Recent advances in multimodal imaging in tetralogy of fallot and double outlet right ventricle.

PURPOSE OF REVIEW: In the ever-evolving field of medical imaging, this review highlights significant advancements in preoperative and postoperative imaging for Tetralogy of Fallot (TOF) and double outlet right ventricle (DORV) over the past 18 months. RECENT FINDINGS: This review showcases innovations in echocardiography such as 3D speckle tracking echocardiography (3DSTE) for assessing right ventricle-pulmonary artery coupling (RVPAC) and Doppler velocity reconstruction (DoVeR) for intracardiac flow fields evaluation. Furthermore, advances in assessment of cardiovascular anatomy using computed tomography (CT) improve the integration of imaging in ablation procedures. Additionally, the inclusion of cardiac magnetic resonance (CMR) parameters as risk score predictors for morbidity, and mortality and for timing of pulmonary valve replacement (PVR) indicates its significance in clinical management. The utilization of 4D flow techniques for postoperative hemodynamic assessment promises new insights into pressure mapping. Lastly, emerging technologies such as 3D printing and 3D virtual reality are expected to improve image quality and surgical confidence in preoperative planning. SUMMARY: Developments in multimodality imaging in TOF and DORV are poised to shape the future of clinical practice in this field.

Urgent and emergent pediatric cardiovascular imaging.

The need for urgent or emergent cardiovascular imaging in children is rare when compared to adults. Patients may present from the neonatal period up to adolescence, and may require imaging for both traumatic and non-traumatic causes. In children, coronary pathology is rarely the cause of an emergency unlike in adults where it is the main cause. Radiology, including chest radiography and computed tomography in conjunction with echocardiography, often plays the most important role in the acute management of these patients. Magnetic resonance imaging can occasionally be useful and may be suitable in more subacute cases. Radiologists' knowledge of how to manage and interpret these acute conditions including knowing which imaging technique to use is fundamental to appropriate care. In this review, we will concentrate on the most common cardiovascular emergencies in the thoracic region, including thoracic traumatic and non-traumatic emergencies and pulmonary vascular emergencies, as well as acute clinical disorders as a consequence of primary and postoperative congenital heart disease. This review will cover situations where cardiovascular imaging may be acutely needed, and not strictly emergencies only. Imaging recommendations will be discussed according to the different clinical presentations and underlying pathology.

Variables associated with nonresponders to high-frequency (10 kHz) spinal cord stimulation.

INTRODUCTION: The use of spinal cord stimulation (SCS) therapy to treat chronic pain continues to rise. Optimal patient selection remains one of the most important factors for SCS success. However, despite increased utilization and the existence of general indications, predicting which patients will benefit from neuromodulation remains one of the main challenges for this therapy. Therefore, this study aims to identify the variables that may correlate with nonresponders to high-frequency (10 kHz) SCS to distinguish the subset of patients less likely to benefit from this intervention. MATERIALS AND METHODS: This was a retrospective single-center observational study of patients who underwent 10 kHz SCS implant. Patients were divided into nonresponders and responders groups. Demographic data and clinical outcomes were collected at baseline and statistical analysis was performed for all continuous and categorical variables between the two groups to calculate statistically significant differences. RESULTS: The study population comprised of 237 patients, of which 67.51% were responders and 32.49% were nonresponders. There was a statistically significant difference of high levels of kinesiophobia, high self-perceived disability, greater pain intensity, and clinically relevant pain catastrophizing at baseline in the nonresponders compared to the responders. A few variables deemed potentially relevant, such as age, gender, history of spinal surgery, diabetes, alcohol use, tobacco use, psychiatric illness, and opioid utilization at baseline were not statistically significant. CONCLUSION: Our study is the first in the neuromodulation literature to raise awareness to the association of high levels of kinesiophobia preoperatively in nonresponders to 10 kHz SCS therapy. We also found statistically significant differences with greater pain intensity, higher self-perceived disability, and clinically relevant pain catastrophizing at baseline in the nonresponders relative to responders. It may be appropriate to screen for these factors preoperatively to identify patients who are less likely to respond to SCS. If these modifiable risk factors are present, it might be prudent to consider a pre-rehabilitation program with pain neuroscience education to address these factors prior to SCS therapy, to enhance successful outcomes in neuromodulation.

