Biomedical subjects

Thomas S Klitzner

Publications and source records attributed to Thomas S Klitzner.

13 recordsLinked to original sources

PubMed2006

Atrioventricular ring reentry in embryonic mouse hearts.

BACKGROUND: During development, AV conduction switches from base-to-apex to apex-to-base conduction after emergence of the conduction system. We hypothesize that after this transition, the bulk of the AV ring, although no longer required for AV conduction, remains transiently able to conduct, providing a potential arrhythmia substrate. We studied AV conduction during this transition and its sensitivity to autonomic modulation. METHODS AND RESULTS: Simultaneous voltage and Ca2+ mapping with RH-237 and Rhod-2 was performed with 2 CCD cameras in embryonic mouse hearts (n = 43). Additionally, isolated calcium mapping was performed in 309 hearts with fluo-3AM. Propagation patterns in voltage and Ca2+ mapping coincided. Arrhythmias were uncommon under basal conditions, with AV block in 14 (4%) and junctional rhythms in 4 (1%). Arrhythmias increased after stimulation with isoproterenol-junctional rhythm in 9 (3%) and ventricular rhythms in 22 (6%)-although AV block decreased (3 hearts, 1%). Adding carbachol after isoproterenol caused dissociated antegrade and retrograde AV ring conduction in 30 (8.6%) of E10.5 and E11.5 hearts, occurring preferentially in the right and left sides of the ring, respectively. In 2 cases, reentry occurred circumferentially around the AV ring, perpendicular to normal propagation. Reentry persisted for multiple beats, lasting from 3 to 22 minutes. No episodes of AV ring reentry occurred in E9.5 hearts. CONCLUSIONS: AV ring reentry can occur by spatial dissociation of antegrade and retrograde conduction during combined adrenergic and muscarinic receptor stimulation. Critical maturation (> E9.5) seems to be required to sustain reentry.

Adrenergic beta-Agonists↗

PubMed2006

Autonomic regulation of calcium cycling in developing embryonic mouse hearts.

In the present study, we combined optical Ca(2+) imaging with immunocytochemistry studies to characterize autonomic regulation of Ca(2+) cycling during early development in isolated embryonic mouse hearts. At embryonic days 9.5-11.5 (E9.5-E11.5), the Ca(2+) transient originated in the superior portion of the right atrium, propagated rapidly through both atria, slowly through the atrio-ventricular (AV) ring, and rapidly through both ventricles. Isoproterenol (ISO) significantly increased heart rate, increased Ca(2+) transient amplitude, rate of rise (RR) and a rate of decay, and shortened AV conduction time, indicating the presence of functional beta-adrenergic receptors. The muscarinic agonist carbachol (CCh) had no effects until 1 day later at E10.5. Both beta1-adrenergic and M2 muscarinic receptors were detected in ventricular muscle sections by immunochemistry at E10.5. Growing nerves, labeled using growth-associated protein 43 antibodies, were detected at the E14.5 stage, but not at E10.5, whereas mature sympathetic nerves, detected by tyrosine hydroxylase (TH) labeling, were not yet present at E14.5. These results demonstrate that functional regulation of Ca(2+) cycling by beta-adrenergic receptors occurs earliest in developing embryonic mouse hearts, followed a day later by muscarinic receptor responsiveness, with autonomic innervation developing later. These results define the functional and structural sequence of autonomic regulation of Ca(2+) transient in the embryonic mouse heart.

Age Factors↗

PubMed2006

Risk factors for deaths occurring within 30 days and 1 year after hospital discharge for cardiac surgery among pediatric patients.

