The VR leadless pacemaker: Results of an expert panel using the RAND/UCLA method.

BACKGROUND: Leadless pacemakers were developed to reduce complications associated with transvenous pacemaker implantation and long-term follow-up. Existing international guidelines lack detailed instructions on patients suitable for leadless pacemaker implantation. Our aim was to develop a consensus document that provides medical guidance for all health professionals involved in the indication and implantation of Transcatheter Pacing System single-chamber device (VR leadless) pacemakers for patients with atrial fibrillation or in sinus rhythm. METHODS: A panel of experts, including interventional and non-interventional cardiologists, used the Research ANd Development/University of California at Los Angeles (RAND/UCLA) method to rate the appropriateness of leadless pacemaker implantation for 64 scenarios in patients with atrial fibrillation and 192 scenarios in sinus rhythm. The scenarios were rated individually and again during a moderated group session. Median ratings and level of agreement were calculated to classify each scenario as appropriate, inappropriate, or questionable. RESULTS: This consensus statement, based on available literature and the experts' opinions, summarizes recommendations for standardizing and optimizing leadless pacemaker implantation. The limitation for vascular access via the superior vena cava was the most influential variable when indicating leadless pacemaker implantation in both patients with atrial fibrillation and patients in sinus rhythm. CONCLUSIONS: Life expectancy, risk of infection, prosthetic valve, left ventricular ejection fraction (LVEF), limitation for vascular access via the superior vena cava, and mobility and exercise capacity determine who is advised to undergo VR leadless pacemaker implantation. More prospective studies are needed to optimize existing recommendations.

Long-term prognosis of patients with life-threatening ventricular arrhythmias induced by coronary artery spasm.

Aims: Coronary artery spasm (CAS) is associated with ventricular arrhythmias (VA). Much controversy remains regarding the best therapeutic interventions for this specific patient subset. We aimed to evaluate the clinical outcomes of patients with a history of life-threatening VA due to CAS with various medical interventions, as well as the need for ICD placement in the setting of optimal medical therapy. Methods and results: A multicentre European retrospective survey of patients with VA in the setting of CAS was aggregated and relevant clinical and demographic data was analysed. Forty-nine appropriate patients were identified: 43 (87.8%) presented with VF and 6 (12.2%) with rapid VT. ICD implantation was performed in 44 (89.8%). During follow-up [59 (17-117) months], appropriate ICD shocks were documented in 12. In 8/12 (66.6%) no more ICD therapies were recorded after optimizing calcium channel blocker (CCB) therapy. SCD occurred in one patient without ICD. Treatment with beta-blockers was predictive of appropriate device discharge. Conversely, non-dihydropyridine CCB therapy was significantly protective against VAs. Conclusion: Patients with life-threatening VAs secondary to CAS are at particularly high-risk for recurrence, especially when insufficient medical therapy is administered. Non-dihydropyridine CCBs are capable of suppressing episodes, whereas beta-blocker treatment is predictive of VAs. Ultimately, in spite of medical intervention, some patients exhibited arrhythmogenic events in the long-term, suggesting that ICD implantation may still be indicated for all.

Etiology and Programming Effects on Shock Efficacy in ICD Recipients.

BACKGROUND: We sought to assess the efficacy of high-energy shocks to restore rhythm and predictors of success in patients with sustained ventricular arrhythmias and implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: Data from 162 patients included in the UMBRELLA study that experienced one or more episodes of ventricular tachycardia (VT) for which ICD shocks of at least 30 Joules were delivered (appropriate high-energy shocks) were analyzed. In total, 456 ventricular arrhythmia episodes were registered. Forty four episodes (9.6%) from 39 patients (24%) had at least one ineffective high-energy shock delivered. Hypertrophic cardiomyopathy was more frequent among patients with unsuccessful shocks (10.3% vs 2.4%). Patients with ineffective shocks had higher proportion of sustained monomorphic ventricular arrhythmias (86.4%; the other 13.6% were sustained polymorphic and ventricular fibrillation [VF]) compared with patients with all their shocks effective (62.9%, P = 0.02). No statistical differences were found between groups in time from detection to the high-energy shock delivery, in tachycardia cycle length, or in antitachycardia pacing, but patients with ineffective high-energy shocks had higher proportion of previously ineffective low-energy shock (9.1% vs 0.5%, P = 0.01). CONCLUSION: We found a substantial rate of ineffective high-energy shocks for the treatment of VT or VF in patients with ICD. High-energy shock efficacy seems to be reduced by hypertrophic cardiomyopathy and by the administration of previous low-energy shocks.

