Cardiac Contractility Modulation in a Model of Repaired Tetralogy of Fallot: A Sheep Model.

The onset of right ventricular dysfunction in patients presenting with congenital heart disease is associated with a dismal long-term outcome and often represents a therapeutic dead end. Our study had several objectives: (1) to analyse the anatomical, functional, histological and cellular characteristics of an animal model of repaired tetralogy of Fallot with right ventricular dysfunction (2) to test the new electrical treatment known as cardiac contractility modulation in this animal model. Seven sheep underwent a first surgery at the age of three weeks aiming to mimic the characteristics of a repaired tetralogy of Fallot. Five controls were sham-operated. Experimental studies were performed 12 months after the initial operation. The hemodynamic, echocardiographic, and mitochondrial function studies were carried out before and after cardiac contractility modulation in closed- and open-chest conditions. In this animal model of right ventricular dysfunction, short-term cardiac contractility modulation was associated with a significant improvement in (a) right ventricular function, as evidenced by a significant increase in right ventricular dP/dt (p < 0.05) (b) left ventricular function evidenced by the increase in left ventricular dP/dt max (p < 0.05) (c) in mitochondrial function (p < 0.05). In this animal model of chronic right ventricular dysfunction, cardiac contractility modulation significantly improved acute cardiac hemodynamic and mitochondrial functions of both ventricles and may represent a promising option in patients with right heart failure.

Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: a multicenter study-part 2.

BACKGROUND: Implantable cardioverter-defibrillator indications in Brugada syndrome remain controversial, especially in asymptomatic patients. Previous outcome data are limited by relatively small numbers of patients or short follow-up durations. We report the outcome of patients with Brugada syndrome implanted with an implantable cardioverter-defibrillator in a large multicenter registry. METHODS AND RESULTS: A total of 378 patients (310 male; age, 46±13 years) with a type 1 Brugada ECG pattern implanted with an implantable cardioverter-defibrillator (31 for aborted sudden cardiac arrest, 181 for syncope, and 166 asymptomatic) were included. Fifteen patients (4%) were lost to follow-up. During a mean follow-up of 77±42 months, 7 patients (2%) died (1 as a result of an inappropriate shock), and 46 patients (12%) had appropriate device therapy (5±5 shocks per patient). Appropriate device therapy rates at 10 years were 48% for patients whose implantable cardioverter-defibrillator indication was aborted sudden cardiac arrest, 19% for those whose indication was syncope, and 12% for the patients who were asymptomatic at implantation. At 10 years, rates of inappropriate shock and lead failure were 37% and 29%, respectively. Inappropriate shock occurred in 91 patients (24%; 4±4 shocks per patient) because of lead failure (n=38), supraventricular tachycardia (n=20), T-wave oversensing (n=14), or sinus tachycardia (n=12). Importantly, introduction of remote monitoring, programming a high single ventricular fibrillation zone (>210-220 bpm), and a long detection time were associated with a reduced risk of inappropriate shock. CONCLUSIONS: Appropriate therapies are more prevalent in symptomatic Brugada syndrome patients but are not insignificant in asymptomatic patients (1%/y). Optimal implantable cardioverter-defibrillator programming and follow-up dramatically reduce inappropriate shock. However, lead failure remains a major problem in this population.

Remote interrogation and reprogramming of cardiac implantable electronic devices using a custom multivendor solution.

BACKGROUND: Until recently, remote interrogation and reprogramming of therapeutic cardiac implantable electronic devices (CIEDs) have been virtually nonexistent owing to technical challenges and safety concerns. It could be extremely useful, in particular in case of emergencies, when patients live far from CIED professionals or during enforced physical distancing. OBJECTIVE: We investigated the feasibility and safety of a custom solution for remote interrogation and reprogramming of CIEDs from various manufacturers in various clinically relevant situations. METHODS: Our solution consists of remote controlling CIED programmers through screen capture and remote cursor control. In this multicenter feasibility study, the primary outcome was technical feasibility (% of success) and safety (absence of complication) of interrogation and reprogramming when indicated in clinically driven encounters. RESULTS: A total of 115 remote interrogations were performed in 110 patients: within the hospital (n = 73), medium range (50-100 km; n = 22), and long range (>5000 km; n = 20). Implanted devices were pacemakers (n = 85) and implantable cardioverter-defibrillators (n = 25) from Abbott (N=13), Biotronik (n = 65), and MicroPort (n = 32). Patients were located in the outpatient clinic, cardiology department, radiology department (magnetic resonance imaging), operating room (per implantation), and intensive care unit. Teleworking was performed in 39 cases. Complete CIED interrogations succeeded in all patients with reprogramming in 56 of 115 sessions (49%). No clinical or technical complications occurred. The time lag for screen interaction was below 1 second. CONCLUSION: Remote interrogation and reprogramming of CIEDs are feasible and safe across disparate clinical contexts and distances. This strategy may enhance health care access and facilitate medical training, tele-expertise, and telework worldwide.

