Safety and interaction of patients with implantable cardiac defibrillators driving a hybrid vehicle.

BACKGROUND: Electromagnetic interference (EMI) can affect the function of implantable cardioverter defibrillators (ICD). Hybrid electric vehicles (HEV) have increased popularity and are a potential source of EMI. Little is known about the in vivo effects of EMI generated by HEV on ICD. OBJECTIVE: This study evaluated the in vivo interaction between EMI generated by HEV with ICD. METHODS AND RESULTS: Thirty patients (73±9 y/o; 80% male) with stable ICD function were exposed to EMI generated by a Toyota Prius Hybrid®. The vehicle was lifted above the ground, allowing safe changes in engine rotation and consequent variations in electromagnetic emission. EMI was measured (NARDA STS® model EHP-50C) and expressed in A/m (magnetic), Volts/m (electrical), and Hertz (frequency). Six positions were evaluated: driver, front passenger, right and left back seats, outside, at the back and front of the car. Each position was evaluated at idle, 30 mph, 60 mph and variable speeds (acceleration-deceleration-brake). All ICD devices were continuously monitored during the study. The levels of EMI generated were low (highest mean levels: 2.09A/m at right back seat at 30 mph; and 3.5V/m at driver seat at variable speeds). No episode of oversensing or inadvertent change in ICD programming was observed. CONCLUSION: It is safe for patients with ICD to interact with HEV. This is the first study to address this issue using an in vivo model. Further studies are necessary to evaluate the interaction of different models of HEV or electric engine with ICD or unipolar pacemakers.

Autologous dermal fibroblast injections slow atrioventricular conduction and ventricular rate in atrial fibrillation in swine.

BACKGROUND: Nonpharmacological ventricular rate control in atrial fibrillation (AF) without producing atrioventricular (AV) block remains a clinical challenge. We investigated the hypothesis that autologous dermal fibroblast (ADF) injection into the AV nodal area would reduce ventricular response during AF without causing AV block. METHODS AND RESULTS: Fourteen pigs underwent electrophysiology study before, immediately, and 28 days after ≈ 200 million cultured ADFs (n = 8) or saline (n = 6) were injected under electroanatomical guidance in the AV nodal area, with continuous 28-day ECG recording. In the ADF group at 28 days postinjection, there were prolongations of PR interval (after versus before: 130 ± 13 versus 113 ± 14 ms, P = 0.04), of AH interval during both sinus rhythm (92 ± 13 versus 76.8 ± 8 ms, P < 0.01) and atrial pacing at 400 ms (102 ± 13 versus 91 ± 9 ms, P < 0.01), and of AV node Wenckebach cycle length (230 ± 19 versus 213 ± 24 ms, P < 0.01), with no changes in the control group. The RR interval during induced AF 28 days after injections was 24% longer in ADF-treated group compared with controls (488 ± 120 versus 386 ± 116 ms, P < 0.001). Histological analysis revealed presence of ADF-labeled cells in the AV nodal area at 28 days. Transient accelerated junctional rhythm during injections, and transient nocturnal Mobitz I AV conduction occurred early postinjection in both groups. CONCLUSIONS: Cells survived for 4 weeks and significantly slowed AV conduction and ventricular rate in acutely induced AF. Critically, despite a large number of injections in the AV nodal area and marked effects on AV conduction, AV block did not occur. Further studies are necessary to determine the clinical feasibility and safety of this strategy for ventricular rate control in AF.

Predictors of severe tricuspid regurgitation in patients with permanent pacemaker or automatic implantable cardioverter-defibrillator leads.

