Hybrid oncocytic/chromophobe renal cell tumor: An integrated genetic and epigenetic characterization of a case.

INTRODUCTION: Hybrid oncocytic/chromophobe tumor (HOCT) is a renal cell neoplasm displaying overlapping cellular and architectural features of both renal oncocytoma (RO) and chromophobe renal cell carcinoma (chRCC). It has been described in the context of oncocytosis, Birt-Hogg-Dubé syndrome, and also sporadically. Thus far, HOCT immunohischemical profile and cytogenetic alterations have been reported, but not epigenetic alterations. Herein, we characterize a HOCT case, including microRNA expression, comparing it to sporadic RO and chRCC. METHODS: An HOCT was entirely submitted. Representative paraffin blocks were selected for histochemical, immunohistochemical and FISH analyses. MicroRNAs were extracted from the two components separately and selected microRNA expression was performed. RESULTS: This 4 cm HOCT, from a 69 year-old female, was composed mainly by oncocytic cells with an insular distribution (RO-like) and areas of larger clarified cells (chRCC-like). The two areas displayed different features: RO-like areas showed negative colloidal iron staining, multifocal CD15, negative CK7, focal multiple tetrasomies, and higher miR21 expression; chRCC-like areas showed colloidal iron diffuse staining with moderate intensity, focal CD15 and CK7, no numeric chromosomic alterations, and higher miR141 and miR200b expression. CONCLUSION: microRNA expression in the two HOCT components is similar to its sporadic tumors counterparts. Morphologic, immunohistochemical, cytogenetic and epigenetic data on this case suggest either two independent pathogenic pathways or an early pathogenic divergence for RO-like and chRCC-like components of HOCT.

Left ventricular pacing threshold and outcome in MADIT-CRT.

INTRODUCTION: High left ventricular (LV) pacing threshold (PT) may in some cases indicate the presence of scarred myocardium, a predictor of poor outcome in cardiac resynchronization therapy (CRT) treated patients. We hypothesized that intraoperative LVPT can be used to determine echocardiographic and clinical responses to CRT. METHODS AND RESULTS: The study comprised 975 patients enrolled in the CRT-D arm of the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). Multivariate regression analysis was performed to evaluate the relationship between LVPT and percent reduction in LV end-systolic volume (ESV) and left atrial volume (LAV) 1 year after CRT. Cox proportional hazards analysis was used to evaluate the relationship between LVPT and heart failure (HF) events or death (primary endpoint) and all-cause death (secondary endpoint). An increasing LVPT was inversely related to percent reduction in both LVESV (P = 0.02) and LAV (P<0.01). Patients with LVPT in the highest quartile (>1.8 V) were less likely to achieve reverse LV remodeling (≥15% LVESV reduction from baseline) than those with LVPT in the lower quartiles (hazard ratios [HR] OR 0.56, P = 0.02). Mean percent reduction in LAV and LVESV was also significantly greater among those with lowest quartile LVPT. Multivariate analysis showed borderline significant 13% (P = 0.06) and significant 22% (P = 0.03) increase in the risk of HF/death and death alone, respectively, per 1 volt increase in LVPT. CONCLUSION: High intraoperative LVPT is associated with significantly lower echocardiographic and clinical response to CRT-D.

Cardiac-resynchronization therapy in heart failure with narrow QRS complexes.

BACKGROUND: Indications for cardiac-resynchronization therapy (CRT) in patients with heart failure include a prolonged QRS interval (> or =120 msec), in addition to other functional criteria. Some patients with narrow QRS complexes have echocardiographic evidence of left ventricular mechanical dyssynchrony and may also benefit from CRT. METHODS: We enrolled 172 patients who had a standard indication for an implantable cardioverter-defibrillator. Patients received the CRT device and were randomly assigned to the CRT group or to a control group (no CRT) for 6 months. The primary end point was the proportion of patients with an increase in peak oxygen consumption of at least 1.0 ml per kilogram of body weight per minute during cardiopulmonary exercise testing at 6 months. RESULTS: At 6 months, the CRT group and the control group did not differ significantly in the proportion of patients with the primary end point (46% and 41%, respectively). In a prespecified subgroup with a QRS interval of 120 msec or more, the peak oxygen consumption increased in the CRT group (P=0.02), but it was unchanged in a subgroup with a QRS interval of less than 120 msec (P=0.45). There were 24 heart-failure events requiring intravenous therapy in 14 patients in the CRT group (16.1%) and 41 events in 19 patients in the control group (22.3%), but the difference was not significant. CONCLUSIONS: CRT did not improve peak oxygen consumption in patients with moderate-to-severe heart failure, providing evidence that patients with heart failure and narrow QRS intervals may not benefit from CRT. (ClinicalTrials.gov number, NCT00132977 [ClinicalTrials.gov].).

