Hypertrophy Regression With N-Acetylcysteine in Hypertrophic Cardiomyopathy (HALT-HCM): A Randomized, Placebo-Controlled, Double-Blind Pilot Study.

RATIONALE: Hypertrophic cardiomyopathy (HCM) is a genetic paradigm of cardiac hypertrophy. Cardiac hypertrophy and interstitial fibrosis are important risk factors for sudden death and morbidity in HCM. Oxidative stress is implicated in the pathogenesis of cardiac hypertrophy and fibrosis. Treatment with antioxidant N-acetylcysteine (NAC) reverses cardiac hypertrophy and fibrosis in animal models of HCM. OBJECTIVE: To determine effect sizes of NAC on indices of cardiac hypertrophy and fibrosis in patients with established HCM. METHODS AND RESULTS: HALT-HCM (Hypertrophy Regression With N-Acetylcysteine in Hypertrophic Cardiomyopathy) is a double-blind, randomized, sex-matched, placebo-controlled single-center pilot study in patients with HCM. Patients with HCM, who had a left ventricular wall thickness of ≥15 mm, were randomized either to a placebo or to NAC (1:2 ratio, respectively). NAC was titrated ≤2.4 g per day. Clinical evaluation, blood chemistry, and 6-minute walk test were performed every 3 months, and electrocardiography, echocardiography, and cardiac magnetic resonance imaging, the latter whenever not contraindicated, before and after 12 months of treatment. Eighty-five of 232 screened patients met the eligibility criteria, 42 agreed to participate; 29 were randomized to NAC and 13 to placebo groups. Demographic, echocardiographic, and cardiac magnetic resonance imaging phenotypes at the baseline between the 2 groups were similar. WSE in 38 patients identified a spectrum of 42 pathogenic variants in genes implicated in HCM in 26 participants. Twenty-four patients in the NAC group and 11 in the placebo group completed the study. Six severe adverse events occurred in the NAC group but were considered unrelated to NAC. The effect sizes of NAC on the clinical phenotype, echocardiographic, and cardiac magnetic resonance imaging indices of cardiac hypertrophy, function, and extent of late gadolinium enhancement-a surrogate for fibrosis-were small. CONCLUSIONS: Treatment with NAC for 12 months had small effect sizes on indices of cardiac hypertrophy or fibrosis. The small sample size of the HALT-HCM study hinders from making firm conclusions about efficacy of NAC in HCM. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01537926.

High frame rate cardiac cine MRI for the evaluation of diastolic function and its direct correlation with echocardiography.

BACKGROUND: Breath-hold cine MR is the method of choice for evaluating left ventricular (LV) systolic function; however, the evaluation of diastolic function remains in the domain of high frame rate echocardiography. Thus, a cine MR technique for simultaneously evaluating LV systolic and diastolic function would be clinically valuable. PURPOSE: To test the feasibility of extracting indices that characterize LV diastolic function from high frame rate cine MR. STUDY TYPE: Single center, prospective. POPULATION: Asymptomatic volunteers (N = 24; age 45.8 ± 12.3 years). FIELD STRENGTH/SEQUENCE: High frame rate (70 fps) cine MR and phase-contrast MR during free breathing were acquired at 1.5T. ASSESSMENT: The following MR-based LV filling metrics were extracted from LV volume changes during the cardiac cycle: 1) the volume-rate ratio, REFP /RLFP (ratio of the peak LV filling rate during the early filling period [EFP] to that during the late filling period [LFP]); and 2) the volume ratio, VEFP /VLFP (the ratio of cumulative LV volume change between the EFP and LFP). These metrics were then compared with traditional transmitral blood flow-based MR and echocardiographic indices. The effect of temporal resolution on these metrics was also evaluated. STATISTICAL TESTS: Bland-Altman and linear regression analyses were used to evaluate the performance of the proposed metrics against traditional indices of diastolic function. RESULTS: The REFP /RLFP and VEFP /VLFP correlated well with E/AQ-flow (r 2 = 0.66 and 0.54, respectively) and E/Aecho (r 2 = 0.58 and 0.49, respectively). Systolic indices remained robust (<3% error) for frame rates ≥20 fps. Although the proposed VEFP /VLFP was robust (<5% error) up to 25 fps, the proposed volume-rate diastolic function metrics were less reliable (>8% error) for frame rates below 35 fps. DATA CONCLUSION: In asymptomatic volunteers, cardiac cine MR images acquired at frame rates >35 fps can be used to extract LV diastolic function indices from the temporal changes in LV volume. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:1571-1582.

