Bradley Porter

Optimized Left Ventricular Endocardial Stimulation Is Superior to Optimized Epicardial Stimulation in Ischemic Patients With Poor Response to Cardiac Resynchronization Therapy: A Combined Magnetic Resonance Imaging, Electroanatomic Contact Mapping, and Hemodynamic Study to Target Endocardial Lead Placement

Objectives The purpose of this study was to identify the optimal pacing site for the left ventricular (LV) lead in ischemic patients with poor response to cardiac resynchronization therapy (CRT). Background LV endocardial pacing may offer benefit over conventional CRT in ischemic patients. Methods We performed cardiac magnetic resonance, invasive electroanatomic mapping (EAM), and measured the acute hemodynamic response (AHR) in patients with existing CRT systems. Results In all, 135 epicardial and endocardial pacing sites were tested in 8 patients. Endocardial pacing was superior to epicardial pacing with respect to mean AHR (% change in dP/dtmax vs. baseline) (11.81 [-7.2 to 44.6] vs. 6.55 [-11.0 to 19.7]; p = 0.025). This was associated with a similar first ventricular depolarization (Q-LV) (75 ms [13 to 161 ms] vs. 75 ms [25 to 129 ms]; p = 0.354), shorter stimulation–QRS duration (15 ms [7 to 43 ms] vs. 19 ms [5 to 66 ms]; p = 0.010) and shorter paced QRS duration (149 ms [95 to 218 ms] vs. 171 ms [120 to 235 ms]; p < 0.001). The mean best achievable AHR was higher with endocardial pacing (25.64 ± 14.74% vs. 12.64 ± 6.76%; p = 0.044). Furthermore, AHR was significantly greater pacing the same site endocardially versus epicardially (15.2 ± 10.7% vs. 7.6 ± 6.3%; p = 0.014) with a shorter paced QRS duration (137 ± 22 ms vs. 166 ± 30 ms; p < 0.001) despite a similar Q-LV (70 ± 38 ms vs. 79 ± 34 ms; p = 0.512). Lack of capture due to areas of scar (corroborated by EAM and cardiac magnetic resonance) was associated with a poor AHR. Conclusions In ischemic patients with poor CRT response, biventricular endocardial pacing is superior to epicardial pacing. This may reflect accessibility to sites that cannot be reached via coronary sinus anatomy and/or by access to more rapidly conducting tissue. Furthermore, guidance to the optimal LV pacing site may be aided by modalities such as cardiac magnetic resonance to target delayed activating sites while avoiding scar.

Autonomic Modulation in Patients with Heart Failure Increases Beat-to-Beat Variability of Ventricular Action Potential Duration

Background: Exaggerated beat-to-beat variability of ventricular action potential duration (APD) is linked to arrhythmogenesis. Sympathetic stimulation has been shown to increase QT interval variability, but its effect on ventricular APD in humans has not been determined. Methods and Results: Eleven heart failure patients with implanted bi-ventricular pacing devices had activation–recovery intervals (ARI, surrogate for APD) recorded from LV epicardial electrodes under constant RV pacing. Sympathetic activity was increased using a standard autonomic challenge (Valsalva) and baroreceptor indices were applied to determine changes in sympathetic stimulation. Two Valsalvas were performed for each study and were repeated, both off and on bisoprolol. In addition sympathetic nerve activity (SNA) was measured from skin electrodes on the thorax using a novel validated method. Autonomic modulation significantly increased mean short-term variability in ARI; off bisoprolol mean STV increased from 3.73 ± 1.3 to 5.27 ± 1.04 ms (p = 0.01), on bisoprolol mean STV of ARI increased from 4.15 ± 1.14 to 4.62 ± 1 ms (p = 0.14). Adrenergic indices of the Valsalva demonstrated significantly reduced beta-adrenergic function when on bisoprolol (Δ pressure recovery time, p = 0.04; Δ systolic overshoot in Phase IV, p = 0.05). Corresponding increases in SNA from rest both off (1.4 uV, p < 0.01) and on (0.7 uV, p < 0.01) bisoprolol were also seen. Conclusions: Beat-to-beat variability of ventricular APD increases during brief periods of increased sympathetic activity in patients with heart failure. Bisoprolol reduces, but does not eliminate, these effects. This may be important in the genesis of ventricular arrhythmias in heart failure patients.

