Update on Management of In-stent Restenosis

In-stent restenosis (ISR) is a common and frequently resistant problem. The pathophysiology of in-stent and nonstent restenosis is different, the former resulting primarily from intimal hyperplasia, while the latter is predominantly a consequence of negative late remodeling. Predictors of ISR are patient and lesion related. When approaching a patient with stent restenosis, false or pseudo-restenosis must be considered. Angiography frequently fails to reveal pseudo-restenosis, and, consequently, intravascular ultrasound can be essential in guiding the most effective strategy. Because of spontaneous neointimal regression, patients with asymptomatic stent restenosis often can be followed and treated medically. The mechanical approaches to ISR include balloon angioplasty alone, debulking plus PTCA, and restenting. For focal lesions (< 10 mm in length) balloon angioplasty at moderately high pressures is often effective. Following balloon dilatation, stent expansion and plaque extrusion equally account for the gain in lumen area. For more diffuse disease, debulking plus balloon angioplasty is preferred, although no randomized data are available. Only restenting is associated with a gain in MID that is comparable to the original stent implant and is not associated with reintrusion of neointima — INSTANT restenosis. Despite aggressive debulking with or without further stenting, diffuse stent restenosis often is resistant to purely mechanical treatment. Nonmechanical approaches, such as localized radiation therapy, will be required to effectively treat this difficult subset of patients.     

Evolution of the Organization of Epicardial Activation Patterns During Ventricular Fibrillation

Activation During Ventricular Fibrillation. Introduction : This study quantified how the organization of epicardial activation changes during the first 40 seconds of ventricular fibrillation (VF).
Activation During Ventricular Fibrillation. Introduction : This study quantified how the organization of epicardial activation changes during the first 40 seconds of ventricular fibrillation (VF).
Methods and Results : Unipolar potentials were mapped from a 504 (24 × 21) electrode array (2-mm interelectrode spacing) on the anterior right ventricle (RV) and left ventricle (LV) epicardium. The array covered approximately 20% of the epicardial surface. In each of seven pigs, six episodes of VF were induced by premature stimulation. One-half second epochs of VF were analyzed, starting 0, 10, 20, 30, and 40 seconds post induction and using novel pattern analysis algorithms. Eight parameters were quantified: (1) the number of wavefronts; (2) the epicardial area activated by wavefronts; (3) the fraction of wavefronts arising from epicardial breakthrough or from a focus; (4) the fraction of wavefronts terminated by conduction block; (5) the multiplicity index (number of distinct activation pathways in the rhythm); (6) the repeatability index (number of times activation pathways are traversed); (7) the activation rate; and (8) the wavefront propagation velocity. The results showed that VF patterns were less organized at 10 than at 0 seconds, with more, smaller wavefronts traversing a larger variety of pathways for fewer repetitions. VF activation patterns then gradually reorganized up to 40 seconds, but by a different mechanism: the spatial size of subpatterns grew, but the dynamics otherwise appeared unchanged. During both transitions, both activation rate and propagation velocity slowed monotonically.
Conclusion : Thus, changes in organization during VF can occur by multiple mechanisms.     

Fundamental Causes of Colorectal Cancer Mortality: The Implications of Informational Diffusion

Context: Colorectal cancer is a major cause of mortality in the United States, with 52,857 deaths estimated in 2012. To explore further the social inequalities in colorectal cancer mortality, we used fundamental cause theory to consider the role of societal diffusion of information and socioeconomic status. Methods: We used the number of deaths from colorectal cancer in U.S. counties between 1968 and 2008. Through geographical mapping, we examined disparities in colorectal cancer mortality as a function of socioeconomic status and the rate of diffusion of information. In addition to providing year‐specific trends in colorectal cancer mortality rates, we analyzed these data using negative binomial regression. Findings: The impact of socioeconomic status (SES) on colorectal cancer mortality is substantial, and its protective impact increases over time. Equally important is the impact of informational diffusion on colorectal cancer mortality over time. However, while the impact of SES remains significant when concurrently considering the role of diffusion of information, the propensity for faster diffusion moderates its effect on colorectal cancer mortality. Conclusions: The faster diffusion of information reduces both colorectal cancer mortality and inequalities in colorectal cancer mortality, although it was not sufficient to eliminate SES inequalities. These findings have important long‐term implications for policymakers looking to reduce social inequalities in colorectal cancer mortality and other, related, preventable diseases.     

