Cardiac Resynchronization Therapy With a Quadripolar Electrode Lead Decreases Complications at 6 Months: Results of the MORE-CRT Randomized Trial.

OBJECTIVES: The aim of this study was to test the hypothesis that a quadripolar left ventricular (LV) lead results in fewer LV lead-related events than a bipolar cardiac resynchronization therapy (CRT) system in a prospective randomized trial. BACKGROUND: Bipolar LV leads cannot be implanted at the optimal site in up to 10% of patients who need CRT, because of anatomic or technical challenges (pacing threshold, phrenic stimulation, or mechanical instability). METHODS: The MORE-CRT (More Options Available With a Quadripolar LV Lead Provide In-Clinic Solutions to CRT Challenges) trial enrolled 1,078 patients. Patients with indications for CRT defibrillator therapy were randomized into 2 groups in a 1:2 ratio: a group with a bipolar CRT lead system (the BiP group; any manufacturer) and a group with a quadripolar CRT system (the Quad group; Quartet LV lead). The primary endpoint was freedom from a composite endpoint of intraoperative and post-operative LV lead-related events at 6 months. RESULTS: A total of 1,074 of 1,078 patients (99%) were randomized and contributed to the primary endpoint. Freedom from the composite endpoint was significantly greater in the Quad than the BiP group (83.0% vs. 74.4%, p = 0.0002). The intraoperative component of the endpoint was met less frequently by Quad group patients (6.26% Quad vs. 12.1% BiP), whereas there was no difference for the post-operative component (7.1% Quad vs. 7.6% BiP). CONCLUSIONS: The Quartet LV system significantly reduced total LV lead-related events at 6 months after implantation compared with a bipolar CRT system. The reduction in events demonstrates the superiority of this quadripolar technology to effectively manage CRT patients. (More Options Available With a Quadripolar LV Lead Provide In-Clinic Solutions to CRT Challenges [MORE-CRT]; NCT01510652).

Pacemaker-induced transient asynchrony suppresses heart failure progression.

Uncoordinated contraction from electromechanical delay worsens heart failure pathophysiology and prognosis, but restoring coordination with biventricular pacing, known as cardiac resynchronization therapy (CRT), improves both. However, not every patient qualifies for CRT. We show that heart failure with synchronous contraction is improved by inducing dyssynchrony for 6 hours daily by right ventricular pacing using an intracardiac pacing device, in a process we call pacemaker-induced transient asynchrony (PITA). In dogs with heart failure induced by 6 weeks of atrial tachypacing, PITA (starting on week 3) suppressed progressive cardiac dilation as well as chamber and myocyte dysfunction. PITA enhanced ß-adrenergic responsiveness in vivo and normalized it in myocytes. Myofilament calcium response declined in dogs with synchronous heart failure, which was accompanied by sarcomere disarray and generation of myofibers with severely reduced function, and these changes were absent in PITA-treated hearts. The benefits of PITA were not replicated when the same number of right ventricular paced beats was randomly distributed throughout the day, indicating that continuity of dyssynchrony exposure is necessary to trigger the beneficial biological response upon resynchronization. These results suggest that PITA could bring the benefits of CRT to the many heart failure patients with synchronous contraction who are not CRT candidates.

Spinal cord stimulation is safe and feasible in patients with advanced heart failure: early clinical experience.

AIMS: Pre-clinical work suggests that upper thoracic spinal cord stimulation (SCS) may have therapeutic effects in the treatment of heart failure (HF). We therefore aim to assess the safety and feasibility of SCS in HF patients. METHODS AND RESULTS: A prospective, randomized, double-blind, crossover pilot study was conducted in symptomatic HF patients receiving optimal medical therapy. Patients were implanted with an SCS system and randomized to an SCS-ACTIVE, delivered at 90% paraesthesia threshold, or an SCS-INACTIVE phase for 3 months, followed by a 1-month washout period and crossover to the alternative phase. The safety of SCS therapy was assessed by death and cardiac events. Implantable cardioverter defibrillator (ICD) function in the presence of SCS was tested by defibrillation testing during SCS system implant and review of real-time and stored electrograms during follow-up. The efficacy of SCS therapy was assessed by changes in patient symptoms, LV function, and BNP level. Nine patients were investigated. In all cases, ICD sensing, detection, and therapy delivery were unaffected by SCS. During follow-up, one patient died and one was hospitalized for HF while in the SCS-INACTIVE phase, and two patients had HF hospitalizations during the SCS-ACTIVE phase. Symptoms were improved in the majority of patients with SCS, while markers of cardiac structure and function were, in aggregate, unchanged. CONCLUSION: This study shows that an SCS system can be safely implanted in patients with advanced HF and that the SCS system does not interfere with ICD function.

