Biomedical subjects

Jack L Titus

Publications and source records attributed to Jack L Titus.

10 recordsLinked to original sources

PubMed2007

Patent foramen ovale: standards for a preclinical model of prevalence, structure, and histopathologic comparability to human hearts.

BACKGROUND: This study evaluated and standardized a Patent Foramen Ovale (PFO) preclinical model in gross anatomic and histopathologic features. METHODS: We examined 150 necropsy-derived domestic porcine hearts, age 4-6 months for PFO prevalence, appearance, and size. Histopathologic preparations were standardized and processed identically to 24 post-mortem human hearts aged 16-62 years. A measurement scheme was developed for PFO atrial openings, tunnel length, and histopathologic features to compare porcine and patient hearts. RESULTS: PFO was found in 32 of the 150 porcine hearts (prevalence 21.3%). Twenty-five porcine PFO underwent standard characterization by tunnel length, and right, and left atrial orifice diameters. Logarithmic regression analysis between porcine PFO tunnel length and left atrial orifice area demonstrated a significant positive relationship (P = 0.0162, R(2) = 0.227). The porcine PFO tunnel length was significantly longer than in humans (12.0 +/- 4.0 mm vs. 7.1 +/- 3.1 mm respectively, P < 0.0001). Histopathologic comparison was made using serial sections perpendicular to the atrial septum and the tunnel long axis. Human and porcine PFO lesions demonstrated strong similarities in tissue cells, connective tissue, and matrix composition. CONCLUSIONS: PFO assessment was standardized in both macroscopically and histopathologically, with quantitative and qualitative comparisons feasible using a porcine preclinical model. PFO prevalence in domestic swine is identical to humans, and microscopic structures very similar to humans. The domestic swine PFO model appears useful to evaluate new interventional closure technologies due to comparability in microscopic features. Tunnel length should be carefully evaluated due to differences across pigs and patients.

Adolescent↗

PubMed2004

Postmortem molecular screening in unexplained sudden death.

OBJECTIVES: We examined the prevalence of defects in arrhythmia-related candidate genes among patients with unexplained sudden cardiac death (SCD). BACKGROUND: Patients with unexplained sudden death may constitute up to 5% of overall SCD cases. For such patients, systematic postmortem genetic analysis of archived tissue, using a candidate gene approach, may identify etiologies of SCD. METHODS: We performed analysis of KCNQ1 (KVLQT1), KCNH2 (HERG), SCN5A, KCNE1, and KCNE2 defects in a subgroup of 12 adult subjects with unexplained sudden death, derived from a 13-year, 270-patient autopsy series of SCD. Archived, paraffin-embedded myocardial tissue blocks obtained at the original postmortem examination were the source of deoxyribonucleic acid for genetic analysis. RESULTS: Two patients were found to have the same HERG defect, a missense mutation in exon 7 (nucleotide change G1681A, coding effect A561T). The mutation was heterozygous in Patient 1, but Patient 2 appeared to be homozygous for the defect. Patch-clamp recordings showed that the A561T mutant channel expressed in human embryonic kidney cells failed to generate HERG current. Western blot analysis implicated a trafficking defect in the protein, resulting in loss of post-translational processing from the immature to the mature form of HERG. No mutations were detected among the remaining four candidate genes. CONCLUSIONS: In this autopsy series, only 2 of 12 patients with unexplained sudden death were observed to have a defect in HERG among five candidate genes tested. It is likely that elucidation of SCD mechanisms in such patients will await the discovery of multiple, novel arrhythmia-causing gene defects.

Adult↗

PubMed2004

Excimer laser ablation for valvular angioplasty in pulmonary atresia and intact ventricular septum.