Evaluation of Cell Therapy on Exercise Performance and Limb Perfusion in Peripheral Artery Disease: The CCTRN PACE Trial (Patients With Intermittent Claudication Injected With ALDH Bright Cells).

BACKGROUND: Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermittent Claudication Injected With ALDH Bright Cells) is a National Heart, Lung, and Blood Institute-sponsored, randomized, double-blind, placebo-controlled, phase 2 exploratory clinical trial designed to assess the safety and efficacy of autologous bone marrow-derived aldehyde dehydrogenase bright (ALDHbr) cells in patients with peripheral artery disease and to explore associated claudication physiological mechanisms. METHODS: All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by 10 injections into the thigh and calf of the index leg. The coprimary end points were change from baseline to 6 months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion measured by magnetic resonance imaging, as well as safety. RESULTS: A total of 82 patients with claudication and infrainguinal peripheral artery disease were randomized at 9 sites, of whom 78 had analyzable data (57 male, 21 female patients; mean age, 66±9 years). The mean±SEM differences in the change over 6 months between study groups for PWT (0.9±0.8 minutes; 95% confidence interval [CI] -0.6 to 2.5; P=0.238), collateral count (0.9±0.6 arteries; 95% CI, -0.2 to 2.1; P=0.116), peak hyperemic popliteal flow (0.0±0.4 mL/s; 95% CI, -0.8 to 0.8; P=0.978), and capillary perfusion (-0.2±0.6%; 95% CI, -1.3 to 0.9; P=0.752) were not significant. In addition, there were no significant differences for the secondary end points, including quality-of-life measures. There were no adverse safety outcomes. Correlative relationships between magnetic resonance imaging measures and PWT were not significant. A post hoc exploratory analysis suggested that ALDHbr cell administration might be associated with an increase in the number of collateral arteries (1.5±0.7; 95% CI, 0.1-2.9; P=0.047) in participants with completely occluded femoral arteries. CONCLUSIONS: ALDHbr cell administration did not improve PWT or magnetic resonance outcomes, and the changes in PWT were not associated with the anatomic or physiological magnetic resonance imaging end points. Future peripheral artery disease cell therapy investigational trial design may be informed by new anatomic and perfusion insights. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01774097.

Two-center clinical validation and quantitative assessment of respiratory triggered retrospectively cardiac gated balanced-SSFP cine cardiovascular magnetic resonance imaging in adults.

BACKGROUND: Breath-hold (BH) requirement remains the limiting factor on the spatio-temporal resolution and coverage of the cine balanced steady-state free precession (bSSFP) cardiovascular magnetic resonance (CMR) imaging. In this prospective two-center clinical trial, we validated the performance of a respiratory triggered (RT) bSSFP cine sequence for evaluation of biventricular function. METHODS: Our study included 23 asymptomatic healthy subjects and 60 consecutive patients from Institute A (n = 39) and Institute B (n = 21) referred for a clinically indicated CMR study. We implemented a RT sequence with a respiratory synchronized drive to steady state (SS) of bSSFP signal, before the commencement of image data acquisition with prospective cardiac arrhythmia rejection and retrospectively cardiac gated reconstruction in real-time. Left (LV) and right (RV) ventricular function and LV mass were evaluated by using RT-bSSFP and conventional BH-bSSFP sequences with one cardiac cycle for SS preparation keeping all the imaging parameters identical. The performance of the sequences was evaluated by using quantitative and semi-quantitative metrics. RESULTS: Global LV and RV functional parameters and LV mass obtained from the RT-bSSFP and BH-bSSFP sequences were in good agreement. Quantitative metrics designed to capture fluctuation in SS signal intensity showed no significant difference between sequences. In addition, blood-to-myocardial contrast was nearly identical between sequences. The combined clinical score for image quality was excellent or good for 100% of cases with the BH-bSSFP and 83% of cases with the RT-bSSFP sequence. The de facto image acquisition time for RT-bSSFP was statistically significantly longer than that for conventional BH-bSSFP (7.9 ± 3.4 min vs. 5.1 ± 2.6 min). CONCLUSIONS: Cine RT-bSSFP is an alternative for evaluating global biventricular function with contrast and spatio-temporal resolutions that are similar to those attained by using the BH-bSSFP sequence, albeit with a modest time penalty and a small reduction in image quality.