Patients with permanent pacemaker or automatic implantable cardioverter-defibrillator (AICD) leads have an increased prevalence of tricuspid regurgitation. However, the roles of cardiac rhythm and lead-placement duration in the development of severe tricuspid regurgitation are unclear. We reviewed echocardiographic data on 26 consecutive patients who had severe tricuspid regurgitation after permanent pacemaker or AICD placement; before treatment, they had no organic tricuspid valve disease, pulmonary hypertension, left ventricular dysfunction, or severe tricuspid regurgitation. We compared the results to those of 26 control subjects who had these same devices but no more than mild tricuspid regurgitation. The patients and control subjects were similar in age (mean, 81 ±6 vs 81 ±8 yr; P = 0.83), sex (male, 42% vs 46%; P = 0.78), and left ventricular ejection fraction (0.60 ±0.06 vs 0.58 ± 0.05; P = 0.4). The patients had a higher prevalence of atrial fibrillation (92% vs 65%; P=0.01) and longer median duration of pacemaker or AICD lead placement (49.5 vs 5 mo; P < 0.001). After adjusting for age, sex, and right ventricular systolic pressure by multivariate logistic regression analysis, we found that atrial fibrillation (odds ratio=6.4; P = 0.03) and duration of lead placement (odds ratio=1.5/yr; P = 0.001) were independently associated with severe tricuspid regurgitation. Out study shows that atrial fibrillation and longer durations of lead placement might increase the risk of severe tricuspid regurgitation in patients with permanent pacemakers or AICDs.

New-onset atrial fibrillation in severe sepsis and risk of stroke and death: a critically appraised topic.

BACKGROUND: Severe sepsis has been associated with an increased risk of new-onset arrhythmias, namely atrial fibrillation (AF). Single-center and small-center studies suggest that new-onset AF is associated with higher mortality and prolonged hospitalization during severe sepsis. However, the relationship between new-onset AF in severe sepsis to prognosis is unknown. OBJECTIVE: To determine whether new-onset AF increases the risk of stroke and death in severe sepsis. METHODS: The objective was addressed through the development of a structured, critically appraised topic. This incorporated a clinical scenario, background information, a structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and fellow-level neurologists, a medical librarian, clinical epidemiologists, and context experts in the fields of vascular neurology, hospital neurology, critical care medicine, and cardiovascular medicine. RESULTS: A recent retrospective, population-based cohort study was selected and appraised to address this prognostic question. Patients were obtained from the California State Inpatient Database administrative claims data from nonfederal acute care hospitals from January 1 through December 31, 2007. Of the 3,144,787 patients, 49,082 (1.56%) had severe sepsis, defined by the validated International Classification of Disease, 9th Revision, Clinical Modification code 995.92. The a priori outcome measures included in-hospital ischemic stroke and mortality. New-onset AF occurred in 5.9% of patients with severe sepsis versus 0.65% of patients without severe sepsis [odds ratio, 6.82; 95% confidence interval (CI), 6.52-7.11; P<0.001]. Compared with severe sepsis patients without new-onset AF, patients with new-onset AF during severe sepsis had greater risks of in-hospital ischemic stroke (2.6% vs. 0.6% strokes; adjusted odds ratio, 2.70; 95% CI, 2.05-3.57; P<0.001) and in-hospital mortality (56% vs. 39% deaths; adjusted relative risk, 1.07; 95% CI, 1.04-1.11; P<0.001). Findings were robust across 2 separate definitions of severe sepsis and multiple sensitivity analyses. CONCLUSIONS: In patients with severe sepsis, new-onset AF seems to increase the risk of in-hospital stroke and mortality compared with patients with no or preexisting AF.

Effects on arrhythmogenesis and arrhythmic threshold of injection of autologous fibroblasts into myocardial infarcts in adult pigs.

