ABSTRACT
BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) and an identified sarcomere mutation have worse outcomes than those without though the underlying mechanism is incompletely understood. The presence of replacement fibrosis measured by late gadolinium enhancement (LGE) and diffuse fibrosis measured by extracellular volume (ECV) using cardiac magnetic resonance imaging (CMR) are associated with ventricular arrhythmias and cardiac mortality. We aimed to associate these two forms of fibrosis with identified sarcomere mutations. METHODS AND RESULTS: Three hundred and thirty-six (336) patients with HCM underwent CMR at a single quaternary referral centre between January 2012 and February 2017. Genetic testing was performed in 73 of these patients, yielding an identified sarcomeric mutation in 29 (G+), no mutation in 39 (G-), and a variant of unknown significance (VUS) in five. LGE was more prevalent in G+ compared to G- patients (86 vs. 56%, OR 4.3, p=0.01) and was more extensive (7.5±5.5% of left ventricular [LV] mass vs. 3.0±3.0%, p<0.001). Global ECV from myocardial segments excluding LGE was similar among both groups (26.9±2.9 vs. 25.6±2.8%, p=0.46). However, in G+ patients ECV was greater in the hypertrophied regions of the basal anteroseptum (30.2±7.0 vs. 26.8±3.6%, p=0.004) and basal inferoseptum (28.1±4.3 vs. 26.2±2.9%, p=0.005). CONCLUSIONS: Genotyped HCM patients with an identified sarcomere mutation have greater LGE and greater regional, but not global, ECV than HCM patients without an identified mutation. This difference in fibrosis may contribute to worse outcomes in patients with an identified HCM mutation.
Subject(s)
Cardiomyopathy, Hypertrophic , Sarcomeres , Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/diagnostic imaging , Contrast Media , Fibrosis , Gadolinium , Humans , Magnetic Resonance Imaging, Cine , Mutation , Myocardium/pathology , Sarcomeres/geneticsABSTRACT
BACKGROUND: Structural left atrial and ventricular abnormalities on the electrocardiogram (ECG) and transthoracic echocardiogram (TTE) at the time of ischemic stroke have been associated with morbidity and mortality. Yet, the prognostic impact of the same in embolic stroke of undetermined source (ESUS), a relevant subtype of ischemic stroke with a unique pathophysiology, has not been well studied to date. Our aim was to assess the predictive impact of left atrio-ventricular ECG and TTE abnormalities on one-year hospital readmission after ESUS from an ongoing single center prospective stroke registry in the U.S. METHODS: We identified 369 ESUS patients who had at least 1 year of complete follow-up between 2013 and 2018. We examined the association of abnormal left atrio-ventricular findings on ECG and TTE, as well as basic demographic and clinical characteristics, measured at index admission with time to 1-year hospital readmission using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards regression. RESULTS: Recurrent ischemic stroke and cardiovascular causes constituted 60% of all readmissions. Patients with left atrial dilation on TTE were more likely to readmitted within 1 year (HR 1.51; 95% CI, 1.04-2.21). Bundle branch block, pathologic Q-wave, and troponin elevation curves diverged, but were not significantly associated with readmission (log-rank p=0.34, p=0.08, p=0.42, respectively). CONCLUSIONS: Following ESUS, left atrial dilation on TTE was associated with 1-year overall hospital readmission, of which cardiovascular and cerebrovascular ischemic events, and heart failure were a notable proportion. Our data support ongoing studies of atrial cardiopathy in ESUS patients.
Subject(s)
Atrial Function, Left , Atrial Remodeling , Brain Ischemia/etiology , Heart Atria/physiopathology , Heart Diseases/physiopathology , Intracranial Embolism/etiology , Patient Readmission , Adult , Aged , Aged, 80 and over , Brain Ischemia/diagnosis , Brain Ischemia/therapy , Echocardiography , Electrocardiography , Female , Heart Atria/diagnostic imaging , Heart Diseases/complications , Heart Diseases/diagnosis , Heart Diseases/therapy , Humans , Intracranial Embolism/diagnosis , Intracranial Embolism/therapy , Male , Middle Aged , Prognosis , Prospective Studies , Recurrence , Registries , Risk Assessment , Risk Factors , Stroke , Time Factors , United StatesABSTRACT
Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy with a wide spectrum of clinical manifestations. Patients can be asymptomatic or suffer major adverse events including sudden cardiac death, ventricular arrhythmias, and heart failure. Identification of individuals with HCM who are at risk for these complications remains challenging. While echocardiography remains the mainstay of diagnostic evaluation, cardiac magnetic resonance imaging (CMR) is an important adjunctive diagnostic modality with emerging applications for risk-stratification of adverse events in the HCM population. Although not included in current guidelines for HCM management, there is increasing evidence to support the use of CMR for routine prognostic assessment of HCM patients. In this review we discuss the use of CMR techniques, including late gadolinium enhancement, T1 mapping, and quantification of extracellular volume fraction, for the risk stratification of three major adverse events in HCM: sudden cardiac death, ventricular arrhythmias, and congestive heart failure.
