David J. Callans

Prognostic importance of defibrillator shocks in patients with heart failure.

BACKGROUND Patients with heart failure who receive an implantable cardioverter-defibrillator (ICD) for primary prevention (i.e., prevention of a first life-threatening arrhythmic event) may later receive therapeutic shocks from the ICD. Information about long-term prognosis after ICD therapy in such patients is limited. METHODS Of 829 patients with heart failure who were randomly assigned to ICD therapy, we implanted the ICD in 811. ICD shocks that followed the onset of ventricular tachycardia or ventricular fibrillation were considered to be appropriate. All other ICD shocks were considered to be inappropriate. RESULTS Over a median follow-up period of 45.5 months, 269 patients (33.2%) received at least one ICD shock, with 128 patients receiving only appropriate shocks, 87 receiving only inappropriate shocks, and 54 receiving both types of shock. In a Cox proportional-hazards model adjusted for baseline prognostic factors, an appropriate ICD shock, as compared with no appropriate shock, was associated with a significant increase in the subsequent risk of death from all causes (hazard ratio, 5.68; 95% confidence interval [CI], 3.97 to 8.12; P<0.001). An inappropriate ICD shock, as compared with no inappropriate shock, was also associated with a significant increase in the risk of death (hazard ratio, 1.98; 95% CI, 1.29 to 3.05; P=0.002). For patients who survived longer than 24 hours after an appropriate ICD shock, the risk of death remained elevated (hazard ratio, 2.99; 95% CI, 2.04 to 4.37; P<0.001). The most common cause of death among patients who received any ICD shock was progressive heart failure. CONCLUSIONS Among patients with heart failure in whom an ICD is implanted for primary prevention, those who receive shocks for any arrhythmia have a substantially higher risk of death than similar patients who do not receive such shocks.

Presence of Left-to-Right Atrial Frequency Gradient in Paroxysmal but Not Persistent Atrial Fibrillation in Humans

Background—Recent studies have demonstrated spatiotemporal organization in atrial fibrillation (AF), with a left-to-right atrial frequency gradient during AF in isolated sheep hearts. We hypothesized that human AF would also manifest a left-to-right atrial frequency gradient. Methods and Results—Thirty-one patients aged 56.7±10.5 years with a history of paroxysmal or persistent (>1 month) AF were included. Recordings were made at each pulmonary vein (PV) ostium and simultaneously from the coronary sinus (CS) and posterior right atrium (RA) during AF. Sequential fast Fourier transforms (FFTs) were performed. FFT profiles were analyzed to determine the dominant frequency (DF). There were 18 patients with paroxysmal AF and 13 with persistent AF. In the paroxysmal group, there was a significant left-to-right atrial DF gradient, with DF highest at the PV/left atrial (LA) junction, intermediate at the CS, and lowest in the RA (6.2±0.8, 5.5±0.7, and 5.1±0.6 Hz, respectively; P<0.001). There were no patients in whom DF was greater at the RA than the PV/LA junction. In the persistent group, there was no significant difference between DF recorded from the LA/PV junction, CS, and RA (6.1±0.7, 5.8±0.6, and 5.8±0.6 Hz, respectively; P=NS). Conclusions—In humans with paroxysmal AF, DFs are highest at the PV/LA junction, intermediate in the CS, and slowest in the posterior RA. These findings agree with animal models that suggest that the posterior LA may play an important role in maintaining paroxysmal AF. The role of the posterior LA in persistent AF requires further study.

