Adaptive versus conventional cardiac resynchronisation therapy in patients with heart failure (AdaptResponse): a global, prospective, randomised controlled trial.

BACKGROUND: Continuous automatic optimisation of cardiac resynchronisation therapy (CRT), stimulating only the left ventricle to fuse with intrinsic right bundle conduction (synchronised left ventricular stimulation), might offer better outcomes than conventional CRT in patients with heart failure, left bundle branch block, and normal atrioventricular conduction. This study aimed to compare clinical outcomes of adaptive CRT versus conventional CRT in patients with heart failure with intact atrioventricular conduction and left bundle branch block. METHODS: This global, prospective, randomised controlled trial was done in 227 hospitals in 27 countries across Asia, Australia, Europe, and North America. Eligible patients were aged 18 years or older with class 2-4 heart failure, an ejection fraction of 35% or less, left bundle branch block with QRS duration of 140 ms or more (male patients) or 130 ms or more (female patients), and a baseline PR interval 200 ms or less. Patients were randomly assigned (1:1) via block permutation to adaptive CRT (an algorithm providing synchronised left ventricular stimulation) or conventional biventricular CRT using a device programmer. All patients received device programming but were masked until procedures were completed. Site staff were not masked to group assignment. The primary outcome was a composite of all-cause death or intervention for heart failure decompensation and was assessed in the intention-to-treat population. Safety events were collected and reported in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02205359, and is closed to accrual. FINDINGS: Between Aug 5, 2014, and Jan 31, 2019, of 3797 patients enrolled, 3617 (95·3%) were randomly assigned (1810 to adaptive CRT and 1807 to conventional CRT). The futility boundary was crossed at the third interim analysis on June 23, 2022, when the decision was made to stop the trial early. 1568 (43·4%) of 3617 patients were female and 2049 (56·6%) were male. Median follow-up was 59·0 months (IQR 45-72). A primary outcome event occurred in 430 of 1810 patients (Kaplan-Meier occurrence rate 23·5% [95% CI 21·3-25·5] at 60 months) in the adaptive CRT group and in 470 of 1807 patients (25·7% [23·5-27·8] at 60 months) in the conventional CRT group (hazard ratio 0·89, 95% CI 0·78-1·01; p=0·077). System-related adverse events were reported in 452 (25·0%) of 1810 patients in the adaptive CRT group and 440 (24·3%) of 1807 patients in the conventional CRT group. INTERPRETATION: Compared with conventional CRT, adaptive CRT did not significantly reduce the incidence of all-cause death or intervention for heart failure decompensation in the included population of patients with heart failure, left bundle branch block, and intact AV conduction. Death and heart failure decompensation rates were low with both CRT therapies, suggesting a greater response to CRT occurred in this population than in patients in previous trials. FUNDING: Medtronic.

Ampere Hour as a Predictor of Cardiac Resynchronization Defibrillator Pulse Generator Battery Longevity: A Multicenter Study.

BACKGROUND: Cardiac resynchronization defibrillator (CRT-D) devices improve survival for New York Heart Association classes II-IV systolic heart failure patients with QRS > 120 ms and left ventricular ejection fraction < 35%. A limitation of 100% CRT pacing is excess battery depletion and pulse generator (PG) replacement compared to VVI or dual-chamber systems. Ampere hour (Ah) measures PG battery capacity and may predict CRT-D device longevity. METHODS: We performed a multicenter retrospective study of all CRT-D devices implanted at our centers from August 1, 2008 to December 31, 2010. Analysis was performed for survival to elective replacement indicator (ERI) between 1.0 Ah, 1.4 Ah, and 2.0 Ah devices, per manufacturers' specifications. RESULTS: One thousand three hundred and two patients were studied through December 31, 2014. Patients were followed for an average of 3.0 ± 1.3 years (794 1.0 Ah, 322 2.0 Ah, and 186 1.4 Ah devices under study). CRT-D generator ERI occurred in 13.5% of 1.0 Ah systems (107 out of 794), versus 3.8% in 1.4 Ah (seven out of 186), and 0.3% in 2.0 Ah devices (one out of 322) over mean follow-up of 3.0 years. Odds ratio (OR) for reaching ERI with 1.0 Ah device versus 1.4 Ah or 2.0 Ah was 9.73, P < 0.0001. Univariate predictors for ERI included 1.0 Ah device and LV pacing output >3V @ 1 ms (OR: 3.74, P < 0.001). LV impedance >1,000 ohms predicted improved device survival (OR: 0.38, P = 0.0025). CONCLUSIONS: CRT-D battery capacity measured by Ah is a strong predictor of survival to ERI for modern systems. Further study on cost and morbidity associated with early PG change in 1.0 Ah systems is warranted.

