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Biomedical subjects

P P Karpawich

Publications and source records attributed to P P Karpawich.

At least 19 recordsLinked to original sources
PubMed2003

Reversible symptomatic dilated cardiomyopathy in older children and young adolescents due to primary non-sinus supraventricular tachyarrhythmias.

Dilated cardiomyopathy (DCM) due to a primary supraventricular tachycardia not originating from the sinus node is not frequently seen in older children or adolescents. However, it is important to recognize this entity as a reversible cause of DCM to avoid costly and inappropriate treatments for these patients. We describe 7 patients who presented with DCM. Five were misdiagnosed as having "sinus" tachycardia secondary to an idiopathic DCM, and 2 were correctly diagnosed as having DCM secondary to an atrial tachycardia. All underwent electrophysiologic treatment of the tachycardia with remission of the DCM.

Adolescent↗
PubMed2001

Myocardial flow reserve in patients with a systemic right ventricle after atrial switch repair.

OBJECTIVES: The purpose of this study was to assess myocardial blood flow (MBF) and flow reserve in systemic right ventricles (RV) in long-term survivors of the Mustard operation. BACKGROUND: There is a high prevalence of systemic RV dysfunction and impaired exercise performance in long-term survivors of the Mustard operation. A mismatch between myocardial blood supply and systemic ventricular work demand has been proposed as a potential mechanism. METHODS: We assessed MBF at rest and during intravenous adenosine hyperemia in 11 long-term survivors of a Mustard repair (age 18+/-5 years, median age at repair 0.7 years, follow-up after repair 17+/-5 years) and 13 healthy control subjects (age 23+/-7 years), using N-13 ammonia and positron emission tomography imaging. RESULTS: There was no difference in basal MBF between the systemic RV of survivors of the Mustard operation and the systemic left ventricle (LV) of healthy control subjects (0.80+/-0.19 vs. 0.74+/-0.15 ml/g/min, respectively, p = NS). However, the hyperemic flows were significantly lower in systemic RVs than they were in systemic LVs (2.34+/-0.0.69 vs. 3.44+/-0.62 ml/g/min respectively, p < 0.01). As a result, myocardial flow reserve was lower in systemic RVs than it was in systemic LVs (2.93+/-0.63 vs. 4.74+/-1.09, respectively, p < 0.01). CONCLUSIONS: Myocardial flow reserve is impaired in systemic RVs in survivors of the Mustard operation. This may contribute to systemic ventricular dysfunction in these patients.

Adolescent↗
PubMed2001

Left ventricular dysfunction after long-term right ventricular apical pacing in the young.

OBJECTIVES: The goal of this study was to assess long-term global left ventricular (LV) function in patients paced from the right ventricular (RV) apex at a young age. BACKGROUND: Ventricular contraction asynchrony with short-term RV apical pacing has been associated with reduced LV pump function and relaxation. The long-term effect of RV apical pacing on global LV function in the young remains unknown. METHODS: Twenty-four patients with normal segmental anatomy paced from the RV apex (follow-up 1 to 19 years) underwent noninvasive assessment of global LV function with automated border detection echocardiography-derived fractional area of change (FAC), coupled with the Doppler index of myocardial performance (MPI). Data were analyzed from 24 RV-paced patients (mean follow-up 9.5 years, age 19 years, body surface area [BSA] 1.6 m2, QRS duration 140 ms) and compared with 33 age- and BSA-matched control subjects (age 16.4 years, BSA 1.6 m2). Multiple linear regression analysis was performed to identify patient variables that can affect these indexes of LV function. RESULTS: Assessment of LV function (median follow-up 10 years) in 24 paced patients demonstrated impaired area- and Doppler flow-derived indexes of LV systolic and diastolic function, compared with those indexes of control subjects (FAC: 52% vs. 60%, p < 0.01; MPI: 0.46 vs. 0.34, p < 0.01). Paced QRS interval and age were found to significantly influence global LV contraction in these patients (R2 = 0.4, p < 0.05). CONCLUSIONS: In the presence of impaired LV function with long-term RV apical pacing, alternative sites of ventricular pacing that simulate normal biventricular electrical activation should be explored to preserve function in pediatric patients in need of long-term pacing.

Adolescent↗
PubMed2001

Biventricular pacing as alternative therapy for dilated cardiomyopathy associated with congenital heart disease.