Cost-effectiveness of a risk-stratified approach to cardiac resynchronisation therapy defibrillators (high versus low) at the time of generator change

Objective Responders to cardiac resynchronisation therapy whose device has a defibrillator component and who do not receive a therapy in the lifetime of the first generator have a very low incidence of appropriate therapy after box change. We investigated the cost implications of using a risk stratification tool at the time of generator change resulting in these patients being reimplanted with a resynchronisation pacemaker. Methods A decision tree was created using previously published data which had demonstrated an annualised appropriate defibrillator therapy risk of 2.33%. Costs were calculated at National Health Service (NHS) national tariff rates (2016–2017). EQ-5D utility values were applied to device reimplantations, admissions and mortality data, which were then used to estimate quality-adjusted life-years (QALYs) over 5 years. Results At 5 years, the incremental cost of replacing a resynchronisation defibrillator device with a second resynchronisation defibrillator versus resynchronisation pacemaker was £5045 per patient. Incremental QALY gained was 0.0165 (defibrillator vs pacemaker), resulting in an incremental cost-effectiveness ratio (ICER) of £305 712 per QALYs gained. Probabilistic sensitivity analysis resulted in an ICER of £313 612 (defibrillator vs pacemaker). For reimplantation of all patients with a defibrillator rather than a pacemaker to yield an ICER of less than £30 000 per QALY gained (current NHS cut-off for approval of treatment), the annual arrhythmic event rate would need to be 9.3%. The budget impact of selective replacement was a saving of £2 133 985 per year. Conclusions Implanting low-risk patients with a resynchronisation defibrillator with the same device at the time of generator change is not cost-effective by current NHS criteria. Further research is required to understand the impact of these findings on individual patients at the time of generator change.

Chronic Right Ventricular Pacing in the Heart Failure Population

Purpose of ReviewWe review the trials that have demonstrated potentially harmful effects from right ventricular (RV) apical pacing as well as reviewing the evidence of alternative RV pacing sites and cardiac resynchronization therapy (CRT) for patients who have heart failure and atrioventricular (AV) block.Recent FindingsThe role of CRT in patients with AV block and impaired left ventricular function remains an important consideration. The BLOCK HF trial demonstrated better outcomes with CRT pacing over RV pacing in patients with left ventricular systolic dysfunction (LVSD) and AV block who were expected to have a high RV pacing burden, but failed to demonstrate a mortality benefit.SummaryCRT seems to have a beneficial effect on left ventricular reverse remodeling, systolic function, and clinical outcomes in patients with New York Heart Association (NYHA) functional class I–III heart failure, moderate to severe LVSD, and AV block compared to RV pacing. However, it is less clear whether there is a similar benefit from CRT in patients with a high percentage of RV pacing who have normal or mild LVSD in the treatment of AV block.

The role of transvenous lead extraction in the management of redundant or malfunctioning pacemaker and defibrillator leads post ELECTRa

Cardiac implantable electronic devices implantation rates have increased over the past decade due to broader indications and an ageing population. Similarly, device and lead complications have also risen. The management of pacemaker/defibrillator leads that are no longer required (redundant) or malfunctioning, can be contentious. There is a need to balance the risk of transvenous lead extraction (TLE) against those of lead abandonment. The recently published European Lead Extraction ConTRolled Registry (ELECTRa) study provides contemporary outcomes for TLE across Europe with important implications for the management of redundant and/or malfunctioning leads. This review article discusses the potential complications for each interventional approach when managing redundant or malfunctioning pacemaker leads.

Predictors and outcomes of patients requiring repeat transvenous lead extraction of pacemaker and defibrillator leads

A proportion of patients who undergo an initial lead extraction procedure will require a second, repeat extraction. Data regarding this clinical entity are scarce and neither the predisposing risk factors for, nor outcomes from, these procedures have been described previously. We sought to determine the incidence, risk factors, and outcomes of repeat lead extraction.

Variation in activation time during bipolar vs extended bipolar left ventricular pacing: SIENIEWICZ et al.

Cardiac resynchronization therapy (CRT) is typically delivered via quadripolar leads that allow stimulation using either true bipolar pacing, where stimulation occurs between two electrodes (BP) on the quadripolar lead, or extended bipole (EBP) left ventricular (LV) pacing, with the quadripolar electrodes and right ventricular coil acting as the cathode and anode, respectively. True bipolar pacing is associated with reductions in mortality and it has been postulated that these differences are the result of enhanced electrical activation.