Characteristics of heart failure patients associated with good and poor response to cardiac resynchronization therapy: a PROSPECT (Predictors of Response to CRT) sub-analysis.

AIMS: Predictors of Response to Cardiac Resynchronization Therapy (CRT) (PROSPECT) was the first large-scale, multicentre clinical trial that evaluated the ability of several echocardiographic measures of mechanical dyssynchrony to predict response to CRT. Since response to CRT may be defined as a spectrum and likely influenced by many factors, this sub-analysis aimed to investigate the relationship between baseline characteristics and measures of response to CRT. METHODS AND RESULTS: A total of 286 patients were grouped according to relative reduction in left ventricular end-systolic volume (LVESV) after 6 months of CRT: super-responders (reduction in LVESV > or =30%), responders (reduction in LVESV 15-29%), non-responders (reduction in LVESV 0-14%), and negative responders (increase in LVESV). In addition, three subgroups were formed according to clinical and/or echocardiographic response: +/+ responders (clinical improvement and a reduction in LVESV > or =15%), +/- responders (clinical improvement or a reduction in LVESV > or =15%), and -/- responders (no clinical improvement and no reduction in LVESV > or =15%). Differences in clinical and echocardiographic baseline characteristics between these subgroups were analysed. Super-responders were more frequently females, had non-ischaemic heart failure (HF), and had a wider QRS complex and more extensive mechanical dyssynchrony at baseline. Conversely, negative responders were more frequently in New York Heart Association class IV and had a history of ventricular tachycardia (VT). Combined positive responders after CRT (+/+ responders) had more non-ischaemic aetiology, more extensive mechanical dyssynchrony at baseline, and no history of VT. CONCLUSION: Sub-analysis of data from PROSPECT showed that gender, aetiology of HF, QRS duration, severity of HF, a history of VT, and the presence of baseline mechanical dyssynchrony influence clinical and/or LV reverse remodelling after CRT. Although integration of information about these characteristics would improve patient selection and counselling for CRT, further randomized controlled trials are necessary prior to changing the current guidelines regarding patient selection for CRT.

Correction to: Abstracts : 29th European Congress of Pathology.

In Poster Sessions, the first-author name was missing from the authorship group originally listed for Abstract PS-01-004 (page S52), entitled "Clinicopathological features of microinvasive breast cancer". The correct authorship group is shown above.

Correction to: Abstracts : 29th European Congress of Pathology.

In Poster Sessions, the first-author name was missing from the authorship group originally listed for Abstract PS-13-001 (page S176), entitled "Gastric carcinoma with lymphoid stroma: Analysis of microsatellite instability and Epstein-Barr virus status". The correct authorship group is shown above.

Conversion of atrial fibrillation to sinus rhythm during treatment with intravenous esmolol or diltiazem: a prospective, randomized comparison.

Prior studies have suggested that intravenous diltiazem reduces the probability of spontaneous conversion of atrial fibrillation (AF) to sinus rhythm in the electrophysiology laboratory and in patients with postoperative AF. Whether diltiazem exerts the same effect in patients presenting to the emergency department (ED) with spontaneous AF is unclear. Fifty patients presenting to the ED with new-onset or paroxysmal AF and a rapid ventricular rate (>100 beats per minute) were randomly assigned to receive intravenous diltiazem or esmolol during the first 24 hours of presentation. Conversion to sinus rhythm occurred in 10 patients (42%) in the diltiazem group compared with 10 patients (39%) in the esmolol group (P = 1.0). Diltiazem does not decrease the likelihood of spontaneous conversion of AF to sinus rhythm in the ED setting.