Biventricular, alternative, and multisite pacing are currently being explored to improve cardiac function among patients with medically refractory, end-stage dilated cardiomyopathies. Although, due to inherent myocardial abnormalities, patients with repaired congenital heart defects may be at a greater risk than others to develop heart failure, often requiring cardiac transplantation. The efficacy of biventricular pacing among these patients is unknown. This report presents a patient with successfully repaired congenital heart disease in infancy who developed a symptomatic dilated cardiomyopathy at 22 years of age. Following biventricular pacing, systemic ventricular function showed a 14% improvement in ventricular dP/dt. One month later, subjective symptoms improved and cardiac ultrasound illustrated a 125% increase in fractional area of change. Exercise stress testing showed a 17% improvement in aerobic work capacity.

Adult↗
PubMed2001

Single-dose pharmacokinetics of sotalol in a pediatric population with supraventricular and/or ventricular tachyarrhythmia.

The pharmacokinetics (PK) of the antiarrhythmic sotalol, which elicits Class III and beta-blocking activity, has not been adequately defined in a pediatric population with tachyarrhythmias. The goal of this single-dose study with administration of sotalol HCl at a dose level of 30 mg/m2 body surface area (BSA) was to define the PK of the drug in the following four age groups: neonates (0-30 days), infants (1 month to 2 years), younger children (> 2 to < 7 years), and older children (7-12 years) with tachyarrhythmias of either supraventricular or ventricular origin. The drug was administered in an extemporaneously compounded syrup formulation prepared from the tablets containing sotalol HCl. For safety, vital signs and adverse events were recorded and the QTc interval and heart rate telemetrically monitored. Scheduled blood samples were taken over a 36-hour time interval following dose administration. The drug concentrations in plasma were measured by a sensitive and specific LC/MS/MS assay. Standard compartment model-independent methods were applied to compute the salient PK parameters of sotalol. Twenty-four clinical sites enrolled 34 patients. Thirty-three had analyzable data. Sotalol was rapidly absorbed, with mean peak concentrations occurring 2 to 3 hours after administration. The elimination of sotalol was characterized by an average half-life of between 7.4 and 9.2 hours in the four age groups. There existed statistically significant linear relationships between apparent total clearance (CL/f) or apparent volume of distribution (V lambda z/f) after oral administration and the covariates BSA, creatinine clearance (CLcr), body weight (BW), or age. The best predictors for CL/f were CLcr and BSA, whereas BW best predicted the V lambda z/f. The total area under the drug concentration-time curve in the smallest children with a BSA < 0.33 m2 was significantly greater than that in the larger children. This finding indicated that the BSA-based dose adjustment used in this study led to a larger exposure in the smallest children, whereas the exposure to the drug was similar in the larger children. The dose of 30 mg/m2 was tolerated well. No serious drug-related adverse events were reported. It can be concluded that the PK of sotalol in the pediatric patients depended only on body size, except for the neonates and smallest infants in whom the disposition of sotalol was determined by both body size and maturation of eliminatory processes.

Adrenergic beta-Antagonists↗
PubMed1999

Altered cardiac histology following apical right ventricular pacing in patients with congenital atrioventricular block.

Previous studies have demonstrated that right ventricular apical pacing inherently alters ventricular contraction, regional blood flow, wall stress, and predisposes to diminished function. However, histological consequences of chronic apical pacing potentially contributing to the observed ventricular dysfunction remain conjectural. Previous canine studies have demonstrated histopathological cellular abnormalities with apically initiated ventricular pacing that may result in the observed diminished ventricular function. To determine if comparable adverse changes also occur in the clinical setting, 16 endomyocardial biopsies were obtained from 14 age-matched patients with congenital complete atrioventricular block (CCAVB) and otherwise normal anatomy, divided into two groups: eight biopsies (median patient age 15.5 years) from patients prior to pacemaker implant and another eight biopsies (median patient age 16 years) from patients following 3-12 years (median 5.5) of chronic ventricular pacing. In one patient, biopsy samples were obtained before and after pacing. Results demonstrated a significant (P<0.05) increase in histopathological alterations among the patient biopsy samples following pacing, consisting of myofiber size variation, fibrosis, fat deposition, sclerosis, and mitochondrial morphological changes. These findings indicate that chronic apical right heart ventricular pacing may adversely alter myocellular growth, especially among the young, on the cellular and subcellular level, potentially contributing to the diminished function observed clinically.