BACKGROUND: Little is known regarding the risk factors for early and late death after hospital discharge among pediatric patients undergoing cardiac surgery. METHODS: Statewide hospital discharge data from California in 1989 to 1999 were used to study outcomes of children <18 years old who had a procedure code (by International Classification of Diseases, Ninth Revision, Clinical Modification) indicating cardiac surgery. The outcome variable was death occurring after hospital discharge. Postdischarge deaths were identified by linking hospital discharge data to statewide death registry data. Cardiac surgical procedures were grouped into 23 categories to adjust for risk involved with the procedures. We used logistic regression to evaluate risk factors for postdischarge mortality, including variables age, sex, race and ethnicity, type of insurance, home income, date and month of surgery, type of admission, hospitals case volume, and the various types of procedures. RESULTS: There were 25,402 cardiac surgery cases with 1505 inhospital deaths. Of 23,897 hospital discharges, 148 deaths (0.62%) occurred within 365 days after discharge, including 37 deaths within 30 days; 44 deaths at 31 to 90 days; and 67 deaths at 91 to 365 days. Logistic regression showed young age was an important risk factor for postdischarge death with an odds ratio of 4.8 for neonates and 3.5 for infants, compared with children >1 year old. Another significant risk factor was the type of procedure. For death <30 days after discharge, Norwood operation (odds ratio 8.4 compared with closure of ventricular septal defect) was a risk factor. For death that occurred between 31 and 365 days, significant risk factors were truncus arteriosus repair, total anomalous pulmonary vein repair, aortopulmonary shunt, and open valvotomy. Sex, race/ethnicity, home income, and hospital case volume were not significant predictors of postdischarge deaths. CONCLUSIONS: Many demographic and socioeconomic variables affecting inhospital death were not significant predictors for postdischarge death. Important risk factors for postdischarge death were young age and the type of surgery performed.

Adolescent↗

PubMed2005

Variations in adult congenital heart disease training in adult and pediatric cardiology fellowship programs.

OBJECTIVES: The purpose of this study was to evaluate adult congenital heart disease (CHD) training among U.S. cardiology fellowship programs. BACKGROUND: Although training recommendations for caring for adults with CHD exist, the educational patterns and numbers of specialists remain unknown. METHODS: We surveyed U.S. directors of 170 adult cardiology and 45 pediatric cardiology (PC) fellowship programs. Adult program surveys contained 1 single-response and 10 multiple-choice questions; pediatric program surveys contained 1 single-response and 13 multiple-choice questions. RESULTS: Ninety-four adult cardiology fellowship directors (55%) and 34 PC directors (76%) responded. Of adult programs, 70% were in university hospitals and 40% were associated with PC groups. Those with PC-affiliation had more adult CHD clinics (p < 0.02) and more adult CHD inpatient (p < 0.02) and outpatient (p < 0.002) visits than those without PC affiliation. Most PC programs were in children's hospitals (38%) or children's hospitals within adult hospitals (50%). Eighty-two percent had associated adult cardiology programs. Pediatric programs followed adult CHD patients in various care settings. Over one-third of adult and pediatric programs had < or = 3 lectures annually regarding adult CHD. Nine adult and 2 pediatric programs offered adult CHD fellowships, and only 31 adult and 11 pediatric fellows pursued advanced CHD training in the last 10 years. CONCLUSIONS: Adult CHD didactic and clinical experiences for cardiology fellows vary widely. Few programs offer advanced CHD training, and the number of specially trained physicians is unlikely to meet projected workforce requirements. Adult cardiology programs with PC affiliation have increased CHD experience and might provide good educational models.

Adult↗

PubMed2005

Changes in the newborn delivery practice and neonatal outcomes as financing changed in Los Angeles County and Orange County, California.

The objective of this investigation was to study changes in newborn delivery during a period of extensive changes in financing mechanisms in Los Angeles County (LAC) and Orange County (OC), California. California hospital discharge data (1990-1999) were used for the analyses. The Herfindahl-Hirschman Index (HHI) was calculated to measure the distribution of newborn deliveries among hospitals. Birth outcomes, including cesarean section rates, in-hospital deaths, interhospital transfers, and selected neonatal morbidities, were assessed. A total of 2,351,209 newborn deliveries in 124 hospitals were recorded. The number of newborn babies delivered per year decreased by 21% during the study period. A dramatic decline in the number of deliveries (up to 80%) was seen in all four LAC county hospitals. The cesarean section rate increased for Medi-Cal patients during the study period, compared with no change in the rate for privately insured patients. The newborn interhospital transfer rate for patients in LAC remained unchanged. The newborn in-hospital mortality rates for both LAC and OC decreased during the study period.

California↗

PubMed2004

Evaluation of safety and efficacy of pacemaker and defibrillator implantation by axillary incision in pediatric patients.