Defibrillation testing of the implantable cardioverter defibrillator: when, how, and by whom?

The implantable cardioverter-defibrillator (ICD) has become an integral part of treatment for a variety of patients with symptomatic, or at risk for, ventricular tachyarrhythmias. The ICD's effectiveness is attributed to its ability to promptly detect and terminate ventricular tachycardia (VT) and fibrillation (VF). The clinical trials that established the positive role of ICD therapy were based on patients who underwent some form of defibrillation testing at the time of implantation. Therefore, since its advent, intraoperative defibrillation testing of the ICD to assure reliable detection and termination of VT/VF has been a standard practice. But because of advances in defibrillator and lead technology, which now facilitates successful device implantation (i.e., low defibrillation energy requirement to allow for an adequate programmed safety margin) in the majority of patients, the necessity of defibrillation testing has been called into attention. Despite substantial progress, it is not altogether clear whether a wholesale abandonment of intraoperative ICD testing is appropriate at this point. We review pertinent data regarding pros and cons of ICD testing and offer a suggestion as to when, how, and who should test ICDs.

Clinical predictors and timing of New York Heart Association class improvement with cardiac resynchronization therapy in patients with advanced chronic heart failure: results from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE-ICD) trials.

BACKGROUND: Based on current patient selection criteria, a significant proportion of recipients of cardiac resynchronization therapy (CRT) do not respond to treatment. The purpose of this analysis is to identify predictors and characterize the timing of response to CRT in patients with advanced heart failure. METHODS: Patients randomized to receive CRT in the MIRACLE and MIRACLE-ICD trials, designed to assess the benefit of CRT compared with standard medical therapy in patients with advanced heart failure, left ventricular ejection fraction <0.35, and QRS > or =130 milliseconds, were included for this analysis. Patients with an improvement of > or =1 New York Heart Association (NYHA) class from baseline to the 6-month follow-up were considered responders and those who had no change or worse NYHA class or died were classified as nonresponders. Responders were subdivided into early (within 1-3 months) and late (6 months). RESULTS: One hundred forty-three (64%) of 224 and 190 (61%) of 313 patients in the MIRACLE and MIRACLE-ICD trials, respectively, responded to therapy, with 81 (57%) of 143 and 100 (53%) of 190 responding early. Several but differing factors predicted CRT response and timing in the two trials with a high sensitivity (89%-90%) but, owing to a low specificity (31%-49%), a modest predictive accuracy (66%-75%). CONCLUSIONS: Based on improvement of > or =1 NYHA class, less than two thirds of patients enrolled in the MIRACLE or MIRACLE-ICD trials responded to CRT, with just more than half responding within the first month. Several factors predicted CRT response and timing, but given their modest predictive accuracy, comparable for both studies, additional methods for selecting candidates most likely to benefit from CRT are needed.

Relation of ejection fraction and inducible ventricular tachycardia to mode of death in patients with coronary artery disease: an analysis of patients enrolled in the multicenter unsustained tachycardia trial.

BACKGROUND: Fifty percent of deaths in patients with coronary disease occur suddenly. Although many factors correlate with increased mortality, there is little information regarding the influence of these factors on mode of death. As such, optimum methods to determine patients most likely to benefit from implantable defibrillator therapy are unclear. METHODS AND RESULTS: We analyzed the relation of ejection fraction and inducible ventricular tachyarrhythmias to mode of death in all 1791 patients enrolled in the Multicenter Unsustained Tachycardia Trial who did not receive antiarrhythmic therapy. Total mortality and arrhythmic deaths/cardiac arrests occurred more frequently in patients with ejection fraction <30% than in those with ejection fraction of 30% to 40%. The percentage of deaths classified as arrhythmic was similar in patients with ejection fraction <30% or > or =30%. The relative contribution of arrhythmic events to total mortality was significantly higher in patients with inducible tachyarrhythmia (58% of deaths in inducible patients versus 46% in noninducible patients, P=0.004). The higher percentage of events that were arrhythmic among patients with inducible tachyarrhythmia appeared more distinct among patients with an ejection fraction > or =30% (61% of events were arrhythmic among inducible patients with ejection fraction > or =30% and only 42% among noninducible patients, P=0.002). CONCLUSIONS: Both low ejection fraction and inducible tachyarrhythmias identify patients with coronary disease at increased mortality risk. Ejection fraction does not discriminate between modes of death, whereas inducible tachyarrhythmia identifies patients for whom death, if it occurs, is significantly more likely to be arrhythmic, especially if ejection fraction is > or =30%.

