The Effect of Chronic Kidney Disease on Mortality with Cardiac Resynchronization Therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves functional status, reduces heart failure hospitalizations, and decreases mortality. Several comorbidities including renal function affect outcomes with CRT. However, moderate to severe chronic kidney disease (CKD) was an exclusion criterion in the large randomized control trials. OBJECTIVE: To evaluate the association of renal function on survival following CRT implantation. METHODS: This was a retrospective analysis of 432 consecutive patients implanted with an implantable cardioverter defibrillator with CRT (CRT-D). The primary end point was defined as death by any cause, and it was determined using hospital records and the U.S. Social Security Death Index. A Kaplan-Meier analysis was performed separating renal dysfunction into renal stage based on glomerular filtration rate. Multivariate analysis was performed to assess the clinical predictors of mortality. RESULTS: Patients were followed for up to 12 years with a mean follow-up time of 4.3 ± 3.2 years. A total of 164 patients (39.3%) died over the course of the study. Patients with normal and mild renal diseases (Stages 1 and 2) had improved survival compared with those with moderate-, severe-, or end-stage (Stages 3-5) renal disease. This effect remained statistically significant after multivariate analysis. The estimated 5-year mortality was 36.3% for stage 1, 33.4% for stage 2, 40.6% for stage 3, and 62.1% for stage 4/5 kidney disease (P = 0.004 by log-rank test). CONCLUSION: CKD is a strong and an independent predictor of long-term mortality among patients undergoing CRT-D implantation.

The effect of left ventricular electrical delay on the acute hemodynamic response with cardiac resynchronization therapy.

INTRODUCTION: Cardiac resynchronization therapy (CRT) improves hemodynamic function, as well as reduces hospitalizations and mortality among patients with systolic dysfunction, QRS prolongation, and heart failure. The magnitude of the hemodynamic response is associated with improved outcomes, so optimization of this parameter is a goal of therapy. The purpose of this study was to evaluate the effect of left ventricular (LV) electrical delay, as assessed by the QLV interval, on the acute hemodynamic response to CRT. METHODS AND RESULTS: This study included 31 patients undergoing biventricular ICD placement. At implant, invasive LV dP/dt was measured by a micromanometer catheter during biventricular (BV) or LV only pacing. Both atrial sensing (AS) and atrial pacing (AP) modes were evaluated at 5 different AV delays, tested in randomized order. The QLV interval was measured at the LV pacing site. Compared with intrinsic rhythm, CRT increased LV dP/dtmax by 9.5 ± 8.8% with BV pacing and 10.0 ± 9.2% with LV pacing (P = 0.38) during AS. With AP, CRT increased LV dP/dtmax by 16.0 ± 10.8% and 15.3 ± 11.1%, respectively (P = 0.47). QLV was strongly correlated with the hemodynamic response in all pacing configurations. Multivariate analysis showed that with BV pacing QLV was an independent predictor of the hemodynamic response with a 1.7% increase in %LV dP/dt for every 10 milliseconds prolongation of QLV. CONCLUSIONS: LV electrical delay is a strong predictor of the acute hemodynamic response to CRT. This relationship is independent of pacing mode.

Safety of continuous anticoagulation with dabigatran during implantation of cardiac rhythm devices.

The perioperative bleeding risk associated with therapeutic anticoagulation at cardiac implantable electronic device implantation has previously been demonstrated to vary by the specific anticoagulant used. Although uninterrupted anticoagulation with warfarin appears to be safe, heparin products have been shown to increase the risk of perioperative bleeding. However, the risk associated with cardiac implantable electronic device implantation with anticoagulation using dabigatran, a novel oral direct thrombin inhibitor, is not known. We performed a prospective observational study of patients receiving dabigatran for anticoagulation who underwent cardiac implantable electronic device implantation from June 2011 through May 2012. The study end points included thromboembolic and bleeding complications within 30 days of surgery. Major bleeding complications were defined as bleeding requiring surgical intervention, prolongation of hospitalization, and discontinuation of the anticoagulant or transfusion of blood products within 30 days of surgery. Minor bleeding complications included the development of a hematoma not requiring additional intervention. The thrombotic end points included stroke, transient ischemic attack, myocardial infarction, pulmonary embolism, and deep vein thrombosis. A total of 25 patients were identified for inclusion. During the index hospitalization, no thromboembolic or bleeding complications developed. No major bleeding complications occurred within 30 days of surgery. One minor bleeding event (4%) occurred within 30 days of surgery in 1 patient who was also receiving dual antiplatelet therapy. In conclusion, although no thromboembolic or major bleeding events were observed, additional studies are required to define the optimal antithrombotic management in the perioperative period.