Adolescent↗
PubMed1998

"In-line" bipolar, steroid-eluting, high impedance, epimyocardial pacing lead.

Recent advances in electrode surface designs have eliminated traditional threshold differences between endo- and epicardial pacing leads. Since the epicardial approach offers the potential of direct left ventricular pacing and the transvenous approach may not be feasible or warranted in all instances, more advanced leads are being designed to optimize epicardial pacing capabilities. This study was conducted to evaluate a bipolar epimyocardial lead. Six immature canines (age 3 months) were instrumented. The lead (Medtronic model 10389) is a single-pass, "in-line" bipolar electrode with low current drain and high impedance, with an intramyocardial steroid-eluting cathode and nonsteroid epicardial anode. Twelve ventricular leads were implanted (two per animal) and the animals followed for 6 months with weekly analysis of pacing and sensing capabilities. Results at explant were compared with implant values and showed no significant differences between sensed R waves or in R wave slew rates in unipolar or bipolar modes. Explant lead impedances remained high in both modes: bipolar, 1658 +/- 331; and unipolar, 1327 +/- 308 omega (P < 0.05). Chronic voltage (V) threshold at 0.5 ms showed no significant change from implant values during the study: unipolar, 0.3 +/- 0.06 versus 1.0 +/- 0.8; and bipolar, 0.4 +/- 0.06 versus 1.6 +/- 1.2. Histologic review showed negligible fibrous reaction at the electrode-tissue interface. This study introduces a high impedance, low threshold, "in-line" bipolar pacing lead design capable of stable chronic pacing with implant facilitated by a single suture technique.

Animals↗
PubMed1998

Chronic performance of a transvenous steroid pacing lead used as an epi-intramyocardial electrode.

Excessive surface fibrosis or fat limits effective electrode insertion in patients requiring epicardial pacing. We present chronic performance of a modified transvenous steroid lead used as an epi-intramyocardial electrode in a patient following repair of a univentricular heart after failure of both standard and steroid-eluting epicardial leads. Low implant threshold values remained stable during a 3-year postimplant interval demonstrating an effective and innovative approach to epicardial pacing.

Bradycardia↗
PubMed1997

Comparative left ventricular function following atrial, septal, and apical single chamber heart pacing in the young.

Ventricular pacing, typically initiated from a RV apical electrode, inherently causes abnormal biventricular activation, decrease LV function, and causes histopathological changes. Since pacing initiated in childhood can be expected to have a more protracted course compared with the adult, the consequences of this alteration in LV hemodynamics gain added significance among the young pacemaker recipient. The purpose of this study was to evaluate the potential of improving paced LV function by a septal electrode implant site. Acute alterations in cardiac index, LV pressure, and contraction indices, including dP/dt, Vmax, and Vpm, were compared among 22 patients (median age 10 years) with normal cardiac anatomy during intracardiac electrophysiological studies. LV hemodynamics were measured during intrinsic rhythms and following 15 minutes of atrial, RV apical, and septal pacing at an appropriate exercise rate for age of 150 ppm. Results showed a significant decrease in LV dP/dt, Vmax, and Vpm, and increase in LV end-diastolic pressure only with apical pacing. Septal pacing, in spite of loss of any atrial contribution to ventricular filling, maintained comparable indices with intrinsic and atrial paced rhythms. This study demonstrates that normalized LV function is maintained by septal and deteriorates with apical pacing acutely among young, nonischemic hearts. Continued evaluation of appropriate pacing electrode designs to permit septal implant is needed to ensure optimal chronically paced LV function.

Adolescent↗
PubMed1997

Steroid-eluting epicardial pacing electrodes: six year experience of pacing thresholds in a growing pediatric population.

