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.

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.

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.

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.

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.

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.

Left Ventricular Noncompaction Detected by Cardiac Magnetic Resonance Screening: A Reexamination of Diagnostic Criteria.

In a previous cross-sectional screening study of 5,169 middle and high school students (mean age, 13.1 ± 1.78 yr) in which we estimated the prevalence of high-risk cardiovascular conditions associated with sudden cardiac death, we incidentally detected by cardiac magnetic resonance (CMR) 959 cases (18.6%) of left ventricular noncompaction (LVNC) that met the Petersen diagnostic criterion (noncompaction:compaction ratio >2.3). Short-axis CMR images were available for 511 of these cases (the Short-Axis Study Set). To determine how many of those cases were truly abnormal, we analyzed the short-axis images in terms of LV structural and functional variables and applied 3 published diagnostic criteria besides the Petersen criterion to our findings. The estimated prevalences were 17.5% based on trabeculated LV mass (Jacquier criterion), 7.4% based on trabeculated LV volume (Choi criterion), and 1.3% based on trabeculated LV mass and distribution (Grothoff criterion). Absent longitudinal clinical outcomes data or accepted diagnostic standards, our analysis of the screening data from the Short-Axis Study Set did not definitively differentiate normal from pathologic cases. However, it does suggest that many of the cases might be normal anatomic variants. It also suggests that cases marked by pathologically excessive LV trabeculation, even if asymptomatic, might involve unsustainable physiologic disadvantages that increase the risk of LV dysfunction, pathologic remodeling, arrhythmias, or mural thrombi. These disadvantages may escape detection, particularly in children developing from prepubescence through adolescence. Longitudinal follow-up of suspected LVNC cases to ascertain their natural history and clinical outcome is warranted.

Multidetector Computed Tomography (MDCT) Angiography in the Pre-Procedural Assessment of Patients Undergoing Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) initially emerged as an alternative option to surgical aortic valve replacement (SAVR) for patients with severe aortic stenosis who were considered either inoperable or high-risk for surgery. However, since its advent the role of TAVR has been continuously evolving on the basis of clinical trials which showed that TAVR is non-inferior to SAVR in patients with moderate as well as low-risk for surgery. Because of recent technological advances, multidetector computer tomography (MDCT) is inherently suitable for the pre-procedural assessment of patients being considered for TAVR within a very short imaging time, MDCT can measure the diameter of the aortic annulus, provide detailed information regarding the status of the entire thoracoabdominal aorta, and assess the caliber of the peripheral vasculature used for transcatheter heart valve delivery. This information helps interventionists make optimal pre-procedural decisions and avoid complications. To familiarize non-imaging specialists with the role of MDCT in TAVR, we provide a concise overview of our approach to using this modality for the pre-procedural assessment of TAVR candidates.

Mitral Valve Flow and Myocardial Motion Assessed with Dual-Echo Dual-Velocity Cardiac MRI.

PURPOSE: To develop a dual-echo phase-contrast (DEPC) MRI approach with which each echo is acquired by using a different velocity sensitivity within one repetition time (TR) and demonstrate the feasibility of this approach to measure transmitral blood flow (E) and myocardial tissue (E m) velocities. MATERIALS AND METHODS: The flow across tubes of known diameter was measured by using the proposed DEPC method and compared with flowmeter measurements and theoretic predictions. Then, with both the DEPC MRI sequence and the conventional single-echo phase-contrast (SEPC) MRI sequence, E, E m, and E/E m were measured in six healthy volunteers (mean age, 49 years ± 13 [standard deviation]) and eight patients (mean age, 54 years ± 15) being evaluated for cardiac disease. Differences between the DEPC and conventional SEPC MRI methods were assessed by percent error, Pearson correlation, and Bland-Altman analyses. RESULTS: Velocities measured in vitro and in vivo by using the SEPC and DEPC MRI approaches were well correlated (r 2 > 0.97), with negligible bias (<0.5 cm/sec) and comparable velocity-to-noise ratios. Imaging times were approximately 19% shorter with the DEPC method (TR, 5.7 msec) than with the SEPC method (TR, 2.8 msec ± 4.2) (P < .05). CONCLUSION: The proposed DEPC method was sensitive to two velocity regimes within a single TR, resulting in a shorter imaging time compared with the imaging time in conventional SEPC MRI. Preliminary human study results suggest the feasibility of using this approach to estimate E/E m.Supplemental material is available for this article.© RSNA, 2020.

Labeling Stem Cells with a New Hybrid Bismuth/Carbon Nanotube Contrast Agent for X-Ray Imaging.