Appropriateness of anteroseptal myocardial infarction nomenclature evaluated by late gadolinium enhancement cardiovascular magnetic resonance imaging.

BACKGROUND: In traditional literature, it appears that "anteroseptal" MIs with Q waves in V1-V3 involve basal anteroseptal segments although studies have questioned this belief. METHODS: We studied patients with first acute anterior Q-wave (>30ms) MI. All underwent late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (MRI). RESULTS: Those with Q waves in V1-V2 (n=7) evidenced LGE >50% in 0%, 43%, 43%, 57%, and 29% of the basal anteroseptal, mid anteroseptal, apical anterior, apical septal segments, and apex, respectively. Patients with Q waves in V1-V3 (n=14), evidenced involvement was 14%, 43%, 43%, 50%, and 7% of the same respective segments. In those with extensive anterior Q waves (n=7), involvement was 0%, 71%, 57%, 86%, and 86%. CONCLUSIONS: Q-wave MI in V1-V2/V3 primarily involves mid- and apical anterior and anteroseptal segments rather than basal segments. Data do not support existence of isolated basal anteroseptal or septal infarction. "Anteroapical infarction" is a more appropriate term than "anteroseptal infarction."

Myocardial Stress Perfusion MRI: Experience in Pediatric and Young-Adult Patients Following Arterial Switch Operation Utilizing Regadenoson.

Dextro-transposition of the great arteries (D-TGA) is one of the most common cyanotic heart lesions. The arterial switch operation (ASO) is the preferred surgical palliation for D-TGA. One of the primary concerns following the ASO is complications arising from the coronary artery transfer. There is a need for myocardial perfusion assessment within ASO patients. There is no report on the utility of regadenoson as a stress agent in children following ASO. Our objective was to observe the safety and feasibility of regadenoson as a pharmacologic stressor for perfusion cardiac MR in a pilot cohort of pediatric and young-adult patients who have undergone ASO. We reviewed our initial experience with regadenoson stress cardiac MR in 36 pediatric and young-adult patients 15.1 ± 4.5 years (range 0.2-22 years) with history of ASO. The weight was 61.6 ± 21.5 kg (range 3.8-93 kg). All patients underwent cardiac MR because of concern for ischemia. Subjects' heart rate and blood pressure were monitored and pharmacologic stress was induced by injection of regadenoson. We evaluated their hemodynamic response and adverse effects using changes in vital signs and onset of symptoms. A pediatric cardiologist and radiologist qualitatively assessed myocardial perfusion and viability images. All stress cardiac MR examinations were completed without adverse events. Resting heart rate was 72 ± 13 beats per minute (bpm) and rose to peak of 120 ± 17 bpm (95 ± 50% increase, p < 0.005) with regadenoson. Image quality was considered good or diagnostic in all cases. A total of 11/36 (31%) patients had a perfusion defect on the stress FPP images. 14 of the 36 patients (39%) underwent cardiac catheterization within 6 months of the CMR and the findings showed excellent agreement. Regadenoson may be a useful coronary hyperemia agent to utilize for pediatric patients following arterial switch procedure when there is concern for ischemia. The ability to administer as a single bolus with one IV makes it advantageous in pediatrics. In a limited number of cases, regadenoson stress perfusion showed excellent agreement with cardiac catheterization.

Identification of established arrhythmogenic right ventricular cardiomyopathy mutation in a patient with the contrasting phenotype of hypertrophic cardiomyopathy.