We successfully implanted 11 pacemakers, 6 defibrillators, and 1 biventricular pacemaker in 18 pediatric patients (15 female; 4 to 15 years, average age: 9) using the retropectoral transvenous approach with a hidden axillary incision. The average follow-up period was 24 months (range 49 months). Eight patients had congenital structural heart conditions (d-transposition of great arteries S/P Mustard operation, d-transposition of great arteries S/P arterial switch operation, truncus arteriosus, right ventricular diverticula, ventricular septal defect, hypertrophic cardiomyopathy). Four patients had acquired heart conditions (dilated cardiomyopathy, myocarditis). Excellent sensing and pacing thresholds were achieved in all attempted implantations. There was no pneumothorax. There was one lead dislodgement. One lead fracture distant from the subclavian vein occurred 4 months after implantation. Implantation of pacemakers and defibrillators via axillary incisions can be safe and effective in pediatric patients. This approach avoids skin erosion when implanting large devices such as defibrillators or biventricular devices in small patients with limited muscle mass while achieving superior aesthetic results. The axillary or extrathoracic venous entry site avoids subclavian crush syndrome.

Adolescent↗

PubMed2004

Parental preference regarding hospitals for children undergoing surgery: a trade-off between travel distance and potential outcome improvement.

OBJECTIVE: To explore parental preference in the choice between a local and a referral hospital for children undergoing heart surgery. METHODS: One hundred three parents or adult primary caregivers of children referred to a pediatric cardiology clinic were interviewed. Participants were presented with hypothetical scenarios in which they or their children had a heart condition requiring elective surgery. The surgery could be performed at either a local hospital or a regional referral hospital. The travel time to the referral hospital was initially presented as 2 h, and the mortality rate was set at 3% for both the local and the referral hospitals. The parents were then presented with scenarios that sequentially increased the mortality of the local hospital and the distance to the referral hospital, and were asked to choose between the local and regional referral hospitals. RESULTS: When the regional referral hospital was 2 h away and the mortality rates for the referral hospital and the local hospital were equal at 3%, 82.5% of participants chose the local hospital for their children. The percentage of participants choosing the local hospital decreased progressively as the mortality rate of the local hospital increased (to 9.7% at 18% mortality). Between 5% and 10% more participants chose the local hospital when the distance to the referral hospital was increased from 2 h to 4 h. There was no difference in age, sex, ethnicity, language, type of insurance, level of education and availability of personal transportation between participants who chose the regional referral hospital and those who chose the local hospital. Participants who lived closer to the hospital at which the survey was conducted were more likely to choose the local hospital. CONCLUSION: The present study defines a relation between potential outcome improvement and increasing travel distance from a patient or parent's perspective. This trade-off is an important consideration when planning for regionalization.

Adolescent↗

PubMed2003

Resources, use, and regionalization of pediatric cardiac services.

Care for children with congenital heart disease requires specialized services and various healthcare resources. The purpose of this article is to provide an updated overview of healthcare resources for infants and children with heart disease. In 2001, there were 1609 certified pediatric cardiologists in the United States. The ratio was approximately 45,000 children younger than 18 years per pediatric cardiologist. It is estimated that more than 19,000 cardiac surgeries are performed in children younger than 18 years in the United States each year. This article also reviews the effect of patient characteristics on access to healthcare and use of pediatric cardiac services, and discusses issues related to optimal use of these resources and the development of an organized approach toward service management by regionalization. The authors believe that improved access to high-quality facilities and providers coupled with thoughtful changes in the healthcare delivery system represent an excellent opportunity for optimizing outcomes for children with heart disease.

Cardiac Surgical Procedures↗

PubMed2002

Female sex as a risk factor for in-hospital mortality among children undergoing cardiac surgery.

BACKGROUND: The purpose of this study was to investigate whether sex disparity in cardiovascular outcomes exists in children who undergo cardiac surgery. METHODS AND RESULTS: Statewide hospital discharge data from California from 1995 to 1997 were used. Children <21 years old who had a procedure code (by ICD9-CM) that indicated cardiac surgery were selected. The outcome variable was binary, in-hospital death versus alive at discharge. Twenty-three surgical procedures were selected and adjusted for risk by procedure type. We used logistic regression analysis to evaluate the effect of sex on in-hospital mortality, controlling for age, race and ethnicity, type of insurance, home income, type of admission, date and month of surgery, hospital case volume, and type of procedure. There were 6593 cases of cardiac surgery, with 345 in-hospital deaths (mortality rate 5.23%). Crude mortality rates for males (4.98%) and females (5.54%) were not significantly different. However, fewer females were neonates, and females had more low-risk procedures than males. Multivariate logistic regression showed that females had a higher odds ratio (OR) for mortality than males (OR 1.51, P<0.01). The OR for mortality was 3.86 for neonates and 2.98 for infants compared with children aged > or =1 year. Low-volume hospitals had higher mortality rates than high-volume hospitals (OR 1.67, P<0.01). The risk-adjusted length of hospital stay and charges were similar between females and males. CONCLUSIONS: For children undergoing cardiac surgery, female sex was associated with 51% higher odds of death than male sex. The mechanism by which female sex acts as a risk factor requires further investigation.