BACKGROUND AND OBJECTIVES: The prognosis for infants with pulmonary atresia and intact ventricular septum (PA/IVS) is poor and they present a major management challenge. Mechanical penetration of the atretic pulmonary valve is an applicable option for decompression of the right ventricle and optimization of left ventricular function. The utilization of laser energy for debulking and vaporization of the atretic valve tissue is a relevant approach due to the potential for controlled, precise mode of energy distribution. STUDY DESIGN/PATIENTS AND METHODS: A 4-month-old female with PA/IVS whose failure to thrive was accompanied by critical hemodynamic abnormalities received successful percutaneous pulmonary valve plate ablation by a 0.9 mm pulsed-wave ultraviolet excimer laser catheter (308 nm wavelength, fluence 50 mJ/mm(2); 30 Hz). A "step-by-step" lasing technique was applied whereby the tip of the emitting laser catheter is advanced ahead of a guide wire that serves mainly as support for positioning of that catheter. RESULTS: Adequate penetration of the atretic tissue enabled introduction of balloon dilations resulting in patency of the atretic valve, decompression of the right ventricle, improved right and left ventricular hemodynamics, and oxygenation. To further investigate the effect of excimer laser energy on atretic valvular tissue this laser was applied in a specimen of heart from an infant who died because of PA/IVS. Histopathologic examination of the irradiated tissue revealed no laser-induced injury to the pulmonary valve. CONCLUSIONS: Thus, laser ablation and penetration of an atretic pulmonary valve is feasible and safe. The penetration of the atretic valve with the laser catheter enables subsequent introduction of various sizes balloon dilations. The application of available laser sources for treatment of congenital heart diseases is reviewed.

Female↗

PubMed2004

Global remodeling of the ventricular interstitium in idiopathic myocardial fibrosis and sudden cardiac death.

OBJECTIVE: Characterization of a distinct, and as yet unexplained phenotype of sudden cardiac death (SCD). BACKGROUND: In a subgroup of patients with SCD, postmortem findings are limited to isolated idiopathic myocardial fibrosis (IMF). The absence of confounding factors may facilitate evaluation of the relationship between myocardial fibrosis and ventricular arrhythmogenesis. METHODS: Six patients with IMF were identified from a postmortem, consecutive 13-year series of 270 subjects presenting with SCD. Ventricular interstitial remodeling was assessed quantitatively and qualitatively and comparisons made with 6 age- and sex-matched control subjects who suffered noncardiac death. Myocardial collagen volume fraction and perivascular fibrosis ratio were determined and evidence for inflammatory response and apoptotic cell death was sought. The potential role of transforming growth factor beta 1 (TGF-beta(1)) in the pathogenesis of IMF was evaluated. RESULTS: Overall myocardial collagen volume fraction was 1.6-fold higher in IMF (mean age 34 +/- 4 yrs) vs. controls (mean age 34 +/- 4 yrs, .022 +/- .001 vs .013 +/- .001; P < .001). Collagen volume fraction increase was diffuse but disproportionately so in the LV inferior wall (3.4-fold increase; .035 +/- .005 vs .012 +/- .018; P < .001). Perivascular fibrosis ratio was also increased (.770 +/- .014 vs .723 +/- .010; P = .007). There was no evidence of either myocardial inflammatory response or myocyte apoptosis in cases or controls. Expression of TGF-beta(1) was significantly increased in IMF vs controls. CONCLUSION: IMF involves diffuse and heterogeneous remodeling of the ventricular interstitium, with a predilection for the LV inferior wall. TGF-beta(1) is a potential mediator of interstitial remodeling in IMF and SCD.

Adult↗

PubMed2004

An obstructive bicuspid aortic valve in the setting of tetralogy of Fallot with pulmonary atresia: a rare combination.

As far as we are aware, a bicuspid aortic valve has not previously been reported in the setting of tetralogy of Fallot and pulmonary atresia. We describe this association in a newborn who presented with a murmur and cyanosis. Echocardiography showed tetralogy of Fallot with pulmonary atresia, and also a moderately stenotic bicuspid aortic valve. The patient underwent open-heart surgery guided by transesophageal echocardiography. Postoperatively, there was only mild obstruction across both outflow tracts. We have also reviewed the pertinent data from our Jesse E. Edwards Registry of Cardiovascular Disease to establish the incidence of bicuspid aortic valve in the setting of obstruction of the right ventricular outflow tract, finding the association in no patients with pulmonary atresia and tetralogy of Fallot, in 0.7% of those with tetralogy of Fallot and pulmonary stenosis, but in 6.6% of those with pulmonary atresia and intact ventricular septum.