Characterization of lethal dengue virus type 4 (DENV-4) TVP-376 infection in mice lacking both IFN-α/ß and IFN-γ receptors (AG129) and comparison with the DENV-2 AG129 mouse model.

Dengue is a mosquito-borne disease caused by four related but distinct dengue viruses, DENV-1 to DENV-4. Dengue is endemic in most tropical countries, and over a third of the world's population is at risk of being infected. Although the global burden is high, no vaccine or antiviral is licensed to combat this disease. An obstacle complicating dengue research is the lack of animal challenge models that mimic human disease. Advances in immunocompromised murine infection models resulted in development of lethal DENV-2, DENV-3 and DENV-4 models in AG129 mice, which are deficient in both the IFN-α/ß receptor (IFN-α/ßR) and the IFN-γ receptor (IFN-γR). These models mimic features of dengue disease in humans. Here, we characterized lethal infection of AG129 mice by DENV-4 strain TVP-376 and found that AG129 mice developed clinical signs of illness and high viral loads in multiple tissues and succumbed 5 days after infection. Moreover, the splenic and hepatic histopathology of TVP-376-infected mice demonstrated the presence of cell activation and destruction of tissue architecture. Furthermore, infected mice had heightened levels of circulating cytokines. Comparison of the virulence phenotypes of DENV-4 strain TVP-376 and DENV-2 strain D2S10 revealed that TVP-376-induced mortality occurred in the absence of both IFN-α/ßR and IFN-γR signalling, but not with intact signalling from the IFN-γR, whereas D2S10 required the absence of IFN-α/ßR signalling only, indicating that it is more virulent than TVP-376. In conclusion, TVP-376 is lethal in AG129 mice, and this model provides a useful platform to investigate vaccine candidates and antivirals against DENV-4.

Clinical impact of remote heart failure management using the multiparameter ICD HeartLogic alert.

INTRODUCTION AND OBJECTIVES: The multiparametric implantable cardioverter-defibrillator HeartLogic index has proven to be a sensitive and timely predictor of impending heart failure (HF) decompensation. We evaluated the impact of a standardized follow-up protocol implemented by nursing staff and based on remote management of alerts. METHODS: The algorithm was activated in HF patients at 19 Spanish centers. Transmitted data were analyzed remotely, and patients were contacted by telephone if alerts were issued. Clinical actions were implemented remotely or through outpatient visits. The primary endpoint consisted of HF hospitalizations or death. Secondary endpoints were HF outpatient visits. We compared the 12-month periods before and after the adoption of the protocol. RESULTS: We analyzed 392 patients (aged 69±10 years, 76% male, 50% ischemic cardiomyopathy) with implantable cardioverter-defibrillators (20%) or cardiac resynchronization therapy defibrillators (80%). The primary endpoint occurred 151 times in 86 (22%) patients during the 12 months before the adoption of the protocol, and 69 times in 45 (11%) patients (P<.001) during the 12 months after its adoption. The mean number of hospitalizations per patient was 0.39±0.89 pre- and 0.18±0.57 postadoption (P<.001). There were 185 outpatient visits for HF in 96 (24%) patients before adoption and 64 in 48 (12%) patients after adoption (P<.001). The mean number of visits per patient was 0.47±1.11 pre- and 0.16±0.51 postadoption (P<.001). CONCLUSIONS: A standardized follow-up protocol based on remote management of HeartLogic alerts enabled effective remote management of HF patients. After its adoption, we observed a significant reduction in HF hospitalizations and outpatient visits.

Remote heart failure management using the HeartLogic algorithm. RE-HEART registry.