Analysis of Deaths in Patients with an Implantable Cardioverter Defibrillator

The cause of death and clinical characteristics of 26 patients that died after implantable cardioverter defibrillator placement were reviewed and compared to the 145 patients still living after a mean follow-up of 17 months. Operative mortality was 4% (7/171) and resulted from postoperative ventricular arrhythmias (four patients), heart failure (two patients), and respiratory failure (one patient). Operative mortality was significantly higher (1.7% vs 9.6%, P less than 0.05) following concomitant surgical procedures. Total late mortality was 11% (18/171). Thirteen deaths (75%) occurred in-hospital from progressive deterioration of left ventricular function (nine patients), arrhythmia (two patients), and noncardiac causes (two patients). Outpatient mortality was 3.5% (6/171) and resulted from presumed sudden cardiac death in five of six patients; two of the five had devices that were inactive, one had high defibrillation thresholds, and two had suspected bradyarrhythmic deaths. One postoperative death and one late in-hospital death were also considered sudden cardiac deaths for a total of seven patients with defibrillation system failures. By multivariant analysis, preoperative clinical characteristics associated with a worse prognosis following defibrillator implantation were identified: presentation as ventricular tachycardia (P less than 0.02), induction of sustained monomorphic ventricular tachycardia (P less than 0.05), poor left ventricular performance (P less than 0.01), poor functional status (P less than 0.001), and the use of diuretics (P less than 0.01). Frequent device discharges (P less than 0.001) and concomitant antitachycardia pacing systems (P less than 0.001) were markers for greater arrhythmia recurrence and were potent predictors of a worse prognosis and particularly sudden death.     

Reduction of Antiarrhythmic Drug Use in Patients Receiving Implantable Cardioverter Defibrillators

Widespread use of implantable cardiovertfir defibrillators (ICDs) for the treatment of ventricular tachycardia (VT) and ventricular fibrillation (VF) occurred in the late 1980s and early 1990s. Additionally, there has been increasing appreciation during this time for both the lack of efficacy and praarrhythmic activity of antiarrhythmic drugs to treat these cardiac arrhythmias. We evaluated the use of antiarrhythmic drugs from 1987 to 1991 (5-year period) at the time of ICD implantation in 25,450 patients. The use of all classes of antiarrhythmic agents decreased from 61% to 24% during this time period (P < 0.05), In addition, there was a significant reduction in antiarrhythmic agent use for each drug class (P < 0.05) with the exception of Class II agents (beta blockers). These changes in drug use occurred independent of any changes in age, sex, ejection fraction, prevalence of coronary artery disease, or type of ventricular arrhythmia (VT vs VF).     

Histopathological Study Following Catheter Guided Radiofrequency Current Ablation of the Slow Pathway in a Patient with Atrioventricular Nodal Reentrant Tachycardia

The present study examined histological changes induced by catheter guided radiofrequency current in a patient with AV nodal reentrant tachycardia who underwent cardiac transplantation 1 week after ablation of the slow pathway. During the electrophysiology study AV nodal conduction curves were discontinuous and AV nodal reentry was induced. At the conclusion of the procedure there was no evidence of slow pathway function. Histological sections from the explanted heart demonstrated a sharply demarcated atrial lesion (5 × 5 × 4 mm) extending from the septal portion of the tricuspid annulus to the posterior border of the AV node. The lesion did not encompass the compact AV node. These observations support the hypothesis that the slow pathway is comprised of atrial approaches to the AV node and is distinct from the compact AV node.     

Orthogonal Ventricular Electrogram Sensing

Inappropriate demand pacing is most commonly due to improper ventricular electrogram sensing. Filters and programmable sensitivities improve eleclrogram sensing of conducted beats, but paced electrograms cannot be sensed by conventional unipolar or bipolar systems. A permanent pacing lead with a standard tip electrode and three orthogonal 0.8 mm² sensing electrodes located circumferentially 2 cm proximal to the pacing tip was tested in 22 patients. The tip electrode was placed in the right ventricular apex in standard pacing position. Orthogonal electrodes were not in contact with ventricular myocardium. Orthogonal ventricular eleclrograms from 54 electrode pairs were compared with unipolar tip electrograms during conducted rhythms and paced beats. Tip ventricular electrograms averaged 12.8 mV with 3.04 mVT waves. Orthogonally recorded ventricular electrograms during conducted beals averaged 8.86 mV with T waves of 1.57 mV. During pacing, tip ventricular electrograms were obscured by the stimulus artifact and repolarization events. Orthogonal ventricular electrograms, however, demonstrated small discrete stimuli of 1.99 mV followed by discrete ventricuJar electrograms of 9.19 mV and T waves of 1.9 mV. Orthogonal ventricular electrograms compared favorably with contacting tip electrograms during conducted beats and provided a redundant sensing capability. During pacing, orthogonal ventricular electrograms allowed the capability for capture verification. A new pacing catheter allows for improved ventricuJar electrogram sensing and capture verification.     