In vitro characterization of cardiac radiofrequency ablation lesions using optical coherence tomography.

Currently, cardiac radiofrequency ablation (RFA) is guided by indirect signals. We demonstrate optical coherence tomography (OCT) characterization of RFA lesions within swine ventricular wedges. Untreated tissue exhibited a consistent birefringence artifact within OCT images due to the organized myocardium, which was not present in treated tissue. Birefringence artifacts were detected by filtering with a Laplacian of Gaussian (LoG) to quantify gradient strength. The gradient strength distinguished RFA lesions from untreated sites (p=5.93 x 10(-15)) with a sensitivity and specificity of 94.5% and 86.7% respectively. This study demonstrates the potential of OCT for monitoring cardiac RFA, confirming lesion formation and providing feedback to avoid complications.

Rational patient selection for catheter ablation of atrial fibrillation.

During the past decade, catheter ablation of atrial fibrillation has been progressively used for the treatment of drug-refractory patients. As experience and technique have evolved, patient selection criteria have been modified to include a wider range of patients. Patients with paroxysmal, persistent, and longstanding persistent atrial fibrillation can be treated with catheter ablation. Catheter ablation is an option for many patients, including older patients (septuagenarians and octogenarians), those with enlarged left atrium, and those with cardiomyopathy. Results and safety are satisfactory and often superior to medical treatment. In patients with structural heart disease, multiple ablative procedures may be required to achieve cure. Ongoing clinical research will provide further insight into future criteria for patient selection.

Palpitation: Extended Electrocardiogram Monitoring: Which Tests to Use and When.

Palpitation is common. It is often accompanied by dizziness, lightheadedness, near syncope, and even syncope. It may be difficult to confirm a diagnosis in patients with infrequent symptoms. Several tools are available to document arrhythmias in the workup of a patient with palpitation, including 24-hour Holter monitoring, 30-day external continuous monitoring, and implantable loop recorders. A number of private companies are now able to empower patients to monitor heart rates and even give accurate rhythm strips. This article reviews the current data on how to make the diagnosis and which tools to use in the primary care setting.

Electrical and hemodynamic function produced by stimulation of atropine sensitive right ventricular nerves in humans.

In mammalian ventricles including humans, it is recognized that parasympathetic ganglia innervate the heart. Little is known about the location and function of right ventricular parasympathetic nerves in humans. We hypothesized that in humans: (1) there are parasympathetic ganglia that supply the right ventricle that can be stimulated via an endocardial catheter and (2) stimulation of these fibers will alter the electrical and hemodynamic function of the right ventricle. Parasympathetic nerve stimulation was performed via an endocardial catheter placed along several sites of the right ventricle, superior vena cava, and right internal jugular area in humans. The spatial extent of parasympathetic innervation was mapped in 1-cm zones across the right ventricle. Cardiac output, heart rate, and atrioventricular conduction were monitored to provide independent assessment of parasympathetic innervation. In all 22 patients, ventricular refractoriness shortened from 12 +/- 3 to 3 +/- 1 ms during parasympathetic nerve stimulation, and the greatest shortening of refractoriness was observed at the base of the right ventricle (p = 0.01). No significant shortening in ventricular refractoriness occurred in areas beyond 2 cm from the right ventricular base. These results were compared by using T table test. The parasympathetic nerve stimulation protocol decreased cardiac output, reaffirming the principle effect of parasympathetic ganglia. Atropine was administered in seven patients. All effects from nerve stimulation were abolished after atropine administration. These results were also compared by using T table test. These data provide the first demonstration of the electrical and hemodynamic function by stimulation of atropine sensitive nerves of the human right ventricle. Greater understanding of parasympathetic innervation may lead to novel therapies for arrhythmias.

