposed DESIRE technique. For quantification analysis, the proposed DL method was not different to the manual segmentation method (p > 0.05) in terms of quantification of LVEF. The reconstruction time for DESIRE was ~32 s (including nonuniform fast Fourier transform [NUFFT]) per dynamic series (40 frames), while the reconstruction time of L+S with GPU acceleration was approximately 3 min. The DL segmentation takes less than 5 s. In conclusion, the proposed DL-based image reconstruction and quantification techniques enabled 1-min image reconstruction for the whole heart and quantification with automatic reconstruction and quantification of the left ventricle function for high-resolution spiral real-time cine imaging with excellent performance.

Alirocumab and plaque volume, calf muscle blood flow, and walking performance in peripheral artery disease: A randomized clinical trial.

BACKGROUND: The distal superficial femoral artery (SFA) is most commonly affected in peripheral artery disease (PAD). The effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab added to statin therapy on SFA atherosclerosis, downstream flow, and walking performance are unknown. METHODS: Thirty-five patients with PAD on maximally tolerated statin therapy were recruited. Patients were randomized to alirocumab 150 mg subcutaneously (n = 18) or matching placebo (n = 17) therapy every 2 weeks for 1 year. The primary outcome was change in SFA plaque volume by black blood magnetic resonance imaging (MRI). Secondary outcomes were changes in calf muscle perfusion by cuff/occlusion hyperemia arterial spin labeling MRI, 6-minute walk distance (6MWD), low-density lipoprotein (LDL) cholesterol, and other biomarkers. RESULTS: Age (mean ± SD) was 64 ± 8 years, 20 (57%) patients were women, 17 (49%) were Black individuals, LDL was 107 ± 36 mg/dL, and the ankle-brachial index 0.71 ± 0.20. The LDL fell more with alirocumab than placebo (mean [95% CI]) (-49.8 [-66.1 to -33.6] vs -7.7 [-19.7 to 4.3] mg/dL; p < 0.0001). Changes in SFA plaque volume and calf perfusion showed no difference between groups when adjusted for baseline (+0.25 [-0.29 to 0.79] vs -0.04 [-0.47 to 0.38] cm3; p = 0.37 and 0.22 [-8.67 to 9.11] vs 3.81 [-1.45 to 9.08] mL/min/100 g; p = 0.46, respectively), nor did 6MWD. CONCLUSION: In this exploratory study, the addition of alirocumab therapy to statins did not alter SFA plaque volume, calf perfusion or 6MWD despite significant LDL lowering. Larger studies with longer follow up that include plaque characterization may improve understanding of the effects of intensive LDL-lowering therapy in PAD (ClinicalTrials.gov Identifier: NCT02959047).

Dynamic cardiac MRI with high spatiotemporal resolution using accelerated spiral-out and spiral-in/out bSSFP pulse sequences at 1.5 T.

OBJECTIVE: To develop two spiral-based bSSFP pulse sequences combined with L + S reconstruction for accelerated ungated, free-breathing dynamic cardiac imaging at 1.5 T. MATERIALS AND METHODS: Tiny golden angle rotated spiral-out and spiral-in/out bSSFP sequences combined with view-sharing (VS), compressed sensing (CS), and low-rank plus sparse (L + S) reconstruction were evaluated and compared via simulation and in vivo dynamic cardiac imaging studies. The proposed methods were then validated against the standard cine, in terms of quantitative image assessment and qualitative quality rating. RESULTS: The L + S method yielded the least residual artifacts and the best image sharpness among the three methods. Both spiral cine techniques showed clinically diagnostic images (score > 3). Compared to standard cine, there were significant differences in global image quality and edge sharpness for spiral cine techniques, while there was significant difference in image contrast for the spiral-out cine but no significant difference for the spiral-in/out cine. There was good agreement in left ventricular ejection fraction for both the spiral-out cine (- 1.6 [Formula: see text] 3.1%) and spiral-in/out cine (- 1.5 [Formula: see text] 2.8%) against standard cine. DISCUSSION: Compared to the time-consuming standard cine (~ 5 min) which requires ECG-gating and breath-holds, the proposed spiral bSSFP sequences achieved ungated, free-breathing cardiac movies at a similar spatial (1.5 × 1.5 × 8 mm3) and temporal resolution (36 ms) per slice for whole heart coverage (10-15 slices) within 45 s, suggesting the clinical potential for improved patient comfort or for imaging patients with arrhythmias or who cannot hold their breath.

