Bioprosthetic valves and laudable inflammation?
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Animals↗
Biomedical subjects
Richard A Hopkins
Publications and source records attributed to Richard A Hopkins.
Münchhausen Syndrome simulating acute aortic dissection.
A young adult man presented to the emergency department reporting a convincing story for acute aortic dissection, a disorder in which diagnostic evaluations should occur in parallel with pharmacologic management. Transesophageal echocardiography demonstrated normal cardiac and aortic structures. Additional history was notable for extensive travel across numerous medical facilities with associated misrepresentation of his diagnosis and treatment. The patient was willing to undergo unpleasant and invasive procedures and succeeded at least once in the past to deceive clinicians to the point of performing a median sternotomy. The intentional presentation of false information leading to unnecessary treatments is consistent with Münchhausen Syndrome.
Acute Disease↗
The new age of cardiac surgery driven by tissue engineering and biotechnology.
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Biotechnology↗
Cardiac outcomes assessment and quality management.
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Databases as Topic↗
Aortic annuloplasty with aortic root reconstruction to prevent patient-prosthesis mismatch.
Part of the ongoing argument concerning patient-prosthesis mismatch (PPM) following aortic valve replacement (AVR) is due to the perception that aortic annulus enlargement procedures increase the risk and technical difficulty of aortic valve surgery. Here, an aortic root reconstruction that involves enlargement of the annulus and tailoring of the aortic root to accommodate larger stented prostheses is presented that has been personally performed in 196 patients with no technique-related surgical deaths or complications, and thus can be carried out without additional risk. This aortic root enlargement aortoplasty and annuloplasty method can be calibrated to all AVRs involving stented manufactured prostheses when these are deemed the prosthesis of choice for the patient with a relatively small annulus and/or aortic root, severe left ventricular hypertrophy, compromised LV function or a very active lifestyle, to achieve predicted EOA values > or = 1.00 cm2/m2.
Animals↗
Correlation between heart valve interstitial cell stiffness and transvalvular pressure: implications for collagen biosynthesis.
It has been speculated that heart valve interstitial cells (VICs) maintain valvular tissue homeostasis through regulated extracellular matrix (primarily collagen) biosynthesis. VICs appear to be phenotypically plastic, inasmuch as they transdifferentiate into myofibroblasts during valve development, disease, and remodeling. Under normal physiological conditions, transvalvular pressures (TVPs) on the right and left side of the heart are vastly different. Hence, we hypothesize that higher left-side TVPs impose larger local tissue stress on VICs, which increases their stiffness through cytoskeletal composition, and that this relation affects collagen biosynthesis. To evaluate this hypothesis, isolated ovine VICs from the four heart valves were subjected to micropipette aspiration to assess cellular stiffness, and cytoskeletal composition and collagen biosynthesis were quantified by using the surrogates smooth muscle alpha-actin (SMA) and heat shock protein 47 (HSP47), respectively. VICs from the aortic and mitral valves were significantly stiffer (P < 0.001) than those from the pulmonary and tricuspid valves. Left-side isolated VICs contained significantly more (P < 0.001) SMA and HSP47 than right-side VICs. Mean VIC stiffness correlated well (r = 0.973) with TVP; SMA and HSP47 also correlated well (r = 0.996) with one another. Assays were repeated for VICs in situ, and, as with in vitro results, left-side VIC protein levels were significantly greater (P < 0.05). These findings suggest that VICs respond to local tissue stress by altering cellular stiffness (through SMA content) and collagen biosynthesis. This functional VIC stress-dependent biosynthetic relation may be crucial in maintaining valvular tissue homeostasis and also prove useful in understanding valvular pathologies.
Animals↗
Tissue engineering of heart valves: decellularized valve scaffolds.
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Heart Valve Prosthesis↗
Surgical patch closure of atrial septal defects.
BACKGROUND: Development of nonsurgical techniques for closure of atrial septal defects (ASD) has prompted reevaluation of current surgical outcomes with an emphasis on less invasive methods. METHODS: This retrospective review is based on a single surgeon's experience between July 1, 1988 and December 21, 2002 with 176 consecutive adult (n = 47) and pediatric (n = 129) surgeries, in which ASD was the primary anatomical diagnosis to ascertain current optimal methods and outcomes expected for surgical closure. Patch closure with pericardium was used in all cases. Surgical methods encompassed three phases. The first phase was defined by traditional sternotomy; the second phase involved a series of technical modifications to shorten incisions and reduce surgical trauma; the third phase consisted of standardized less invasive techniques based upon age and gender with "bikini line" incisions for adult females, limited median sternotomy for adult males, and mini-median sternotomy for children. All patients underwent echocardiography to assess ASD closure. RESULTS: There were no deaths. The most frequent perioperative complications were atrial fibrillation (adult 10%, pediatric 1.2%) and post pericardiotomy syndrome (adult 2%, pediatric 4.7%). All patients had secure and complete closure of ASDs with no residual shunts (trivial or otherwise) documented by echocardiography. No less invasive procedures required conversion. CONCLUSIONS: Surgical technique evolved from standard sternotomy to limited access incisions using modified cannulation techniques and incision locations determined by age and gender of the patient without deterioration in outcome quality. Both standard and less invasive surgical methods can achieve secure closure of the septum with biological patches, which are incorporated into the tissue structure of the heart and which are free from materials-related failure modes. Patient satisfaction is enhanced by utilizing the least invasive, least traumatic, and most cosmetically appealing techniques for access and cardiopulmonary bypass.