The poor retention and survival of cells after transplantation to solid tissue represent a major obstacle for the effectiveness of stem cell-based therapies. The ability to track stem cells in vivo can lead to a better understanding of the biodistribution of transplanted cells, in addition to improving the analysis of stem cell therapies' outcomes. Here, we described the use of a carbon nanotube-based contrast agent (CA) for X-ray computed tomography (CT) imaging as an intracellular CA to label bone marrow-derived mesenchymal stem cells (MSCs). Porcine MSCs were labeled without observed cytotoxicity. The CA consists of a hybrid material containing ultra-short single-walled carbon nanotubes (20-80 nm in length, US-tubes) and Bi(III) oxo-salicylate clusters which contain four Bi3+ ions per cluster (Bi4C). The CA is thus abbreviated as Bi4C@US-tubes.

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.

Acute type I aortic dissection with or without antegrade stent delivery: Mid-term outcomes.

OBJECTIVE: We determined the effect of antegrade stent delivery in the descending thoracic aorta on short- and mid-term clinical and imaging outcomes for patients who underwent repair of acute DeBakey type I aortic dissection. METHODS: Outcomes were evaluated for 178 patients who underwent acute type I aortic dissection between 2005 and 2016 (standard repair, n = 115 [64.6%]; antegrade stent delivery, n = 63 [35.4%]). Propensity score match and multivariable analyses were performed to assess outcomes. RESULTS: The stent and standard repair groups had similar rates of operative mortality (30-day or in-hospital) (12.7% vs 17.4%, P = .41), persistent stroke (6.3% vs 5.3%, P = .75), and persistent paraplegia/paraparesis (1.6% vs 0.9%, P = 1.0). Propensity score match analysis indicated that the operative mortality rate was higher in the standard repair group (P = .059), which the multivariable analysis confirmed. The persistent stroke rate was nonsignificantly higher in the stent group (P = .66). Persistent paraplegia/paraparesis rates were similar in both groups (P = 1.0), and the overall rates of spinal cord ischemia were nonsignificantly higher in the stent group (P = .18). During follow-up (mean duration, 4.6 ± 3.6 y), computed tomography showed that stented patients more often had remodeling of the descending thoracic aorta (P = .0002) and somewhat more often had remodeling of the thoracoabdominal aorta (P = .13). Stented patients also had fewer subsequent procedures (P = .25). The 3- and 5-year survivals were 73.3% ± 6.9% and 49.9% ± 7.6% in the matched stented group and 66.3% ± 9.4% and 41.6% ± 7.7% in the matched standard group, respectively (P = .015 for overall survival). CONCLUSIONS: In the short term, antegrade stent delivery was associated with less operative mortality. In the mid-term, promising remodeling of the false lumen was seen in stented patients, as were (nonsignificantly) lower rates of subsequent procedures in the thoracoabdominal aorta. Mid-term survival was also greater in the stented patients.

High-Risk Cardiovascular Conditions in Sports-Related Sudden Death: Prevalence in 5,169 Schoolchildren Screened via Cardiac Magnetic Resonance.

Improving preparticipation screening of candidates for sports necessitates establishing the prevalence of high-risk cardiovascular conditions (hr-CVC) that predispose young people to sudden cardiac death (SCD). Our accurate, novel protocol chiefly involved the use of cardiac magnetic resonance (CMR) to estimate this prevalence. Middle and high school students from a general United States population were screened by means of questionnaires, resting electrocardiograms, and CMR to determine the prevalence of 3 types of hr-CVC: electrocardiographic abnormalities, cardiomyopathies, and anomalous coronary artery origin from the opposite sinus with intramural coronary course (ACAOS-IM). We examined the range of normal left ventricular size and function in the main study cohort (schoolchildren 11-14 yr old). We defined diagnostic criteria for hr-CVC and compared the cardiac measurements of these younger participants with those of older children whom we examined (age, 15-18 yr). From 5,169 completed diagnostic studies (mean participant age, 13.06 ± 1.78 yr), CMR results revealed 76 previously undiagnosed cases of hr-CVC (1.47% of the total cohort): 11 of dilated cardiomyopathy (14.5%), 3 of nonobstructive hypertrophic cardiomyopathy (3.9%), 23 ACAOS-IM cases (30.3%; 6 left-ACAOS and 17 right-ACAOS), 4 Wolff-Parkinson-White patterns (5.3%), 34 prolonged QT intervals (44.7%), and 1 Brugada pattern (1.3%). Cardiomyopathies were significantly more prevalent in the older children. Of note, we identified 959 cases (18.5%) of left ventricular noncompaction. If our estimate is accurate, only 1.47% of school-age sports participants will need focused secondary evaluations; the rest can probably be reassured about their cardiac health after one 30-minute screening study.

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.

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.

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.