Shape memory polymers with enhanced visibility for magnetic resonance- and X-ray imaging modalities.

Currently, monitoring of minimally invasive medical devices is performed using fluoroscopy. The risks associated with fluoroscopy, including increased risk of cancer, make this method especially unsuitable for pediatric device delivery and follow-up procedures. A more suitable method is magnetic resonance (MR) imaging, which makes use of harmless magnetic fields rather than ionizing radiation when imaging the patient; this method is safer for both the patient and the performing technicians. Unfortunately, there is a lack of research available on bulk polymeric materials to enhance MR-visibility for use in medical devices. Here we show the incorporation of both physical and chemical modifying agents for the enhancement of both MR and X-ray visibility. Through the incorporation of these additives, we are able to control shape recovery of the polymer without sacrificing the thermal transition temperatures or the mechanical properties. For long-term implantation, these MR-visible materials do not have altered degradation profiles, and the release of additives is well below significant thresholds for daily dosages of MR-visible compounds. We anticipate our materials to be a starting point for safer, MR-visible medical devices incorporating polymeric components. STATEMENT OF SIGNIFICANCE: Shape memory polymers (SMPs) are polymeric materials with unique shape recovery abilities that are being considered for use in biomedical and medical device applications. This paper presents a methodology for the development of MR and X-ray visible SMPs using either a chemically loaded or physical loaded method during polymer synthesis. Such knowledge is imperative for the development and clinical application of SMPs for biomedical devices, specifically for minimally-invasive vascular occlusion treatments, and while there are studies pertaining to the visibility of polymeric particles, little work has been performed on the utility of biomaterials intended for medical devices and the impact of how adding multiple functionalities, such as imaging, may impact material safety and degradation.

Shape memory polymers with visible and near-infrared imaging modalities: Synthesis, characterization and in vitro analysis.

Shape memory polymers (SMPs) are promising for non-invasive medical devices and tissue scaffolds, but are limited by a lack of visibility under clinical imaging. Fluorescent dyes are an alternative to radiocontrast agents in medical applications, they can be utilized in chemical sensors and monitors and may be anti-microbial agents. Thus, a fluorescent SMP could be a highly valuable biomaterial system. Here, we show that four fluorescent dyes (phloxine B (PhB), eosin Y (Eos), indocyanine green(IcG), and calcein (Cal)) can be crosslinked into the polymer backbone to enhance material optical properties without alteration of shape memory and thermomechanical properties. Examinations of the emission wavelengths of the materials compared with the dye solutions showed a slight red shift in the peak emissions, indicative of crosslinking of the material. Quantitative analysis revealed that PhB enabled visibility through 1 cm of blood and through soft tissue. We also demonstrate the utility of these methods in combination with radio-opaque microparticle additives and the use of laser-induced shape recovery to allow for rapid shape recovery below the glass transition temperature. The crosslinking of fluorescent dyes into the SMP enables tuning of physical properties and shape memory and independently of the fluorescence functionality. This fluorescent SMP biomaterial system allows for use of multiple imaging modalities with potential application in minimally invasive medical devices.

Factors affecting the development of atrial fibrillation and atrial flutter (AF/AFL) following autologous hematopoietic SCT (auto-HSCT).

The use of autologous hematopoietic SCT (auto-HSCT) has expanded to include older patients. Increasing age is a well-appreciated risk factor for the development of atrial fibrillation and/or atrial flutter (AF/AFL) in the general population. As more elderly patients undergo auto-HSCT, the risk of developing AF/AFL post transplant may also increase. However, few data evaluating other risk factors for the development of AF/AFL following auto-HSCT exist. Therefore, we performed a retrospective study to determine the incidence of AF/AFL following auto-HSCT and to determine the risk factors associated with the development of AF/AFL. Patients who developed AF/AFL were compared with a group of patients who received auto-HSCT within the same time period (April 1999 to May 2005) and were within 5 years of age. Of the 516 patients who underwent auto-HSCT at the University of Nebraska Medical Center 44 (8.5%) developed AF/AFL at a median time of 4 days (range, days 1-9) following auto-HSCT. In multivariate analysis, risk factors for developing AF/AFL were older age, odds ratio and 95% CI of 1.14 (1.07-1.21), elevated serum creatinine level, 2.69 (1.00-7.22), history of previous arrhythmia, 9.33 (3.01-28.99), and history of previous mediastinal irradiation, 11.12 (1.33-92.96).