Myocardial dysfunction is strongly associated with a higher rate of ventricular arrhythmia and sudden death. Clinical studies indicate that intramyocardial injection of autologous cells to augment contractile function may modify the arrhythmogenic substrate. The aim of this study was to assess the effects of epicardial injections of autologous dermal fibroblasts in infarcted pigs on the incidence of spontaneous and induced ventricular tachycardia. In eight pigs, myocardial infarction was induced, and the skin was excised for fibroblast isolation, culture, and labeling with bromodeoxyuridine (BrdU). After 3 weeks, animals received epicardial injection of the autologous fibroblasts (n = 4) or saline (n = 4) across the scarred and border zone regions, with continuous ECG monitoring for the following 4 weeks. Electrophysiologic study with programmed stimulation was performed before injections and at sacrifice, and histological analysis was performed. ECG monitoring showed that the fibroblast group had a lower total number of ectopic ventricular complexes per day when compared to the control group (58 ± 119 versus 478 ± 1,308 respectively; p = 0.013) and fewer episodes of non-sustained ventricular arrhythmia per day (0 episodes versus 31 ± 148 respectively; p = 0.001). Inducibility during programmed ventricular stimulation was no different between the groups. Histological analysis disclosed the presence of viable BrdU-labeled cells in injected areas. This study showed that fibroblasts can be safely transplanted in an infarcted heart and survive for at least 4 weeks. Fibroblast injection did not increase the inducibility of ventricular tachycardia, and reduced the incidence of spontaneous ventricular tachycardia.

Bone marrow-derived B cells preserve ventricular function after acute myocardial infarction.

OBJECTIVES: In view of evidence that mature cells play a role in modulating the stem cell niche and thereby stem cell potential and proliferation, we hypothesized that a mature bone marrow (BM) mononuclear cell (MNC) infusion subfraction may have particular potency in promoting hematopoietic or resident stem cell-induced cardiac repair post-infarction. BACKGROUND: Treatment of acute myocardial infarction (MI) with BM MNC infusion has shown promise for improving patient outcomes. However, clinical data are conflicting, and demonstrate modest improvements. BM MNCs consist of different subpopulations including stem cells, progenitors, and differentiated leukocytes. METHODS: Stem cells (c-kit+) and subsets of mature cells including myeloid lineage, B and T-cells were isolated from bone marrow harvested from isogeneic donor rats. Recipient rats had baseline echocardiography then coronary artery ligation; 1 x 10(6) cells (enriched subpopulations or combinations of subpopulations of BM MNC) or saline was injected into ischemic and ischemic border zones. Cell subpopulations were either injected fresh or after overnight culture. After 2 weeks, animals underwent follow-up echocardiography. Cardiac tissue was assayed for cardiomyocyte proliferation and apoptosis. RESULTS: Fractional ventricular diameter shortening was significantly improved compared with saline (38 +/- 3.2%) when B cells alone were injected fresh (44 +/- 3.0%, p = 0.035), or after overnight culture (51 +/- 2.9%, p < 0.001), or after culture with c-kit+ cells (44 +/- 2.4%, p = 0.062). B cells reduced apoptosis at 48 h after injection compared with control cells (5.7 +/- 1.2% vs. 12.6 +/- 2.0%, p = 0.005). CONCLUSIONS: Intramyocardial injection of B cells into early post-ischemic myocardium preserved cardiac function by cardiomyocyte salvage. Other BM MNC subtypes were either ineffective or suppressed cardioprotection conferred by an enriched B cell population.

Radiotherapy-induced pacemaker and implantable cardioverter defibrillator malfunction.

It is well known that ionizing radiation can interfere with circuits in permanent pacemakers and implantable cardioverter defibrillators. Contemporary implantable cardiac devices use complementary metal-oxide silicon in combination with other very sensitive transistors. These sensitive components are especially susceptible to electromagnetic and ionizing radiation, which can potentially cause permanent damage. Electromagnetic interference is, in general, a transient phenomenon. Radiologic imaging tests have been implicated in rare cases of implantable device dysfunction and these events have been mostly transient. The American Association of Physicists in Medicine last published recommendations regarding irradiation of pacemakers in 1994. This publication is outdated and may not be pertinent for the current technology used both in the field of artificial cardiac pacing and defibrillation and in the field of radiation oncology. Updated guidelines are definitely needed.

Electromechanical activation sequence in normal heart.

This article summarizes the recent experimental and theoretic data regarding the normal electromechanical activation sequence of the left ventricle (LV). First, the cardiac electrical sequence is presented with a brief insight into the wave front of electrical activation that develops from the organized transmural spread of action potentials. Second, the regional heterogeneity in electromechanical coupling and myofiber stretch-shortening kinematics are presented. Finally, the transmural shortening and lengthening sequences are linked with the myofiber architecture of the left ventricular wall to explain the global three-dimensional twisting deformation of the LV. Integrating the electrical and mechanical domains of myocardial function provides vital insights into the macroscopic physiologic behavior of a beating heart.