Characterization of Endocardial Electrophysiological Substrate in Patients With Nonischemic Cardiomyopathy and Monomorphic Ventricular Tachycardia

Background—Although catheter mapping has been used to define the endocardial electrogram characteristics in patients with ventricular tachycardia (VT) and coronary disease, characterization of the electrophysiological substrate in patients with VT and nonischemic cardiomyopathy is limited. Methods and Results—Left ventricular endocardial electroanatomical mapping was performed in 19 patients with nonischemic cardiomyopathy and monomorphic VT with an average of 178±83 sites per chamber mapped. Abnormal bipolar electrogram was defined as endocardial voltage signal amplitude of <1.8 mV. The extent and location of abnormal endocardium was estimated by measuring areas of abnormal electrogram recordings from 3D voltage maps. The origin of VT was approximated by identifying sites of entrainment with concealed fusion or early presystolic activity and/or by pace mapping. Abnormal electrograms were recorded over a 41±28 cm2 area that represented 20±12% of total endocardial surface. The majority of patients (14/19 patients) had only a modest area (<25%) of endocardial abnormality. All patients had abnormal low-voltage endocardial areas located near the ventricular base in the perivalvular region. There were 3±1 VT morphologies per patient. The majority (88%) of the 57 mapped VTs originated from the ventricular base, corresponding to regions with abnormal endocardial electrograms. Conclusions—Electroanatomical mapping in patients with monomorphic VT and nonischemic cardiomyopathy typically demonstrates a modest-sized basal area of endocardial electrogram abnormalities. The VT site of origin corresponds to these basal electrogram abnormalities. These findings have important implications regarding strategies for VT ablation in this setting.

Atrial Fibrillation and Heart Failure Treatment Considerations for a Dual Epidemic

Atrial fibrillation (AF) and heart failure have emerged as new cardiovascular epidemics over the last decade.1 Heart failure affects ≈5 million patients in the United States, and >550 000 patients are diagnosed with new heart failure each year.2 Although the incidence of heart failure remained stable over the past 50 years, the prevalence of heart failure in the United States has steadily increased. Heart failure is the primary reason for 12 to 15 million office visits and 6.5 million hospital days yearly.3 From 1990 to 1999, the annual number of hospitalizations increased from ≈800 000 to >1 million for heart failure as a primary diagnosis and from 2.4 to 3.6 million for heart failure as a primary or secondary diagnosis.4 The steadily increasing number of patients with heart failure is due partially to better treatment and “salvage” of patients with acute myocardial infarctions earlier in life.2 As a consequence, heart failure carries a significant economic burden on our society because it is the most common discharge diagnosis and because more Medicare dollars are spent for the diagnosis and treatment of heart failure than for any other diagnosis.5 In 2007, the American Heart Association estimated that

A conformal, bio-interfaced class of silicon electronics for mapping cardiac electrophysiology.

33 billion was spent on heart failure alone.6 AF is the most common arrhythmia in clinical practice, accounting for approximately one third of admissions resulting from cardiac rhythm disturbances. An estimated 2.3 million people in North America have AF. During the last 20 years, hospital admissions for AF have increased by 66% for a number of reasons, including the aging of the population, the rising prevalence of chronic heart disease, and more frequent diagnosis as a result of increased monitoring.7 The recent Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study projected that the prevalence of AF …

Electroanatomic Substrate and Ablation Outcome for Suspected Epicardial Ventricular Tachycardia in Left Ventricular Nonischemic Cardiomyopathy