INTRODUCTION AND OBJECTIVES: HeartLogic is a multiparametric algorithm incorporated into implantable cardioverter-defibrillators (ICD). The associated alerts predict impending heart failure (HF) decompensations. Our objective was to analyze the association between alerts and clinical events and to describe the implementation of a protocol for remote management in a multicenter registry. METHODS: We evaluated study phase 1 (the investigators were blinded to the alert state) and phases 2 and 3 (after HeartLogic activation, managed as per local practice and with a standardized protocol, respectively). RESULTS: We included 288 patients from 15 centers. In phase 1, the median observation period was 10 months and there were 73 alerts (0.72 alerts/patient-y), with 8 hospitalizations and 2 emergency room admissions for HF (0.10 events/patient-y). There were no HF hospitalizations outside the alert period. In the active phases, the median follow-up was 16 (95%CI, 15-22) months and there were 277 alerts (0.89 alerts/patient-y); 33 were associated with HF hospitalizations or HF death (n=6), 46 with minor decompensations, and 78 with other events. The unexplained alert rate was 0.39 alerts/patient-y. Outside the alert state, there was only 1 HF hospitalization and 1 minor HF decompensation. Most alerts (82% in phase 2 and 81% in phase 3; P=.861) were remotely managed. The median NT-proBNP value was higher within than outside the alert state (7378 vs 1210 pg/mL; P <.001). CONCLUSIONS: The HeartLogic index was frequently associated with HF-related events and other clinically relevant situations, with a low rate of unexplained events. A standardized protocol allowed alerts to be safely and remotely detected and appropriate action to be taken on them.

Validation of multiparametric approaches for the prediction of sudden cardiac death in patients with Brugada syndrome and electrophysiological study.

INTRODUCTION AND OBJECTIVES: Multiparametric scores have been designed for better risk stratification in Brugada syndrome (BrS). We aimed to validate 3 multiparametric approaches (the Delise score, Sieira score and the Shanghai BrS Score) in a cohort with Brugada syndrome and electrophysiological study (EPS). METHODS: We included patients diagnosed with BrS and previous EPS between 1998 and 2019 in 23 hospitals. C-statistic analysis and Cox proportional hazard regression models were used. RESULTS: A total of 831 patients were included (mean age, 42.8±13.1; 623 [75%] men; 386 [46.5%] had a type 1 electrocardiogram (ECG) pattern, 677 [81.5%] were asymptomatic, and 319 [38.4%] had an implantable cardioverter-defibrillator). During a follow-up of 10.2±4.7 years, 47 (5.7%) experienced a cardiovascular event. In the global cohort, a type 1 ECG and syncope were predictive of arrhythmic events. All risk scores were significantly associated with events. The discriminatory abilities of the 3 scores were modest (particularly when these scores were evaluated in asymptomatic patients). Evaluation of the Delise and Sieira scores with different numbers of extra stimuli (1 or 2 vs 3) did not substantially improve the event prediction c-index. CONCLUSIONS: In BrS, classic risk factors such as ECG pattern and previous syncope predict arrhythmic events. The predictive capabilities of the EPS are affected by the number of extra stimuli required to induce ventricular arrhythmias. Scores combining clinical risk factors with EPS help to identify the populations at highest risk, although their predictive abilities remain modest in the general BrS population and in asymptomatic patients.

Long-term prognosis of women with Brugada syndrome and electrophysiological study.

BACKGROUND: A male predominance in Brugada syndrome (BrS) has been widely reported, but scarce information on female patients with BrS is available. OBJECTIVE: The purpose of this study was to investigate the clinical characteristics and long-term prognosis of women with BrS. METHODS: A multicenter retrospective study of patients diagnosed with BrS and previous electrophysiological study (EPS) was performed. RESULTS: Among 770 patients, 177 (23%) were female. At presentation, 150 (84.7%) were asymptomatic. Females presented less frequently with a type 1 electrocardiographic pattern (30.5% vs 55.0%; P <.001), had a higher rate of family history of sudden cardiac death (49.7% vs 29.8%; P <.001), and had less sustained ventricular arrhythmias (VAs) on EPS (8.5% vs 15.1%; P = .009). Genetic testing was performed in 79 females (45% of the sample) and was positive in 34 (19%). An implantable cardioverter-defibrillator was inserted in 48 females (27.1%). During mean (± SD) follow-up of 122.17 ± 57.28 months, 5 females (2.8%) experienced a cardiovascular event compared to 42 males (7.1%; P = .04). On multivariable analysis, a positive genetic test (18.71; 95% confidence interval [CI] 1.82-192.53; P = .01) and atrial fibrillation (odds ratio 21.12; 95% CI 1.27-350.85; P = .03) were predictive of arrhythmic events, whereas VAs on EPS (neither with 1 or 2 extrastimuli nor 3 extrastimuli) were not. CONCLUSION: Women with BrS represent a minor fraction among patients with BrS, and although their rate of events is low, they do not constitute a risk-free group. Neither clinical risk factors nor EPS predicts future arrhythmic events. Only atrial fibrillation and positive genetic test were identified as risk factors for future arrhythmic events.