BACKGROUND: Advances in the nucleic acid sequencing technologies have ushered in the era of genetic-based "precision medicine". Applications of the genetic discoveries to practice of medicine, however, are hindered by phenotypic variability of the genetic variants. The report illustrates extreme pleiotropic phenotypes associated with an established causal mutation for hereditary cardiomyopathy. CASE PRESENTATION: We report a 61-year old white female who presented with syncope and echocardiographic and cardiac magnetic resonance (CMR) imaging findings consistent with the diagnosis of hypertrophic cardiomyopathy (HCM). The electrocardiogram, however, showed a QRS pattern resembling an Epsilon wave, a feature of arrhythmogenic right ventricular cardiomyopathy (ARVC). Whole exome sequencing (mean depth of coverage of exons 178X) analysis did not identify a pathogenic variant in the known HCM genes but identified an established causal mutation for ARVC. The mutation involves a canonical splice accepter site (c.2146-1G > C) in the PKP2 gene, which encodes plakophillin 2. Sanger sequencing confirmed the mutation. PKP2 is the most common causal gene for ARVC but has not been implicated in HCM. Findings on echocardiography and CMR during the course of 4-year follow up showed septal hypertrophy and a hyperdynamic left ventricle, consistent with the diagnosis of HCM. However, neither baseline nor follow up echocardiography and CMR studies showed evidence of ARVC. The right ventricle was normal in size, thickness, and function and there was no evidence of fibro-fatty infiltration in the myocardium. CONCLUSIONS: The patient carries an established pathogenic mutation for ARVC and a subtle finding of ARVC but exhibits the classic phenotype of HCM, a contrasting phenotype to ARVC. The case illustrates the need for detailed phenotypic characterization for patients with hereditary cardiomyopathies as well as the challenges physicians face in applying the genetic discoveries in practicing genetic-based "precision medicine".

Comparison of Low-Dose Higher-Relaxivity and Standard-Dose Lower-Relaxivity Contrast Media for Delayed-Enhancement MRI: A Blinded Randomized Crossover Study.

OBJECTIVE: The gadolinium-based MRI contrast agent gadobenate dimeglumine has nearly twice the MR relaxivity of gadopentetate dimeglumine at 1.5 T. The purpose of this study was to determine whether a lower dose (0.1 mmol/kg) of gadobenate dimeglumine can be used to obtain delayed-enhancement MR images comparable to those obtained with a standard dose (0.2 mmol/kg) of gadopentetate dimeglumine. SUBJECTS AND METHODS: In this blinded randomized crossover study, 20 patients with known myocardial infarction underwent two separate delayed-enhancement MRI examinations after receiving 0.1 mmol/kg gadobenate dimeglumine and 0.2 mmol/kg gadopentetate dimeglumine (random administration). The conspicuity of lesion enhancement 5, 10, and 20 minutes after contrast administration was quantified as relative enhancement ratio (RER). RESULTS: With either gadolinium-based contrast agent, damaged myocardium had higher signal intensity than normal remote myocardium (RER > 4) on delayed-enhancement MR images, and the blood RER declined over time after contrast administration. The blood RER was not significantly higher for gadobenate dimeglumine than for gadopentetate dimeglumine at 5 and 10 minutes. Nevertheless, there was a larger reduction in blood RER for gadobenate dimeglumine than for gadopentetate dimeglumine between 5 and 10 minutes and between 10 and 20 minutes. The volumes of enhancement were similar for gadobenate dimeglumine (13.6 ± 8.8 cm(3)) and gadopentetate dimeglumine (13.5 ± 8.9 cm(3)) (p = 0.98). The mean difference in Bland-Altman analysis for delayed-enhancement volume between the agents was 0.1 cm(3). CONCLUSION: Qualitatively and quantitatively, delayed-enhancement MR images of ischemic myocardium obtained with 0.1 mmol/kg gadobenate dimeglumine are comparable to those obtained with 0.2 mmol/kg gadopentetate dimeglumine 5, 10, and 20 minutes after contrast administration.

Evaluation of a subject specific dual-transmit approach for improving B1 field homogeneity in cardiovascular magnetic resonance at 3T.