Indications for pacemaker implantation in the pediatric population often include sinus or atrioventricular node dysfunction following surgery for congenital heart defects. However, patient size, cardiac defects, and vascular and valvular concerns may limit transvenous lead utilization. Since the epicardial surface of these patients often exhibits variable degrees of fibrosis from scar tissue formation or pericardial adhesions, chronic low output (2.5/1.6 V, 0.3 ms) epicardial pacing from implant is not currently recommended in children due to frequent threshold changes and electrode exit block. As a result, pacing in children is often viewed as a less efficient system than in adults. The addition of steroid combined with newer low threshold electrode designs however stabilizes the electrode-tissue interface and eliminates postimplant changes seen with standard smooth surface electrodes potentially permitting efficient chronic pacemaker application to all patient ages. The stability of chronic low output epicardial pacing with steroid-eluting electrodes was prospectively studied in 22 patients (ages 2 days-18.5 years, median 3.5 years) for up to 6 years. Chronic pulse width thresholds were compared according to implant site and association of prior cardiac surgery. A total of 26 pacing leads were implanted. The acute implant mean pulse width threshold (2.5 V) for all the electrodes studied was 0.10 ms +/- 0.05 ms. Stable low thresholds were maintained for up to 6 years without significant variation from implant. Mean ventricular pulse width thresholds (0.12 ms +/- 0.05 ms) were significantly higher (P < 0.001) than atrial thresholds (0.06 ms +/- 0.03 ms) at implant and throughout the study period. The thresholds in the patients following cardiac surgery were comparable to those without previous cardiac surgery (P = NS). Stable low thresholds may be chronically maintained for up to 6 years for epicardial steroid-eluting electrodes irrespective of pacing site or associated cardiac surgery.

Adolescent↗
PubMed1994

Improved epimyocardial pacing: initial experience with a new bipolar, steroid-eluting, high impedance lead design.

Epicardial pacing typically is associated with decreased pacing and sensing capabilities compared with the endocardial approach. Since endocardial pacing is neither appropriate nor possible in all instances, this study was conducted to evaluate a new concept in a chronic epimyocardial lead design in six 3-month-old growing dogs. The new bifurcated lead (Medtronic model 10401) is a low current drain, high impedance, steroid-eluting, bipolar design. The implant is facilitated by a suture attached with an atraumatic needle. Twelve ventricular leads were implanted (2 per animal) and followed for 6 months with weekly analysis of pacing and sensing capabilities. Results at explant were compared with implant values. There were no significant differences between implant and explant in sensed R waves, or in the slew rate of the R wave in unipolar or bipolar modes. Lead impedances at explant remained high in both modes: bipolar, 1550 +/- 223; unipolar, 1234 +/- 262 omega (P < 0.05). Chronic voltage (v) threshold at 0.5 msec showed no significant change from implant values during the study: unipolar, 0.4 +/- 0.2 vs 0.7 +/- 0.3; bipolar, 0.5 +/- 0.4 vs 1 +/- 0.5. Histologic evaluations of the electrode tissue interface demonstrated negligible fibrotic capsule formation. This study introduces a new, easily implanted, high impedance, low threshold, bipolar epimyocardial pacing lead design with excellent chronic pacing and sensing characteristics.

Animals↗
PubMed1993

Ambulatory arrhythmia screening in symptomatic children and young adults: comparative effectiveness of Holter and telephone event recordings.

Effective initial identification of potential cardiac arrhythmias in symptomatic children is difficult due to the infrequency, brief duration, and vague nature of subjective complaints in the young. Although both telephone event and Holter monitoring are used for this purpose, no comparative studies of the initial screening efficacy of either have been performed. A total of 202 consecutive symptomatic children (age 11 days to 26 years, mean 10.2 years) were evaluated for potential cardiac arrhythmias with either 24-h Holter (97 patients) or telephone event (105 patients) recorders and grouped according to the presence or absence of congenital heart defects, normal or abnormal resting electrocardiogram (ECG), and presence or absence of cardiac surgery. The results showed 30% of all recordings (61% event; 14% Holter) failed to substantiate any arrhythmias in spite of subjective symptoms. Event recordings showed a better correlation of sensed symptoms with arrhythmias (32%) compared to Holters (5%) (p < 0.01) with 73% of Holter recordings performed during both asymptomatic and arrhythmia-free 24-h periods. Holter monitoring was more effective in detecting nonsensed and asymptomatic events (8% versus 0.5%, (p < 0.01), among high-risk children. This study demonstrates that although both monitoring devices are applicable to children, each has inherent limitations and usefulness. These must be considered in choosing either device to permit their most optimal and cost-effective application.