Conjugation to nickel-chelating nanolipoprotein particles increases the potency and efficacy of subunit vaccines to prevent West Nile encephalitis.

Subunit antigens are attractive candidates for vaccine development, as they are safe, cost-effective, and rapidly produced. Nevertheless, subunit antigens often need to be adjuvanted and/or formulated to produce products with acceptable potency and efficacy. Here, we describe a simple method for improving the potency and efficacy of a recombinant subunit antigen by its immobilization on nickel-chelating nanolipoprotein particles (NiNLPs). NiNLPs are membrane mimetic nanoparticles that provide a delivery and presentation platform amenable to binding any recombinant subunit immunogens featuring a polyhistidine tag. A His-tagged, soluble truncated form of the West Nile virus (WNV) envelope protein (trE-His) was immobilized on NiNLPs. Single inoculations of the NiNLP-trE-His produced superior anti-WNV immune responses and provided significantly improved protection against a live WNV challenge compared to mice inoculated with trE-His alone. These results have broad implications in vaccine development and optimization, as NiNLP technology is well-suited to many types of vaccines, providing a universal platform for enhancing the potency and efficacy of recombinant subunit immunogens.

Antitachycardia pacing for shock prevention in patients with hypertrophic cardiomyopathy and ventricular tachycardia.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) carries an increased risk of sudden death due to ventricular arrhythmias (VAs). The implantable cardioverter-defibrillator (ICD) is a well-established therapy for treatment of VA. Monomorphic ventricular tachycardias (MVTs) are frequent in HCM patients and suitable for antitachycardia pacing (ATP) termination. OBJECTIVE: The purpose of this study was to describe ventricular tachycardia (VT) characteristics in a population of HCM patients with ICD and to study the effectiveness and safety of ATP for MVT. METHODS: Data were obtained from the multicenter prospective observational UMBRELLA trial, which included all patients with HCM and ICD followed by the CareLink Monitoring System. All episodes of VA were collected and analyzed. ATP effectiveness and safety were described, and factors related to ATP effectiveness were studied with generalized estimating equation (GEE) models. RESULTS: Among 251 patients followed for 47 months, 67 (26.7%) were implanted as secondary prevention. Fifty-six patients presented 326 episodes of VA (286 [87%] MVT). Mean cycle length was 312 ± 64 ms. Among 264 MVTs that received ICD therapy, 202 (76.5%) were ATP terminated. The first ATP burst was effective in 169 episodes (68.4%), and overall effectiveness of the first or second ATP burst was 73.8%. Multivariate GEE-adjusted analysis showed 2 variables related to ATP effectiveness: programming fast VT zone On vs Off (odds ratio [OR] 2.4; 95% confidence interval [CI] 1.5-5.2; P = .03) and programming ≥2 ATP bursts vs 1 burst only (OR 1.6; 95% CI 1.2-3.4; P = .04; and OR 2.9; 95% CI 1.8-6.3; P = .02; respectively). CONCLUSION: MVT is the predominant VA in HCM patients with ICD. ATP is highly effective in terminating the majority of MVTs, and its proved effectiveness should guide device selection and programming in order to avoid unnecessary high-energy shocks.

Usefulness of ventricular dyssynchrony measured using M-mode echocardiography to predict response to resynchronization therapy.

There are discordant data about the utility of septal-to-posterior wall motion delay (SPWMD) assessed using M-mode echocardiography to predict an improvement with cardiac resynchronization therapy (CRT). Baseline SPWMD was measured using M-mode in a parasternal short-axis view in a series of 67 patients undergoing CRT and followed up after 6 months. Heart failure was caused by coronary artery disease in 27 patients. Clinical responders were patients who were alive, had not undergone heart transplantation, and also increased the distance walked in 6 minutes by >10%. Baseline SPWMDs were mean 155 +/- 113 ms and median 135. Thirty-four patients (51%) had an SPWMD >130 ms. At 6-month follow-up, there were 17 nonresponders. At baseline, there were no significant differences between patients with SPWMD >130 or <130 ms in age, drug therapy, permanent atrial fibrillation, New York Heart Association functional class, underlying cause of cardiomyopathy, QRS duration, left ventricular (LV) ejection fraction, LV dimensions, or neurohormonal activation (norepinephrine and atrial and brain natriuretic peptide). At 6-month follow-up, baseline SPWMD was not associated with clinical response, New York Heart Association functional class, distance walked in 6 minutes, LV reverse remodeling, or neurohormonal activation. SPWMD >130 ms was also not a predictor. In conclusion, SPWMD is not a good predictor of response to CRT.