A cost effectiveness study establishing the impact and accuracy of implementing the NICE guidelines lowering plasma NTproBNP threshold in patients with clinically suspected heart failure at our institution

AIMS The 2014 National Institute of Clinical Excellence (NICE) guidelines on the management of acute heart failure recommended using a plasma NT-proBNP threshold of 300pg/ml to assist in ruling out the diagnosis of heart failure (HF), updating previous guidelines recommending using a threshold of 400pg/ml. NICE based their recommendations on 6 studies performed in other countries. This study sought to determine the diagnostic and economic implications of using these thresholds in a large unselected UK population. METHODS Patient and clinical demographics were recorded for all consecutive suspected HF patients over 12months, as well as clinical outcomes including time to HF hospitalisation and time to death (follow up 15.8months). RESULTS Of 1995 unselected patients admitted with clinically suspected HF, 1683 (84%) had a NTproBNP over the current NICE recommended threshold, of which 35% received a final diagnosis of HF. Lowering the threshold from 400 to 300pg/ml would have involved screening an additional 61 patients and only would have identified one new patient with HF (sensitivity 0.985, NPV 0.976, area under the curve (AUC) at 300pg/ml 0.67; sensitivity 0.983, NPV 0.977, AUC 0.65 at 400pg/ml). The economic implications of lowering the threshold would have involved additional costs of £42,842.04 (£702.33 per patient screened, or £ 42,824.04 per new HF patient). CONCLUSION Applying the recent updated NICE guidelines to an unselected real world population increases the AUC but would have a significant economic impact and only identified one new patient with heart failure.

Understanding non-response to cardiac resynchronisation therapy: common problems and potential solutions

Heart failure is a complex clinical syndrome associated with a significant morbidity and mortality burden. Reductions in left ventricular (LV) function trigger adaptive mechanisms, leading to structural changes within the LV and the potential development of dyssynchronous ventricular activation. This is the substrate targeted during cardiac resynchronisation therapy (CRT); however, around 30–50% of patients do not experience benefit from this treatment. Non-response occurs as a result of pre-implant, peri-implant and post implant factors but the technical constraints of traditional, transvenous epicardial CRT mean they can be challenging to overcome. In an effort to improve response, novel alternative methods of CRT delivery have been developed and of these endocardial pacing, where the LV is stimulated from inside the LV cavity, appears the most promising.

Beat-to-Beat Variability of Ventricular Action Potential Duration Oscillates at Low Frequency During Sympathetic Provocation in Humans

Background: The temporal pattern of ventricular repolarization is of critical importance in arrhythmogenesis. Enhanced beat-to-beat variability (BBV) of ventricular action potential duration (APD) is pro-arrhythmic and is increased during sympathetic provocation. Since sympathetic nerve activity characteristically exhibits burst patterning in the low frequency range, we hypothesized that physiologically enhanced sympathetic activity may not only increase BBV of left ventricular APD but also impose a low frequency oscillation which further increases repolarization instability in humans. Methods and Results: Heart failure patients with cardiac resynchronization therapy defibrillator devices (n = 11) had activation recovery intervals (ARI, surrogate for APD) recorded from left ventricular epicardial electrodes alongside simultaneous non-invasive blood pressure and respiratory recordings. Fixed cycle length was achieved by right ventricular pacing. Recordings took place during resting conditions and following an autonomic stimulus (Valsalva). The variability of ARI and the normalized variability of ARI showed significant increases post Valsalva when compared to control (p = 0.019 and p = 0.032, respectively). The oscillatory behavior was quantified by spectral analysis. Significant increases in low frequency (LF) power (p = 0.002) and normalized LF power (p = 0.019) of ARI were seen following Valsalva. The Valsalva did not induce changes in conduction variability nor the LF oscillatory behavior of conduction. However, increases in the LF power of ARI were accompanied by increases in the LF power of systolic blood pressure (SBP) and the rate of systolic pressure increase (dP/dtmax). Positive correlations were found between LF-SBP and LF-dP/dtmax (rs = 0.933, p < 0.001), LF-ARI and LF-SBP (rs = 0.681, p = 0.001) and between LF-ARI and LF-dP/dtmax (rs = 0.623, p = 0.004). There was a strong positive correlation between the variability of ARI and LF power of ARI (rs = 0.679, p < 0.001). Conclusions: In heart failure patients, physiological sympathetic provocation induced low frequency oscillation (~0.1 Hz) of left ventricular APD with a strong positive correlation between the LF power of APD and the BBV of APD. These findings may be of importance in mechanisms underlying stability/instability of repolarization and arrhythmogenesis in humans.