Imaging in Hypertrophic Cardiomyopathy: Beyond Risk Stratification.

A multimodality imaging evaluation in hypertrophic cardiomyopathy is often used for risk stratification. Recent developments in imaging have allowed for better diagnosis, prognosis, and decision-making for a variety of therapies from medical to interventional. Echocardiography and magnetic resonance have been integral in evaluating subtype, left ventricular function, tissue characterization, left atrial measurements, valvular function, and presence of left ventricular aneurysm and outflow tract obstruction. These factors have helped to quantify risk of atrial fibrillation and determine the likely usefulness of pharmacologic therapy and septal reduction therapy. This review covers these in detail.

Toward Replacing Late Gadolinium Enhancement With Artificial Intelligence Virtual Native Enhancement for Gadolinium-Free Cardiovascular Magnetic Resonance Tissue Characterization in Hypertrophic Cardiomyopathy.

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is the gold standard for noninvasive myocardial tissue characterization but requires intravenous contrast agent administration. It is highly desired to develop a contrast agent-free technology to replace LGE for faster and cheaper CMR scans. METHODS: A CMR virtual native enhancement (VNE) imaging technology was developed using artificial intelligence. The deep learning model for generating VNE uses multiple streams of convolutional neural networks to exploit and enhance the existing signals in native T1 maps (pixel-wise maps of tissue T1 relaxation times) and cine imaging of cardiac structure and function, presenting them as LGE-equivalent images. The VNE generator was trained using generative adversarial networks. This technology was first developed on CMR datasets from the multicenter Hypertrophic Cardiomyopathy Registry, using hypertrophic cardiomyopathy as an exemplar. The datasets were randomized into 2 independent groups for deep learning training and testing. The test data of VNE and LGE were scored and contoured by experienced human operators to assess image quality, visuospatial agreement, and myocardial lesion burden quantification. Image quality was compared using a nonparametric Wilcoxon test. Intra- and interobserver agreement was analyzed using intraclass correlation coefficients (ICC). Lesion quantification by VNE and LGE were compared using linear regression and ICC. RESULTS: A total of 1348 hypertrophic cardiomyopathy patients provided 4093 triplets of matched T1 maps, cines, and LGE datasets. After randomization and data quality control, 2695 datasets were used for VNE method development and 345 were used for independent testing. VNE had significantly better image quality than LGE, as assessed by 4 operators (n=345 datasets; P<0.001 [Wilcoxon test]). VNE revealed lesions characteristic of hypertrophic cardiomyopathy in high visuospatial agreement with LGE. In 121 patients (n=326 datasets), VNE correlated with LGE in detecting and quantifying both hyperintensity myocardial lesions (r=0.77-0.79; ICC=0.77-0.87; P<0.001) and intermediate-intensity lesions (r=0.70-0.76; ICC=0.82-0.85; P<0.001). The native CMR images (cine plus T1 map) required for VNE can be acquired within 15 minutes and producing a VNE image takes less than 1 second. CONCLUSIONS: VNE is a new CMR technology that resembles conventional LGE but without the need for contrast administration. VNE achieved high agreement with LGE in the distribution and quantification of lesions, with significantly better image quality.

A Slice-Low-Rank Plus Sparse (slice-L + S) Reconstruction Method for k-t Undersampled Multiband First-Pass Myocardial Perfusion MRI.