Coronary sinus lead placement via the internal jugular vein in patients with advanced heart failure: a simplified percutaneous approach.

BACKGROUND: Placement of coronary sinus (CS) leads is usually achieved via the left cephalic-axillary-subclavian (CAS) venous system. In some cases, however, such as lack of venous access a right side approach is required. Cannulation of the CS via the right CAS vein is often technically difficult, leaving the right IJ vein as a suitable alternative. OBJECTIVE: The feasibility of IJ vein as a conduit for transvenous left ventricular (LV) pacing in patients with heart failure (HF) has not been reported. METHODS AND RESULTS: Between July 2002 and April 2004, we implanted 339 biventricular devices in patients with moderate-to-severe HF. In 15 patients with similar clinical characteristics, in whom the left CAS vein could not be used, the CS leads were placed via the right CAS venous system (n = 5) or the IJ vein (n = 10). The ten patients (6 men and 4 women; age 66 +/- 15 years; LV ejection fraction .19 +/- .07; QRS duration 183 +/- 35 ms) who required IJ CS lead placement had no procedure related complications and all retained appropriate LV pacing and showed significant improvement in HF symptoms after a median follow-up of 12 months (6 to 22 months). CONCLUSIONS: Thus, in patients with HF for whom the traditional CAS venous approach cannot be used (left side) or is technically difficult (right side), CS leads can be deployed safely via the right IJ vein. In these situations, it seems appropriate to consider this approach prior to the more invasive epicardial approaches.

Tissue removal by ultrasound evaluation (the TRUE study): the Jetstream G2 system post-market peripheral vascular IVUS study.

BACKGROUND: Balloon angioplasty and stenting of infra-inguinal lesions is limited by poor long-term patency rates. Atherectomy decreases plaque burden and provides an alternative means of revascularizing patients with peripheral arterial disease. The Jetstream G2™ (Pathway Medical Technologies, Inc., Kirkland, Washington) is a newer rotational aspiration atherectomy device, uniquely combining rotablation with aspiration capability. We evaluated the debulking properties of this device by analyzing changes in the plaque volume and composition and vessel size using intravascular ultrasound (IVUS) and virtual histology (VH). Freedom from target lesion revascularization (TLR) at 6 and 12 months was also evaluated. METHODS AND RESULTS: Eighteen patients with peripheral arterial disease requiring intervention (severe claudication despite optimal medical treatment or critical limb ischemia) were treated with rotational atherectomy. The mean age was 69.6 ± 11 years, 66.7% were male, and 44.4% had diabetes. The mean total plaque volume decreased by 56.6 mm³ (479.8 ± 172.5 mm³ to 423.2 ± 156.6 mm³; p < 0.0001), which resulted in a mean luminal volume increase of 64.3 mm³ (148.4 ± 84.1 mm³ to 212.7 ± 72.1 mm³; p < 0.0001). This was achieved without significant Dotter effect with either technique, as evidenced by the virtually unchanged vessel volume before and after treatment (628.3 ± 158.5 mm³ and 635.9 ± 169.0 mm³, respectively; p = 0.22). There was a significant reduction in fibrotic and fibro-fatty plaque volume, with no appreciable effect on necrotic core and dense calcium. There were no reported procedure-related complications and the 6- and 12-month TLR rate was 11% (2/18). CONCLUSION: Atherectomy with the Jetstream G2 system results in substantial plaque volume reduction by removing fibrotic and fibro-fatty plaque. This resulted in substantial luminal volume expansion without concomitant vessel expansion. There were no major procedure-related complications, along with a relatively low 6- and 12-month rate of TLR. Future studies involving a larger number of patients are warranted to examine the potential clinical benefits of this promising technology.