Relationship between number of prior lumbar spine surgeries and outcomes following spinal cord stimulator implantation: A multisite, retrospective pooled analysis.

OBJECTIVES: Lumbar spine surgery is a common procedure for treating disabling spine-related pain. In recent decades, both the number and cost of spine surgeries have increased despite technological advances and modification in surgical technique. For those patients that have continued uncontrolled back and/or lower extremity pain following lumbar spine surgery, spinal cord stimulation (SCS) has emerged as a viable treatment option. However, the impact of lumbar spine surgical history remains largely unstudied. Specifically, the current study considers the impact of number of prior lumbar spine surgeries on pain relief outcomes following SCS implantation. MATERIALS AND METHODS: We queried the electronic medical record of five separate pain practices for all patients who have undergone a SCS implant between January 1, 2017, and March 1, 2020. Inclusion criteria consisted of any patients with an SCS implant who underwent a prior lumbar spine surgery. The primary outcome was the mean calculated percentage pain relief in patients based on number of prior lumbar spine surgeries. RESULTS: There was a total of 1974 total SCS implant cases identified across five separate pain clinics. There was no difference in mean calculated pain relief in patients with one prior spine surgery versus those with two or more prior spine surgeries (28.2% vs. 25.8%, adjusted ß-coefficient -3.1, 95% CI -8.9 to 2.7, p = 0.290). Similarly, when analyzing number of spine surgeries as a continuous variable, there was no association between number of spine surgeries and calculated pain relief (adjusted ß-coefficient -1.5, 95% CI -4.0 to 1.1, p = 0.257). Additionally, after patients were stratified based on waveform, there was no association between number of prior lumbar spine surgeries (analyzed both as a categorical and continuous variable) and calculated percentage pain relief. CONCLUSIONS: This multicentered retrospective study found that there was no significant difference in pain scores in individuals who received SCS following one or more lumbar spine surgeries. Additionally, the waveform of the SCS device had no statistically significant impact on post-operative pain scores following one or more lumbar spine surgeries.

Pomiferin targets SERCA, mTOR, and P-gp to induce autophagic cell death in apoptosis-resistant cancer cells, and reverses the MDR phenotype in cisplatin-resistant tumors in vivo.

Drug resistance in cancer has been classified as innate resistance or acquired resistance, which were characterized by apoptotic defects and ABC transporters overexpression respectively. Therefore, to preclude or reverse these resistance mechanisms could be a promising strategy to improve chemotherapeutic outcomes. In this study, a natural product from Osage Orange, pomiferin, was identified as a novel autophagy activator that circumvents innate resistance by triggering autophagic cell death via SERCA inhibition and activation of the CaMKKß-AMPK-mTOR signaling cascade. In addition, pomiferin also directly inhibited the P-gp (MDR1/ABCB1) efflux and reversed acquired resistance by potentiating the accumulation and efficacy of the chemotherapeutic agent, cisplatin. In vivo study demonstrated that pomiferin triggered calcium-mediated tumor suppression and exhibited an anti-metastatic effect in the LLC-1 lung cancer-bearing mouse model. Moreover, as an adjuvant, pomiferin potentiated the anti-tumor effect of the chemotherapeutic agent, cisplatin, in RM-1 drug-resistant prostate cancer-bearing mouse model by specially attenuating ABCB1-mediated drug efflux, but not ABCC5, thereby promoting the accumulation of cisplatin in tumors. Collectively, pomiferin may serve as a novel effective agent for circumventing drug resistance in clinical applications.

Assessment of liver fibrosis using a 3-dimensional high-resolution late gadolinium enhancement sequence in children and adolescents with Fontan circulation.