Incidence and management of prolonged charge times in the Medtronic model 7219 implantable cardioverter defibrillator.

The Medtronic Jewel PCD model 7219, introduced in 1994, was the first downsized, pectoral implantable cardioverter defibrillator (ICD), and many of these units are approaching or have reached the elective replacement indicator (ERI). Unlike later Medtronic ICDs and most other ICDs, in which ERI is defined by battery voltage, the ERI in the model 7219 series is defined when either the capacitor charge time to full output is repeatedly> or =14.5 s or when battery voltage is< or =4.91 V. In this study we examined which of the two ERI criteria was met first in patients with this device model. We also assessed the effects of manual dumping and recharging and of increasing the automatic capacitor reformation frequency on prolonged charge times. In 16 patients with follow-up <2 years, 15 reached the charge time ERI before battery voltage ERI. Manual dumping and recharging led to spuriously low charge times due to residual charge at the start of recharging, and increasing the automatic capacitor reformation frequency to once a month did not decrease prolonged charge times. Because of persistently prolonged charge times, 15 patients had generator changes. None of these patients had reached battery voltage ERI (battery voltage at time of explantation 5.06+/-0.06 V). Thus in this early pectoral device, prolonged charge times occur commonly before battery voltage ERI is reached. Whether prolonged charge times will have an impact on device longevity in later model ICDs is unknown.

Potential risk of vasovagal syncope for motor vehicle driving.

Vasovagal syncope is the most common cause of syncope, but its risk for driving remains uncertain. We analyzed the clinical characteristics of patients who had syncope during driving and subsequently underwent the head-up tilt test (HUTT). Of the 245 consecutive patients undergoing HUTT, 23 (9%) had > or =1 episode of syncope during driving. HUTT was positive in 19 (group A) and negative in 4 (group B) patients. No patient had structural heart disease. In group A, the driving incident occurred on the first syncope in 3 patients, and the other 16 patients had 1 to 4 episodes of prior syncope not associated with driving. In group B, the driving incident occurred on the first syncope in 1 patient, and the other 3 patients had prior syncope (3 episodes in each) not associated with driving. Seven group A and 1 group B patients had 2 syncope-related driving incidents, and the remaining patients had only 1 syncope-related driving incident. The syncope-related driving incidents caused personal injury in 7 group A and 2 group B patients. One incident in 1 group A patient caused the death of another driver. After HUTT, all but 1 patient in group A received medical treatment and only 1 patient in group B received empirical beta-blocker therapy. During the follow-up of 51+/-26 months, 1 patient died and another was lost to follow-up. Of the remaining patients, 4 patients had recurrence of syncope and 2 patients had presyncope in group A. One of these patients had another syncope-related driving incident. No group B patient had syncope recurrence. A second etiology of syncope was never found in any patient. We conclude that vasovagal syncope during driving is not uncommon in patients referred for syncope evaluation. Early medical attention to patients with vasovagal syncope may help reduce syncope-related driving incidents.

Usefulness of ibutilide in facilitating successful external cardioversion of refractory atrial fibrillation.

We repeated direct-current cardioversion of atrial fibrillation after ibutilide injection in patients who failed conventional cardioversion. Eleven of 12 patients (92%) had successful cardioversion and avoided the need for internal cardioversion.

The mean ventricular fibrillation cycle length: a potentially useful parameter for programming implantable cardioverter defibrillators.