CUTANEOUS MYIASIS FOLLOWING TRAVEL TO BELIZE

Two days after returning from Belize, a 70-vear-old man developed three nonhealing ulcers with serosanguinous drainage on the right posterior ankle. He recalled mildly pruritic "mosquito bites" on the ankles prior to leaving Belize, but no evidence of skin breakdown. Tbe patient denied fever, chills, or other systemic symptoms associated witb his skin lesions.
A one-week course of cephalexin, 500 mg po q.i.d., given for "superficial cellulitis," failed to improve the plaque on the right ankle. The patient was evaluated in the dermatology department 4 weeks after his return from Belize with no progression of the ankle lesions. The examination showed a 4 x7 cm indurated, nontender, erythematous plaque with three sinuses draining serosanguinous fluid (Fig. 1).
A skin biopsy was performed on an area containing a draining sinus tract and submitted for routine and special stains. Tissue and wound cultures were negative for bacteria (aerobic and anaerobic), fungi, mycobacteria, and Leishmania .
Histopathologic Findings : The deep retlcular dermis and subcutis showed an extensive, polymorphous, inflammatory reaction surrounding a parasitic structure that measured 1.8 mm in diameter (Fig. 2). The parasite had a thick eosinophilic cuticle with striated muscle visible around the out-lines of the alimentary tube and other organs (Fig. 3). The morphologic appearance of the parasite was consistent with the larva of a fly, most likely of the Dermatobia species.
Clinical Course : Conservative treatment with polymyxin B sulfate-bacitracin zinc ointment and ace wrap occlusion for 2 days resulted in the extraction of two mature larvae (Fig. 4). The patient reported the sensation of "movement" within the sinuses immediately prior to larval extraction. The third larval specimen was contained in the skin biopsy tissue. All three sites of larval penetration showed rapid healing following the extraction of the larvae.     

ALBERT'S SOLUTION VERSUS POTASSIUM HYDROXIDE SOLUTION IN THE DIAGNOSIS OF TINEA VERSICOLOR

Background. The diagnosis of tinea versicolor can usually be made by clinical examination. Either potassium hydroxide (KOH) or Wood's light fluorescence are used to corroborate the diagnosis. Albert's solution has been reported as a method of visualizing dermatophytes. We compared Albert's solution to KOH in the diagnostic evaluation of tinea versicolor. Methods. Twenty patients with clinical tinea versicolor were examined for the presence of hyphae and/or spores utilizing Albert's solution or KOH (20%) with dimethyl sulfoxide. Results. All patients were positive for hyphae and/or spores by both methods. Preparations with Alberts' stains were faster and easier to read. Conclusions. Albert's solution is an alternate method to stain for fungal elements in patients with tinea versicolor.     

The Effects of Aminorex and Related Compounds on Brain Monoamines and Metabolites in CBA Mice

Acute and long-term neurochemical effects of aminorex, an appetite-suppressing drug related to amphetamine in chemical structure, and stereoisomers of its analogues were examined and compared with those of 3,4-methylenedioxymethylarnphetamine (MDMA) and fenfluramine. Aminorex and its analogues, with exception of 45, 5S-dimethylaminorex, did not cause the long-term neurotransmitter depletion in either the dopaminergic or 5-HT-ergic systems that was observed after MDMA or fenfluramine in CBA mice. These results are discussed in terms of possible structurally related mechanisms of neurotoxicity. The acute neurochemical effects showed that aminorex and analogues all produced increases in 5-hydroxytryptamine (5-HT) levels, unlike fenfluramine and MDMA in the present study or in published data. This suggests that inhibition of 5-HT metabolism, rather than direct 5-HT release, may be involved in their anorectic effect. The parallel study of acute dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) changes suggest that in CBA mice MDMA may be a better dopamine releaser and this may contribute to its dopaminergic neurotoxicity. However the ability to release dopamine or 5-HT, or both, may be important, but not the only factor involved in causing the long-term neurotoxicity observed with amphetamine derivatives.