OBJECTIVES: To assess abnormal liver enhancement on 15-20 min delayed 3D high-resolution late gadolinium enhancement (3D HR LGE) sequence in patients with Fontan circulation. METHODS: Retrospective study of pediatric Fontan patients (< 18 years old) with combined cardiac-liver MRI from January 2018 to August 2021. Abnormal hepatic enhancement was graded (0-3) for each lobe, summed for a total liver enhancement score (0-6), and compared to repaired tetralogy of Fallot (rTOF) patients. Correlations with other hepatic imaging biomarkers were performed. Temporal relationships of enhancement compared to traditional early portal venous and 5-7-min delayed phase liver imaging were analyzed. RESULTS: The Fontan group (n = 35, 13 ± 3.4 years old, median time from Fontan 10 (9-12) years) had 23/35 (66%) with delayed 3D HR LGE total liver enhancement score > 0 (range 0-5), with greater involvement of the right lobe (1 (0-1) vs 0 (0-1), p < 0.01). The rTOF group (n = 35, 14 ± 2.6 years old) had no abnormal enhancement. In the Fontan group, total liver enhancement was 3 (2-4) in the early portal venous phase, lower at 1 (1-2) in the 5-7-min delayed phase (p < 0.01), and lowest at 1 (0-2) in the 15-20-min delayed phase (p = 0.03). 3D HR LGE enhancement correlated inversely with portal vein flow (rs = - 0.42, p = 0.01) and positively with left lobe stiffness (rs = 0.51, p < 0.01). The enhancement score decreased in 13/35 (37%) between the 5-7- and 15-20-min delayed phases. CONCLUSIONS: Liver fibrosis can be assessed on 3D HR LGE sequences in patients with Fontan circulation, correlates with other imaging biomarkers of Fontan liver disease, and may add information for hepatic surveillance in this population. KEY POINTS: • Abnormal liver enhancement on 3D HR LGE sequences in Fontan patients likely represents liver fibrosis and is seen in up to 66% of children and adolescents with variable distribution and severity. • The degree of 3D HR LGE liver enhancement correlates with decreased portal vein flow and increased left hepatic lobe stiffness.

Myocardial late gadolinium enhancement using delayed 3D IR-FLASH in the pediatric population: feasibility and diagnostic performance compared to single-shot PSIR-bSSFP.

BACKGROUND: This study compares three-dimensional (3D) high-resolution (HR) late gadolinium enhancement (LGE; 3D HR-LGE) imaging using a respiratory navigated, electrocardiographically-gated inversion recovery gradient echo sequence with conventional LGE imaging using a single-shot phase-sensitive inversion recovery (PSIR) balanced steady-state free precession (bSSFP; PSIR-bSSFP) sequence for routine clinical use in the pediatric population. METHODS: Pediatric patients (0-18 years) who underwent clinical cardiovascular magnetic resonance (CMR) with both 3D HR-LGE and single-shot PSIR-bSSFP LGE between January 2018 and June 2020 were included. Image quality (0-4) and detection of LGE in the left ventricle (LV) (per 17 segments), in the right ventricle (RV) (per 3 segments), as endocardial fibroelastosis (EFE), at the hinge points, and at the papillary muscles was analyzed by two blinded readers for each sequence. Ratios of the mean signal intensity of LGE to normal myocardium (LGE:Myo) and to LV blood pool (LGE:Blood) were recorded. Data is presented as median (1st-3rd quartiles). Wilcoxon signed rank test and chi-square analyses were used as appropriate. Inter-rater agreement was analyzed using weighted κ-statistics. RESULTS: 102 patients were included with median age at CMR of 8 (1-13) years-old and 44% of exams performed under general anesthesia. LGE was detected in 55% of cases. 3D HR LGE compared to single-shot PSIR-bSSFP had longer scan time [4:30 (3:35-5:34) vs 1:11 (0:47-1:32) minutes, p < 0.001], higher image quality ratings [3 (3-4) vs 2 (2-3), p < 0.001], higher LGE:Myo [23.7 (16.9-31.2) vs 5.0 (2.9-9.0), p < 0.001], detected more segments of LGE in both the LV [4 (2-8) vs 3 (1-7), p = 0.045] and RV [1 (1-1) vs 1 (0-1), p < 0.001], and also detected more cases of LGE with 13/56 (23%) of patients with LGE only detectable by 3D HR LGE (p < 0.001). 3D HR LGE specifically detected a greater proportion of RV LGE (27/27 vs 17/27, p < 0.001), EFE (11/11 vs 5/11, p = 0.004), and papillary muscle LGE (14/15 vs 4/15, p < 0.001). Inter-rater agreement for the recorded variables ranged from 0.42 to 1.00. CONCLUSIONS: 3D HR LGE achieves greater image quality and detects more LGE than conventional single-shot PSIR-bSSFP LGE imaging, and should be considered an alternative to conventional LGE sequences for routine clinical use in the pediatric population.

