A novel stress echocardiography pattern for myocardial bridge with invasive structural and hemodynamic correlation.
Journal of the American Heart Association
2013; 2 (2)
Prospective Transcriptomic Pathway Analysis of Human Lymphatic Vascular Insufficiency: Identification and Validation of a Circulating Biomarker Panel
2012; 7 (12)
Patients with a myocardial bridge (MB) and no significant obstructive coronary artery disease (CAD) may experience angina presumably from ischemia, but noninvasive assessment has been limited and the underlying mechanism poorly understood. This study seeks to correlate a novel exercise echocardiography (EE) finding for MBs with invasive structural and hemodynamic measurements.Eighteen patients with angina and an EE pattern of focal end-systolic to early-diastolic buckling in the septum with apical sparing were prospectively enrolled for invasive assessment. This included coronary angiography, left anterior descending artery (LAD) intravascular ultrasound (IVUS), and intracoronary pressure and Doppler measurements at rest and during dobutamine stress. All patients were found to have an LAD MB on IVUS. The ratios of diastolic intracoronary pressure divided by aortic pressure at rest (Pd/Pa) and during dobutamine stress (diastolic fractional flow reserve [dFFR]) and peak Doppler flow velocity recordings at rest and with stress were successfully performed in 14 patients. All had abnormal dFFR (?0.75) at stress within the bridge, distally or in both positions, and on average showed a more than doubling in peak Doppler flow velocity inside the MB at stress. Seventy-five percent of patients had normalization of dFFR distal to the MB, with partial pressure recovery and a decrease in peak Doppler flow velocity.A distinctive septal wall motion abnormality with apical sparing on EE is associated with a documented MB by IVUS and a decreased dFFR. We posit that the septal wall motion abnormality on EE is due to dynamic ischemia local to the compressed segment of the LAD from the increase in velocity and decrease in perfusion pressure, consistent with the Venturi effect.
View details for DOI 10.1161/JAHA.113.000097
View details for PubMedID 23591827
Patient-Specific Induced Pluripotent Stem Cells as a Model for Familial Dilated Cardiomyopathy
SCIENCE TRANSLATIONAL MEDICINE
2012; 4 (130)
In our previous transcriptional profiling of a murine model, we have identified a remarkably small number of specific pathways with altered expression in lymphedema. In this investigation, we utilized microarray-based transcriptomics of human skin for an unbiased a priori prospective candidate identification, with subsequent validation of these candidates through direct serum assay. The resulting multi-analyte biomarker panel sensitively should sensitively discriminate human lymphedema subjects from normal individuals.We enrolled 63 lymphedema subjects and 27 normals in our attempt to discover protein analytes that can distinguish diseased individuals from controls. To minimize technical and biologically irrelevant variation, we first identified potential candidates by performing transcriptional microarray analysis on paired diseased and normal skin specimens sampled from the same individuals. We focused our attention on genes with corresponding protein products that are secreted and took these candidates forward to a protein multiplex assay applied to diseased and normal subjects. We developed a logistic regression-based model on an eventual group of six proteins and validated our system on a separate cohort of study subjects. The area under the receiver operating characteristic curve was calculated to be 0.87 (95% CI : 0.75 to 0.97).We have developed an accurate bioassay utilizing proteins representing four central pathogenetic modalities of the disease: lymphangiogenesis, inflammation, fibrosis, and lipid metabolism, suggesting that these proteins are directly related to the pathogenesis of the tissue pathology in lymphatic vascular insufficiency. Further studies are warranted to determine whether this newly-identified biomarker panel will possess utility as an instrument for in vitro diagnosis of early and latent disease; the ultimate applicability to risk stratification, quantitation of disease burden, and response to therapy can easily be envisioned.
View details for DOI 10.1371/journal.pone.0052021
View details for Web of Science ID 000312483300046
View details for PubMedID 23272198
Advances in microfluidic PCR for point-of-care infectious disease diagnostics
2011; 29 (6): 830-839
Characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure, dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy in patients. DCM is the most common diagnosis leading to heart transplantation and places a significant burden on healthcare worldwide. The advent of induced pluripotent stem cells (iPSCs) offers an exceptional opportunity for creating disease-specific cellular models, investigating underlying mechanisms, and optimizing therapy. Here, we generated cardiomyocytes from iPSCs derived from patients in a DCM family carrying a point mutation (R173W) in the gene encoding sarcomeric protein cardiac troponin T. Compared to control healthy individuals in the same family cohort, cardiomyocytes derived from iPSCs from DCM patients exhibited altered regulation of calcium ion (Ca(2+)), decreased contractility, and abnormal distribution of sarcomeric ?-actinin. When stimulated with a ?-adrenergic agonist, DCM iPSC-derived cardiomyocytes showed characteristics of cellular stress such as reduced beating rates, compromised contraction, and a greater number of cells with abnormal sarcomeric ?-actinin distribution. Treatment with ?-adrenergic blockers or overexpression of sarcoplasmic reticulum Ca(2+) adenosine triphosphatase (Serca2a) improved the function of iPSC-derived cardiomyocytes from DCM patients. Thus, iPSC-derived cardiomyocytes from DCM patients recapitulate to some extent the morphological and functional phenotypes of DCM and may serve as a useful platform for exploring disease mechanisms and for drug screening.
View details for DOI 10.1126/scitranslmed.3003552
View details for Web of Science ID 000303045900004
View details for PubMedID 22517884
Molecular methods for pathogen detection in blood
2010; 375 (9710): 178-179
Global burdens from existing or emerging infectious diseases emphasize the need for point-of-care (POC) diagnostics to enhance timely recognition and intervention. Molecular approaches based on PCR methods have made significant inroads by improving detection time and accuracy but are still largely hampered by resource-intensive processing in centralized laboratories, thereby precluding their routine bedside- or field-use. Microfluidic technologies have enabled miniaturization of PCR processes onto a chip device with potential benefits including speed, cost, portability, throughput, and automation. In this review, we provide an overview of recent advances in microfluidic PCR technologies and discuss practical issues and perspectives related to implementing them into infectious disease diagnostics.
View details for DOI 10.1016/j.biotechadv.2011.06.017
View details for Web of Science ID 000296821900024
View details for PubMedID 21741465