Safety of intramyocardial injection of autologous bone marrow cells to treat myocardial ischemia in pigs.

OBJECTIVE: The purpose of this study is to determine the potential adverse consequences of intracardiac injections of bone marrow mononuclear cells (BMCs) to facilitate the revascularization of ischemic myocardium. BACKGROUND: Bone marrow mononuclear cells are used to treat heart failure, though there are few studies that evaluated the safety of BMC transplantation for chronic myocardial ischemia. METHODS: The pigs received coronary ameroid constrictors to induce chronic myocardial ischemia and left ventricular dysfunction. At 4 weeks, autologous BMCs were injected intramyocardially by Boston Scientific Stiletto catheter with low-dose (10(7) cells) or high-dose BMC (10(8)). Control animals received saline. Blood samples were collected for hematological and chemical indices, including cardiac enzyme levels at regular time intervals postinfarction. At 7 weeks, animals underwent electrophysiological study to evaluate the arrhythmic potential of transplanted BMC, followed by necropsy and histopathology. RESULTS: No mortalities were associated with intramyocardial delivery of BMC or saline. At Day 0, the total creatine phosphokinase (CPK) was in the normal range in all groups. All groups had significant elevations in CPK after ameroid placement, with no significant differences between groups. At 7 weeks, CPK in all groups had returned to pretreatment levels. Electrophysiological assessment revealed that one control animal had an inducible arrhythmia. No arrhythmias were induced in low- or high-dose BMC-treated pigs. There were no histopathological changes associated with BMC injection. CONCLUSION: This study showed, in a clinically relevant large-animal model, that catheter-based intramyocardial injection of autologous BMC into ischemic myocardium is safe.

Toxic vessel reaction to an absorbable polymer-based paclitaxel-eluting stent in pig coronary arteries.

OBJECTIVES: The goal of this study was to evaluate a new drug-eluting stent (DES) comprising a bioabsorbable polymer eluting a moderate dose of paclitaxel in a clinically relevant animal model. BACKGROUND: Although DES limit restenosis, adverse vascular pathologies and toxicities continue to be of major concern. Optimization of DES components, especially completely absorbable polymers, may reduce these toxicities. METHODS: Bare-metal (BM), absorbable polymer coating only (POLY), and polymer-based paclitaxel-eluting (PACL) stents were implanted in porcine coronary arteries using intravascular ultrasound (IVUS) to optimize stent apposition. The dose density of paclitaxel was 0.30-0.35 mcg/mm2, with in vitro elution studies demonstrating a gradual elution over 6-8 weeks. The animals were terminated at 1 week, 1 month and 3 months. Histopathologic and histomorphometric analyses were perform. RESULTS: The arteries with PACL showed extensive smooth muscle cell necrosis at 1 week and poor apposition of stent struts at 1 month (malapposition measured as gap width between strut and internal elastic lamina), with greater gap width compared to the BM and POLY groups (0.22 mm +/- 0.02 vs. 0.03 mm +/- 0.02 and 0.02 mm +/- 0.01, respectively; p < 0.001). At 3 months, the PACL group showed rebound neointimal thickness and histological percent stenosis compared to the BM group (0.48 mm +/- 0.14 vs. 0.07 mm +/- 0.02, respectively; p < 0.001 and 59% +/- 11 vs. 17% +/- 2, respectively; p < 0.001). CONCLUSIONS: Despite in vitro data showing slow, sustained release of paclitaxel from a bioabsorbable polymer, the porcine coronary artery model demonstrated a sequence of medial necrosis, stent malapposition and late neointimal thickening. Since the therapeutic window for paclitaxel may be narrower than currently inferred, thorough preclinical testing coupled with the polymer development process for stents eluting paclitaxel is needed.