Flexible electronics and sensors that adhere to the surfaces of living, moving tissues allow detailed mapping of cardiac electrical activity in a porcine animal model. My Beating Heart The heart is tricky to work with. Usually in constant motion, it has to be stopped for most cardiac surgery and its health is most often checked by EKG measurements of net electrical activity from outside the body. When damage to the heart causes life-threatening arrhythmias, physicians can only get a get a rough idea about where the problem is located by painstakingly recording from one part of the heart after another. Improvements in electronic circuit design and fabrication, as reported here by Viventi et al., can enable sophisticated, multiunit electrodes to stay in close contact with biological tissue, making monitoring and stimulation of the living, moving heart a realistic goal. The new type of device is a multilayer circuit fabricated on a 25-μm-thick, plastic sheet of polyimide, with a built-in array of 288 gold electrodes. It is flexible but the design keeps the sensitive electronics in the neutral plane so that it still functions, even when bent. Each electrode has its own amplifier, which magnifies the tiny biological currents, and multiplexer, which allows the output of all 288 electrodes to be conveyed by only 36 wires. Electrically active devices inside the wet interior of the body can easily leak current, so the authors guarded against this by encapsulating the device in a trilayer coating of polyimide, silicon nitride, and epoxy. Most (75%) of the devices they made leaked less than 10 μA, an industry standard, and maintained this performance for at least 3 hours. To map cardiac function with their flexible electrode array, the researchers applied it to the exposed epicardial surface of the beating porcine heart. Functional for more than 10,000 bending cycles, the electrodes could record normal heart beats or beats driven by a second pacing electrode at high resolution. With a high signal-to-noise ratio of about 34 dB, conduction of a moving wave of cardiac activation was readily apparent as it swept across the array of electrodes with each contraction. The authors constructed an isochronal map of heart activation, determining that the conduction velocity was 0.9 mm per millisecond. Heart physiology is not the only possible application for these flexible electrodes. The brain is also a curved, wet organ that can only be accessed by individually wired electrodes at present. Muscles are electrically active moving tissues, found both within internal organs and as effectors for the limbs. The ability to house electrodes, amplifiers, and multiplexers in a flexible, biocompatible plastic sheet that can snuggle up right against the organ of interest will improve our ability to stimulate and monitor living tissues. In all current implantable medical devices such as pacemakers, deep brain stimulators, and epilepsy treatment devices, each electrode is independently connected to separate control systems. The ability of these devices to sample and stimulate tissues is hindered by this configuration and by the rigid, planar nature of the electronics and the electrode-tissue interfaces. Here, we report the development of a class of mechanically flexible silicon electronics for multiplexed measurement of signals in an intimate, conformal integrated mode on the dynamic, three-dimensional surfaces of soft tissues in the human body. We demonstrate this technology in sensor systems composed of 2016 silicon nanomembrane transistors configured to record electrical activity directly from the curved, wet surface of a beating porcine heart in vivo. The devices sample with simultaneous submillimeter and submillisecond resolution through 288 amplified and multiplexed channels. We use this system to map the spread of spontaneous and paced ventricular depolarization in real time, at high resolution, on the epicardial surface in a porcine animal model. This demonstration is one example of many possible uses of this technology in minimally invasive medical devices.

Repetitive monomorphic tachycardia from the left ventricular outflow tract : Electrocardiographic patterns consistent with a left ventricular site of origin

OBJECTIVES The aim of the study was to define the epicardial substrate and ablation outcome in patients with left ventricular nonischemic cardiomyopathy (NICM) and suspected epicardial ventricular tachycardia (VT). BACKGROUND Ventricular tachycardia in NICM often originates from the epicardium. METHODS Twenty-two patients with NICM underwent detailed endocardial and epicardial bipolar voltage maps and VT ablation for suspected epicardial VT. Eight patients with normal hearts and idiopathic VT served to define normal epicardial electrograms. Low-voltage regions were also assessed for wide (>80 ms), split, or late electrograms. RESULTS Normal epicardial bipolar voltage was identified as >1.0 mV on the basis of the reference population. Confluent low-voltage areas were present in 18 epicardial (82%) and 12 endocardial (54%) maps and were typically over basal lateral LV. In the 18 patients with epicardial VT on the basis of activation/pacemapping, the mean epicardial area was greater than the endocardial low-voltage area (55.3 +/- 33.5 cm(2) vs. 22.9 +/- 32.4 cm(2), p < 0.01). Epicardial low-voltage areas showed 49.7% wide (>80 ms), split, and/or late electrograms rarely seen in the reference patients (2.3%). During follow-up of 18 +/- 7 months, ablation resulted in VT elimination in 15 of 21 patients (71%) including 14 of 18 patients (78%) with epicardial VT. CONCLUSIONS In patients with NICM and VT of epicardial origin, the substrate is characterized by areas of basal LV epicardial > endocardial bipolar low voltage. The electrograms in these areas are not only small (<1.0 mV) but wide (>80 ms), split, and/or late, and help identify the substrate targeted for successful ablation.