PURPOSE: The synergistic use of k-t undersampling and multiband (MB) imaging has the potential to provide extended slice coverage and high spatial resolution for first-pass perfusion MRI. The low-rank plus sparse (L + S) model has shown excellent performance for accelerating single-band (SB) perfusion MRI. METHODS: A MB data consistency method employing ESPIRiT maps and through-plane coil information was developed. This data consistency method was combined with the temporal L + S constraint to form the slice-L + S method. Slice-L + S was compared to SB L + S and the sequential operations of split slice-GRAPPA and SB L + S (seq-SG-L + S) using synthetic data formed from multislice SB images. Prospectively k-t undersampled MB data were also acquired and reconstructed using seq-SG-L + S and slice-L + S. RESULTS: Using synthetic data with total acceleration rates of 6-12, slice-L + S outperformed SB L + S and seq-SG-L + S (N = 7 subjects) with respect to normalized RMSE and the structural similarity index (P < 0.05 for both). For the specific case with MB factor = 3 and rate 3 undersampling, or for SB imaging with rate 9 undersampling (N = 7 subjects), the normalized RMSE values were 0.037 ± 0.007, 0.042 ± 0.005, and 0.031 ± 0.004; and the structural similarity index values were 0.88 ± 0.03, 0.85 ± 0.03, and 0.89 ± 0.02 for SB L + S, seq-SG-L + S, and slice-L + S, respectively (P < 0.05 for both). For prospectively undersampled MB data, slice-L + S provided better image quality than seq-SG-L + S for rate 6 (N = 7) and rate 9 acceleration (N = 7) as scored by blinded experts. CONCLUSION: Slice-L + S outperformed SB-L + S and seq-SG-L + S and provides 9 slice coverage of the left ventricle with a spatial resolution of 1.5 mm × 1.5 mm with good image quality.

DEep learning-based rapid Spiral Image REconstruction (DESIRE) for high-resolution spiral first-pass myocardial perfusion imaging.

The objective of the current study was to develop and evaluate a DEep learning-based rapid Spiral Image REconstruction (DESIRE) technique for high-resolution spiral first-pass myocardial perfusion imaging with whole-heart coverage, to provide fast and accurate image reconstruction for both single-slice (SS) and simultaneous multislice (SMS) acquisitions. Three-dimensional U-Net-based image enhancement architectures were evaluated for high-resolution spiral perfusion imaging at 3 T. The SS and SMS MB = 2 networks were trained on SS perfusion images from 156 slices from 20 subjects. Structural similarity index (SSIM), peak signal-to-noise ratio (PSNR), and normalized root mean square error (NRMSE) were assessed, and prospective images were blindly graded by two experienced cardiologists (5: excellent; 1: poor). Excellent performance was demonstrated for the proposed technique. For SS, SSIM, PSNR, and NRMSE were 0.977 [0.972, 0.982], 42.113 [40.174, 43.493] dB, and 0.102 [0.080, 0.125], respectively, for the best network. For SMS MB = 2 retrospective data, SSIM, PSNR, and NRMSE were 0.961 [0.950, 0.969], 40.834 [39.619, 42.004] dB, and 0.107 [0.086, 0.133], respectively, for the best network. The image quality scores were 4.5 [4.1, 4.8], 4.5 [4.3, 4.6], 3.5 [3.3, 4], and 3.5 [3.3, 3.8] for SS DESIRE, SS L1-SPIRiT, MB = 2 DESIRE, and MB = 2 SMS-slice-L1-SPIRiT, respectively, showing no statistically significant difference (p = 1 and p = 1 for SS and SMS, respectively) between L1-SPIRiT and the proposed DESIRE technique. The network inference time was ~100 ms per dynamic perfusion series with DESIRE, while the reconstruction time of L1-SPIRiT with GPU acceleration was ~ 30 min. It was concluded that DESIRE enabled fast and high-quality image reconstruction for both SS and SMS MB = 2 whole-heart high-resolution spiral perfusion imaging.

Cocoa to Improve Walking Performance in Older People With Peripheral Artery Disease: The COCOA-PAD Pilot Randomized Clinical Trial.