In programming the implantable cardioverter defibrillator (ICD), the ventricular tachycardia (VT) detection cycle length (CL) is based on the CL of the documented tachycardia but the ventricular fibrillation (VF) detection CL is set arbitrarily. Appropriate programming of VF detection may not only reduce the incidence of inappropriate ICD shocks for non-VF rhythms but can also avoid the fatal underdetection of VF. The mean VFCL may provide a useful parameter for optimal ICD programming for VF detection if it is reproducible. This study examined the intrapatient reproducibility and interpatient variation of the mean VFCL in 30 ICD patients (25 men and 5 women, mean age 63 +/- 13 years). A total of 210 VF episodes (7 +/- 4 per patient, range 3-17) induced by T-wave shocks (166) or AC (44) at the ICD implant (30 patients) and the predischarge test (12 of 30 patients) were analyzed. The mean VFCL was calculated from the stored V-V intervals in the ICDs. Although the mean VFCL varied significantly from 171 +/- 6 to 263 +/- 11 ms (P < 0.01) among different patients, it was reproducible among different VF episodes in an individual patient (maximal variation 4-50 ms, P > 0.05). The mean VFCL was not significantly different between patients with and without antiarrhythmic drugs (210 +/- 32 vs 210 +/- 23 ms, P > 0.05) and was correlated with the ventricular effective refractory period (r = 0.5, P < 0.05). The mean VFCL varies greatly among different patients but remains reproducible in an individual patient, suggesting that the mean VFCL may serve as a reference for ICD programming of VF detection.

Evaluation and management of atrial fibrillation in the emergency department.

AF is the most common sustained cardiac arrhythmia. Recognition and appropriate management of AF is important to optimize care of concurrent medical problems and prevent long-term consequences. DC cardioversion under sedation should be performed in patients with pulmonary edema, angina, or hypotension. Ventricular rate control is the first choice in stable patients with rapid ventricular rate. Anticoagulation should be considered in all patients with AF duration < 48 hours, except for those under 65 years old and having no other risk factors of stroke. Recent data imply that early attempts at cardioversion may increase success rates and decrease AF recurrence rates. Thus, transesophageal echocardiogram-guided early cardioversion may become more widely used.

Causes and consequences of discontinuation of the implantable cardioverter-defibrillator therapy in non-terminally ill patients.

Infection and implantable cardioverter-defibrillator shocks are important contributing factors to discontinuation of cardioverter-defibrillator therapy in non-terminally ill patients. These patients are at a high risk of sudden cardiac death despite continued antiarrhythmic drug therapy.

Defibrillator patch electrode constriction: an underrecognized entity.

Pericardial constriction associated with the placement of intrapericardial defibrillator patches is a rare occurrence that is reported only one tenth as often in defibrillator patients as in patients undergoing other types of cardiac operations. Although this discrepancy may be attributable to a lower incidence of constriction with the defibrillator patch electrode procedure, it may also indicate a failure to recognize that progressive right heart failure and signs of low cardiac output that could be due to pericardial constriction and not progressive systolic dysfunction. Because surgical removal of the patches and decortication of the epicardial surface is the only effective therapy, it is important to recognize this uncommon, but profoundly debilitating entity.

Clinical comparison of acute single to dual chamber pacing in chronotropically incompetent patients with left ventricular dysfunction.

Dual chamber, rate responsive (DDDR) pacing is felt to be superior to ventricular, rate responsive (VVIR) pacing since it more closely mimics the normal electrical and hemodynamic activity of the heart. This reasoning has been used to justify the higher initial costs and increased complexity of dual chamber system. This study was designed to determine if objective criteria could be identified during acute testing justify implanting a dual chamber instead of a single chamber system in patients with left ventricular dysfunction. Eight patients with DDDR pacemakers (implanted for chronotropic incompetence) and left ventricular dysfunction underwent exercise radionuclide angiography and graded exercise treadmill testing. Each patient performed the tests in the single (VVIR) and dual (DDDR) chamber modes in a randomized, blinded fashion. We found that objective parameters such as ejection fraction (31% +/- 13% vs 31% +/- 10%), exercise tolerance (6.1 +/- 2.7 min vs 6.3 +/- 2.9 min), oxygen consumption (VO2) (941 +/- 286 mL/min vs 994 +/- 314 mL/min), carbon dioxide production (VCO2) (995 +/- 332 mL/min vs 1054 +/- 356 mL/min), and maximum attainable workload (43 +/- 24 W vs 46 +/- 22 W) did not differ between the single and dual chamber pacing modes. These findings suggest that in the acute setting, the additional cost and complexity of dual chamber, rate responsive pacing cannot be justified by objective improvements in exercise tolerance in patients with underlying left ventricular dysfunction.