A prospective, randomized comparison of the acute hemodynamic effects of biventricular and left ventricular pacing with cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is most commonly performed with biventricular (BiV) pacing. Left ventricular (LV) only pacing is an alternative pacing configuration for CRT, but comparative studies with BiV pacing have shown inconsistent results. This may be due to differences in LV activation pattern, which could be differentially affected by atriventricular (AV) programming or atrial pacing (AP). OBJECTIVE: The purpose of this study was to compare AV optimization and the effect of atrial overdrive pacing on the acute hemodynamic response of LV and BiV CRT. METHODS: This study included 28 patients undergoing CRT. At implant, invasive LV dP/dt was measured by a micromanometer catheter during BiV or LV pacing in atrial sensing (AS) and AP modes at five different AV delays (AVDs), tested in randomized order. RESULTS: Compared with intrinsic rhythm, CRT with AS increased LV dP/dt by 12% ± 10% during LV pacing and by 11% ± 11% during BiV pacing (P = .15). With atrial overdrive pacing, CRT increased LV dP/dt by 17% ± 10% with LV pacing and by 17% ± 11% during BiV pacing (P = NS vs. LV; P <.001 vs. AS). The optimal AVD was significantly longer with AP (LV 202 ± 63 ms vs. 131 ± 42 ms during AS; BiV 195 ± 71 ms vs. 134 ± 43 ms during AS) but did not differ between LV and BiV pacing. CONCLUSION: In this study, AP increases LV dP/dt during CRT but requires a substantially longer AVD. However, the optimal AVDs were similar for LV and BiV as were the magnitudes of the responses during CRT, suggesting that programmed AVDs are interchangeable in these two configurations.

Defibrillation thresholds in hypertrophic cardiomyopathy.

BACKGROUND: Defibrillation threshold (DFT) testing is performed in part to ensure an adequate safety margin for the termination of spontaneous ventricular arrhythmias. Left ventricular mass is a predictor of high DFTs, so patients with hypertrophic cardiomyopathy (HCM) are often considered to be at risk for increased defibrillation energy requirements. However, there are little prospective data addressing this issue. OBJECTIVE: To assess DFTs in patients with HCM and evaluate the clinical predictors of elevated DFTs. METHODS: Eighty-nine consecutive patients with HCM and 600 control patients with ischemic or nonischemic cardiomyopathy underwent a uniform modified step-down DFT testing protocol. DFT was compared between the control and HCM populations. Predictors of elevated DFT were evaluated in the HCM group. RESULTS: There was no difference in DFT between HCM and control groups (10.4 ± 5.8 J vs 11.2 ± 5.6 J, respectively). Among patients with HCM, clinical parameters such as left ventricular ejection fraction, interventricular septal thickness, left ventricular mass, and QRS duration were not predictive of an elevated DFT. Only 3 patients (3.4%) with HCM had a DFT >20 J. CONCLUSION: Patients with HCM do not have elevated DFTs as compared to more typical populations undergoing implantable cardioverter-defibrillator implant; high-energy devices or complex lead systems are not needed routinely in this population.

Randomized comparison of defibrillation thresholds from the right ventricular apex and outflow tract.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) leads are traditionally placed in the right ventricular apex (RVA), in part because this is considered the preferred vector for minimizing defibrillation threshold (DFT). However, if adequate DFT safety margins are attainable, ICD leads placed in the right ventricular outflow tract (RVOT) might confer advantages if frequent ventricular pacing is anticipated. OBJECTIVE: The purpose of this study was to compare RVA with RVOT transvenous ICD lead position on DFT. METHODS: This was a prospective, randomized, crossover study of RVA versus RVOT DFT in 33 patients undergoing left pectoral ICD placement. A binary search algorithm was used to measure DFT, with initial lead position tested in randomized order. The relationship between RVOT position and DFT was assessed by evaluation of the distance between RVA and RVOT. RESULTS: The study population had a mean age of 59 ± 12 years and ejection fraction of 33% ± 14%. Mean DFT in the RVA was 9.8 ± 7.3 J versus 10.8 ± 7.2 J in the RVOT (P = .53), with no correlation between RVOT location and DFT. CONCLUSION: The study found no evidence that ICD lead placement in the RVOT is associated with significantly higher DFT than lead placement in the RVA.