Preservation of the anterior fat pad paradoxically decreases the incidence of postoperative atrial fibrillation in humans.

OBJECTIVES: The goal of this study was to determine if parasympathetic nerves in the anterior fat pad (FP) can be stimulated at the time of coronary artery bypass surgery (CABG), and if dissection of this FP decreases the incidence of postoperative atrial fibrillation (AF). BACKGROUND: The human anterior epicardial FP contains parasympathetic ganglia and is often dissected during CABG. Changes in parasympathetic tone influence the incidence of AF. METHODS: Fifty-five patients undergoing CABG were randomized to anterior FP preservation (group A) or dissection (group B). Nerve stimulation was applied to the FP before and after surgery. Sinus cycle length (CL) was measured during stimulation. The incidence of postoperative AF was recorded. RESULTS: Of the 55 patients enrolled, 26 patients were randomized to group A, and 29 patients were randomized to group B. In all of the 55 patients, the FP was identified before initiating cardiopulmonary bypass by CL prolongation with stimulation (865.5 +/- 147.9 ms vs. 957.9 +/- 155.1 ms, baseline vs. stimulation, p < 0.001). In group A, stimulation at the conclusion of surgery increased sinus CL (801.8 +/- 166.4 ms vs. 890.9 +/- 178.2 ms, baseline vs. stimulation, p < 0.001). In group B, repeat stimulation failed to increase sinus CL (853.6 +/- 201.6 ms vs. 841.4 +/- 198.4 ms, baseline vs. stimulation, p = NS). The incidence of postoperative AF in group A (7%) was significantly less than that in group B (37%) (p < 0.01). CONCLUSIONS: This is the first study demonstrating that direct stimulation of the human anterior epicardial FP slows sinus CL. This parasympathetic effect is eliminated with FP dissection. Preservation of the human anterior epicardial FP during CABG decreases incidence of postoperative AF.

Biventricular pacing for congestive heart failure: early experience in surgical epicardial versus coronary sinus lead placement.

OBJECTIVE: Biventricular pacing (BVP) has recently been introduced for the treatment of refractory congestive heart failure. Coronary sinus lead placement for left ventricular pacing is technically difficult, has a risk of lead dislodgement, and has long procedure times. Surgical epicardial lead placement has the potential advantage of the visual selection of an optimal pacing site, does not need exposure to ionic radiation, and allows lead multiplicity, but it does require a thoracotomy and general anesthesia. We report our early experience of BVP with both modalities. METHODS: BVP was performed in 12 patients with New York Heart Association (NYHA) class IV congestive heart failure (10 men, 2 women). Mean patient age was 68.7 years (range, 41-83 years). Surgical epicardial leads were placed through a 2- to 3-inch incision via a left fourth or fifth intercostal thoracotomy in 4 patients with single lung ventilation under general anesthesia. The other 8 patients underwent transvenous coronary sinus lead placement under conscious sedation. RESULTS: Postoperative NYHA class status improved from class IV to class II in 8 patients and to class III in 3 patients. In 5 of the 8 patients who had undergone follow-up echocardiography with mitral regurgitation, the severity of the mitral regurgitation improved. The mean left ventricular ejection fractions before and after BVP were 18.3% +/- 8.3% and 20.5% +/- 8.0%, respectively (P =.16). Mean fluoroscopy and total procedure times for transvenous lead placement were 77 +/- 19 minutes and 266 +/- 117 minutes, respectively. The mean surgery time for epicardial lead placement was 122 +/- 13 minutes. There were no differences between the 2 methods in pacing threshold or in lead dislodgement. There were no complications related to the surgery or the laboratory procedure. CONCLUSION: In patients with NYHA class IV congestive heart failure, epicardial lead placement through a minithoracotomy for BVP was performed safely with benefits equivalent to those of coronary sinus lead placement and with a shorter procedure time.

