Zachary I. Whinnett

Noninvasive Electrocardiographic Mapping to Improve Patient Selection for Cardiac Resynchronization Therapy Beyond QRS Duration and Left Bundle Branch Block Morphology

OBJECTIVESnThis study sought to investigate whether noninvasive electrocardiographic activation mapping is a useful method for predicting response to cardiac resynchronization therapy (CRT).nnnBACKGROUNDnOne third of the patients appear not to respond to CRT when they are selected according to QRS duration.nnnMETHODSnWe performed electrocardiographic activation mapping in 33 consecutive CRT candidates (QRS durationxa0≥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.nnnRESULTSnElectrocardiographic 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; pxa0< 0.001; LVTAT: 115 ± 21 ms vs. 91 ± 34 ms; pxa0= 0.03). LBBB and NICD patients had similar right ventricular total activation times (62 ± 30 ms vs. 58 ± 26 ms; pxa0= 0.7). The area under the receiver-operating characteristic curve indicated that VEU (area under the curve [AUC]:xa00.88) was significantly superior to QRS duration (AUC: 0.73) and LVTAT (AUC: 0.72) for predicting CRT response (pxa0<xa00.05). With a 50-ms cutoff value, VEU identified CRT responders with 90% sensitivity and 82% specificity whether LBBB was present or not.nnnCONCLUSIONSnVentricular electrical uncoupling measured by electrocardiographic mapping predicted clinical CRT response better than QRS duration or the presence of LBBB.

Attenuation of Wave Reflection by Wave Entrapment Creates a “Horizon Effect” in the Human Aorta

Wave reflection is thought to be important in the augmentation of blood pressure. However, identification of distal reflections sites remains unclear. One possible explanation for this is that wave reflection is predominately determined by an amalgamation of multiple proximal small reflections rather than large discrete reflections originating from the distal peripheries. In 19 subjects (age, 35–73 years), sensor-tipped intra-arterial wires were used to measure pressure and Doppler velocity at 10-cm intervals along the aorta, starting at the aortic root. Incident and reflected waves were identified and timings and magnitudes quantified using wave intensity analysis. Mean wave speed increased along the length of the aorta (proximal, 6.8±0.9 m/s; distal, 10.7±1.5 m/s). The incident wave was tracked moving along the aorta, taking 55±4 ms to travel from the aortic root to the distal aorta. However, the timing to the refection site distance did not differ between proximal and distal aortic measurement sites (proximal aorta, 48±5 ms versus distal aorta, 42±4 ms; P=0.3). We performed a second analysis using aortic waveforms in a nonlinear model of pulse-wave propagation. This demonstrated very similar results to those observed in vivo and also an exponential attenuation in reflection magnitude. There is no single dominant refection site in or near the distal aorta. Rather, there are multiple reflection sites along the aorta, for which the contributions are attenuated with distance. We hypothesize that rereflection of reflected waves leads to wave entrapment, preventing distal waves being seen in the proximal aorta.

Improvement in Coronary Blood Flow Velocity with Acute Biventricular Pacing is Predominantly Due to an Increase in a Diastolic Backward-Travelling Decompression (Suction) Wave