RATIONALE: Cocoa and its major flavanol component, epicatechin, have therapeutic properties that may improve limb perfusion and increase calf muscle mitochondrial activity in people with lower extremity peripheral artery disease (PAD). OBJECTIVE: In a phase II randomized clinical trial, to assess whether 6 months of cocoa improved walking performance in people with PAD, compared with placebo. METHODS AND RESULTS: Six-month double-blind, randomized clinical trial in which participants with PAD were randomized to either cocoa beverage versus placebo beverage. The cocoa beverage contained 15 g of cocoa and 75 mg of epicatechin daily. The identical appearing placebo contained neither cocoa nor epicatechin. The 2 primary outcomes were 6-month change in 6-minute walk distance measured 2.5 hours after a study beverage at 6-month follow-up and 24 hours after a study beverage at 6-month follow-up, respectively. A 1-sided P<0.10 was considered statistically significant. Of 44 PAD participants randomized (mean age, 72.3 years [±7.1]; mean ankle brachial index, 0.66 [±0.15]), 40 (91%) completed follow-up. Adjusting for smoking, race, and body mass index, cocoa improved 6-minute walk distance at 6-month follow-up by 42.6 m ([90% CI, +22.2 to +∞] P=0.005) at 2.5 hours after a final study beverage and by 18.0 m ([90% CI, -1.7 to +∞] P=0.12) at 24 hours after a study beverage, compared with placebo. In calf muscle biopsies, cocoa improved mitochondrial COX (cytochrome c oxidase) activity (P=0.013), increased capillary density (P=0.014), improved calf muscle perfusion (P=0.098), and reduced central nuclei (P=0.033), compared with placebo. CONCLUSIONS: These preliminary results suggest a therapeutic effect of cocoa on walking performance in people with PAD. Further study is needed to definitively determine whether cocoa significantly improves walking performance in people with PAD. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02876887. Visual Overview: An online visual overview is available for this article.

Data-driven modelling of mutational hotspots and in silico predictors in hypertrophic cardiomyopathy.

BACKGROUND: Although rare missense variants in Mendelian disease genes often cluster in specific regions of proteins, it is unclear how to consider this when evaluating the pathogenicity of a gene or variant. Here we introduce methods for gene association and variant interpretation that use this powerful signal. METHODS: We present statistical methods to detect missense variant clustering (BIN-test) combined with burden information (ClusterBurden). We introduce a flexible generalised additive modelling (GAM) framework to identify mutational hotspots using burden and clustering information (hotspot model) and supplemented by in silico predictors (hotspot+ model). The methods were applied to synthetic data and a case-control dataset, comprising 5338 hypertrophic cardiomyopathy patients and 125 748 population reference samples over 34 putative cardiomyopathy genes. RESULTS: In simulations, the BIN-test was almost twice as powerful as the Anderson-Darling or Kolmogorov-Smirnov tests; ClusterBurden was computationally faster and more powerful than alternative position-informed methods. For 6/8 sarcomeric genes with strong clustering, Clusterburden showed enhanced power over burden-alone, equivalent to increasing the sample size by 50%. Hotspot+ models that combine burden, clustering and in silico predictors outperform generic pathogenicity predictors and effectively integrate ACMG criteria PM1 and PP3 to yield strong or moderate evidence of pathogenicity for 31.8% of examined variants of uncertain significance. CONCLUSION: GAMs represent a unified statistical modelling framework to combine burden, clustering and functional information. Hotspot models can refine maps of regional burden and hotspot+ models can be powerful predictors of variant pathogenicity. The BIN-test is a fast powerful approach to detect missense variant clustering that when combined with burden information (ClusterBurden) may enhance disease-gene discovery.

Machine Learning for Early Detection of Hypoxic-Ischemic Brain Injury After Cardiac Arrest.

BACKGROUND: Establishing whether a patient who survived a cardiac arrest has suffered hypoxic-ischemic brain injury (HIBI) shortly after return of spontaneous circulation (ROSC) can be of paramount importance for informing families and identifying patients who may benefit the most from neuroprotective therapies. We hypothesize that using deep transfer learning on normal-appearing findings on head computed tomography (HCT) scans performed after ROSC would allow us to identify early evidence of HIBI. METHODS: We analyzed 54 adult comatose survivors of cardiac arrest for whom both an initial HCT scan, done early after ROSC, and a follow-up HCT scan were available. The initial HCT scan of each included patient was read as normal by a board-certified neuroradiologist. Deep transfer learning was used to evaluate the initial HCT scan and predict progression of HIBI on the follow-up HCT scan. A naive set of 16 additional patients were used for external validation of the model. RESULTS: The median age (interquartile range) of our cohort was 61 (16) years, and 25 (46%) patients were female. Although findings of all initial HCT scans appeared normal, follow-up HCT scans showed signs of HIBI in 29 (54%) patients (computed tomography progression). Evaluating the first HCT scan with deep transfer learning accurately predicted progression to HIBI. The deep learning score was the most significant predictor of progression (area under the receiver operating characteristic curve = 0.96 [95% confidence interval 0.91-1.00]), with a deep learning score of 0.494 having a sensitivity of 1.00, specificity of 0.88, accuracy of 0.94, and positive predictive value of 0.91. An additional assessment of an independent test set confirmed high performance (area under the receiver operating characteristic curve = 0.90 [95% confidence interval 0.74-1.00]). CONCLUSIONS: Deep transfer learning used to evaluate normal-appearing findings on HCT scans obtained early after ROSC in comatose survivors of cardiac arrest accurately identifies patients who progress to show radiographic evidence of HIBI on follow-up HCT scans.