Adolescent↗
PubMed1993

The effects of rate responsive pacing on exercise performance in the postoperative univentricular heart.

Following the Fontan operation for definitive palliation of the univentricular heart, sinus node dysfunction, and/or atrioventricular block requiring pacemaker therapy is common. In previous studies ventricular rate responsive pacing (VVI,R) resulted in improved exercise performance over VVI pacing in anatomically normal hearts with either sinus node disease or atrioventricular block. In this study, the usefulness of both VVI,R and DDD,R pacing are evaluated in the postoperative univentricular heart following the Fontan operation. Eight postoperative Fontan patients with sinus node disease or atrioventricular block underwent exercise testing using a treadmill protocol. Six patients had single chamber ventricular pacemakers and two patients had dual chambered rate responsive pacemakers. Median age at exercise testing was 14 years. Patients were tested in the VVI, VVI,R, and DDD,R modes acting as their own controls. Heart rate, work rate, oxygen consumption, and respiratory exchange ratio were monitored continuously. Heart rate was significantly increased in the rate responsive modes compared to the VVI mode. In spite of the significant increase in heart rate, there was no change in maximal work rate or oxygen consumption. There was also no significant change in oxygen consumption at ventilatory anaerobic threshold. From these data we would conclude that VVI,R pacing in postoperative univentricular hearts does not result in improved exercise performance and that further study with DDD,R pacing is needed to determine its usefulness in this group of patients.

Adolescent↗
PubMed1992

Septal His-Purkinje ventricular pacing in canines: a new endocardial electrode approach.

Ventricular activation sequences and cardiac performance are influenced by pacing sites. Stimulation of or close to the specialized atrioventricular (AV) conduction system optimizes paced ventricular function compared to alternative epi- or endocardial muscle conduction sites. This study reports a new endocardial electrode implant approach to approximate septal His-Purkinje ventricular pacing. Five 6-month-old beagles were used. A custom, platinum-iridium, exposed helical screw electrode (Medtronic, Inc.), 4.5-mm long, with a 17.8-mm2 surface area, was designed with a polyurethane covered 4 filar MP35N nickle conductor lead. An 8 French sheath (USCI, Inc.) was modified as introducer to permit simultaneous implant intracardiac pressure and electrogram recordings. Following a thoracotomy, the introducer was inserted through the right atrial appendage and advanced to record optimal His-bundle electrogram while maintaining atrial pressure along the septal tricuspid valve annulus. After electrode implant, ECG demonstrated narrow paced QRS morphology. Mean implant values showed sensed R wave 6.3 mV, slew rate 0.65 V/sec, pacing impedance 319 ohms, and threshold 0.9 V/3.3 mA at 0.5-msec output. Necropsy showed implant above the tricuspid annulus with electrode extension into and contained within the proximal ventricular septum. This study demonstrates that an endocardial septal approach to His-Purkinje ventricular pacing to optimize paced ventricular function is feasible with a new electrode design and precise septal implant technique. Alternative introducer designs may permit transvenous application of this approach.

Animals↗
PubMed1992

Improved chronic epicardial pacing in children: steroid contribution to porous platinized electrodes.

Although new "low threshold" epicardial electrodes combine steroid with a porous, platinized-platinum surface, the actual contribution of steroid elution has not been established. We evaluated this new electrode surface design with and without steroid in 13 children, ages 1-22 years. Both electrodes are unipolar and of similar surface area. The Medtronic Model 4951-P is a barb design for epimyocardial insertion without steroid while the Model 10295A is a steroid eluting, epicardial disk-shaped design. Both electrodes were implanted for atrial and ventricular pacing. At implant, sensed P and R waves, and pacing impedances were comparable between both electrodes. There were no significant differences between initial measured pulse width or calculated energy thresholds for the first 2 months following implant. Strength-duration curves for both electrodes at 1 month were comparable to implant values. After 2 months, the threshold of the nonsteroid electrode peaked and stabilized at a significantly higher (P less than 0.05) level than the more constant steroid eluting electrode. This difference continued for the first year following implant. We conclude that the new porous, platinized-platinum electrode design intrinsically limits initial electrode-tissue interface reactivity in children and improves epicardial pacing with low chronic threshold values. Steroid elution augments these intrinsic qualities by maintaining fibrous capsule stability with more constant low thresholds over time.

Bradycardia↗