Background— Normal coronary blood flow is principally determined by a backward-traveling decompression (suction) wave in diastole. Dyssynchronous chronic heart failure may attenuate suction, because regional relaxation and contraction overlap in timing. We hypothesized that biventricular pacing, by restoring left ventricular (LV) synchronization and improving LV relaxation, might increase this suction wave, improving coronary flow. Method and Results— Ten patients with chronic heart failure (9 males; age 65±12; ejection fraction 26±7%) with left bundle-branch block (LBBB; QRS duration 174±18 ms) were atriobiventricularly paced at 100 bpm. LV pressure was measured and wave intensity calculated from invasive coronary flow velocity and pressure, with native conduction (LBBB) and during biventricular pacing at atrioventricular (AV) delays of 40 ms, 120 ms, and separately preidentified hemodynamically optimal AV delay. In comparison with LBBB, biventricular pacing at separately preidentified hemodynamically optimal AV delay (BiV-Opt) enhanced coronary flow velocity time integral by 15% (7%–25%) (P=0.007), LV dP/dtmax by 15% (10%–21%) (P=0.005), and negdP/dtmax by 17% (9%–22%) (P=0.005). The cumulative intensity of the diastolic backward decompression (suction) wave increased by 26% (18%–54%) (P=0.005). The majority of the increase in coronary flow velocity time integral occurred in diastole (69% [41%–84% ]; P=0.047). The systolic compression waves also increased: forward by 36% (6%–49%) (P=0.022) and backward by 38% (20%–55%) (P=0.022). Biventricular pacing at AV delays of 120 ms generated a smaller LV dP/dtmax (by 12% [5%–23% ], P=0.013) and negdP/dtmax (by 15% [8%–40% ]; P=0.009) increase than BiV-Opt, against LBBB as reference; BiV-Opt and biventricular pacing at AV delays of 120 ms were not significantly different in coronary flow velocity time integral or waves. Biventricular pacing at AV delays of 40 ms was no different from LBBB. Conclusions— When biventricular pacing improves LV contraction and relaxation, it increases coronary blood flow velocity, predominantly by increasing the dominant diastolic backward decompression (suction) wave.

Comparison of different invasive hemodynamic methods for AV delay optimization in patients with cardiac resynchronization therapy: Implications for clinical trial design and clinical practice

Background Reproducibility and hemodynamic efficacy of optimization of AV delay (AVD) of cardiac resynchronization therapy (CRT) using invasive LV dp/dtmax are unknown. Method and results 25 patients underwent AV delay (AVD) optimisation twice, using continuous left ventricular (LV) dp/dtmax, systolic blood pressure (SBP) and pulse pressure (PP). We compared 4 protocols for comparing dp/dtmax between AV delays: Immediate absolute: mean of 10 s recording of dp/dtmax acquired immediately after programming the tested AVD, Delayed absolute: mean of 10 s recording acquired 30 s after programming AVD, Single relative: relative difference between reference AVD and the tested AVD, Multiple relative: averaged difference, from multiple alternations between reference and tested AVD. We assessed for dp/dtmax, LVSBP and LVPP, test–retest reproducibility of the optimum. Optimization using immediate absolute dp/dtmax had poor reproducibility (SDD of replicate optima = 41 ms; R2 = 0.45) as did delayed absolute (SDD 39 ms; R2 = 0.50). Multiple relative had better reproducibility: SDD 23 ms, R2 = 0.76, and (p < 0.01 by F test). Compared with AAI pacing, the hemodynamic increment from CRT, with the nominal AV delay was LVSBP 2% and LVdp/dtmax 5%, while CRT with pre-determined optimal AVD gave 6% and 9% respectively. Conclusions Because of inevitable background fluctuations, optimization by absolute dp/dtmax has poor same-day reproducibility, unsuitable for clinical or research purposes. Reproducibility is improved by comparing to a reference AVD and making multiple consecutive measurements. More than 6 measurements would be required for even more precise optimization — and might be advisable for future study designs. With optimal AVD, instead of nominal, the hemodynamic increment of CRT is approximately doubled.

Cardiac resynchronisation therapy optimisation strategies: Systematic classification, detailed analysis, minimum standards and a roadmap for development and testing

In this article an international group of CRT specialists presents a comprehensive classification system for present and future schemes for optimising CRT. This system is neutral to the measurement technology used, but focuses on little-discussed quantitative physiological requirements. We then present a rational roadmap for reliable cost-effective development and evaluation of schemes. A widely recommended approach for AV optimisation is to visually select the ideal pattern of transmitral Doppler flow. Alternatively, one could measure a variable (such as Doppler velocity time integral) and pick the highest. More complex would be to make measurements across a range of settings and fit a curve. In this report we provide clinicians with a critical approach to address any recommendations presented to them, as they may be many, indistinct and conflicting. We present a neutral scientific analysis of each scheme, and equip the reader with simple tools for critical evaluation. Optimisation protocols should deliver: (a) singularity, with only one region of optimality rather than several; (b) blinded test-retest reproducibility; (c) plausibility; (d) concordance between independent methods; and (e) transparency, with all steps open to scrutiny. This simple information is still not available for many optimisation schemes. Clinicians developing the habit of asking about each property in turn will find it easier to win now down the broad range of protocols currently promoted. Expectation of a sophisticated enquiry from the clinical community will encourage optimisation protocol-designers to focus on testing early (and cheaply) the basic properties that are vital for any chance of long term efficacy.