Optimizing the programation of cardiac resynchronization therapy devices in patients with heart failure and left bundle branch block.

This study was conducted to investigate the clinical impact of cardiac resynchronization device optimization. A series of 100 consecutive patients received cardiac resynchronization therapy. In the first 49 patients, an empirical atrioventricular delay of 120 ms was set, with simultaneous biventricular stimulation (interventricular [VV] interval=0 ms). In the next 51 patients, systematic atrioventricular optimization was performed. VV optimization was also performed, selecting 1 VV delay: right or left ventricular preactivation (+30 or -30 ms) or simultaneous (VV interval=0 ms), according to the best synchrony obtained by tissue Doppler-derived wall displacement. At follow-up, patients who were alive without cardiac transplantation and showed improvement of >or=10% in the distance walked in the 6-minute walking test were considered responders. There were no differences between the 2 groups at baseline. Left ventricular ejection fraction improved in the 2 groups, but left ventricular cardiac output improved only in the optimized group. At 6 months, patients with optimized devices walked slightly further in the 6-minute walking test (497+/-167 vs 393+/-123 m, p<0.01), with no differences in New York Heart Association functional class or quality of life compared with nonoptimized patients. Overall, the number of nonresponders were similar in the 2 groups (27% vs 23%, p=NS). In conclusion, the echocardiographic optimization of cardiac resynchronization devices provided a slight incremental clinical benefit at midterm follow-up. Simple and rapid methods to routinely optimize the devices are warranted.

Electrocardiographic optimization of interventricular delay in cardiac resynchronization therapy: a simple method to optimize the device.

INTRODUCTION: Echocardiography is widely used to optimize CRT programming, but it is time-consuming. This study aimed to correlate the optimal interventricular pacing (V-V) interval obtained by echo with the optimal V-V interval obtained by a simpler method based on the surface ECG. METHODS AND RESULTS: Three V-V intervals were tested: LV preactivation at -30 ms, simultaneous biventricular pacing (0 ms), and RV preactivation at +30 ms. The one that achieved the best LV synchrony was chosen as the optimal V-V. This result was then compared with two different ECG measurements. The first ECG method considered the best V-V to be that which achieved the narrowest QRS. The second V-V method consisted in measuring the interval from the pacing spike to the beginning of the fast deflexion of the QRS complex in leads V1, V2, first pacing from the LV (T1), and after from the RV (T2). The T2-T1 interval was considered as a surrogate measurement of interventricular delay and defined as the best V-V. A cohort of 31 consecutive patients treated with CRT was studied. Optimal V-V interval obtained by echo was -30 ms in 25 patients (80%), +30 ms in three patients (10%), and 0 ms in the remaining three patients (10%). Echo results had 32% coincidence with the first ECG method (r = 0.2, P = NS) and 83% coincidence with the second ECG method (r = 0.81 P< 0.001). CONCLUSIONS: The time difference in the fast ventricular depolarization observed between RV and LV stimulation in the surface ECG shows a good correlation with the V-V optimization chosen according to echo.

Relation of response to cardiac resynchronization therapy to left ventricular reverse remodeling.

Cardiac resynchronization therapy (CRT) reverses left ventricular (LV) remodeling in patients with congestive heart failure. However, the mechanisms leading to the clinical response to CRT remain unclear. The aim of this study was to analyze whether patients who improve clinically have greater LV reverse remodeling than nonresponders after a 12-month follow-up period. The sample comprised 64 consecutive patients with heart failure, complete left bundle branch block, and LV ejection fractions (EFs) < or =35% who were treated with CRT. Doppler echocardiographic scans were taken just before and immediately after the implantation of the pacemakers and at 6- and 12-month follow-up examinations. LV diameters, volumes, and EFs were compared. Responders were defined as those patients who were alive without cardiac transplantation and with > or =10% improvement in the 6-minute walking test after 1 year of follow-up. There were no clinical differences at baseline between responders and nonresponders. At 6- and 12-month follow-up, LV dimensions decreased significantly in responders but did not change in nonresponders. Furthermore, LVEFs improved only in responders. In conclusion, patients who clinically respond to CRT have greater LV reverse remodeling than nonresponders after 6 and 12 months of follow-up. The effect of CRT on LV remodeling may explain, at least in part, the clinical benefit of this therapy.