Scatter diagram analysis: a new technique for discriminating ventricular tachyarrhythmias.

With the increasing flexibility allowed by implantable cardioverter defibrillators that use tiered therapy, it is important to match the therapy with the arrhythmia. In this article we present scatter diagram analysis, a new computationally efficient two-channel algorithm for distinguishing monomorphic ventricular tachycardia (VT) from polymorphic ventricular tachycardia and ventricular fibrillation (VF). Scatter diagram analysis plots the amplitude from one channel versus the amplitude from another channel on a graph with a 15 x 15 grid. The fraction (percentage) of the 225 grid blocks occupied by at least one sample point is then determined. We found that monomorphic VT traces nearly the same path in space and occupies a smaller percentage of the graph than a nonregular rhythm such as polymorphic VT or VF. Scatter diagram analysis was tested on 27 patients undergoing intraoperative implantable cardioverter defibrillator testing. Passages of 4.096 seconds were obtained from rate (bipolar epicardial) and morphology (patch) leads, and digitized at 125 Hz. Scatter diagram analysis distinguished 13 episodes of monomorphic VT (28.6% +/- 4.0%) from 27 episodes of polymorphic VT or VF (48.0% +/- 8.2%) with P < 0.0005. There was overlap in only one monomorphic VT episode and one polymorphic VT or VF episode.

Options in managing the patient with high defibrillation thresholds.

The desired defibrillation threshold (DFT) obtained during intraoperative testing of an implantable cardioverter defibrillator (ICD) should be 10 J lower than the maximal energy delivered by the ICD generator. Of the 206 patients undergoing ICD implantation since December 1986, 8 (3.9%) have had initial DFTs with less than the 10-J safety margin using the standard large patch-large patch configuration. Patches were implanted by left thoracotomy in 6 and sternotomy in 1, and 1 had implantation of a transvenous defibrillation lead and subcutaneous patch. Of note, 6 (75%) of the 8 patients with high DFTs had prior open heart operations, half were on a regimen of long-term amiodarone therapy, and the mean left ventricular mass index was quite large but not significantly greater than that of patients with low DFTs. Multiple techniques was tried to improve the DFTs in this group. Satisfactory DFTs were eventually obtained in 7 (88%); the threshold was lowered from a mean of 41.4 +/- 3.8 J to 26.9 +/- 8.8 J (p = 0.002). The most effective techniques were addition of a superior vena cava lead attached by a Y connector to one of the large patch leads in some patients and conversion to a biphasic-waveform generator in 2 others. Adding a third epicardial lead did not lower the DFTs. There were no major postoperative complications or deaths attributable to these supplemental procedures. Using these techniques, satisfactory DFTs were obtained in almost all patients with an ICD.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined toxicity of zidovudine and antituberculosis chemotherapy.

Because antituberculosis agents and zidovudine are commonly used in HIV-infected patients, we performed a cohort study to determine the toxicity of such combined therapy. A group of 24 consecutive human immunodeficiency virus (HIV)-infected patients with tuberculosis who received concomitant antituberculosis therapy and zidovudine (tuberculosis group) were compared with 24 patients who received zidovudine but not antituberculosis medications (comparison group). Comparison patients were matched to tuberculosis patients by age, sex, ethnic group, month of starting zidovudine, and CD4 cell count. Most tuberculosis patients received isoniazid, rifampin, pyrazinamide, and ethambutol initially, followed by isoniazid and rifampin for a mean total duration of 8.4 months. Baseline clinical and laboratory parameters in tuberculosis and comparison patients were similar, except for the mean hemoglobin (11.2 g/dl in tuberculosis patients versus 12.9 g/dl in comparison patients, p = 0.03). The mean zidovudine dose in tuberculosis and comparison patients was approximately 500 mg/day, and the mean duration of zidovudine therapy was 10.3 and 9.6 months, respectively. Symptoms occurred during therapy with similar frequency in both groups. The frequency and severity of leukopenia and granulocytopenia were similar in tuberculosis and comparison patients, but marked anemia (hemoglobin less than 9.5 g/dl) developed in 50% of tuberculosis patients and 17% of comparison patients (p = 0.03). The maximum decrease in hemoglobin during therapy was similar in both groups (mean of 2.0 versus 1.6 g/dl, respectively), suggesting that the higher frequency of marked anemia in tuberculosis patients was due to their lower baseline hemoglobin values. Although transfusions were required in five tuberculosis patients and one comparison patient, zidovudine was not permanently discontinued in any patient because of anemia.(ABSTRACT TRUNCATED AT 250 WORDS)