Frequency, Risk Factors, and Outcomes of Unplanned Readmission to the Neurological Intensive Care Unit after Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Unplanned readmission to the neurological intensive care unit (ICU) is an underinvestigated topic in patients admitted after spontaneous intracerebral hemorrhage (ICH). The purpose of this study is to investigate the frequency, clinical risk factors, and outcome of bounce back to the neurological ICU in a cohort of patients admitted after ICH. METHODS: This is a retrospective observational study inspecting bounce back to the neurological ICU in patients admitted with spontaneous ICH over an 8-year period. For each patient, demographics, medical history, clinical presentation, length of ICU stay, unplanned readmission to neurological ICU, cause of readmission, and mortality were reviewed. Bounce back to the neurological ICU was defined as an unplanned readmission to the neurological ICU from a general floor service during the same hospitalization. A multivariable analysis was used to define independent variables associated with bounce back to the neurological ICU as well as association between bounce back to the neurological ICU and mortality. The significance level was set at p < 0.05. RESULTS: A total of 221 patients were included. Among those, 20 (9%) had a bounce back to the neurological ICU. Respiratory complications (n = 11) was the most common reason for bounce back to the neurological ICU, followed by neurological (n = 5) and cardiological (n = 4) complications. In a multivariable logistic regression, location of hemorrhage in the basal ganglia (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.0-8.9, p = 0.03) and dysphagia at the time of transfer (OR: 3.9, 95% CI: 1.0-15.4, p = 0.04) were significantly associated with bounce back to the neurological ICU. After we controlled for ICH score, readmission to the ICU was also independently associated with higher mortality (OR: 14.1, 95% CI: 2.8-71.7, p < 0.01). CONCLUSIONS: Bounce back to the neurological ICU is not an infrequent complication in patients with spontaneous ICH and is associated with higher hospital length of stay and mortality. We identified relevant and potentially modifiable risk factors associated with bounce back to the neurological ICU. Future prospective studies are necessary to develop patient-centered strategies that may improve transition from the neurological ICU to the general floor.

High spatial resolution spiral first-pass myocardial perfusion imaging with whole-heart coverage at 3 T.

PURPOSE: To develop and evaluate a high spatial resolution (1.25 × 1.25 mm2 ) spiral first-pass myocardial perfusion imaging technique with whole-heart coverage at 3T, to better assess transmural differences in perfusion between the endocardium and epicardium, to quantify the myocardial ischemic burden, and to improve the detection of obstructive coronary artery disease. METHODS: Whole-heart high-resolution spiral perfusion pulse sequences and corresponding motion-compensated reconstruction techniques for both interleaved single-slice (SS) and simultaneous multi-slice (SMS) acquisition with or without outer-volume suppression (OVS) were developed. The proposed techniques were evaluated in 34 healthy volunteers and 8 patients (55 data sets). SS and SMS images were reconstructed using motion-compensated L1-SPIRiT and SMS-Slice-L1-SPIRiT, respectively. Images were blindly graded by 2 experienced cardiologists on a 5-point scale (5, excellent; 1, poor). RESULTS: High-quality perfusion imaging was achieved for both SS and SMS acquisitions with or without OVS. The SS technique without OVS had the highest scores (4.5 [4, 5]), which were greater than scores for SS with OVS (3.5 [3.25, 3.75], P < .05), MB = 2 without OVS (3.75 [3.25, 4], P < .05), and MB = 2 with OVS (3.75 [2.75, 4], P < .05), but significantly higher than those for MB = 3 without OVS (4 [4, 4], P = .95). SMS image quality was improved using SMS-Slice-L1-SPIRiT as compared to SMS-L1-SPIRiT (P < .05 for both reviewers). CONCLUSION: We demonstrated the successful implementation of whole-heart spiral perfusion imaging with high resolution at 3T. Good image quality was achieved, and the SS without OVS showed the best image quality. Evaluation in patients with expected ischemic heart disease is warranted.