Electrical storm in the early phase of HeartMate® II device implantation: Incidence, risk factors and prognosis.

BACKGROUND: Ventricular arrhythmia is common after left ventricular assist device (LVAD) implantation, especially in the early postoperative phase (<30 days). AIM: To identify the incidence of and risk factors for electrical storm (ES) occurring within 30 days of HeartMate® II implantation. METHODS: We reviewed data from all consecutive patients undergoing HeartMate® II device implantation at our institution from January 2008 to December 2014. Patient demographic data, pharmacotherapies and outcomes were collected. The primary endpoint was occurrence of early ES (within 30 days of surgery), defined as three or more separate episodes of sustained ventricular arrhythmia within a 24-hour interval, requiring appropriate therapy. RESULTS: Forty-three patients (mean age 56.7±11.2 years; 39 men) were included. At HeartMate® II implantation, mean left ventricular ejection fraction was 20±5%, 32 (74.4%) patients had ischaemic cardiomyopathy and 31 (72.1%) were implanted with an indication of bridge to cardiac transplantation. During follow-up, 12 (27.9%) patients experienced early ES after HeartMate® II implantation (median delay 9.1±7.8 days). Early ES was more frequent in larger patients (body surface area 1.99 vs 1.81 m2; P<0.01), tended to be associated with previous sustained ventricular tachycardia (50.0% vs 22.6%; P=0.08), previous implantable cardioverter-defibrillator implantation (66.7% vs 38.7%; P=0.09), discontinuation of long-term beta-blocker therapy (75.0% vs 45.2%; P=0.08), weaning of adrenergic drugs after the third day (66.7% vs 35.5%; P=0.06) and the use of extracorporeal life support (50% vs 22.6%; P=0.079), but was not associated with the cardiomyopathy aetiology or the indication for assistance. Catheter ventricular tachycardia ablation was performed in six (14.0%) patients. Early ES was associated with a significantly higher all-cause mortality rate at the 30th day (33.3% vs 6.5%; P=0.02). CONCLUSION: ES is a common and pejorative feature in the early postoperative period.

Distinctive Left Ventricular Activations Associated With ECG Pattern in Heart Failure Patients.

BACKGROUND: In contrast to patients with left bundle branch block (LBBB), heart failure patients with narrow QRS and nonspecific intraventricular conduction delay (NICD) display a relatively limited response to cardiac resynchronization therapy. We sought to compare left ventricular (LV) activation patterns in heart failure patients with narrow QRS and NICD to patients with LBBB using high-density electroanatomic activation maps. METHODS AND RESULTS: Fifty-two heart failure patients (narrow QRS [n=18], LBBB [n=11], NICD [n=23]) underwent 3-dimensional electroanatomic mapping with a high density of mapping points (387±349 LV). Adjunctive scar imaging was available in 37 (71%) patients and was analyzed in relation to activation maps. LBBB patients typically demonstrated (1) a single LV breakthrough at the septum (38±15 ms post-QRS onset); (2) prolonged right-to-left transseptal activation with absence of direct LV Purkinje activity; (3) homogeneous propagation within the LV cavity; and (4) latest activation at the basal lateral LV. In comparison, both NICD and narrow QRS patients demonstrated (1) multiple LV breakthroughs along the posterior or anterior fascicles: narrow QRS versus LBBB, 5±2 versus 1±1; P=0.0004; NICD versus LBBB, 4±2 versus 1±1; P=0.001); (2) evidence of early/pre-QRS LV electrograms with Purkinje potentials; (3) rapid propagation in narrow QRS patients and more heterogeneous propagation in NICD patients; and (4) presence of limited areas of late activation associated with LV scar with high interindividual heterogeneity. CONCLUSIONS: In contrast to LBBB patients, narrow QRS and NICD patients are characterized by distinct mechanisms of LV activation, which may predict poor response to cardiac resynchronization therapy.

Diagnostic value of isoproterenol testing in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Although the Task Force Criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) have recently been updated, the diagnosis remains challenging in the early stages. The aim of this study was to evaluate the diagnostic value of ß-adrenergic stimulation in ARVC. METHODS AND RESULTS: We evaluated 412 consecutive patients (213 men, age 41.5±16 years) referred for premature ventricular contractions evaluation or suspected ARVC. Isoproterenol testing was performed with continuous infusion of isoproterenol (45 µg/min) for 3 minutes. It was considered positive if there were either (1) polymorphic premature ventricular contractions with ≥1 couplet or (2) sustained or nonsustained ventricular tachycardia with left bundle branch block excluding right ventricular outflow tract ventricular tachycardia. ARVC was diagnosed in 35 patients at initial evaluation (23 men, aged 42±15 years). Isoproterenol testing was positive in 32 of 35 (91.4%) patients with ARVC and in 42 of 377 (11.1%) patients without ARVC (P<0.0001). Sensitivity, specificity, positive, and negative predictive values of isoproterenol testing to diagnose ARVC were 91.4%, 88.9%, 43.2%, and 99.1%, respectively. During a mean follow-up period of 5.6±4.4 years, 6 additional patients met diagnostic criteria for ARVC. Importantly, initial isoproterenol testing was positive in 6 of 6 (100%) of these patients. Survival free from ARVC diagnosis was significantly lower in the positive isoproterenol group than in the negative isoproterenol group (P<0.0001, exact log-rank test). CONCLUSIONS: Ventricular arrhythmogenicity during isoproterenol testing is highly sensitive (sensitivity, 91.4%) for the diagnosis of ARVC, particularly in its early stages.