BACKGROUND: Radiofrequency (RF) shading artifacts degrade image quality while performing cardiovascular magnetic resonance (CMR) at higher field strengths. In this article, we sought to evaluate the effect of local RF (B1 field) shimming by using a dual-source-transmit RF system for cardiac cine imaging and to systematically evaluate the effect of subject body type on the B1 field with and without local RF shimming. METHODS: We obtained cardiac images from 37 subjects (including 11 patients) by using dual-transmit 3T CMR. B1 maps with and without subject-specific local RF shimming (exploiting the independent control of transmit amplitude and phase of the 2 RF transmitters) were obtained. Metrics quantifying B1 field homogeneity were calculated and compared with subject body habitus. RESULTS: Local RF shimming across the region encompassed by the heart increased the mean flip angle (µ) in that area (88.5 ± 15.2% vs. 81.2 ± 13.3%; P = 0.0014), reduced the B1 field variation by 42.2 ± 13%, and significantly improved the percentage of voxels closer to µ (39% and 82% more voxels were closer to ± 10% and ± 5% of µ, respectively) when compared with no RF shimming. B1 homogeneity was independent of subject body type (body surface area [BSA], body mass index [BMI] or anterior-posterior/right-left patient width ratio [AP/RL]). Subject specific RF (B1) shimming with a dual-transmit system improved local RF homogeneity across all body types. CONCLUSION: With or without RF shimming, cardiac B1 field homogeneity does not depend on body type, as characterized by BMI, BSA, and AP/RL. For all body types studied, cardiac B1 field homogeneity was significantly improved by performing local RF shimming with 2 independent RF-transmit channels. This finding indicates the need for subject-specific RF shimming.

Secondary Holocord Syringomyelia Associated With Spinal Hemangioblastoma in a 29-Year-Old Female.

Syringomyelia is a neurological condition characterized by the presence of fluid-filled cavities within the spinal cord, resulting in progressive neurological deficits. Secondary holocord syringomyelia, a rare manifestation in the entire spinal cord, is associated with spinal hemangioblastomas. We report the case of a 29-year-old female who presented with neck and bilateral upper limb pain and numbness. She was diagnosed with secondary holocord syringomyelia associated with a spinal hemangioblastoma and underwent conservative management. Magnetic resonance imaging plays a critical role in diagnosing neurological conditions. The management of spinal hemangioblastomas and syringomyelia can be challenging and requires a multidisciplinary approach to patient care. In this report, we discuss the clinical presentation, diagnosis, and management of a patient with secondary holocord syringomyelia associated with spinal hemangioblastoma.

Unmasking Acute Lymphoblastic Leukemia in a Chiropractic Patient With Musculoskeletal Complaints.

A 67-year-old woman presented to a chiropractor with a four-week history of neck and low back pain, lower extremity paresthesia, profound fatigue, and cutaneous pallor. Previous cervical radiographs had revealed multilevel degenerative spondylosis. However, abnormal hematological indices, including severe thrombocytopenia and anemia, prompted concerns of an underlying hematopoietic malignancy. Interdisciplinary collaboration facilitated expedient hematological assessment, confirming acute lymphoblastic leukemia (ALL), as evidenced by lymphoblasts in a peripheral blood smear and bone marrow biopsy. Karyotyping detected a Philadelphia chromosomal mutation; the patient therefore received oral targeted tyrosine kinase inhibition coupled with serial intrathecal chemotherapy. Complete remission was achieved. However, sensorimotor symptoms persisted due to herpetic neuralgia secondary to immunosuppression. This complex case underscores the role of chiropractors as primary contact clinicians in identifying sinister pathologies underlying musculoskeletal complaints via judicious history-taking, physical evaluation, and interpretation of investigational findings. Interprofessional collaboration is pivotal in formulating an effective therapeutic strategy to improve the prognosis of patients with this disease.

Thyroid Cancer Presenting as Neck Pain at a Chiropractic Clinic.

We report an unusual case of metastatic papillary thyroid carcinoma presenting with progressive neck pain in a 58-year-old female with known bilateral thyroid nodules. Despite initial benign ultrasonographic findings and trials of conservative therapy for over 2 months, the patient's anterior neck pain and unremitting symptoms prompted concern regarding an underlying orthopedic condition. She sought chiropractic consultation, and MRI revealed pathologic vertebral fractures. Biopsy of the thyroid and vertebral bone lesions demonstrated metastatic thyroid carcinoma. The patient was diagnosed with papillary thyroid cancer. The early detection of metastatic disease is critical for optimizing oncological treatment and outcomes. This case highlights the importance of close follow-up when the initial workup or management fails, consideration of sinister pathologies in high-risk patients, and a multidisciplinary approach to complex conditions. It provides an important reminder not to attribute unresolved symptoms to benign causes without serial re-evaluation, especially in patients with known risks, such as thyroid disease. A high index of suspicion and openness to atypical disease presentations is fundamental to avoid missed opportunities for diagnosis and prompt treatment.