Diagnostic Accuracy of Spiral Whole-Heart Quantitative Adenosine Stress Cardiovascular Magnetic Resonance With Motion Compensated L1-SPIRIT.

BACKGROUND: Variable density spiral (VDS) pulse sequences with motion compensated compressed sensing (MCCS) reconstruction allow for whole-heart quantitative assessment of myocardial perfusion but are not clinically validated. PURPOSE: Assess performance of whole-heart VDS quantitative stress perfusion with MCCS to detect obstructive coronary artery disease (CAD). STUDY TYPE: Prospective cross sectional. POPULATION: Twenty-five patients with chest pain and known or suspected CAD and nine normal subjects. FIELD STRENGTH/SEQUENCE: Segmented steady-state free precession (SSFP) sequence, segmented phase sensitive inversion recovery sequence for late gadolinium enhancement (LGE) imaging and VDS sequence at 1.5 T for rest and stress quantitative perfusion at eight short-axis locations. ASSESSMENT: Stenosis was defined as ≥50% by quantitative coronary angiography (QCA). Visual and quantitative analysis of MRI data was compared to QCA. Quantitative analysis assessed average myocardial perfusion reserve (MPR), average stress myocardial blood flow (MBF), and lowest stress MBF of two contiguous myocardial segments. Ischemic burden was measured visually and quantitatively. STATISTICAL TESTS: Student's t-test, McNemar's test, chi-square statistic, linear mixed-effects model, and area under receiver-operating characteristic curve (ROC). RESULTS: Per-patient visual analysis demonstrated a sensitivity of 84% (95% confidence interval [CI], 60%-97%) and specificity of 83% [95% CI, 36%-100%]. There was no significant difference between per-vessel visual and quantitative analysis for sensitivity (69% [95% CI, 51%-84%] vs. 77% [95% CI, 60%-90%], P = 0.39) and specificity (88% [95% CI, 73%-96%] vs. 80% [95% CI, 64%-91%], P = 0.75). Per-vessel quantitative analysis ROC showed no significant difference (P = 0.06) between average MPR (0.68 [95% CI, 0.56-0.81]), average stress MBF (0.74 [95% CI, 0.63-0.86]), and lowest stress MBF (0.79 [95% CI, 0.69-0.90]). Visual and quantitative ischemic burden measurements were comparable (P = 0.85). DATA CONCLUSION: Whole-heart VDS stress perfusion demonstrated good diagnostic accuracy and ischemic burden evaluation. No significant difference was seen between visual and quantitative diagnostic performance and ischemic burden measurements. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Civilian Firearm-Inflicted Brain Injury: Coagulopathy, Vascular Injuries, and Triage.

PURPOSE OF REVIEW: Civilian firearm-inflicted penetrating brain injury (PBI) carries high morbidity and mortality. Concurrently, the evidence base guiding management decisions remains limited. Faced with large volume of PBI patients, we have made observations in relation to coagulopathy and cerebrovascular injuries. We here review this literature in addition to the question about early prognostication as it may inform neurosurgical decision-making. RECENT FINDINGS: The triad of coagulopathy, low motor score, and radiographic compression of basal cisterns comprises a phenotype of injury with exceedingly high mortality. PBI leads to high rates of cerebral arterial and venous injuries, and projectile trajectory is emerging as an independent predictor of outcome. The combination of coagulopathy with cerebrovascular injury creates a specific endophenotype. The nature and role of coagulopathy remain to be deciphered, and consideration to the use of tranexamic acid should be given. Prospective controlled trials are needed to create clinical evidence free of patient selection bias.