Improvement in acute contractility and hemodynamics with multipoint pacing via a left ventricular quadripolar pacing lead.

INTRODUCTION: A quadripolar left ventricular (LV) pacing can deliver multipoint pacing (MPP). It is unknown if this confers improved cardiac function compared to conventional cardiac resynchronization therapy (CRT). METHODS AND RESULTS: We aimed to characterize changes in acute cardiac contractility and hemodynamics with multisite left ventricular "multipoint" pacing (MPP) in a prospective multicenter study in patients implanted with a CRT-defibrillator incorporating a quadripolar LV lead. The device was programmed to deliver MPP acutely pacing with eight configurations of varying timing delays. Global peak LV radial strain and LV outflow velocity time integral (LVOT VTI) were measured for conventional CRT and each MPP configuration. Out of the eight tested MPP configurations, the one that yielded the best echocardiographic measurement for each patient was defined as "optimal MPP". Forty CRT recipients had complete radial strain datasets suitable for analysis. Compared to conventional CRT, the mean peak radial strain was significantly higher for the optimal MPP configuration (18.3 ± 7.4 vs. 9.3 ± 5.3%, p < 0.001), and at least one MPP configuration was significantly superior (>20%) in 63% of patients. LVOT VTI data were collected in a subset of 13 patients. In these patients, mean VTI was significantly higher for optimal MPP compared to conventional CRT (13.5 ± 2.7 vs. 10.9 ± 3.3 cm, p < 0.01). CONCLUSION: MPP delivered via a quadripolar LV lead resulted in a significant improvement in acute cardiac contractility and hemodynamics compared to conventional CRT in the majority of patients studied. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01044784.

Design of an acute dP/dt hemodynamic measurement protocol to isolate cardiac effect of pacing.

BACKGROUND: Invasively measured maximum increase in left ventricular pressure (LV dP/dtmax) has been used to assess biventricular (BiV) pacing. We quantified extracardiac factors contributing to its variability, and developed a protocol to minimize these effects in an acute pacing experiment. METHODS AND RESULTS: Continuous pressure was recorded by a guidewire sensor placed in the LV. Four to six test pacing interventions were performed, each repeated 3 times and followed by a baseline pacing configuration. Maximum increase in LV dP/dtmax from any measurement of BiV pacing was median 20.3% in 25 patients, compared with BiV pacing off. When directly comparing sequential measurements with BiV pacing on and off, median increase was 7.4%. Noncardiac sources of modulation included respiratory variation (6.4%), drift from first to last baseline measurement (5.0%), and discrepancy among repeated recordings of the same pacing intervention (3.3%). Comparing test interventions to interleaved baseline measurements reduced discrepancy among recordings to 2.1%; P < .001. CONCLUSIONS: With repeated measurements of baseline state, and by comparing test interventions only to baseline measurements performed before and after, it is possible to minimize extracardiac factors and focus on the effects of test pacing interventions.

Acute effects of multisite left ventricular pacing on mechanical dyssynchrony in patients receiving cardiac resynchronization therapy.