Relationship between acute improvement in left ventricular function to 6-month outcomes after cardiac resynchronization therapy in patients with chronic heart failure.

The long-term impact of cardiac resynchronization therapy (CRT)-induced acute improvement in left ventricular (LV) function is largely unknown. The goal of this study was to evaluate the significance of acute improvement in LV function resulting from CRT in patients with chronic heart failure (HF). The authors compared 6-month clinical composite score (CCS) and LV end-systolic (ESV) reduction (≥15% from baseline) response rates of CRT-treated patients enrolled in the Predictors of Response to CRT (PROSPECT) trial who showed an acute increase (≥15% from baseline) in LV ejection fraction (EF) vs those who did not show a similar change in EF. Of the 396 patients who had pre-implant and post-implant EF measurements, 78 (19.7%) had an increase in EF and 318 (80.3%) did not. Acute reduction of mitral regurgitation by at least one grade occurred in 26% and 23% of patients with and without an acute increase in EF, respectively. Patients with an acute increase in EF had significantly lower baseline EF and smaller LV volumes but otherwise similar characteristics. At 6 months, LVEF and LV volumes were significantly higher and lower in the increased EF group, respectively; however, CCS improvement (70.5% vs 69.5%) and LVESV reduction (57.1% vs 54.9%) response rates were comparable in the two groups. An acute ≥15% increase in LVEF with CRT does not predict 6-month effects of CRT on patient outcomes or LV reverse remodeling. That such findings occur in patients with smaller LV volumes, however, may provide additional insight into the mechanisms responsible for CRT-induced long-term improvement in LV function and clinical benefit.

Paced left ventricular QRS width and ECG parameters predict outcomes after cardiac resynchronization therapy: PROSPECT-ECG substudy.

BACKGROUND: For patients with symptomatic New York Heart Association class III or IV, ejection fraction ≤ 35%, and QRS ≥ 130 ms, cardiac resynchronization therapy (CRT) has become an established treatment option. However, use of these implant criteria fails to result in clinical or echocardiographic improvement in 30% to 45% of CRT patients. METHODS AND RESULTS: The Predictors of Response to CRT (PROSPECT)-ECG is a substudy of the prospective observational PROSPECT trial. ECGs collected before, during, and after CRT implantation were analyzed. Primary outcomes were improvement in clinical composite score (CCS) and reduction of left ventricular end systolic volume (LVESV) of >15% after 6 months. Age, sex, cause of cardiomyopathy, myocardial infarction location, right ventricular function, mitral regurgitation, preimplantation QRS width, preimplantation PR interval, preimplantation right ventricular-paced QRS width, preimplantation axis categories, LV-paced QRS width, postimplantation axis categories, difference between biventricular (Bi-V) pacing and preimplantation QRS width, and QRS bundle branch morphological features were analyzed univariably in logistic regression models to predict outcomes. All significant predictors (α=0.1), age, and sex were used for multivariable analyses. Cardiomyopathy cause interaction and subanalyses were also performed. In multivariable analyses, only QRS left bundle branch morphological features predicted both CCS (odds ratio [OR]=2.46, P=0.02) and LVESV (OR=2.89, P=0.048) response. The difference between Bi-V and preimplantation QRS width predicted CCS improvement (OR=0.89, P=0.04). LV-paced QRS width predicted LVESV reduction (OR=0.86, P=0.01). Specifically, an LV-paced QRS width of ≤ 200 ms was predictive of nonischemic LVESV reduction (OR=5.12, P=0.01). CONCLUSIONS: Baseline left bundle branch QRS morphological features, LV-paced QRS width, and the difference between Bi-V and preimplantation QRS width can predict positive outcomes after CRT and may represent a novel intraprocedural method to optimize coronary sinus lead placement. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00253357.