Role of transesophageal echocardiography among patients with atrial fibrillation undergoing electrophysiology testing.

External or internal shocks administered to terminate ventricular arrhythmias as a part of electrophysiology or implantable cardioverter-defibrillator testing, can inadvertently cardiovert atrial fibrillation (AF). Moreover, anticoagulation therapy is often withheld in these patients in anticipation of an invasive procedure. The risk of embolic events during these procedures has not been well described. Accordingly, the present study was a prospective evaluation of the incidence of left atrial (LA) thrombus and AF cardioversion among patients undergoing ventricular arrhythmia assessment. Transesophageal echocardiography was routinely performed on 44 consecutive patients in AF with subtherapeutic anticoagulation undergoing electrophysiology or implantable cardioverter-defibrillator testing. Arrhythmia induction was not performed when LA thrombus was present. The incidence and clinical predictors of thrombus, the inadvertent cardioversion of AF, and adverse events related to the procedure were assessed during the subsequent 4 to 6 weeks. Left atrial thrombus was observed in 12 patients (27%). Sinus rhythm was restored in 29 patients (91%), at least transiently, who underwent testing with a shock delivered. No adverse neurologic or hemorrhagic complications were observed. Univariate analysis identified no predictors of LA thrombus or cardioversion to sinus rhythm. In conclusion, LA thrombus and cardioversion to sinus rhythm are common among patients with AF undergoing an evaluation of ventricular arrhythmias. Transesophageal echocardiography performed before the procedure in patients with subtherapeutic anticoagulation is warranted to minimize embolic complications. This strategy appears to be a safe method to guide diagnostic testing in this patient population.

Acute hemodynamic effects of atrial pacing with cardiac resynchronization therapy.

BACKGROUND: Chronotropic incompetence is common among patients with advanced heart failure (HF), thus atrial pacing (AP) is frequently utilized in this population. The hemodynamic effects of AP during cardiac resynchronization therapy (CRT) have not been well studied. OBJECTIVE: The purpose of this study was to compare the acute hemodynamic response during CRT of AP with that during atrial sensing (AS). METHODS: This study included 26 patients undergoing CRT. At implant, invasive left ventricular (LV) dP/dt was measured by a micromanometer catheter during biventricular pacing in AS and AP modes at 5 different atrioventricluar delays (AVD), tested in randomized order. Postimplant, echocardiography was performed to obtain aortic and mitral flow velocity integrals at baseline (no CRT) and during CRT. RESULTS: Compared with intrinsic rhythm, CRT increased LV dP/dt by 11 +/- 11% during AS (heart rate: 74 +/- 13 bpm) and by 17 +/- 11% during AP (heart rate: 86 +/- 12 bpm, P < 0.001). The AVD associated with maximal hemodynamic response (AVD(max)) during AP was 72 +/- 40 ms longer than during AS. However, aortic and mitral flow velocity integrals decreased by 15-20% during AP. The aortic and mitral flow velocities at AVD(max) for LV dP/dt(max) were highly correlated with their maximum values (r > 0.98). CONCLUSION: AP increases LV dP/dt during CRT, but requires a substantially longer AV delay. However, AP results in modest reductions of LV filling and stoke volume. Further studies are needed to assess the long-term impact of AP on HF functional status and LV remodeling.

Disparities in preferences for receiving support and education among patients with implantable cardioverter defibrillators.

BACKGROUND: The implantable cardioverter-defibrillator (ICD) is the established treatment for patients with a history of or at risk for sudden cardiac arrest. Patients receiving an ICD are diverse, and little is known regarding their preferences for support and education postimplantation. The purpose of this study was to examine race, gender, and age preferences for receiving support and education (e.g., written, verbal). METHODS: Participants (N = 108, 75% Caucasian, 74% male, age 65 +/- 11 years) completed a research team-designed survey at a regularly scheduled clinic visit with the cardiac electrophysiologist at an academic medical center or offsite clinic. Descriptive statistics, Pearson chi(2), and independent t-tests were conducted. RESULTS: The study demonstrates important associations between race, gender, and age with patient preferences for support and education with regard to ICD care. African Americans preferred written materials (P = 0.006) and a phone call with the cardiologist (P =0.036). Women preferred an ICD support group (P = 0.023), a phone call with the device nurse (P = 0.027), and a professional counselor (P = 0.049). Women's choice to receive education from their cardiologist approached significance (P = 0.055). Patients < or =67 years of age preferred to receive support via an Internet chat room with other ICD patients (P =0.036), and to receive education via an Internet Web site (P = 0.022). CONCLUSIONS: Findings suggest methods of providing better care to ICD patients by offering them support and educational materials in their preferred modality. These data can aid in optimizing clinical care. Incorporating assessments of individual preferences into future clinical trial design is desirable.