Lung Cancer With Vertebral Metastases Presenting as Low Back Pain in the Chiropractic Office: A Case Report.

Lung cancer commonly metastasizes to the skeletal system, and when affecting the spine, it may initially be mistaken for a typical musculoskeletal source of back pain. We report a previously healthy 52-year-old male non-smoker with an eight-week history of low back pain that radiated into his left thigh and recent weight loss, yet no respiratory symptoms. Initially, the patient visited his primary care physician, who suspected a musculoskeletal condition and prescribed a nonsteroidal anti-inflammatory drug and muscle relaxant, then referred the patient to the chiropractor. Based on the patient's pain pattern, limited mobility, and other features, the chiropractor suspected a lumbar disc herniation. However, the patient's condition worsened during a one-week trial of care, so the chiropractor ordered magnetic resonance imaging (MRI) and, as the findings suggested vertebral metastasis, promptly referred the patient to an oncologist, who confirmed a diagnosis of lung adenocarcinoma via positron emission tomography (PET)/computed tomography and biopsy. Chiropractors should be aware of warning signs of malignancy, such as unexplained weight loss or progressive worsening despite treatment. If providers suspect spinal metastasis, they should order advanced imaging such as an MRI and refer patients to an oncologist for timely care.

Sacral Chordoma Presenting as Back Pain in the Chiropractic Clinic: A Case Report.

Cases of lumbar and gluteal pain are commonly encountered in chiropractic clinics, with a broad differential diagnosis primarily centered on musculoskeletal conditions. This report presents the second documented case of sacral chordoma diagnosed at a chiropractic clinic and emphasizes the importance of considering alternative diagnoses and interdisciplinary collaboration in patient care. A 42-year-old man presented to a chiropractic clinic with complaints of lumbar and gluteal pain. The initial conservative management based on a presumptive musculoskeletal diagnosis was ineffective. Suspicion of an alternative etiology prompted a referral for imaging, which revealed a sacral chordoma. An interdisciplinary collaboration involving orthopedic surgeons, oncologists, radiologists, and other healthcare professionals was initiated to optimize the treatment outcomes of this rare and aggressive tumor. This case report underscores the importance of maintaining a high index of suspicion in cases of musculoskeletal presentations in chiropractic clinics and the critical role of advanced imaging in establishing a definitive diagnosis. Interdisciplinary collaboration is essential for managing complex conditions such as sacral chordomas, ensuring the delivery of the highest quality of care, and optimizing patient outcomes. Chiropractors play a crucial role in identifying, referring, and contributing to the management of patients with complex presentations as part of a comprehensive multidisciplinary treatment plan.

Gadolinium-Based Contrast Agents: Updates and Answers to Typical Questions Regarding Gadolinium Use.

Gadolinium-based contrast agents have expanded the diagnostic usefulness and capability of magnetic resonance imaging. Despite their highly favorable safety profile, these agents have been associated with nephrogenic systemic fibrosis in a small number of patients who have advanced kidney disease. Recently, trace amounts of gadolinium deposition in the brain and other organs have been reported after contrast exposure, even in patients with normal renal function. In this review, we provide a brief overview of recent updates and discuss typical clinical situations related to the use of gadolinium-based contrast agents.

A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF).