Use of cholesterol-rich nanoparticles that bind to lipoprotein receptors as a vehicle to paclitaxel in the treatment of breast cancer: pharmacokinetics, tumor uptake and a pilot clinical study.

PURPOSE: In animal experiments paclitaxel oleate associated with a cholesterol-rich nanoemulsion concentrated in the neoplastic tissues and showed reduced toxicity and increased antitumor activity compared with paclitaxel-Cremophor EL. Here, a clinical study was performed in breast cancer patients to evaluate the tumoral uptake, pharmacokinetics and toxicity of paclitaxel associated to nanoemulsions. METHODS: Twenty-four hours before mastectomy [(3)H]-paclitaxel oleate associated with [(14)C]-cholesteryl oleate-nanoemulsion or [(3)H]-paclitaxel in Cremophor EL were injected into five patients for collection of blood samples and fragments of tumor and normal breast tissue. A pilot clinical study of paclitaxel-nanoemulsion administered at 3-week intervals was performed in four breast cancer patients with refractory advanced disease at 175 and 220 mg/m(2) dose levels. RESULTS: T (1/2) of paclitaxel oleate associated to the nanoemulsion was greater than that of paclitaxel (t (1/2) = 15.4 +/- 4.7 and 3.5 +/- 0.80 h). Uptake of the [(14)C]-cholesteryl ester nanoemulsion and [(3)H]-paclitaxel oleate by breast malignant tissue was threefold greater than the normal breast tissue and toxicity was minimal at the two dose levels. CONCLUSIONS: Our results suggest that the paclitaxel-nanoemulsion preparation can be advantageous for use in the treatment of breast cancer because the pharmacokinetic parameters are improved, the drug is concentrated in the neoplastic tissue and the toxicity of paclitaxel is reduced.

Limitations of ejection fraction for prediction of sudden death risk in patients with coronary artery disease: lessons from the MUSTT study.

OBJECTIVES: We determined the contribution of multiple variables to predict arrhythmic death and total mortality risk in patients with coronary disease and left ventricular dysfunction. We then constructed an algorithm to predict risk of mortality and sudden death. BACKGROUND: Many factors in addition to ejection fraction (EF) influence the prognosis of patients with coronary disease. However, there are few tools to use this information to guide clinical decisions. METHODS: We evaluated the relationship between 25 variables and total mortality and arrhythmic death in 674 patients enrolled in the MUSTT (Multicenter Unsustained Tachycardia Trial) study that did not receive antiarrhythmic therapy. We then constructed risk-stratification algorithms to weight the prognostic impact of each variable on arrhythmic death and total mortality risk. RESULTS: The variables having the greatest prognostic impact in multivariable analysis were functional class, history of heart failure, nonsustained ventricular tachycardia not related to bypass surgery, EF, age, left ventricular conduction abnormalities, inducible sustained ventricular tachycardia, enrollment as an inpatient, and atrial fibrillation. The model demonstrates that patients whose only risk factor is EF < or =30% have a predicted 2-year arrhythmic death risk <5%. CONCLUSIONS: Multiple variables influence arrhythmic death and total mortality risk. Patients with EF < or =30% but no other risk factor have low predicted mortality risk. Patients with EF >30% and other risk factors may have higher mortality and a higher risk of sudden death than some patients with EF < or =30%. Thus, risk of sudden death in patients with coronary disease depends on multiple variables in addition to EF.

Estimation of the optimal VV delay by an IEGM-based method in cardiac resynchronization therapy.

Determination of the optimal interventricular (VV) delay in cardiac resynchronization therapy currently relies on costly, time-consuming echocardiographic (ECHO) methods. This study evaluated the performance of a new intracardiac electrogram (IEGM)-based VV method compared to the aortic velocity time integral (AVTI) method of VV delay optimization. The study included two patient groups. Eleven patients enrolled by a single center in the Rhythm II ICD trial underwent prospective comparisons of the AVTI at the VV interval determined by the IEGM VV method versus the maximum AVTI at the echocardiographically determined optimal VV delay. In 61 patients enrolled in the RHYTHM VV trial, the same testing methods were compared retrospectively. In the prospective study, the maximum AVTI by the ECHO-based method (24.3 +/- 7.9 cm), was closely correlated with maximum AVTI by the IEGM-based method (23.9 +/- 7.9 cm; concordance correlation coefficient = 0.99; 95% confidence, lower limit of 98%. Likewise, in the retrospective analysis, the ECHO-determined maximum AVTI (22.1 +/- 8.2 cm) was similar to that determined by the IEGM-based method (20.9 +/- 8.3 cm; concordance correlation coefficient = 0.98; 95% confidence, lower limit of 97%).