The effect of dofetilide on ventricular defibrillation thresholds.

INTRODUCTION: High defibrillation threshold (DFT) with an inadequate defibrillation safety margin remains an infrequent but troubling problem associated with defibrillator implantation. Dofetilide is a selective class III antiarrhythmic drug that reduces DFTs in a canine model. We hypothesized that dofetilide would reduce DFTs in humans, obviating the need for complex lead systems. METHODS AND RESULTS: Sixteen consecutive patients with DFTs > or =20 J delivered energy at implant-received dofetilide therapy and underwent follow-up DFT testing acutely following drug loading and/or chronically (128 +/- 94 days). Amiodarone was discontinued in four patients at implantation. With dofetilide, DFTs decreased from 28 +/- 4 J to 19 +/- 7 J (P < 0.0001), resulting in a safety margin of 15 +/- 8 J for the implanted devices. Five patients subsequently had spontaneous arrhythmias terminated successfully with shocks. CONCLUSION: Dofetilide reduces DFTs sufficiently to prevent the need for more complex lead systems. This strategy should be considered when an inadequate defibrillation safety margin is present.

Implantable cardioverter-defibrillator therapy for primary prevention of sudden death after alcohol septal ablation of hypertrophic cardiomyopathy.

OBJECTIVES: The purpose of this study was to examine the effects of alcohol septal ablation (ASA) on ventricular arrhythmias among patients with obstructive hypertrophic cardiomyopathy (HCM), as measured by appropriate implantable cardioverter-defibrillator (ICD) discharges. BACKGROUND: Alcohol septal ablation is an effective therapy for patients with symptomatic HCM. However, concern has been raised that ASA may be proarrhythmic secondary to the iatrogenic scar created during the procedure. The impact of ASA on ventricular arrhythmias has not been well described. METHODS: This prospective study included 123 consecutive patients with obstructive HCM who underwent ASA and had an ICD implanted for primary prevention of sudden cardiac death (SCD). The ICDs were implanted based on commonly accepted risk factors for SCD in the HCM population. Data from ICD interrogations during routine follow-up were collected. RESULTS: Nine appropriate ICD shocks were recorded over a mean follow-up of 2.9 years in the cohort, which had a mean of 1.5 +/- 0.9 risk factors for SCD. Using Kaplan-Meier survival analysis, the estimated annual event rate was 2.8% over 3-year follow-up. There were no significant differences in the incidence of risk factors between patients who did and did not receive appropriate shocks. CONCLUSIONS: The annual rate of appropriate ICD discharges after ASA is low and less than that reported previously for primary prevention of SCD in HCM. This suggests that ASA is not proarrhythmic. Traditional SCD risk factors did not predict ICD shocks in this cohort.

Optimization of superior vena cava coil position and usage for transvenous defibrillation.

BACKGROUND: Prior studies of active pectoral implantable defibrillator (ICD) lead systems demonstrated a lowering of defibrillation thresholds (DFTs) with the addition of a superior vena cava (SVC) coil. These studies were done on fixed-tilt waveforms where a large reduction in impedance leads to large phase duration changes. OBJECTIVE: The present study was designed to evaluate the SVC coil benefit and intercoil spacing on DFTs with a "tuned" waveform. METHODS: This prospective, multicenter study included 113 patients randomized at implant to a 17-cm and a 21-cm intercoil spacing ICD lead. DFTs were measured with SVC coil turned ON versus OFF in a random order, using an optimized binary search method. RESULTS: DFT voltage (423 +/- 120 vs. 438 +/- 118 V; P = .042) and stored energy (9.8 +/- 5.6 vs. 10.2 +/- 5.8 J; P = .043) were significantly reduced with the SVC coil ON. However, intercoil distance had no significant effect on DFT voltage (437.3 +/- 115.1 vs. 407.7 +/- 123.8 V; P = .19) or stored energy (10.3 +/- 5.4 vs. 9.2 +/- 5.8 J; P = .31). Subgroup analyses showed that the dual-coil leads were most effective when placed in the high position (innominate vein-SVC junction) or when the single-coil shock impedance was > or =58 Omega, regardless of intercoil spacing. CONCLUSION: With a tuned waveform, the addition of an SVC coil to the shocking pathway reduces DFTs, although this difference was smaller than reported previously. Intercoil distance had no significant effect on the defibrillation parameters.