BACKGROUND: Autologous bone marrow mononuclear cell (ABMMNC) therapy has shown promise in patients with heart failure (HF). Cell function analysis may be important in interpreting trial results. METHODS: In this prospective study, we evaluated the safety and efficacy of the transendocardial delivery of ABMMNCs in no-option patients with chronic HF. Efficacy was assessed by maximal myocardial oxygen consumption, single photon emission computed tomography, 2-dimensional echocardiography, and quality-of-life assessment (Minnesota Living with Heart Failure and Short Form 36). We also characterized patients' bone marrow cells by flow cytometry, colony-forming unit, and proliferative assays. RESULTS: Cell-treated (n = 20) and control patients (n = 10) were similar at baseline. The procedure was safe; adverse events were similar in both groups. Canadian Cardiovascular Society angina score improved significantly (P = .001) in cell-treated patients, but function was not affected. Quality-of-life scores improved significantly at 6 months (P = .009 Minnesota Living with Heart Failure and P = .002 physical component of Short Form 36) over baseline in cell-treated but not control patients. Single photon emission computed tomography data suggested a trend toward improved perfusion in cell-treated patients. The proportion of fixed defects significantly increased in control (P = .02) but not in treated patients (P = .16). Function of patients' bone marrow mononuclear cells was severely impaired. Stratifying cell results by age showed that younger patients (≤60 years) had significantly more mesenchymal progenitor cells (colony-forming unit fibroblasts) than patients >60 years (20.16 ± 14.6 vs 10.92 ± 7.8, P = .04). Furthermore, cell-treated younger patients had significantly improved maximal myocardial oxygen consumption (15 ± 5.8, 18.6 ± 2.7, and 17 ± 3.7 mL/kg per minute at baseline, 3 months, and 6 months, respectively) compared with similarly aged control patients (14.3 ± 2.5, 13.7 ± 3.7, and 14.6 ± 4.7 mL/kg per minute, P = .04). CONCLUSIONS: ABMMNC therapy is safe and improves symptoms, quality of life, and possibly perfusion in patients with chronic HF.

Ultrafast Computation of Left Ventricular Ejection Fraction by Using Temporal Intensity Variation in Cine Cardiac Magnetic Resonance.

Cardiac magnetic resonance enables comprehensive cardiac evaluation; however, intense time and labor requirements for data acquisition and processing have discouraged many clinicians from using it. We have developed an alternative image-processing algorithm that requires minimal user interaction: an ultrafast algorithm that computes left ventricular ejection fraction (LVEF) by using temporal intensity variation in cine balanced steady-state free precession (bSSFP) short-axis images, with or without contrast medium. We evaluated the algorithm's performance against an expert observer's analysis for segmenting the LV cavity in 65 study participants (LVEF range, 12%-70%). In 12 instances, contrast medium was administered before cine imaging. Bland-Altman analysis revealed quantitative effects of LV basal, midcavity, and apical morphologic variation on the algorithm's accuracy. Total computation time for the LV stack was <2.5 seconds. The algorithm accurately delineated endocardial boundaries in 1,132 of 1,216 slices (93%). When contours in the extreme basal and apical slices were not adequate, they were replaced with manually drawn contours. The Bland-Altman mean differences were <1.2 mL (0.8%) for end-diastolic volume, <5 mL (6%) for end-systolic volume, and <3% for LVEF. Standard deviation of the difference was ≤4.1% of LV volume for all sections except the midcavity in end-systole (8.3% of end-systolic volume). We conclude that temporal intensity variation-based ultrafast LVEF computation is clinically accurate across a range of LV shapes and wall motions and is suitable for postcontrast cine SSFP imaging. Our algorithm enables real-time processing of cine bSSFP images on a commercial scanner console within 3 seconds in an unobtrusive automated process.

Young athletes: Preventing sudden death by adopting a modern screening approach? A critical review and the opening of a debate.