The long-term use of zidovudine in patients with severe immune-mediated thrombocytopenia secondary to infection with HIV.

Various treatments for HIV-related thrombocytopenia have been reported. Since etiologies of the thrombocytopenia may differ with regard to risk group treatment outcomes may also vary. We have recently studied the long-term use of zidovudine in individuals with sexually transmitted HIV infection and severe thrombocytopenia. Twenty-five men, median age 34 years (range, 23-51 years), were treated with zidovudine (1000 mg/day) for a median duration of 12 months (range, 2.5- less than 26 months). Nineteen patients (76%) had had episodes of symptomatic bleeding secondary to thrombocytopenia prior to study entry. All patients bleeding symptoms resolved with therapy. Six (24%) achieved a complete response, with normalization of platelet counts, while 11 patients (44%) achieved a partial response, giving an overall response rate of 68%. The median time to partial or complete normalization of platelet counts was 12 weeks (range, 4-62 weeks). Toxicities were minimal during the study period. Only one patient developed an AIDS-defining diagnosis while on therapy. We conclude that patients with sexually transmitted HIV infection and immune thrombocytopenia may need a prolonged period of therapy with zidovudine to achieve a platelet response. Other treatment modalities may be required for the 30% of patients who do not respond to zidovudine.

Fast Fourier transformation of the entire low amplitude late QRS potential to predict ventricular tachycardia.

Signal-averaged electrocardiograms (X, Y and Z leads) were acquired from 24 patients with coronary artery disease and recurrent ventricular tachycardia, 24 control patients with coronary artery disease and 23 normal subjects to assess the discriminant value of fast Fourier transformation of the entire late potential period of the QRS complex. Analysis of the vector magnitude in the temporal domain (25 to 250 Hz bandpass filters) measured high frequency QRS duration, the duration of terminal signals less than 40 microV and the root mean square voltage of the last 40 ms. Late potentials were defined as terminal signals greater than 25 Hz that were less than 40 microV. Analysis in the frequency domain used a 120 ms window that encompassed (had onset with) all of the late potential, but the mean value was first subtracted to eliminate a direct current component. High frequency spectral areas (60 to 120 Hz) and the percent high frequency (100 x [60 to 120 Hz/0 to 120 Hz]) were calculated. Results in both temporal and frequency domains were similar in control patients with coronary artery disease and normal subjects. Patients with ventricular tachycardia had a longer high frequency QRS complex (p less than 0.0001) and longer high frequency terminal signals less than 40 microV (p less than 0.0004), but not significantly lower voltage in the last 40 ms. The most useful temporal domain measurement was high frequency QRS duration (if greater than or equal to 120 ms, odds ratio = 8.2). Patients with ventricular tachycardia had increased high frequency spectral areas (p less than 0.0002) in the late potential, and the percent high frequency was especially increased (p = 0.0000; if percent high frequency greater than 3.1%, odds ratio = 18.4). The odds ratio and the area under the receiver operating characteristic curve were both greater for percent high frequency than for high frequency QRS duration (p less than 0.03). All patients with ventricular tachycardia had a high frequency QRS complex greater than or equal to 107 ms or percent high frequency greater than or equal to 3.1% (sensitivity 100%). For a high frequency QRS complex greater than or equal to 107 ms and percent high frequency greater than or equal to 3.1%, specificity was 96%. Therefore, high frequencies in late potentials, not their duration or reduced voltage, most usefully identify patients with coronary artery disease who are prone to ventricular tachycardia.