Comparative Evaluation of Four Risk Scores for Predicting Mortality in Patients With Implantable Cardioverter-defibrillator for Primary Prevention.

INTRODUCTION AND OBJECTIVES: Several clinical risk scores have been developed to identify patients at high risk of all-cause mortality despite implantation of an implantable cardioverter-defibrillator. We aimed to examine and compare the predictive capacity of 4 simple scoring systems (MADIT-II, FADES, PACE and SHOCKED) for predicting mortality after defibrillator implantation for primary prevention of sudden cardiac death in a Mediterranean country. METHODS: A multicenter retrospective study was performed in 15 Spanish hospitals. Consecutive patients referred for defibrillator implantation between January 2010 and December 2011 were included. RESULTS: A total of 916 patients with ischemic and nonischemic heart disease were included (mean age, 62 ± 11 years, 81.4% male). Over 33.4 ± 12.9 months, 113 (12.3%) patients died (cardiovascular origin in 86 [9.4%] patients). At 12, 24, 36, and 48 months, mortality rates were 4.5%, 7.6%, 10.8%, and 12.3% respectively. All the risk scores showed a stepwise increase in the risk of death throughout the scoring system of each of the scores and all 4 scores identified patients at greater risk of mortality. The scores were significantly associated with all-cause mortality throughout the follow-up period. PACE displayed the lowest c-index value regardless of whether the population had heart disease of ischemic (c-statistic = 0.61) or nonischemic origin (c-statistic = 0.61), whereas MADIT-II (c-statistic = 0.67 and 0.65 in ischemic and nonischemic cardiomyopathy, respectively), SHOCKED (c-statistic = 0.68 and 0.66, respectively), and FADES (c-statistic = 0.66 and 0.60) provided similar c-statistic values (P ≥ .09). CONCLUSIONS: In this nontrial-based cohort of Mediterranean patients, the 4 evaluated risk scores showed a significant stepwise increase in the risk of death. Among the currently available risk scores, MADIT-II, FADES, and SHOCKED provide slightly better performance than PACE.

Primary Prevention of Sudden Death in Patients With Valvular Cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Few data exist on the outcomes of valvular cardiomyopathy patients referred for defibrillator implantation for primary prevention. The aim of the present study was to describe the outcomes of this cardiomyopathy subgroup. METHODS: This multicenter retrospective study included consecutive patients referred for defibrillator implantation to 15 Spanish centers in 2010 and 2011, and to 3 centers after 1 January 2008. RESULTS: Of 1174 patients, 73 (6.2%) had valvular cardiomyopathy. These patients had worse functional class, wider QRS, and a history of atrial fibrillation vs patients with ischemic (n=659; 56.1%) or dilated (n=442; 37.6%) cardiomyopathy. During a follow-up of 38.1 ± 21.3 months, 197 patients (16.7%) died, without significant differences among the groups (19.2% in the valvular cardiomyopathy group, 15.8% in the ischemic cardiomyopathy group, and 17.9% in the dilated cardiomyopathy group; P=.2); 136 died of cardiovascular causes (11.6%), without significant differences among the groups (12.3%, 10.5%, and 13.1%, respectively; P=.1). Although there were no differences in the proportion of appropriate defibrillator interventions (13.7%, 17.9%, and 18.8%; P=.4), there was a difference in inappropriate interventions (8.2%, 7.1%, and 12.0%, respectively; P=.03). CONCLUSIONS: All-cause and cardiovascular mortality in patients with valvular cardiomyopathy were similar to those in other patients referred for defibrillator implantation. They also had similar rates of appropriate interventions. These data suggest that defibrillator implantation in this patient group confers a similar benefit to that obtained by patients with ischemic or dilated cardiomyopathy.

Predictors of lack of response to resynchronization therapy.