Subject(s)
Cardiomyopathy, Hypertrophic/diagnostic imaging , Contrast Media/administration & dosage , Gadolinium/administration & dosage , Magnetic Resonance Imaging , Myocardium/pathology , Ventricular Remodeling , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/physiopathology , Cardiomyopathy, Hypertrophic/complications , Cardiomyopathy, Hypertrophic/pathology , Cardiomyopathy, Hypertrophic/physiopathology , Death, Sudden, Cardiac/etiology , Heart Failure/etiology , Heart Failure/physiopathology , Humans , Predictive Value of Tests , Prognosis , Risk Assessment , Risk FactorsSubject(s)
Arrhythmias, Cardiac/diagnostic imaging , Carcinoma, Renal Cell/diagnostic imaging , Heart Neoplasms/secondary , Kidney Neoplasms/diagnostic imaging , Palliative Care/methods , Tricuspid Valve Insufficiency/diagnostic imaging , Angiogenesis Inhibitors/therapeutic use , Anticoagulants/therapeutic use , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Female , Heart Neoplasms/diagnostic imaging , Heart Neoplasms/drug therapy , Heparin/therapeutic use , Humans , Indazoles , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Middle Aged , Pyrimidines/therapeutic use , Radiography, Thoracic , Sulfonamides/therapeutic use , Tricuspid Valve Insufficiency/pathology , Tumor BurdenABSTRACT
A 49-year-old man presented to the emergency department with acute-onset dyspnoea and hypoxaemia 1 day following nasal surgery for obstructive sleep apnoea. A chest X-ray showed diffuse bilateral pulmonary infiltrates. Supplemental 100% fractional inspired oxygen (FiO2) via non-rebreather mask was delivered with resulting arterial oxygen tension:FiO2 ratio of 67. Transthoracic echocardiogram demonstrated normal heart function. A clinical diagnosis of severe acute respiratory distress syndrome (ARDS) was promptly made. Based on patient preference to avoid intubation and following a multidisciplinary approach, we decided to initiate venovenous extracorporeal membrane oxygenation (VV-ECMO) as an alternative strategy to mechanical ventilation. Though he ultimately required brief mechanical ventilation during ECMO cannulation, the patient spent a total of 5 days on VV-ECMO and a total of 8 days in the intensive care unit. Six days after discharge, his pulmonary function test demonstrated no significant abnormalities. We present a rare case of early initiation of VV-ECMO in a patient with severe ARDS that served as a bridge to recovery.
Subject(s)
Respiratory Distress Syndrome/diagnosis , Diagnosis, Differential , Dyspnea/etiology , Extracorporeal Membrane Oxygenation , Humans , Male , Middle Aged , Postoperative Complications/diagnosis , Postoperative Complications/therapy , Respiration, Artificial , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/therapy , Rhinoplasty/adverse effects , Sleep Apnea, Obstructive/surgeryABSTRACT
Reliable, noninvasive methods for diagnosing and prognosing sinusoidal obstruction syndrome (SOS) early after hematopoietic cell transplantation (HCT) are needed. We used a quantitative mass spectrometry-based proteomics approach to identify candidate biomarkers of SOS by comparing plasma pooled from 20 patients with and 20 patients without SOS. Of 494 proteins quantified, we selected 6 proteins (L-Ficolin, vascular cell adhesion molecule-1 [VCAM1], tissue inhibitor of metalloproteinase-1, von Willebrand factor, intercellular adhesion molecule-1, and CD97) based on a differential heavy/light isotope ratio of at least 2 fold, information from the literature, and immunoassay availability. Next, we evaluated the diagnostic potential of these 6 proteins and 5 selected from the literature (suppression of tumorigenicity-2 [ST2], angiopoietin-2 (ANG2), hyaluronic acid [HA], thrombomodulin, and plasminogen activator inhibitor-1) in samples from 80 patients. The results demonstrate that together ST2, ANG2, L-Ficolin, HA, and VCAM1 compose a biomarker panel for diagnosis of SOS. L-Ficolin, HA, and VCAM1 also stratified patients at risk for SOS as early as the day of HCT. Prognostic Bayesian modeling for SOS onset based on L-Ficolin, HA, and VCAM1 levels on the day of HCT and clinical characteristics showed >80% correct prognosis of SOS onset. These biomarkers may provide opportunities for preemptive intervention to minimize SOS incidence and/or severity.
Subject(s)
Biomarkers/blood , Hematopoietic Stem Cell Transplantation/adverse effects , Hepatic Veno-Occlusive Disease/diagnosis , Hyaluronic Acid/blood , Lectins/blood , Vascular Cell Adhesion Molecule-1/blood , Adolescent , Adult , Bayes Theorem , Child , Child, Preschool , Cohort Studies , Female , Hepatic Veno-Occlusive Disease/blood , Hepatic Veno-Occlusive Disease/mortality , Humans , Intercellular Adhesion Molecule-1/blood , Male , Mass Spectrometry/methods , Middle Aged , Prognosis , Proteomics , Risk Assessment , Tissue Inhibitor of Metalloproteinase-1/blood , Young Adult , von Willebrand Factor/analysis , FicolinsABSTRACT
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective form of tumor immunotherapy available to date and the frequency of transplants continues to increase worldwide. However, while allo-HSCT usually induces a beneficial graft-versus leukemia effect, a major source of morbidity and mortality following allo-HSCT is graft-versus-host disease (GVHD). Currently available diagnostic and staging tools frequently fail to identify those at higher risk for GVHD morbidity, treatment unresponsiveness, and death. Furthermore, there are shortcomings in the risk stratification of patients before GVHD clinical signs develop. In parallel, recent years have been characterized by an explosive evolution of omics technologies, largely due to technological advancements in chemistry, engineering, and bioinformatics. Building on these opportunities, plasma biomarkers have been identified and validated as promising diagnostic and prognostic tools for acute GVHD. This review summarizes current information on the types of GVHD biomarkers, the omics tools used to identify them, the biomarkers currently validated as acute GVHD markers, and future recommendations for incorporating biomarkers into new grading algorithms for risk-stratifying patients and creating more personalized treatment courses. Future directions will include randomized evaluations of these biomarkers in multicenter prospective studies while extending on the need for biomarkers of chronic GVHD.