Mechanisms of Organized Left Atrial Tachycardias Occurring After Pulmonary Vein Isolation

OBJECTIVES This study sought to characterize the electrocardiographic patterns predictive of left ventricular sites of origin of repetitive monomorphic ventricular tachycardia (RMVT). BACKGROUND RMVT typically arises from the right ventricular outflow tract (RVOT) in patients without structural heart disease. The incidence of left ventricular sites of origin in this syndrome is unknown. METHODS Detailed endocardial mapping of the RVOT was performed in 33 consecutive patients with RMVT during attempted radiofrequency ablation. Left ventricular mapping was also performed if pace maps obtained from the RVOT did not reproduce the configuration of the induced tachycardia. RESULTS Pace maps identical in configuration to the induced tachycardia were obtained from the RVOT in 29 of 33 patients. Application of radiofrequency energy at sites guided by pace mapping resulted in elimination of RMVT in 24 (83%) of 29 patients. In four patients (12%), pace maps obtained from the RVOT did not match the induced tachycardia. All four patients had a QRS configuration during RMVT with precordial R wave transitions at or before lead V2. In two patients, RMVT was mapped to the mediosuperior aspect of the mitral valve annulus, near the left fibrous trigone; catheter ablation at that site was successful in both. In two patients, RMVT was mapped to the basal aspect of the superior left ventricular septum. Catheter ablation was not attempted because His bundle deflections were recorded from this site during sinus rhythm. CONCLUSIONS RMVT can arise from the outflow tract of both the right and left ventricles. RMVTs with a precordial R wave transition at or before lead V2 are consistent with a left ventricular origin.

Electrocardiographic Patterns of Superior Right Ventricular Outflow Tract Tachycardias: Distinguishing Septal and Free-Wall Sites of Origin

Background—A proarrhythmic consequence of pulmonary vein (PV) isolation can be a recurrent organized left atrial (LA) tachycardia after ablation. This arrhythmia is frequently referred to as “left atrial flutter,” but the mechanism and best ablation strategy have not been determined. Methods and Results—Isolation of arrhythmogenic PVs was initially performed by segmental ostial PV ablation guided by a circular mapping catheter in 341 patients. Patients whose predominant recurrent arrhythmia was a persistent organized tachycardia returned for mapping and ablation. Recurrent organized LA tachycardias (cycle length 253±33 ms, range 213 to 328 ms) occurred in 10 (2.9%) of 341 patients (age 59±9 years, 1 woman). Mapping was consistent with a focal origin in 8 patients and with macroreentry in 1 patient and was unclear in 1 patient owing to degeneration to atrial fibrillation. Focal tachycardias originated from reconnected segments of prior isolated PVs (6 patients), the posterior LA (1 patient), or the superior septum (1 patient). Focal atrial tachycardias were ablated with point lesions that targeted the earliest activation. All reconnected PVs were also reisolated. Reentrant LA flutter occurred around the left PVs in 1 patient. After 6.7±2.3 months of follow-up, 9 (90%) of 10 patients were arrhythmia free (4 of whom were taking antiarrhythmic drug therapy), and one was having recurrent atrial fibrillation. Conclusions—Recurrent organized LA tachycardia after PV isolation is uncommon and typically has a focal origin from reconnected PV ostia. Reisolation of the PV and ablation of non-PV foci are sufficient to treat this proarrhythmia. Linear lesions are only required when a macroreentrant mechanism is present.

Electroanatomic Substrate and Outcome of Catheter Ablative Therapy for Ventricular Tachycardia in Setting of Right Ventricular Cardiomyopathy

ECG Patterns of RVOT Tachycardias. Introduction: The superior right ventricular outflow tract (RVOT) septum and free wall are common locations of origin for outflow tract ventricular tachycardias (VT). We hypothesized that (1) unique ECG morphologies of pace maps from septal and free‐wall sites in the superior RVOT could be identified using magnetic electroanatomic mapping for accurate anatomical localization; and (2) this ECG information could help facilitate pace mapping and accurate VT localization.