About 30% of patients treated with cardiac resynchronization therapy (CRT) do not respond to treatment. The aim of this study was to identify clinical predictors of lack of improvement in patients receiving CRT. From 197 consecutive patients scheduled to receive CRT, 143 fulfilled the inclusion criteria. Mean age was 68 +/- 7 years and 79% were men. Heart failure was due to ischemic heart disease in 49 patients (34%). Mean QRS duration was 165 +/- 26 ms, and left ventricular ejection fraction was 27 +/- 7%. Nonresponder patients were defined as those who died of heart failure, underwent heart transplantation, or did not increase the distance walked in 6 minutes >10%. At 6-month follow-up, there were 28 nonresponders (20%). Among nonresponders, 2 patients received a heart transplantation and 9 patients died of heart failure. In logistic regression analysis, independent predictors of lack of response to CRT were ischemic heart disease (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.2 to 7; p = 0.023), severe mitral regurgitation (OR 3.5, 95% CI 1.3 to 9; p = 0.014), and left ventricular end-diastolic diameter > or =75 mm (OR 3.1, 95% CI 1.1 to 8; p = 0.026). Patients with these 3 predictors had a probability response of 27%.

[An overview of Telehealth experiences in Peru]. / Una visión panorámica de las experiencias de Telesalud en Perú.

This article presents the main experiences of telehealth conducted in Peru between 2002 and 2010. It analyzes information from published literature and unpublished documents about experiences of public and private Telehealth. From this information, 26 experts were consulted about the characteristics of the identified Telehealth experiences. A database of 38 experiences, which are described and analyzed in this publication was produced. Reflections and recommendations are presented to expand the use of Telehealth in Peru.

A Dengue Virus Type 4 Model of Disseminated Lethal Infection in AG129 Mice.

Dengue is a mosquito-borne disease of global public health significance that is caused by four serologically and genetically related viruses (DENV-1 to DENV-4). Most human DENV infections are asymptomatic, but clinical cases can range in severity from a relatively mild self-limiting illness to a severe life-threatening disease. Infection with one serotype of DENV results in life-long homotypic immunity but only short term heterotypic protection. There are no licensed vaccines or antivirals for dengue due in part to difficulty in developing small animal models that mimic the systemic disease seen in humans. Consequently, an important advance was the description of models of DENV-2 infection in AG129 mice (deficient in interferon alpha/beta and gamma receptor signaling) that resemble human disease. However, the need for well characterized models of disease due to DENV-1, -3, and -4 still remains. Here we describe a new AG129 mouse model utilizing a non-mouse-adapted Thai human DENV-4 strain 703-4. Following intraperitoneal challenge, animals experience a rapidly progressive lethal infection without developing neurologic clinical signs of disease. High virus titers are seen in multiple visceral tissues including the liver, spleen and large intestine, and the infected animals develop vascular leakage and thrombocytopenia, hallmarks of human dengue. Taken together, our studies demonstrate that this model is an important addition to the field of dengue research particularly in understanding similarities and differences in the pathologic basis of the disease caused by different DENV serotypes and in determining comparative efficacy of putative vaccines and antivirals.

[Predictors of lack of clinical improvement at mid-term follow-up with cardiac resynchronization therapy]. / Predictores de ausencia de mejoría clínica a medio plazo con la terapia de resincronización cardíaca.

INTRODUCTION: About 30% of all patients do not respond to cardiac resynchronization therapy for heart failure. The objective of the study was to analyze the variables that may predict the lack of response. PATIENTS AND METHOD: We analyzed the results in a series of 63 patients who received cardiac resynchronization with a biventricular device. Clinical and left ventricular function parameters were evaluated at the beginning of the study and at 6 months. Responders were defined as those who were alive, had not received a heart transplant, and who achieved more than a 10% increase in distance in the 6-minute walking test. RESULTS: Mean age was 68.3 (8) years, 51 patients (81%) were men, and NYHA functional class was III-IV in 79.4%. Mean left ventricular ejection fraction was 22.4% (6)%, QRS width was 177 (25) ms, and 77.8% were in sinus rhythm. Almost half (46%, n=29) had ischemic heart disease. At 6-month follow-up, 69.8% of the patients were responders. Ischemic heart disease, sustained monomorphic ventricular tachycardia and a degree of mitral regurgitation >II/IV before implantation were associated with lack of response. No association was found for any of the other baseline variables. Logistic regression analysis identified all three of the aforementioned variables as independent predictors of lack of response: ischemic heart disease OR=4.8, 95% CI, 1.2-18.3, P=.023; ventricular tachycardia OR=8.7, 95% CI, 1.8-41.3, P=.007; and mitral regurgitation OR=8.03, 95% CI, 1.7-37.1, P=.008. CONCLUSION: The likelihood of responding to resynchronization therapy is lower in patients with ischemic heart disease, significant mitral regurgitation, or sustained monomorphic ventricular tachycardia.