Adolescent↗
Intracardiac yolk sac tumor and dysrhythmia as an etiology of pediatric syncope.
This report describes a new etiology of pediatric syncope. Epilepsy, brain anomalies, infection, electrolyte abnormalities, and trauma are commonly identified etiologies of seizures in the pediatric population. We report here a child with third-degree heart block and right ventricular outflow tract obstruction related to an intracardiac tumor presenting with syncope and seizure-like activity. Echocardiography revealed a large (3 x 8-cm) intracardiac mass filling the right atrium, extending across the tricuspid valve into the right ventricle and crossing the atrial septum into the left atrium, extending into the left ventricular outflow tract. She underwent emergent cardiopulmonary bypass with removal of the majority of the tumor mass, clearing both the left and right ventricular outflow tracts of obstruction and repairing the tricuspid valve. Postoperative cardiac conduction remained blocked and required permanent pacing. The initial serum alpha-fetoprotein level was grossly elevated, and the tumor showed characteristic histopathologic features of a yolk sac tumor. Four years after the completion of her chemotherapy, she remains clinically well, with no evidence of recurrent tumor by echocardiography or radiographic studies, and her alpha-fetoprotein remains in the normal range. The clinical manifestations of tumor infiltration of the heart with complete heart block resulting in loss of consciousness with tonic-clonic movements are detailed. Although rare, cardiac syncope has multiple known causes and should be suspected in any patient with sudden loss of consciousness and pallor. In the pediatric population, cardiac rhythm disturbances are typically the result, rather than the cause, of acute cardiac emergencies. Pediatricians should be aware of depressed cardiac output and dysrhythmias as etiologies of new-onset syncope. Evaluation should include a cardiac assessment with electrocardiogram to exclude a life-threatening arrhythmia as a potential cause.
Electrocardiography↗
Prototype anionic detergent technique used to decellularize allograft valve conduits evaluated in the right ventricular outflow tract in sheep.
BACKGROUND AND AIM OF THE STUDY: Biodegradable polymeric materials or extracellular matrix scaffolds are used in tissue-engineered heart valve designs, with the expectation of replicating the anatomic, histological and biomechanical characteristics of semi-lunar valves. The study aim was to evaluate the extent of in-vivo recellularization and the explant pathology findings of a prototype anionic, non-denaturing detergent and endonuclease technique used to decellularize allograft (homograft) valve conduits implanted in the right ventricular outflow tract (RVOT) of sheep, and to identify possible risks associated with tissue-engineered heart valve conduits based on decellularized allograft semilunar valve scaffolds. METHODS: Valve conduits were decellularized using a solution of N-lauroylsarcosinate and endonucleases, rinsed in lactated Ringers solution, and stored in an antibiotic solution at 4 degrees C until implanted. Explanted valves and unimplanted controls were examined macroscopically, radiographically (for calcification) and histologically using immunohistochemistry (IHC), routine and special histological stains, transmission electron microscopy (TEM) and polarized light microscopy (evaluation of collagen crimp). RESULTS: Cells and cellular remnants were uniformly absent in the decellularized cusps, but occasional focal sites of arterial wall smooth muscle cells and to a greater extent subvalvular cardiac myocytes were variably retained. The trilaminar histological structure of the cusp was preserved. Valve conduit-related pathology consisted of intracuspal hematoma formation, collagen fraying, thinning of the conduit wall, and inflammatory cells associated with cardiac myocyte remnants. Cuspal calcification was not seen, but elastic fibers in the conduit wall and retained subvalvular cardiac myocyte remnants were liable to calcification. Fibrous sheath formation was present on the luminal surface of the conduit and extended over the cuspal surfaces to a variable extent. Myofibroblast-like cells repopulated the conduit wall and the basal region of the cusp. Re-endothelialization was variably present on the cuspal surfaces. CONCLUSION: Explant pathology findings showed that in-vivo recellularization occurred, but was focally limited to regions of the arterial wall and cusp base. Safety concerns related to detergent and endonuclease use were identified. Methods to eliminate the potential for structural deterioration and enhance the rate and extent of recellularization of valve conduit tissue are required. Pathology findings showed implantation of valve conduits in the RVOT of juvenile sheep for 20 weeks to be a reliable animal model for the initial in-vivo assessment of decellularized valves. A 20-week period may be insufficient however to evaluate the long-term safety and effectiveness of a tissue-engineered valve conduit, as these depend on effective and phenotypically appropriate recellularization accompanied by sustained cell viability and function.