Early Determinants of Neurocritical Care Unit Length of Stay in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The present study considers patients with spontaneous intracerebral hemorrhage (ICH) admitted to the neurocritical care unit (NCCU) through the Emergency Department (ED). It aims to identify patient-specific clinical variables that can be assessed on presentation and that are associated with prolonged NCCU length of stay (LOS). METHODS: A cross-sectional, single-center, retrospective analysis of ICH patients directly admitted from the ED to the NCCU over an 8-year period was performed. Patients' demographics, clinical exam characteristics, serum laboratory values, intubation status, and neurosurgical procedures at presentation were recorded. Head computed tomography scans obtained on presentation were reviewed. LOS was calculated based on the number of midnights spent in the NCCU. Prolonged LOS was determined using a change point analysis, adopting the method of Taylor which utilizes CUMSUM charts and bootstrap analysis. A decision tree model was trained and validated to identify reliable variables associated with prolonged LOS. RESULTS: Two hundred and five patients with ICH were analyzed. Prolonged LOS was calculated to be a stay that exceeds 8 days; 68 patients (33%) had a prolonged LOS in NCCU. Median LOS did not differ between survivors and patients who died in hospital. Clinical variables explored through the decision tree model were intubation status, neurosurgical intervention (EVD, decompression or evacuation within 24 h from presentation), and components of the ICH score: age, GCS, hematoma volume, the presence of intraventricular hemorrhage (IVH), and infratentorial location. The model accuracy was 0.8 and AUC was 0.83 (95% CI 0.78-0.89). CONCLUSION: We propose an ICH-LOS model based on neurosurgical intervention, intubation status and GCS at presentation to predict prolonged LOS in the NCCU in patients with ICH. This simple clinical tool, if prospectively validated, could help with medical planning, contribute to patient care-directed conversations, assist in optimizing hospital resource utilization, and, more importantly, motivating patient-specific interventions aimed at optimizing outcomes and decreasing LOS.

Cerebrovascular Complications in Early Survivors of Civilian Penetrating Brain Injury.

BACKGROUND: This study investigates the presence of cerebrovascular injuries in a large sample of civilian penetrating brain injury (PBI) patients, determining the prevalence, radiographic characteristics, and impact on short-term outcome. METHODS: We retrospectively reviewed patients with PBI admitted to our institution over a 2-year period. Computed tomography head scans, computer tomography angiograms and venograms of the intracranial vessels were evaluated to determine the wound trajectory, intracranial injury characteristics, and presence of arterial (AI) and venous sinus (VSI) injuries. Demographics, clinical presentation, and treatment were also reviewed. Discharge disposition was used as surrogate of short-term outcome. RESULTS: Seventy-two patients were included in the study. The mechanism of injury was gunshot wounds in 71 patients and stab wound in one. Forty-one of the 72 patients (60%) had at least one vascular injury. Twenty-six out of 72 patients suffered an AI (36%), mostly pseudoaneurysms and occlusions, involving the anterior and middle cerebral arteries. Of the 72 patients included, 45 had dedicated computed tomography venograms, and of those 22 had VSI (49%), mainly manifesting as superior sagittal sinus occlusion. In a multivariable regression model, intraventricular hemorrhage at presentation was associated with AI (OR 9.9, p = 0.004). The same was not true for VSI. CONCLUSION: Acute traumatic cerebrovascular injury is a prevalent complication in civilian PBI, frequently involving both the arterial and venous sinus systems. Although some radiographic features might be associated with presence of vascular injury, assessment of the intracranial vasculature in the acute phase of all PBI is essential for early diagnosis. Treatment of vascular injury remains variable depending on local practice.

Temporal Evolution and Outcomes of Non-Traumatic Intracerebral Hemorrhage in Hospitalized Patients.

OBJECTIVE: To investigate the radiographic features, temporal evolution, and outcome of patients who develop non-traumatic intracerebral hemorrhage (ICH) while hospitalized for other causes. METHODS: We retrospectively reviewed consecutive Emergency Department ICH (ED-ICH) and in-hospital ICH (IH-ICH) over an 8-year period. Variables including demographics, medical history, lab values, lead time to diagnosis, defined as time from last known well to first CT scan, and clinical characteristics, follow-up CT scan, as well as the frequency of withdrawal of life support were compared in the two groups. Mortality in correlation with ICH score was assessed. RESULTS: Sixty-One IH-ICH and 216 ED-ICH patients were compared. History of cardiac disease, cancer, coagulopathy and higher SOFA score at time of diagnosis were significantly higher in the IH-ICH group (all P< 0.01). Time from symptom onset to diagnosis was shorter in the IH-ICH group (median 95 versus 117 minutes, P=0.011). Thirty six percent of IH-ICH fell into a worse ICH category when recalculated 6 hours from initial scan time, compared to only 10% of the ED-ICH. ICH score was well calibrated in ED-ICH when assessed both at diagnosis and 6 hours later, but underestimated actual mortality in the IH-ICH, particularly at ICH scores 0 to 3. End of life measures were pursued in 69% of IH-ICH group compared to 19% in the ED-ICH group. CONCLUSIONS: IH-ICH, is associated with higher overall mortality rates and often times heralds withdrawal of life sustaining therapies in patients. In addition, IH-ICH in comparison to ED-ICH, significantly changes in severity metrics within the first 6 hours. ICH score is not accurate and not calibrated to reflect reasonable stratification of mortality in IH-ICH. Prospective validation and investigation of variables accounting for higher IH-ICH mortality are needed.