A clinically relevant large-animal model for evaluation of tissue-engineered cardiac surgical patch materials.

Extracellular matrix (ECM) scaffolds may be useful as a tissue engineering approach toward myocardial regeneration in the infarcted heart. An appropriate large-animal model for testing the utility of biologically derived ECM in this application is needed. The purpose of this study was to develop such a model for optimal procedural success during and after patch implantation surgery. Myocardial infarction (MI) was created by embolization of the diagonal artery (DA) branch of the left anterior descending coronary artery with collagen suspension. After 4 to 6 weeks, 14 pigs received patch implant (ECM or expanded polytetrafluoroethylene). Six pigs were infarcted in the first DA and seven pigs in the second DA. Electrophysiology study was performed within 3 days before surgery. During surgery, the size and location of the infarct were measured. Infarcted myocardium (1.5-cm diameter) was transmurally excised under partial cardiopulmonary bypass. Patches (3-cm diameter) were sutured to the endomyocardial defect. Four pigs died postoperatively. After 1 month, 10 pigs were euthanized and the locations of patches were examined. Success rate of patch implant in the second DA (85.7%) was higher than the first DA (50%) group. Infarct size in the second DA was smaller than in the first DA (4.6+/-1.2 vs. 10.8+/-2.4 cm(2), P<.05). The second DA was more anteriorly positioned, which enabled easier access from the midsternal thoracotomy. However, the first DA was more laterally located requiring more manipulation of the heart during surgery. Electrophysiology revealed no ventricular tachyarrhythmia in the second DA but 33.3% in the first DA group (P<.05). At necropsy, the endocardial position of the first DA-infarct patches was anteroapical, whereas the second DA-infarct patches were more basolateral and often involved the anterior papillary muscle. The success rate of patch implant was associated with infarction size and location, and may be related to arrhythmic substrate. Experimental MI created by the second DA embolization is a feasible model for investigation of tissue-engineered cardiac patch implantation. This large-animal model is also suitable for study of cell therapy via endocardial catheter-based approaches or open surgical methods.

Interação de fárnmacos e alimentos com a warfarina / Drug and diet interaction with warfarin

A warfarina é uma droga comumente usada para o controle e a prevenção de fenômenos tromboembólicos. O controle de sua ação, entretanto, é notoriamente complexo, em decorrência de diversos fatores extrínsecos e intrínsecos, como idade, ingesta e absorção de vitamina K, e interações farmacológicas. Para pacientes em uso de warfarina, caso haja qualquer modificação na dieta ou na prescrição médica, recomenda-se intensificar os níveis de anticoagulação.

Impact of intraaortic balloon counterpulsation on arterial blood flow in juvenile pigs with heart failure.

OBJECTIVES: To assess the impact of intraaortic balloon counterpulsation on coronary, renal and aortic blood flow in an animal heart failure model. BACKGROUND: Heart failure exacerbations are still often treated with inotropic medications despite a lack of evidence demonstrating any benefit with these drugs. Intraaortic balloon counterpulsation may be considered in certain cases a bridge to recovery. METHODS: Four juvenile pigs underwent pacemaker implantation to induce a rapid-pacing mediated dilated cardiomyopathy. After approximately 4 weeks of rapid pacing, the mean ejection fraction was reduced to 28.8+/-9.5% with a mean systolic blood pressure of 64/44 mmHg. The pigs then underwent surgical placement of flow probes around the circumflex coronary artery, renal artery and infrarenal aorta. A Millar catheter was used to calculate Dp/Dt and a Swan-Ganz to calculate cardiac output. Data were recorded at baseline and after 10 minutes of balloon pumping. The pigs were euthanized post-procedure. RESULTS: Coronary blood flow was increased 9.7% by balloon counterpulsation from 38.3 +/- 12.0 to 42.0+/-11.4 ml/s (p=NS). Renal blood flow was reduced 11.9% by counterpulsation from 130.0+/-88.6 ml/s to 114.5+/-76.6 ml/s (p=NS). Infrarenal aortic blood flow was not changed (mean of 900 ml/s with and without counterpulsation); blood pressure, cardiac output and Dp/Dt were not changed after 10 minutes of pumping. There was little impact observed by changing the position of the balloon closer to or farther away from the apex of the aortic arch. CONCLUSION: Intraaortic balloon counterpulsation did not significantly improve hemodynamics in the pig heart failure model. This may be attributed to the high compliance of the juvenile pig's aorta, thus attenuating the pressure wave generated by counterpulsation. A larger volume balloon would merit investigation for this application.