Angiography↗

PubMed2003

Cardiac pathologic findings reveal a high rate of sudden cardiac death of undetermined etiology in younger women.

BACKGROUND: Between 1989 and 1998 there was a 21% increase in estimated sudden cardiac death among US women aged 35 to 44 years. In contrast, the sudden cardiac death rate in age-matched men showed a decreasing trend (-2.8%). Due to under-representation of younger adults in published autopsy series, etiologies of sudden cardiac death merit further investigation. METHODS: We reviewed autopsy and detailed cardiac pathologic findings in younger women (age 35-44 years) from a 270-patient, 13-year (1984-1996) autopsy series of sudden cardiac death, and performed comparisons with findings in age-matched men. RESULTS: Women aged 35 to 44 years constituted 32% of all women in the series compared to men, who constituted 24% of total men (P =.004 vs women). A presumptive cause of sudden cardiac death could not be determined in 13 women (50%). Among women, 6 cases (22%) had significant coronary artery disease. Findings in others included coronary artery anomalies (n = 3), myocarditis (n = 2), hypertrophic cardiomyopathy (n = 1), coronary artery dissection (n = 1) and accessory pathway (n = 1). In younger men, a presumptive cause of sudden cardiac death remained undetermined in only 24% (P =.025 vs younger women), and coronary artery disease accounted for 40% of cases. CONCLUSIONS: In younger women, despite autopsy and detailed cardiac pathologic examination, an attributable cause of sudden cardiac death was not determined in 50% of cases; a 2-fold increase compared to men of the same age. Given the dynamic and multifactorial nature of sudden cardiac death, comprehensive population-based investigations are likely to be necessary to further investigate this unexpected sex-based disparity.

Adult↗

PubMed2002

Sudden death in patients with implantable cardioverter defibrillators: the importance of post-shock electromechanical dissociation.

OBJECTIVES: The purpose of this study was to determine the mechanisms of sudden death (SD) in patients with ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]) treated with an implantable cardioverter defibrillator (ICD). BACKGROUND: Despite ICD therapy, some patients with VT/VF still die suddenly. Optimal ICD use requires determination of the mechanisms of these residual SDs. METHODS: We reviewed 320 patient deaths during trials of Medtronic transvenous ICD systems (Medtronic Inc., Minneapolis, Minnesota). Sudden deaths were further categorized according to mechanism. Post-shock electromechanical dissociation (EMD) describes a scenario where VT/VF was appropriately detected and treated by an ICD shock that restored a physiologic rhythm, but death still occurred immediately by EMD. RESULTS: A mode of death could be ascribed for 317 patients-90 (28%) were sudden, 156 (49%) were non-sudden cardiac, and 71 (22%) were noncardiac. A mechanism of SD was proposed for 68 patients-20 (29%) had post-shock EMD, 17 (25%) had VT/VF uncorrected by shocks, 11 (16%) had primary electromechanical dissociation, 9 (13%) had incessant VT/VF, 5 (7%) had VT/VF after their ICD was deactivated or removed, and 6 (9%) had single instances of various other terminal events. Only New York Heart Association functional class independently predicted SD by post-shock EMD. CONCLUSIONS: The most common mechanism of SD in patients with an ICD is VT/VF treated with an appropriate shock followed by EMD. As this mechanism accounted for 29% of the SDs to which a cause could be ascribed, this mechanism of SD warrants further investigation.

Aged↗

PubMed2002

Creation of an intra-atrial communication with a new Amplatzer shunt prosthesis: preliminary results in a swine model.