Adolescent↗

PubMed2002

HIV type 1 glycoprotein 120 inhibits cardiac myocyte contraction.

Cardiomyopathy is a common, life-threatening, but poorly understood complication of HIV infection. The purpose of the present study is to study the effects of an HIV surface envelope protein, glycoprotein 120 (gp120), on cell contraction and L-type Ca(2+) current in rabbit ventricular myocytes. Rabbit ventricular cells were isolated by an enzyme dissociation method. Cell contractions were induced by electric field stimulation. Whole cell L-type Ca(2+) channel currents were measured by the whole cell voltage-clamp technique. We found that perfusion with solution containing gp120 (0.1 microg/ml) derived from HIV-1(SF2) significantly inhibited field-stimulated contractions and L-type Ca(2+) current in rabbit ventricular myocytes as compared with perfusion with buffer alone. These results suggest that HIV-1 gp120 may directly contribute to cardiac dysfunction as seen in many HIV patients.

Animals↗

PubMed2002

Azimilide inhibits multiple cardiac potassium currents in human atrial myocytes.

BACKGROUND: Studies in animal cell preparations suggest that azimilide may produce a more desirable rate-dependent profile of class III action as a result of its effects on both the slowly (I(Ks)) and rapidly (I(Kr)) activating components of potassium current (I(K)). However, relatively little is known about the effects of azimilide on K(+) currents in human atrial cells. The present study investigated the effect of azimilide on the inward rectifier potassium current (I(K1)), delayed rectifier potassium current (I(K)), ultrarapid delayed rectifier current (I(Kur)), and transient outward potassium current (I(to)) in isolated single human atrial myocytes. METHODS: The tight-seal, whole-cell voltage clamp technique was used to investigate the acute effects of azimilide on K(+) currents in single human atrial myocytes. The cells were isolated enzymatically from atrial tissues that were obtained from patients undergoing open-heart surgeries, with the approval of the local Institutional Review Board. RESULTS: The average cell capacitance of the human atrial myocytes was 77.5 +/- 2.8 pF (Mean +/- standard error of mean, total 28 cells from 17 patients). We found that 100 microM of azimilide in the extracellular solution significantly inhibited the inward rectifier potassium current (12.3 +/- 3.1 vs 6.7 +/- 2.0 pA/pF, n = 12, P < 0.05) at the testing potential of -100 mV. Superfusion with 100 microM of azimilide for 10 minutes inhibited I(K) by 51.7 +/- 5.1% (from 3.4 +/- 0.5 to 1.6 +/- 0.2 pA/pF, n = 9, P < 0.01) at the clamping membrane potential of +40 mV. Human atrial cell I(Kur) was inhibited with 100 microM of azimilide by 38.6 +/- 4.4% (from 3.9 +/- 0.5 to 2.3 +/- 0.2 pA/pF, n = 9, P < 0.01, test potential = 40 mV). We also found that the average peak current amplitude of I(to) in these cells was significantly inhibited with 100 microM of azimilide by 60.3 +/- 5.9% (from 10.3 +/- 1.5 to 3.6 +/- 0.3 pA/pF, n = 6, P < 0.01, test potential = 50 mV). CONCLUSION: The present study provides direct evidence that azimilide inhibits multiple cellular transmembrane K(+) currents in freshly isolated human atrial myocytes. Inhibition of these K(+) currents by azimilide, especially of I(Ks) and I(Kur) is likely to be the electrophysiologic basis for the prolongation of the action potential duration in the human atria which mediates its known antifibrillatory effects in atrial fibrillation and flutter.

Analysis of Variance↗

PubMed2002

Can regionalization decrease the number of deaths for children who undergo cardiac surgery? A theoretical analysis.