Preventing sudden cardiac death (SCD) in athletes is a primary duty of sports cardiologists. Current recommendations for detecting high-risk cardiovascular conditions (hr-CVCs) are history and physical examination (H&P)-based. We discuss the effectiveness of H&P-based screening versus more-modern and accurate methods. In this position paper, we review current authoritative statements and suggest a novel alternative: screening MRI (s-MRI), supported by evidence from a preliminary population-based study (completed in 2018), and a prospective, controlled study in military recruits (in development). We present: 1. Literature-Based Comparisons (for diagnosing hr-CVCs): Two recent studies using traditional methods to identify hr-CVCs in >3,000 young athletes are compared with our s-MRI-based study of 5,169 adolescents. 2. Critical Review of Previous Results: The reported incidence of SCD in athletes is presently based on retrospective, observational, and incomplete studies. H&P's screening value seems minimal for structural heart disease, versus echocardiography (which improves diagnosis for high-risk cardiomyopathies) and s-MRI (which also identifies high-risk coronary artery anomalies). Electrocardiography is valuable in screening for potentially high-risk electrophysiological anomalies. 3. Proposed Project : We propose a prospective, controlled study (2 comparable large cohorts: one historical, one prospective) to compare: (1) diagnostic accuracy and resulting mortality-prevention performance of traditional screening methods versus questionnaire/electrocardiography/s-MRI, during 2-month periods of intense, structured exercise (in military recruits, in advanced state of preparation); (2) global costs and cost/efficiency between these two methods. This study should contribute significantly toward a comprehensive understanding of the incidence and causes of exercise-related mortality (including establishing a definition of hr-CVCs) while aiming to reduce mortality.

Prognostic significance of delayed-enhancement magnetic resonance imaging: survival of 857 patients with and without left ventricular dysfunction.

BACKGROUND: Left ventricular ejection fraction is a powerful independent predictor of survival in cardiac patients, especially those with coronary artery disease. Delayed-enhancement magnetic resonance imaging (DE-MRI) can accurately identify irreversible myocardial injury with high spatial and contrast resolution. To date, relatively limited data are available on the prognostic value of DE-MRI, so we sought to determine whether DE-MRI findings independently predict survival. METHODS AND RESULTS: The medical records of 857 consecutive patients who had complete cine and DE-MRI evaluation at a tertiary care center were reviewed regardless of whether the patients had coronary artery disease. The presence and extent of myocardial scar were evaluated qualitatively by a single experienced observer. The primary, composite end point was all-cause mortality or cardiac transplantation. Survival data were obtained from the Social Security Death Index. The median follow-up was 4.4 years; 252 patients (29%) reached one of the end points. Independent predictors of mortality or transplantation included congestive heart failure, ejection fraction, and age (P<0.0001 for each), as well as scar index (hazard ratio, 1.26; 95% confidence interval, 1.02 to 1.55; P=0.033). Similarly, in subsets of patients with or without coronary artery disease, scar index also independently predicted mortality or transplantation (hazard ratio, 1.33; 95% confidence interval, 1.05 to 1.68; P=0.018; and hazard ratio, 5.65; 95% confidence interval, 1.74 to 18.3; P=0.004, respectively). Cox regression analysis showed worse outcome in patients with any DE in addition to depressed left ventricular ejection fraction (<50%). CONCLUSIONS: The degree of DE detected by DE-MRI appears to strongly predict all-cause mortality or cardiac transplantation after adjustment for traditional, well-known prognosticators.

High temporal resolution SSFP cine MRI for estimation of left ventricular diastolic parameters.

PURPOSE: To obtain high temporal resolution (HTR) magnetic resonance (MR) steady-state free-precession (SSFP) cine cardiac images by using multichannel radiofrequency (RF) hardware and parallel imaging techniques; to study the effect of temporal resolution; and to compare the derived left ventricular (LV) diastolic filling parameters with echocardiographic results. MATERIALS AND METHODS: HTR images were acquired in 13 healthy volunteers using a 1.5 T scanner with 32 RF channels and sensitivity encoding (SENSE) and k-t broad-use linear-acquisition speedup technique (k-t BLAST) imaging techniques. LV diastolic parameters were calculated and compared to conventional echocardiographic indices such as the isovolumic relaxation time (IVRT) and E/A ratio. The need for HTR was assessed and the MR results were compared with echocardiographic results. RESULTS: The HTR (approximately 6-ms) images yielded higher peak filling rates, peak ejection rates, and peak atrial filling rates. A progressive decline in filling and ejection rates was observed with worsening temporal resolution. The IVRTs and E/A ratios measured with MR versus echocardiography were in broad agreement. Also, SENSE and k-t BLAST yielded similar diastolic functional parameters. CONCLUSION: With SENSE or k-t BLAST and modern hardware, HTR cine images can be obtained. The lower temporal resolutions (30-50 ms) used in clinical practice reduce LV filling rates by