Implantable devices for management of chronic heart failure: defibrillators and biventricular pacing therapy.

PURPOSE OF REVIEW: With chronic heart failure already an epidemic in the USA, its prevalence is expected to rise significantly in the future. Despite improved survival with pharmacologic therapy, the morbidity and mortality of patients with heart failure remain high. The purpose of this review, therefore, is to present recent data on the non-pharmacologic, device-based treatment of patients with chronic heart failure. RECENT FINDINGS: The implantable cardioverter-defibrillator has become standard treatment for the prevention of sudden, arrhythmic death. Recent well-designed clinical trials have led to device-based therapy as an important component in the management of patients with systolic left ventricular dysfunction (resulting from both ischemic and non-ischemic etiologies) and symptomatic chronic heart failure. Implantable cardioverter-defibrillator therapy alone (without biventricular pacing) results in a significant reduction in the overall mortality of patients with mild and moderate heart failure. Biventricular pacing (or cardiac resynchronization therapy) with or without a back-up implantable cardioverter-defibrillator, compared with optimal pharmacologic therapy, improves symptoms, quality of life, exercise tolerance, left ventricular function, and the survival of patients with advanced heart failure, a left ventricular ejection fraction of 35% or less, and intraventricular conduction delays (QRS > 120 ms), although up to approximately 30% of patients do not respond to cardiac resynchronization therapy. Ongoing and planned studies should clarify which patients are most likely to respond to cardiac resynchronization therapy and elucidate its role in those with a normal (< 120 ms) QRS (approximately 70% of patients with heart failure). SUMMARY: Device therapy (implantable cardioverter-defibrillator and cardiac resynchronization therapy) should be considered an integral, but adjunctive, part of the management of patients with chronic heart failure who are receiving appropriate medical therapy. The type of device used will depend on the individual patient's clinical characteristics.

Intraoperative testing of the implantable cardioverter-defibrillator: how much is enough?

INTRODUCTION: Defibrillation testing of the implantable cardioverter-defibrillator (ICD) is considered a standard and required practice at the time of implantation. How much testing, if any in some cases, should be performed, however, remains unknown. METHODS AND RESULTS: Included in this retrospective analysis were 835 patients (77% men; age 65 +/- 13 years) who received transvenous ICDs between January 1996 and December 2003. One hundred twenty-nine (15.5%) had intraoperative defibrillation threshold (DFT) testing, 503 (60.2%) had limited defibrillation safety margin testing, and 203 (24.3%) had no defibrillation testing. We compared the outcome (success of ICD therapies against spontaneous VT/VF events and survival) of the three groups of patients, who in some respects had important clinical differences. The success of the first delivered shocks against VT/VF was similar for DFT (91%), safety margin testing (91%), and no-testing (92%) groups; and the second shocks terminated the remaining episodes in all three groups. Sudden-death-free survival rates were similar in the three groups, however, the overall long-term survival rate was significantly lower in the no-testing group (58%) than in the DFT (74%) and safety margin testing (69%) groups (P < 0.0005). Multivariate analysis found no strong predictors of sudden death, but there were several independent predictors of overall mortality including lack of ICD testing (HR: 2.031, CI: 1.253-3.290, P = 0.004). CONCLUSION: In this select patient cohort, success of ICD therapies and sudden-death-free survival were similar in patients who had DFT, safety margin testing, and no testing, but overall survival was significantly lower in the no-testing group. Thus in the absence of prospective mortality data, a minimum of safety margin ICD testing should remain standard practice.