OBJECTIVE: The association between high case volumes and better patient outcomes has been demonstrated for many surgical procedures and medical treatments, including surgery for children with congenital heart disease. To simulate the effects of regionalization of pediatric cardiac surgery, we assessed the impact of reducing the number of pediatric cardiac centers on surgical mortality and patient's travel distance. METHODS: This study used abstracted statewide hospital discharge data from California from 1995 to 1997. Case volume and in-hospital mortality for pediatric cardiac surgeries at each hospital were calculated. All hospitals that performed > or =10 pediatric cardiac surgeries in 1995 to 1997 were included in the analysis. To simulate regionalization, we "closed" the hospital with the lowest case volume and redistributed patients from this hospital to the nearest remaining hospitals. The number of in-hospital deaths was then recalculated using the original mortality rate of each remaining hospital multiplied by its new case volume. A multivariate logistic regression was conducted to determine the odds ratios of mortality of various types of surgery compared with closure of ventricular septal defect. This result was used for adjusting for the case-mix of the hospitals. Regionalization simulation analysis was repeated, and the number of deaths was recalculated using this adjustment of hospital case-mix. We also examined the increase in travel distance of patients to the hospitals as a result of the regionalization simulation. RESULTS: In California, 6592 children underwent cardiac surgeries in 1995 to 1997 with 352 in-hospital deaths (overall mortality rate: 5.34%). A quadratic regression model demonstrated that a high surgical volume was associated with a low mortality rate. We found demarcations between low- and medium-volume hospitals at 70 cases per year and medium- and high-volume hospitals at 170 cases per year. With adjustment for hospital case-mix, we found that 41 deaths could be avoided when all patients from low-volume hospitals were referred, and 83 deaths could be avoided when all patients from low- and medium-volume hospitals were referred to high-volume hospitals (overall mortality rate decreased to 4.08%). The average travel distance for pediatric cardiac surgery was 45.4 miles, which increased by 12.7 miles when all surgeries were referred to high-volume hospitals. When only the 733 high-risk patients were referred from low- and medium-volume hospitals to high-volume hospitals, 49 deaths could be avoided, yielding an overall mortality rate of 4.60%. CONCLUSIONS: Theoretical regionalization of pediatric cardiac surgery is associated with a reduction in surgical mortality from 5.34% to 4.08% when all cases were referred to high-volume hospitals, or decrease to 4.60% when high-risk cases were referred. Although regionalization is associated with an important decrease in the number of deaths, it also increases the travel distance for patients. Additional studies on the costs and benefits of regionalization are needed to determine the best strategies to improve outcomes for children who undergo cardiac surgery.

California↗

PubMed2002

Clinical management of infants with hypoplastic left heart syndrome in the United States, 1988-1997.

OBJECTIVES: To evaluate changes in the clinical management of infants with hypoplastic left heart syndrome (HLHS) over a 10-year period. BACKGROUND: Orthotopic heart transplantation (OHT) and the Norwood procedure have emerged as the treatment options for HLHS over the last 2 decades. METHODS: We used 1988-1997 hospital discharge data from the National Inpatient Sample dataset. Patients < or =30 days of age with a principal diagnosis of HLHS were identified. Clinical management included the Norwood procedure, OHT, in-hospital death without surgery, discharge home without surgery, and transfer to another hospital. Multivariate logistic regression was used to evaluate variables associated with the choice of management. RESULTS: There were 1986 cases of HLHS with 812 in-hospital deaths, yielding a mortality rate 40.9%. The in-hospital mortality rate decreased from 54.4% in 1988 to 38.1% in 1997. The proportion of patients treated with the Norwood procedure increased from 8% in 1988 to 34% in 1997. The proportion of patients who died in the hospital without surgery decreased over time while the percentage discharged from the hospital without surgery or transferred to another hospital remained relatively unchanged. The in-hospital mortality rate was significantly lower in the OHT group compared with the Norwood group (26.2% vs 46.0%). We found no differences in gender, race, type of insurance, or home income between patients treated with the Norwood procedure compared with those who received comfort care. Patients from a later era, in the South, and in teaching hospitals were more likely to undergo the Norwood procedure. CONCLUSIONS: Between 1988 and 1997, the proportion of infants with HLHS treated with the Norwood procedure increased while the use of comfort care decreased. Gender, race/ethnicity, type of medical insurance, and home income did not correlate with treatment choices.

Cardiac Surgical Procedures↗