Toward guidance of epicardial cardiac radiofrequency ablation therapy using optical coherence tomography.

Radiofrequency ablation (RFA) is the standard of care to cure many cardiac arrhythmias. Epicardial ablation for the treatment of ventricular tachycardia has limited success rates due in part to the presence of epicardial fat, which prevents proper rf energy delivery, inadequate contact of ablation catheter with tissue, and increased likelihood of complications with energy delivery in close proximity to coronary vessels. A method to directly visualize the epicardial surface during RFA could potentially provide feedback to reduce complications and titrate rf energy dose by detecting critical structures, assessing probe contact, and confirming energy delivery by visualizing lesion formation. Currently, there is no technology available for direct visualization of the heart surface during epicardial RFA therapy. We demonstrate that optical coherence tomography (OCT) imaging has the potential to fill this unmet need. Spectral domain OCT at 1310 nm is employed to image the epicardial surface of freshly excised swine hearts using a microscope integrated bench-top scanner and a forward imaging catheter probe. OCT image features are observed that clearly distinguish untreated myocardium, ablation lesions, epicardial fat, and coronary vessels, and assess tissue contact with catheter-based imaging. These results support the potential for real-time guidance of epicardial RFA therapy using OCT imaging.

Real-time monitoring of cardiac radio-frequency ablation lesion formation using an optical coherence tomography forward-imaging catheter.

Radio-frequency ablation (rfa) is the standard of care for the treatment of cardiac arrhythmias; however, there are no direct measures of the successful delivery of ablation lesions. Optical coherence tomography (OCT) imaging has the potential to provide real-time monitoring of cardiac rfa therapy, visualizing lesion formation and assessing tissue contact in the presence of blood. A rfa-compatible forward-imaging conical scanning probe is prototyped to meet this need. The forward-imaging probe provides circular scanning, with a 2-mm scan diameter and 30-mum spot size. During the application of rf energy, dynamics are recorded at 20 frames per second with a 40-kHz A-line rate. Real-time monitoring of cardiac rfa lesion formation and imaging in the presence of blood is demonstrated ex vivo in a swine left ventricle with a forward, flexible, circular scanning OCT catheter.

Implantable cardioverter defibrillator (ICD) for polymorphic ventricular tachycardia (VT) due to coronary vasospasm.

We report a case of a young woman who presented with atypical angina. During an episode of chest pain she had a documented run of sustained polymorphic ventricular tachycardia (VT). In addition to medical therapy, she received an ICD to prevent future episodes of sudden cardiac death.

The future of fellowship training in clinical cardiac electrophysiology: Program directors' perspective 2008.

BACKGROUND: At the Clinical Cardiac Electrophysiology (CCEP) program directors' annual meeting during the 2008 scientific sessions of the Heart Rhythm Society, a consensus emerged for an urgent need to strengthen and rejuvenate fellowship training in clinical cardiac electrophysiology. OBJECTIVE: A writing group of the Heart Rhythm Society Clinical Research and Training Committee was charged with defining these issues. METHODS: A comprehensive questionnaire designed by the writing group was used to conduct an on-line survey of the 101 CCEP program directors in the United States. Data collected included types of programs, current status of programs, duration of fellowship, teaching responsibilities of faculty, responsibilities of fellows, and volume of electrophysiology procedures. Survey responses were collated and analyzed by the writing group. RESULTS: Given the rapid evolution and increased complexity of current electrophysiology procedures, program directors were of the opinion that 1 year of clinical electrophysiology training may no longer be adequate. A need to strengthen both research and didactic training components of fellowship training was also acknowledged. The number of electrophysiology procedures performed by trainees varied greatly between programs, and standardization of didactic training and procedural volume would be welcomed. Recent trends were recognized that indicate the need for a detailed national work-force analysis in CCEP. CONCLUSION: Through this national survey, program directors identified specific areas of need for standardization and strengthening of current fellowship training in CCEP. Based on these, specific measures can be taken to ensure the future of CCEP training.

Intracardiac alternans compared to surface T-wave alternans as a predictor of ventricular arrhythmias in humans.