Meta-analysis of symptomatic response attributable to the pacing component of cardiac resynchronization therapy

Prognostic benefit from CRT compared with controls is well established. Symptomatic response rates, however, are controversial and have never been systematically evaluated with standard subtraction of control rates to establish the incremental symptomatic response effect of CRT pacing.

Robotic assistance and general anaesthesia improve catheter stability and increase signal attenuation during atrial fibrillation ablation.

AIMSnRecurrent arrhythmias after ablation procedures are often caused by recovery of ablated tissue. Robotic catheter manipulation systems increase catheter tip stability which improves energy delivery and could produce more transmural lesions. We tested this assertion using bipolar voltage attenuation as a marker of lesion quality comparing robotic and manual circumferential pulmonary vein ablation for atrial fibrillation (AF).nnnMETHODS AND RESULTSnTwenty patients were randomly assigned to robotic or manual AF ablation at standard radiofrequency (RF) settings for our institution (30 W 60 s manual, 25 W 30 s robotic, R30). A separate group of 10 consecutive patients underwent robotic ablation at increased RF duration, 25 W for 60 s (R60). Lesions were marked on an electroanatomic map before and after ablation to measure distance moved and change in bipolar electrogram amplitude during RF. A total of 1108 lesions were studied (761 robotic, 347 manual). A correlation was identified between voltage attenuation and catheter movement during RF (Spearmans rho -0.929, P < 0.001). The ablation catheter was more stable during robotic RF; 2.9 ± 2.3 mm (R30) and 2.6 ± 2.2 mm (R60), both significantly less than the manual group (4.3 ± 3.0 mm, P < 0.001). Despite improved stability, there was no difference in signal attenuation between the manual and R30 group. However, there was increased signal attenuation in the R60 group (52.4 ± 19.4%) compared with manual (47.7 ± 25.4%, P = 0.01). When procedures under general anaesthesia (GA) and conscious sedation were analysed separately, the improvement in signal attenuation in the R60 group was only significant in the procedures under GA.nnnCONCLUSIONSnRobotically assisted ablation has the capability to deliver greater bipolar voltage attenuation compared with manual ablation with appropriate selection of RF parameters. General anaesthesia confers additional benefits of catheter stability and greater signal attenuation. These findings may have a significant impact on outcomes from AF ablation procedures.

Microbiologic Characteristics and In Vitro Susceptibility to Antimicrobials in a Large Population of Patients with Cardiovascular Implantable Electronic Device Infection

Microbiologic Characteristics and In Vitro Susceptibility to Antimicrobials.

The Acute Effects of Changes to AV Delay on BP and Stroke Volume Potential Implications for Design of Pacemaker Optimization Protocols