Imaging of pediatric cardiac tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Cardiac tumors in children are rare and the majority are benign. The most common cardiac tumor in children is rhabdomyoma, usually associated with tuberous sclerosis complex. Other benign cardiac masses include fibromas, myxomas, hemangiomas, and teratomas. Primary malignant cardiac tumors are exceedingly rare, with the most common pathology being soft tissue sarcomas. This paper provides consensus-based imaging recommendations for the evaluation of patients with cardiac tumors at diagnosis and follow-up, including during and after therapy.

Low- and high-frequency spinal cord stimulation and arterial blood pressure in patients with chronic pain and hypertension: a retrospective study.

PURPOSE: Evidence suggests that traditional low-frequency spinal cord stimulation (LF-SCS) reduces arterial blood pressure (BP) in patients with chronic pain and hypertension independent of improved pain symptoms. However, it remains unclear whether high-frequency spinal cord stimulation (HF-SCS) also lowers BP in chronic pain patients with hypertension. Therefore, in a retrospective study design, we tested the hypothesis that clinic BP would be significantly reduced following implantation of HF-SCS in patients with chronic pain and hypertension. METHODS: Clinic BP within 3 months before and after surgical implantation of either a LF-SCS or HF-SCS device between 2010 and 2020 were collected from electronic medical records at The University of Kansas Health System (TUKHS). RESULTS: A total of 132 patients had available records of clinic BP (64 ± 13 years of age). Patients with hypertension (n = 32) demonstrated a significantly greater reduction in systolic BP (-8 ± 12 versus 2 ± 9 mmHg, P < 0.001) following implantation compared with normotensive patients (n = 100). Importantly, the change in BP was inversely related to baseline BP independent of age and sex following implantation of HF-SCS (n = 70, R = -0.50, P < 0.001) or LF-SCS (n = 62, R = -0.42, P = 0.001). Higher pain scores before implantation were not associated with reduction in systolic BP (R = 0.10, P = 0.43) or diastolic BP (R = -0.08, P = 0.53) (n = 69) after implantation. CONCLUSION: These findings confirm previous studies showing reduced BP following implantation of LF-SCS in patients with chronic pain and hypertension and provide novel data regarding reduced BP following implantation of newer generation HF-SCS devices.

Cardiac Magnetic Resonance Imaging to Determine Single Ventricle Function in a Pediatric Population is Feasible in a Large Trial Setting: Experience from the Single Ventricle Reconstruction Trial Longitudinal Follow up.

The Single Ventricle Reconstruction (SVR) Trial was a randomized prospective trial designed to determine survival advantage of the modified Blalock-Taussig-Thomas shunt (BTTS) vs the right ventricle to pulmonary artery conduit (RVPAS) for patients with hypoplastic left heart syndrome. The primary aim of the long-term follow-up (SVRIII) was to determine the impact of shunt type on RV function. In this work, we describe the use of CMR in a large cohort follow up from the SVR Trial as a focused study of single ventricle function. The SVRIII protocol included short axis steady-state free precession imaging to assess single ventricle systolic function and flow quantification. There were 313 eligible SVRIII participants and 237 enrolled, ages ranging from 10 to 12.5 years. 177/237 (75%) participants underwent CMR. The most common reasons for not undergoing CMR exam were requirement for anesthesia (n = 14) or ICD/pacemaker (n = 11). A total of 168/177 (94%) CMR studies were diagnostic for RVEF. Median exam time was 54 [IQR 40-74] minutes, cine function exam time 20 [IQR 14-27] minutes, and flow quantification time 18 [IQR 12-25] minutes. There were 69/177 (39%) studies noted to have intra-thoracic artifacts, most common being susceptibility artifact from intra-thoracic metal. Not all artifacts resulted in non-diagnostic exams. These data describe the use and limitations of CMR for the assessment of cardiac function in a prospective trial setting in a grade-school-aged pediatric population with congenital heart disease. Many of the limitations are expected to decrease with the continued advancement of CMR technology.