BACKGROUND: A novel quadripolar left ventricular (LV) pacing lead has the ability to deliver multisite LV pacing (MSLV). We set out to characterize the safety and changes in acute mechanical dyssynchrony with MSLV in cardiac resynchronization therapy (CRT) patients. METHODS AND RESULTS: Prospective multicenter study in 52 patients receiving CRT. An acute pacing protocol comprising 8 MSLV configurations covering a range of delays was compared with conventional CRT (baseline). Transthoracic tissue Doppler imaging (TDI) was used to measure the standard deviation of time to peak contraction of 12 LV segments (Ts-SD) and delayed longitudinal contraction. No ventricular arrhythmia occurred in any of the 52 patients. Complete TDI datasets were collected in 41 patients. Compared with baseline: 1) The mean Ts-SD was significantly lower for the optimal MSLV configuration (35.3 ± 36.4 vs 50.2 ± 29.1 ms; P < .001); 2) at least 1 MSLV configuration exhibited a significant dyssynchrony improvement in 63% of patients; and 3) the mean number of LV segments with delayed longitudinal contractions was significantly reduced with the optimal MSLV configuration (0.37 ± 7.99 vs 2.20 ± 0.19; P < .001). CONCLUSIONS: Acute MSLV was acutely safe, and a proportion of MSLV vectors resulted in a significant reduction in echocardiographic dyssynchrony compared with conventional CRT.

Acute haemodynamic comparison of multisite and biventricular pacing with a quadripolar left ventricular lead.

AIMS: Pacing from multiple sites in the left ventricle (LV) may bring about further resynchronization of the diseased heart compared with biventricular (BiV) pacing. We compared acute haemodynamic response (LV dP/dtmax) of multisite and BiV pacing using a quadripolar LV lead. METHODS AND RESULTS: In 21 patients receiving cardiac resynchronization therapy, a quadripolar LV lead and conventional right atrial and ventricular leads were connected to an external pacing system. A guidewire pressure sensor was placed in the LV for continuous dP/dt measurement. Four multisite pacing configurations were tested three times each and compared with BiV pacing using the distal LV electrode. Nineteen patients had useable haemodynamic data. Median increase in LV dP/dtmax with BiV vs. atrial-only pacing was 8.2% (interquartile range 2.3%, 15.7%). With multisite pacing using distal and proximal LV electrodes, median increase in LV dP/dtmax was 10.2% compared with atrial-only pacing (interquartile range 6.1%, 25.6%). In 16 of 19 patients (84%), two or more of the four multisite pacing configurations increased LV dP/dtmax compared with BiV pacing. Overall, 72% of all tested configurations of multisite pacing produced greater LV dP/dtmax than obtained with BiV pacing. Pacing from most distal and proximal electrodes was the most common optimal configuration, superior to BiV pacing in 74% of patients. CONCLUSION: In the majority of patients, multisite pacing improved acute systolic function further compared with BiV pacing. Pacing with the most distal and proximal electrodes of the quadripolar LV lead most commonly yielded greatest LV dP/dtmax.

Feasibility of using multivector impedance to monitor pulmonary congestion in heart failure patients.

PURPOSE: Pulmonary edema (PE) is associated with fluid accumulation in the lungs. Device-based impedance measurements have been used to detect fluid overload prior to hospitalization. However, studies have reported a high false positive rate (FPR). The objective of this study was to develop and test a new multivector impedance-based algorithm that reliably tracks PE clinical events. METHODS: We enrolled patients with implanted CRT-Ds in 23 US centers within 2 weeks of device implant. Six-vector impedance data was collected automatically by the CRT-Ds every 30 min during emergency department visits/hospitalizations and every 2 h at all other times. Detection algorithms for cardiac resynchronization therapy defibrillator (CRT-D) and implantable cardiac defibrillator (ICD) devices were developed using those impedance vectors that would be available in corresponding devices and retrospectively evaluated. RESULTS: There were 75 patients (69 % male), mean age 66 ± 12 years, with a LVEF of 23 ± 6 % and QRS of 149 ± 25 ms. Twenty-one major clinical events occurred over 8.2 ± 2.6 months of follow-up time. CRT-D vector combinations resulted in a sensitivity of 71.4 % (95 % confidence interval 47.8-88.7) and a FPR of 0.56 (0.30-0.94) false positives per patient-year (FPs/pt-yr); ICD vector combinations resulted in a sensitivity of 61.9 % (38.4-81.9) and a FPR of 0.63 (0.36-0.90) FPs/pt-yr. In comparison, the single-vector RVCoil-Can implementation of this algorithm resulted in a sensitivity of 57.1 % (34.0-78.2) and a FPR of 0.74 (0.44-1.12) FPs/pt-yr. CONCLUSIONS: This multivector impedance algorithm was effective in tracking PE clinical events in this patient population. Additional studies are needed to prospectively evaluate the performance of this algorithm in a larger population.