Background— The AV delay optimization of biventricular pacemakers (cardiac resynchronization therapy) may maximize hemodynamic benefit but consumes specialist time to conduct echocardiographically. Noninvasive BP monitoring is a potentially automatable alternative, but it is unknown whether it gives the same information and similar precision (signal/noise ratio). Moreover, the immediate BP increment on optimization has been reported to decay away: it is unclear whether this is the result of an (undesirable) decrease in stroke volume or a (desirable) compensatory relief of peripheral vasoconstriction.nnMethods and Results— To discriminate between these alternative mechanisms, we measured simultaneous beat-to-beat stroke volume (flow) using Doppler echocardiography, and BP using finger photoplethysmography, during and after AV delay changes from 40 to 120 ms in 19 subjects with cardiac pacemakers. BP and stroke volume both increased immediately ( P <0.001, within 1 heartbeat). BP showed a clear decline a few seconds later (average rate, −0.65 mm Hg/beat; r =0.95 [95% CI, 0.86–0.98]); in contrast, stroke volume did not decline ( P =0.87). The immediate BP increment correlated strongly with the stroke volume increment ( r =0.74, P <0.001). The signal/noise ratio was 3-fold better for BP than stroke volume (6.8±3.5 versus 2.3±1.4; P <0.001).nnConclusions— Improving AV delay immediately increases BP, but the effect begins to decay within a few seconds. Reassuringly, this is because of compensatory vasodilatation rather than reduction in cardiac function. Pacemaker optimization will never be reliable unless there is an adequate signal/noise ratio. Using BP rather than Doppler minimizes noise. The early phase (before vascular compensation) has the richest signal lode.Background— The AV delay optimization of biventricular pacemakers (cardiac resynchronization therapy) may maximize hemodynamic benefit but consumes specialist time to conduct echocardiographically. Noninvasive BP monitoring is a potentially automatable alternative, but it is unknown whether it gives the same information and similar precision (signal/noise ratio). Moreover, the immediate BP increment on optimization has been reported to decay away: it is unclear whether this is the result of an (undesirable) decrease in stroke volume or a (desirable) compensatory relief of peripheral vasoconstriction. Methods and Results— To discriminate between these alternative mechanisms, we measured simultaneous beat-to-beat stroke volume (flow) using Doppler echocardiography, and BP using finger photoplethysmography, during and after AV delay changes from 40 to 120 ms in 19 subjects with cardiac pacemakers. BP and stroke volume both increased immediately (P<0.001, within 1 heartbeat). BP showed a clear decline a few seconds later (average rate, −0.65 mm Hg/beat; r=0.95 [95% CI, 0.86–0.98]); in contrast, stroke volume did not decline (P=0.87). The immediate BP increment correlated strongly with the stroke volume increment (r=0.74, P<0.001). The signal/noise ratio was 3-fold better for BP than stroke volume (6.8±3.5 versus 2.3±1.4; P<0.001). Conclusions— Improving AV delay immediately increases BP, but the effect begins to decay within a few seconds. Reassuringly, this is because of compensatory vasodilatation rather than reduction in cardiac function. Pacemaker optimization will never be reliable unless there is an adequate signal/noise ratio. Using BP rather than Doppler minimizes noise. The early phase (before vascular compensation) has the richest signal lode.

Acute hemodynamic benefits of biventricular and single-site systemic ventricular pacing in patients with a systemic right ventricle

BACKGROUNDnPatients treated by atrial redirection surgery (Senning or Mustard procedure) for transposition of the great arteries (TGA) have an important risk for heart failure caused by dysfunction of the systemic right ventricle. Conventional nonsystemic ventricular pacing (non-systVP) may even further increase this risk.nnnOBJECTIVEnWe investigated the effects of endocardial non-systVP, biventricular pacing (BiVP), and single-site systemic ventricular pacing (systVP) on systolic cardiac pump function in patients with TGA and status post atrial redirection surgery (SenningMustardTGA).nnnMETHODSnDuring clinically indicated catheterization in 9 patients with SenningMustardTGA, endocardial ventricular stimulation (overdrive DDD mode; 80-90 beats/min) was applied with temporary pacing leads at the nonsystemic and the systemic ventricle. Acute changes in the maximal rate of pressure rise (dP/dtmax) and systolic pressure of the systemic ventricle, as induced by non-systVP, systVP, and BiVP compared to reference, were assessed with a pressure wire within the systemic ventricle. Reference was AAI pacing with a similar heart rate (n = 7) or non-systVP at a lower heart rate than that during stimulation at experimental sites (85 beats/min vs 90 beats/min; n = 2).nnnRESULTSnSystemic dP/dtmax and systolic ventricular pressure were significantly higher during systVP (+15.6% and +5.1%, respectively) and BiVP (+14.3% and +4.9%, respectively, compared with non-systVP). In 6 of 7 patients, systemic dP/dtmax was higher during BiVP and systVP than during AAI pacing.nnnCONCLUSIONSnIn a population of patients with SenningMustardTGA, acute hemodynamic effects of endocardial systVP and BiVP were significantly and equally better than those of non-systVP. In some patients, systVP and BiVP might even be better than ventricular activation by the intrinsic conduction system.