Pulmonary veins isolation to treat patients with refractory paroxysmal atrial fibrillation: clinical results after a single procedure.

OBJECTIVE: The purpose of this study was to access the clinical outcome of patients submitted to a single procedure of radiofrequency pulmonary veins (PV) isolation to treat refractory paroxysmal atrial fibrillation (AF). METHODS: This study included 49 consecutive patients (36 male; mean age 54+/-10 years old) who had frequent symptomatic paroxysmal AF refractory to at least three antiarrhythmic drugs. We used a circular decapolar catheter for mapping PVs - left atrial connections and a 4-mm distal tip catheter for ablation (30 W and 50 C), aiming to achieve electrical isolation of 3 -4 PVs. RESULTS: Twenty-five patients (51%) did not present any AF recurrence in a mean follow-up of 12+/-5 months. Twenty-four (49%) had at least one recurrence during outcome; twenty (83%) of them within the first month after the procedure and four after two to nine months. After introducing antiarrhythmic drugs 15 (63%) patients were under control, 10 were asymptomatic and five complained of sporadic short duration AF episodes. Nine (37%) patients remained very symptomatic despite the use of antiarrhythmic drugs and were referred to a new procedure of PV isolation. No patient presented major complications. At the end of the follow-up, 35 (71%) patients remained in stable sinus rhythm with no AF recurrences after a single procedure, 50% of them without antiarrhythmic drugs. CONCLUSION: Most patients who present symptomatic paroxysmal AF refractory to antiarrhythmic drugs obtain a good clinical control after a single PV isolation procedure.

Isolamento das veias pulmonares para tratamento da fibrilação atrial paroxística: resultados clínicos após um único procedimento / Pulmonary veins isolation to treat patients with refractory paroxysmal atrial fibrillation: clinical results after a single procedure

OBJETIVO: Avaliar a evolução clínica dos pacientes com fibrilação atrial paroxística submetidos a um único procedimento de isolamento das veias pulmonares. MÉTODOS: Estudados 49 pacientes consecutivos (36 homens; idade média de 53±10 anos) com episódios freqüentes e sintomáticos de fibrilação atrial paroxística de difícil controle clínico. Para mapeamento da junção do átrio esquerdo com as veias pulmonares, foi utilizado o cateter decapolar circular Lasso e para ablação 30 watts e 50ºC, um cateter com ponta deflectível e eletrodo distal de 4mm. RESULTADOS: Em seguimento médio de 12±5 meses, 25 (51 por cento) pacientes não apresentaram recorrência de fibrilação atrial e 24 (49 por cento) apresentaram pelo menos uma recorrência. Em 20 (83 por cento), a 1ª crise ocorreu antes do 1º mês e em 4, após 2 a 9 meses. Após a introdução de drogas antiarrítmicas, 15 (63 por cento) pacientes apresentaram melhora importante, 10 tornaram-se assintomáticos, 5 referiam crises raras, auto-limitadas e de curta duração e 9 (37 por cento) permaneceram com as manifestações clínicas inalteradas, apesar das drogas antiarrítmicas e foram encaminhados à nova intervenção. No final do seguimento, 35 (71 por cento) pacientes permaneciam em ritmo sinusal estável sem recorrência de fibrilação atrial, após um único procedimento, 50 por cento dos quais sem drogas antiarrítmicas. CONCLUSAO: A maioria dos pacientes com fibrilação atrial paroxística sintomática, não controlados com medicação antiarrítmica, obtém controle clínico após um único procedimento de isolamento das veias pulmonares.