A prospective comparison of AV delay programming methods for hemodynamic optimization during cardiac resynchronization therapy.

INTRODUCTION: There are several methods for programming the optimal AV delay (AVD) during cardiac resynchronization therapy (CRT). These include Doppler echocardiographic measurements of mitral inflow or aortic outflow velocities, an arbitrarily fixed AVD, and calculations based on intracardiac electrogram (EGM) intervals. The present study was designed to compare the acute effects of AVD programming methods during CRT. METHODS AND RESULTS: We studied 28 patients at CRT implant with invasive measurements of LV dP/dt to determine the effect of AVD during atrial sensed (AS) and atrial paced (AP) modes. The optimal AVD, defined as that resulting in the maximal LV dP/dt, was then compared with that predicted by several noninvasive methods. CRT increased LV dP/dt 11% +/- 11% during AS (heart rate: 73 +/- 14 bpm) and 17% +/- 12% during AP (heart rate: 86 +/- 12 bpm) (P < 0.001 vs AS). There was an excellent correlation between the EGM method and the maximum achievable LV dP/dt (AS: R2 = 0.99, P < 0.0001, AP: R2 = 0.96, P < 0.0001) and this method performed better than other techniques. CONCLUSIONS: An electrogram-based optimization method accurately predicts the optimal AVD among patients over a wide range of QRS intervals during CRT in both AS and AP modes. This simple technique may obviate the need for echocardiography for AVD programming.

Clinical trials update: sudden cardiac death prevention by implantable device therapy.

Sudden cardiac death represents an enormous public health problem in all developed countries of the world. In the United States, sudden cardiac death occurs in more than 400,000 people each year and is the leading cause of death. In sudden cardiac death, the heart abruptly and unexpectedly ceases to function (cardiac arrest), presumably because of an electrical disturbance. Individuals deemed high risk for sudden cardiac death may be treated with implantable defibrillators. This article highlights evidence from randomized, controlled trials of implantable device therapy used in prevention of sudden cardiac death.

Efficacy of transthoracic cardioversion of atrial fibrillation using a biphasic, truncated exponential shock waveform at variable initial shock energies.

Biphasic shocks are more effective than damped sine wave monophasic shocks for transthoracic cardioversion (CV) of atrial fibrillation (AF), but the optimal protocol for CV with biphasic shocks has not been defined. We conducted a prospective, randomized study of 120 consecutive patients with persistent AF to delineate the dose-response curve for CV of AF with a biphasic truncated exponential shock waveform and to identify clinical predictors of shock efficacy. Our data suggest that the initial shock energy for CV with this waveform should be 200 J if the patient weighs <90 kg and 360 J if the patient weighs >/=90 kg.

Effectiveness of rapid atrial pacing for termination of drug refractory atrial fibrillation: results of a dual chamber implantable cardioverter defibrillator trial.

There is increasing interest in the use of an implantable cardioverter defibrillator (ICD) to manage atrial tachyarrhythmias. Although device-based shock therapy is highly effective in terminating persistent atrial tachyarrhythmias, atrial overdrive pacing may also be useful, particularly when this therapy is applied early after the onset of an arrhythmia. A dual-chamber ICD (Medtronic 7250 Jewel AF(R)) has been studied in 267 patients with drug-refractory symptomatic AF. The patients were enrolled as part of multicenter clinical trial to evaluate the safety and efficacy of the device to manage atrial tachyarrhythmias in the absence of a standard ventricular ICD indication. The device discriminates atrial tachycardia (AT) from atrial fibrillation (AF) based on cycle length and regularity, and employs multiple methods of atrial overdrive pacing as well as shocks to terminate tachyarrhythmia episodes. Patients were followed for an average of 15.8 +/- 9.3 months. A majority (63%) of patients presented with a history of persistent AF and 34% presented with a history of paroxysmal AF. The pacing therapies terminated 54% of AT episodes and 27% of AF episodes. In patients with persistent AF, 75% of the AT/AF episodes that were successfully terminated by pacing lasted