Spinal cord stimulation protects against atrial fibrillation induced by tachypacing.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to modulate atrial electrophysiology and confer protection against ischemia and ventricular arrhythmias in animal models. OBJECTIVE: To determine whether SCS reduces the susceptibility to atrial fibrillation (AF) induced by tachypacing (TP). METHODS: In 21 canines, upper thoracic SCS systems and custom cardiac pacing systems were implanted. Right atrial and left atrial effective refractory periods were measured at baseline and after 15 minutes of SCS. Following recovery in a subset of canines, pacemakers were turned on to induce AF by alternately delivering TP and searching for AF. Canines were randomized to no SCS therapy (CTL) or intermittent SCS therapy on the initiation of TP (EARLY) or after 8 weeks of TP (LATE). AF burden (percent AF relative to total sense time) and AF inducibility (percentage of TP periods resulting in AF) were monitored weekly. After 15 weeks, echocardiography and histology were performed. RESULTS: Effective refractory periods increased by 21 ± 14 ms (P = .001) in the left atrium and 29 ± 12 ms (P = .002) in the right atrium after acute SCS. AF burden was reduced for 11 weeks in EARLY compared with CTL (P <.05) animals. AF inducibility remained lower by week 15 in EARLY compared with CTL animals (32% ± 10% vs 91% ± 6%; P <.05). AF burden and inducibility were not significantly different between LATE and CTL animals. There were no structural differences among any groups. CONCLUSIONS: SCS prolonged atrial effective refractory periods and reduced AF burden and inducibility in a canine AF model induced by TP. These data suggest that SCS may represent a treatment option for AF.

Pacing electrode selection in a quadripolar left heart lead determines presence or absence of phrenic nerve stimulation.

A 60-year-old ischaemic patient presented for routine cardiac resynchronization therapy (CRT)-D implantation. An investigational quadripolar left ventricular lead was placed in the posterolateral vein. Phrenic nerve stimulation (PNS) was observed, but it occurred during pacing from only one of the four electrodes. A lead with multiple pacing electrodes is a potential alternative to physical adjustment of the lead or discontinuing CRT when PNS occurs.

Lead design and initial applications of a new lead for long-term endovascular vagal stimulation.

BACKGROUND: Vagal nerve stimulation (VNS) has negative chronotropic and dromotropic effects. We developed and tested an endovascular spiral vagal stimulation lead (ESVL) designed to follow the projection of the cardiac branches of the vagus nerve around the superior vena cava (SVC) to optimize VNS. METHODS: ESVL contained six 5-mm coil electrodes, spaced 5-mm apart with a spiral guidewire to provide shape. The tightness and diameter of the guidewire were changed before each placement to simulate different lead designs. Various 2-, 3-, and 4-electrode combinations were used and several lead positions were tested each time. Each VNS protocol included 2-12 V, 15-second pulse trains at 20 Hz, with 2 ms pulse duration. A basket catheter (BC) was used as control and to approximate the initial VNS location. The VNS protocol was performed at the optimal location, using first the BC and then several ESVL configurations. RESULTS: VNS caused a voltage-dependent decrease in heart rate (HR). Using the optimal ESVL configuration at 7 V, HR decreased by 30.4% (37.2 bpm) in dog no. 1 and 12.4% (16.6 bpm) in dog no. 2, versus 15.5% (16.6 bpm) and 16.7% (19.5 bpm) with the BC. CONCLUSIONS: A new endovascular spiral lead that takes advantage of the anatomy of the cardiac branches of the vagus nerve in the SVC was developed. VNS using ESVL produced significant HR slowing at voltages slightly below the highest pulse generator output of 7.5 V, which may be suitable for long-term implantation.