Inversion of T Waves on Admission is Associated with Mortality in Spontaneous Intracerebral Hemorrhage.

INTRODUCTION: Cardiac dysfunction directly caused by spontaneous intracerebral hemorrhage (ICH) is a poorly understood phenomenon, and its impact on outcome is still uncertain. The aim of this study is to investigate the relationship between electrocardiographic (EKG) abnormalities and mortality in ICH. METHODS: This is a retrospective study analyzing EKG patterns on admission in patients admitted with ICH at a tertiary care center over an eight-year period. For each patient, demographics, medical history, clinical presentation, EKG on admission and during hospitalization, and head CT at presentation were reviewed. Mortality was noted. RESULTS: A total of 301 ICH patients were included in the study. The most prevalent EKG abnormalities were QTc prolongation in 56% of patients (n = 168) followed by inversion of T waves (TWI) in 37% of patients (n = 110). QTc prolongation was associated with ganglionic location (p = 0.03) and intraventricular hemorrhage (IVH) (p = 0.01), TWIs were associated with ganglionic location (p = 0.02), and PR prolongation was associated with IVH (p = 0.01), while QRS prolongation was associated with lobar location (p < 0.01). Volume of ICH, hemispheric laterality, and involvement of insular cortex were not correlated with specific EKG patterns. In a logistic regression model, after correcting for ICH severity and prior cardiac history, presence of TWI was independently associated with mortality (OR: 3.04, CI:1.6-5.8, p < 0.01). Adding TWI to ICH score improved its prognostic accuracy (AUC 0.81, p = 0.04). Disappearance of TWI during hospitalization did not translate into improvement of survival (p = 0.5). CONCLUSION: Presence of TWI on admission is an independent and unmodifiable factor associated with mortality in ICH. Further research is needed to elucidate the pathophysiologic mechanisms underlying electrocardiographic changes after primary intracerebral hemorrhage.

Post-Trial Enhanced Deployment and Technical Performance with the MISTIE Procedure per Lessons Learned.

OBJECTIVE: We hypothesize that procedure deployment rates and technical performance with minimally invasive surgery and thrombolysis for intracerebral hemorrhage (ICH) evacuation (MISTIE) can be enhanced in post-trial clinical practice, per Phase III trial results and lessons learned. MATERIALS AND METHODS: We identified ICH patients and those who underwent MISTIE procedure between 2017-2021 at a single site, after completed enrollments in the Phase III trial. Deployment rates, complications and technical outcomes were compared to those observed in the trial. Initial and final hematoma volume were compared between site measurements using ABC/2, MISTIE trial reading center utilizing manual segmentation, and a novel Artificial Intelligence (AI) based volume assessment. RESULTS: Nineteen of 286 patients were eligible for MISTIE. All 19 received the procedure (6.6% enrollment to screening rate 6.6% compared to 1.6% at our center in the trial; p=0.0018). Sixteen patients (84%) achieved evaculation target < 15 mL residual ICH or > 70% removal, compared to 59.7% in the trial surgical cohort (p=0.034). No poor catheter placement occurred and no surgical protocol deviations. Limitations of ICH volume assessments using the ABC/2 method were shown, while AI based methodology of ICH volume assessments had excellent correlation with manual segmentation by experienced reading centers. CONCLUSIONS: Greater procedure deployment and higher technical success rates can be achieved in post-trial clinical practice than in the MISTIE III trial. AI based measurements can be deployed to enhance clinician estimated ICH volume. Clinical outcome implications of this enhanced technical performance cannot be surmised, and will need assessment in future trials.