A nitinol shunt device was applied in six minipigs to create a precise intra-atrial shunt. This self-expanding shunt device consists of two retention disks of 2-8 mm, a 4 mm connecting waist with a 10 mm eccentric hole. It requires a 7 Fr introducer sheath. The device is attached to the delivery cable with a microscrew. Placement technique is identical to that of Amplatzer septal occluder. Balloon dilation was performed immediately and 1 month after placement. One animal died from general anesthesia before device placement. Left atrial angiography showed a patent intra-atrial shunt in 5/5 pigs immediately and 4/4 in 1- to 3-month follow up. Postmortem examination demonstrated patent shunts partially or completely neoendothelialized. The shunt device was found to be an effective and safe way to create a permanent atrial communication.

Alloys↗

PubMedDate not supplied

Giant aneurysms of coronary arteries and saphenous vein grafts: angiographic findings and histopathological correlates.

INTRODUCTION: Giant aneurysms that develop in native coronary arteries or saphenous vein grafts are morphologically defined as abnormally expanded outpouching vascular structures >4 cm in diameter. The location, morphology, and content of giant aneurysms account for adverse cardiovascular effects. METHODS: Two cases of giant aneurysms were studied comprehensively by noninvasive and invasive cardiac methods and subsequent histopathology. The first patient had a giant aneurysm that developed over a course of several years in a saphenous vein graft whereas the second patient had a giant aneurysm occurring within a native coronary artery. Accompanying clinical and angiographic findings are described. RESULTS: Atherosclerosis and thrombosis were among the prominent histopathological findings. CONCLUSIONS: Atherosclerosis and associated thrombosis within giant aneurysms result in obstruction of flow, distal embolization, and development of acute coronary syndromes including recurrent ischemic chest pain, unstable angina, and acute myocardial infarction. The options for clinical management of giant coronary or vein graft aneurysms include surgical excision, percutaneous coil occlusion and stent deployment, or medical approach.

Aged↗

PubMedDate not supplied

Aneurysm of fossa ovalis in adults: a pathologic study.

BACKGROUND: Aneurysm of the fossa ovalis is an out pouching, space-occupying, interatrial septal structure. The anatomic morphology and characteristics of this aneurysm are of interest for pathologists and cardiologists alike. METHODS: We identified 33 specimens of adult hearts with a large size aneurysm of the fossa ovalis (length equal to or more than 10 mm from the plane of the atrial septum) in a registry of cardiovascular disease. Anatomic-morphologic features of these aneurysms were examined by macroscopic and histopathologic studies. RESULTS: Nineteen aneurysms were from females (57%) and 14 were from males (43%). Most aneurysms had a dome shape with maximal length of the aneurysmal excursion into an atrium varying from 10 to 35 mm (mean 16+/-5 mm) and width varying from 16 to 40 mm (mean 24+/-6 mm). Twenty-four aneurysms (73%) protruded into the right atrium while only nine (27%) penetrated into the left atrium. In 24 patients the interatrial ostium II was patent, and in 22 (91%) of them, abnormal increased intracardiac pressure was deemed responsible for the formation of the aneurysm. Among nine patients in whom the foramen ovale was closed, eight (89%) had an aneurysm protruding into the right atrium, and only one aneurysm penetrated into the left atrium. In six patients, the aneurysm further stretched an already patent foramen ovale resulting in creation of an atrial septal defect so that bidirectional shunting could occur, and in three cases, the aneurysm narrowed the inferior vena caval orifice. In three hearts, the aneurysm wall had endocardial fibrosis, and in three other specimens, a focal mural thrombus was present on the aneurysmal surface. Most common associated cardiac conditions in this series included atherosclerotic coronary artery disease (51%), aortic valvular disease (21%) and mitral valve disease (24%). CONCLUSIONS: Aneurysm of the fossa ovalis is a space-occupying, redundant structure, most commonly with a dome shape. In a majority of cases, the formation of this aneurysm relates to the effect of extrinsic mechanisms, which create abnormally elevated intracardiac pressures. The aneurysm protruded into the right atrium in 73% of cases. Endocardial fibrosis and a focal mural thrombus were present in several cases on the aneurysmal wall. Bidirectional shunt via stretched patent foramen ovale and distal embolization can contribute to complications related to the aneurysm.

Adult↗