BACKGROUND: Microvolt T-wave alternans (MTWA) measured from the surface electrocardiogram (ECG) is a marker of sudden cardiac death (SCD). Recently, it has been suggested that intracardiac alternans (ICA) detected from the endocardium underlies MTWA and is a marker of electrical instability leading to ventricular arrhythmias. As such, ICA may be used in future implantable cardioverter-defibrillators (ICDs) to monitor periods of electrical instability before ICD therapy. We examined whether electrical instability, as measured by MTWA, can be detected by ICA located from the right ventricle and if ICA can predict ventricular arrhythmias in patients with ICDs. METHODS: Both MTWA and ICA were measured simultaneously during atrial pacing in 68 patients undergoing electrophysiology study (EPS). ICA was measured from unipolar electrograms acquired from a catheter at the apical, mid, and basal regions of the right ventricle in 48 patients and at the apical region alone in 20 patients. Indications for EPS included nonsustained ventricular tachycardia, cardiomyopathy, syncope, near syncope, or palpitation. RESULTS: Fifty-six of 68 patients had cardiomyopathy with left ventricular ejection fraction (LVEF)

T-wave alternans: marker, mechanism, and methodology for predicting sudden cardiac death.

Sudden cardiac death (SCD) is a leading cause of cardiovascular mortality. Therefore, identifying patients at highest risk for SCD is crucial. Conventional noninvasive markers of SCD are inadequate because of low positive predictive value. The presence of visible T-wave alternans (TWA) on electrocardiogram often predicts the occurrence of lethal ventricular arrhythmias. Signal processing methods have made it possible to detect microvolt-level and visually inapparent TWA on electrocardiogram. TWA is caused by underlying regional inhomogeneities of ventricular repolarization, which predispose patients to have ventricular arrhythmias. Microvolt TWA provoked either by atrial pacing, pharmacological stress, or exercise is a promising marker of arrhythmia vulnerability. Several large trials have shown TWA to be comparable or superior to other noninvasive markers and electrophysiologic study in the prediction of SCD. The patient populations in these trials include post myocardial infarction, both ischemic and nonischemic heart failure, and suspected arrhythmias. Prospective trials regarding benefits of implantation of cardioverter-defibrillator therapy based on TWA results are ongoing.

Identification and characterization of atrioventricular parasympathetic innervation in humans.

INTRODUCTION: We hypothesized that in humans there is an epicardial fat pad from which parasympathetic ganglia supply the AV node. We also hypothesized that the parasympathetic nerves innervating the AV node also innervate the right atrium, and the greatest density of innervation is near the AV nodal fat pad. METHODS AND RESULTS: An epicardial fat pad near the junction of the left atrium and right inferior pulmonary vein was identified during cardiac surgery in seven patients. A ring electrode was used to stimulate this fat pad intraoperatively during sinus rhythm to produce transient complete heart block. Subsequently, temporary epicardial wire electrodes were sutured in pairs on this epicardial fat pad, the high right atrium, and the right ventricle by direct visualization during coronary artery bypass surgery in seven patients. Experiments were performed in the electrophysiology laboratory 1 to 5 days after surgery. Programmed atrial stimulation was performed via an endocardial electrode catheter advanced to the right atrium. The catheter tip electrode was moved in 1-cm concentric zones around the epicardial wires by fluoroscopic guidance. Atrial refractoriness at each catheter site was determined in the presence and absence of parasympathetic nerve stimulation (via the epicardial wires). In all seven patients, an AV nodal fat pad was identified. Fat pad stimulation during and after surgery caused complete heart block but no change in sinus rate. Fat pad stimulation decreased the right atrial effective refractory period at 1 cm (280 +/- 42 msec to 242 +/- 39 msec) and 2 cm (235 +/- 21 msec to 201 +/- 11 msec) from the fat pad (P = 0.04, compared with baseline). No significant change in atrial refractoriness occurred at distances >2 cm. The response to stimulation decreased as the distance from the fat pad increased. CONCLUSION: For the first time in humans, an epicardial fat pad was identified from which parasympathetic nerve fibers selectively innervate the AV node but not the sinoatrial node. Nerves in this fat pad also innervate the surrounding right atrium.