Animals↗
Aortic valve leaflet sparing and salvage surgery: evolution of techniques for aortic root reconstruction.
Over the past 20 years, a series of procedures have been designed to reconstruct the aortic root of patients with aortic insufficiency, in whom the pathology and hence the surgery spares the valve leaflets. Such techniques have various names. Usually 'valve sparing' is used in context with chronic aortic dissection or aortic root aneurysm as in patients with Marfan's syndrome. 'Aortic valve salvage' tends to be the term of choice for similar surgical reconstruction in the setting of aortic dissection. 'Aortic valve repair' is often chosen when direct surgical procedures are performed on the leaflets themselves. All of the techniques have evolved based upon an increased understanding of the functional anatomy of the aortic root complex. The different technical approaches, their applications and results need to be understood by the cardiology community. The failure modes for such techniques are specific and different from prosthetic valve failure modes, but are adequately followed with echocardiography. Over two-thirds of patients remain free of re-development of significant aortic insufficiency at 8-10 years following surgery. The overall patient survival is more dependent upon the underlying cardiovascular status of the patient than the surgical technique itself. Perioperative mortalities vary between 0 and 6% and are comparable to composite valve+graft techniques and isolated aortic valve replacement, in which the operative mortality approximates 3.3-4%. Long-term results are good to excellent and spare the patient anticoagulation and prosthetic valve disease.
Aortic Dissection↗
Tricuspid valve biopsy: a potential source of cardiac myofibroblast cells for tissue-engineered cardiac valves.
BACKGROUND AND AIMS OF THE STUDY: As progress is made in the development of a tissue-engineered cardiac valve, the need for a reliable cell source is particularly important. A technique has been developed for the reliable biopsy of tricuspid valve leaflets. Expanding the harvested cells in culture is feasible and provides a source of leaflet cells that are structurally and functionally similar to the pulmonary and aortic valve leaflet cells that they may replace. METHODS: Thirteen sheep underwent tricuspid valve biopsy. Transthoracic echocardiography (TTE) was performed to evaluate function and guide the subsequent biopsy. Myofibroblasts were isolated from the biopsy samples, expanded in culture through 10 passages, and evaluated with immunocytochemistry for valve cell markers. Two animals were sacrificed acutely, two animals died during the immediate postoperative period, and nine animals survived for four weeks or more. RESULTS: All preoperative and pre-explantation echocardiograms were normal. Both animals sacrificed acutely showed that the tricuspid valve leaflet was indeed biopsied with this technique. Two perioperative deaths occurred; one animal died secondary to injury of the chorda tendinea with subsequent destruction of the posterior leaflet; another died from disruption of the superior vena cava that led to irreversible cardiac tamponade. At sacrifice (2 to 17 weeks), all other animals showed intact tricuspid valves with normal leaflet anatomy. All cultured biopsies generated myofibroblasts that were immunocytochemically positive for alpha smooth muscle actin, chondroitin sulfate, vimentin and fibronectin. CONCLUSION: Biopsy of the tricuspid valve to obtain recipient cardiac valve leaflet cells is possible, and the technique is simple and reliable. Biopsy of the leaflet does not compromise function. Interstitial cells can be harvested and expanded in culture. Cellular structure and function is preserved and is similar to that of other cardiac leaflet cells. Tricuspid valve leaflet biopsies are a potential source for harvesting cells to be used in the development of a tissue-engineered cardiac valve.
Actins↗
Comparison of three myofibroblast cell sources for the tissue engineering of cardiac valves.
The objective of this study was to evaluate the capacity of three clinically useful tissue sources: tricuspid valve leaflet (TVL), carotid artery (CA), and jugular vein (JV), to generate myofibroblasts for potential use in a tissue-engineered cardiac valve replacement. Tissue biopsies of clinically appropriate sizes obtained from juvenile sheep were used for this work. Cells obtained from all three tissue sources exhibited a myofibroblast phenotype in vitro, as demonstrated by their immunoreactivity with antibodies directed against vimentin, alpha-smooth muscle actin, fibronectin, and chondroitin sulfate. Protein synthesis characteristics were defined for the key extracellular matrix components: collagen, glycosaminoglycans, and elastin. Among the three sources, JV generated the highest numbers of cells, and JV cells produced the largest amount of collagen per cell. These data suggest that venous tissue, with its relative ease of accessibility, may generate myofibroblasts potentially useful for the interstitial cellular component of a tissue-engineered cardiac valve.
Actins↗