Noninvasive electrocardiographic mapping to improve patient selection for cardiac resynchronization therapy: beyond QRS duration and left bundle branch block morphology.

OBJECTIVES: This study sought to investigate whether noninvasive electrocardiographic activation mapping is a useful method for predicting response to cardiac resynchronization therapy (CRT). BACKGROUND: One third of the patients appear not to respond to CRT when they are selected according to QRS duration. METHODS: We performed electrocardiographic activation mapping in 33 consecutive CRT candidates (QRS duration ≥120 ms). In 18 patients, the 12-lead electrocardiographic morphology was left bundle branch block (LBBB), and in 15, it was nonspecific intraventricular conduction disturbance (NICD). Three indexes of electrical dyssynchrony were derived from intrinsic maps: right and left ventricular total activation times and ventricular electrical uncoupling (VEU) (difference between the left ventricular [LV] and right ventricular mean activation times). We assessed the ability of these parameters to predict response, measured using a clinical composite score, after 6 months of CRT. RESULTS: Electrocardiographic maps revealed homogeneous patterns of activation and consistently greater VEU and LV total activation time (LVTAT) in patients with LBBB compared with heterogeneous activation sequences and shorter VEU and LVTAT in NICD patients (VEU: 75 ± 12 ms vs. 40 ± 22 ms; p < 0.001; LVTAT: 115 ± 21 ms vs. 91 ± 34 ms; p = 0.03). LBBB and NICD patients had similar right ventricular total activation times (62 ± 30 ms vs. 58 ± 26 ms; p = 0.7). The area under the receiver-operating characteristic curve indicated that VEU (area under the curve [AUC]: 0.88) was significantly superior to QRS duration (AUC: 0.73) and LVTAT (AUC: 0.72) for predicting CRT response (p < 0.05). With a 50-ms cutoff value, VEU identified CRT responders with 90% sensitivity and 82% specificity whether LBBB was present or not. CONCLUSIONS: Ventricular electrical uncoupling measured by electrocardiographic mapping predicted clinical CRT response better than QRS duration or the presence of LBBB.

Acute hemodynamic response to biventricular pacing in heart failure patients with narrow, moderately, and severely prolonged QRS duration.

BACKGROUND: The efficacy of biventricular (BiV) pacing in patients with a narrow or moderately prolonged QRS duration remains questionable. OBJECTIVE: To assess the hypothesis that electrical dyssynchrony is required to obtain hemodynamic benefit from BiV pacing by investigating the relationship between intrinsic QRS duration and hemodynamic response to BiV pacing in a patient population covering a broad spectrum of QRS duration. METHODS: Eighty-two consecutive heart failure patients underwent cardiac resynchronization therapy implantation irrespective of their QRS duration. Thirty-four patients had a narrow QRS duration (<120 ms), whereas 11 patients had a moderately prolonged QRS duration (≥120 to <150 ms) and 37 patients had a severely prolonged QRS duration (≥150 ms). After implantation, invasive left ventricular (LV) dP/dt measurements were compared between intrinsic rhythm and simultaneous BiV pacing with an optimized atrioventricular delay. RESULTS: A high correlation (r = .65; P < .001) was observed between baseline QRS duration and changes in LV dP/dt(max) induced by BiV pacing. BiV pacing was ineffective in patients with a narrow QRS duration (+0.4% ± 6.1%; P = ns). No significant increase in LV dP/dt(max) was observed in patients with a QRS duration of ≥120 to <150 ms (+4.4% ± 6.9%; P = .06), whereas patients with a QRS duration of ≥150 ms exhibited a significant increase in LV dP/dt(max) (+17.1% ± 13.4%; P <.001). Only 9% of the patients with a narrow QRS duration exhibited a ≥10% increase in LV dP/dt(max). CONCLUSIONS: Baseline QRS duration is linearly related to acute hemodynamic response to BiV pacing. Patients with a narrow QRS duration do not derive hemodynamic improvement. This improvement is also limited in patients with a moderately prolonged QRS duration, raising questions about the potential clinical benefit of this therapy in these patients.