Acute effects of biventricular pacing in heart failure patients with a normal ejection fraction and mechanical dyssynchrony.

OBJECTIVES: We tested the acute effects of resynchronization in heart failure patients with a normal (>50%) left ventricular (LV) ejection fraction (HFNEF) and mechanical dyssynchrony. METHODS: Twenty-four HFNEF patients (72 ± 6 years, 5 male) with mechanical dyssynchrony (standard deviation of electromechanical time delay among 12 LV segments >35 ms) were studied with temporary pacing catheters in the right atrium, LV, and right ventricle (RV), and high-fidelity catheters for pressure recording. Using selected atrioventricular (AV) intervals of 60, 90, 120, 150, and 180 ms to optimize transmitral flow during simultaneous biventricular pacing, the RV-LV (VV) interval was then evaluated at RV30, RV15, 0, LV15, LV30, and LV45 (RV or LV indicates which ventricle was paced first, the number indicates by how many ms). RESULTS: During simultaneous pacing, longer AV intervals were associated with improved LV pressure-derivative minimums and increased aortic pressures (p < 0.05 vs. normal sinus rhythm). In the VV interval from RV30 to LV45, there was a graded increase in the aortic velocity time integral and a decrease in dyssynchrony during simultaneous or LV-first pacing (p < 0.05 vs. normal sinus rhythm). CONCLUSIONS: For HFNEF patients with mechanical dyssynchrony, acute simultaneous biventricular or LV-first pacing with longer AV intervals reduced mechanical dyssynchrony and improved diastolic and systolic hemodynamics.

Ineffective Cardiac Resynchronization Pacing is Associated with Poor Outcomes in a Nationwide Cohort Analysis.

BACKGROUND: Delivery of cardiac resynchronization therapy (CRT) requires left ventricular myocardial capture to achieve clinical benefits. OBJECTIVE: We sought to determine whether ineffective pacing impacts survival. METHODS: Ineffective ventricular pacing (VP) was defined as the difference between percent delivered CRT (%VP) and percent EffectivCRTTM in CRT devices. Using the Optum® de-identified Electronic Health Record dataset (Optum® EHR) and Medtronic CareLinkTM data warehouse, we identified patients implanted with applicable devices with at least 30 days follow-up. Kaplan-Meier and Cox proportional hazards models assessed the impact of %VP and % ineffective VP on survival. RESULTS: Among 7,987 patients with 2.1±1.0 years follow up, increasing ineffective VP was associated with decreasing survival: the highest observed survival was in the quartile with <0.08% ineffective VP and the lowest survival was in the quartile with >1.47% ineffective VP (85.1% vs. 75.7% at 3 years, p<0.001). As expected, patients with more than the median %VP of 97.7% had better survival than patients with <97.7% VP (84.2% vs. 77.8%, p < 0.001). However, patients that had >97.7% VP but >2% ineffective VP had similar survival to patients with <97.7% VP but ≤2% ineffective VP (81.6% vs 79.4%, p = 0.54). A multivariable Cox proportional hazards model demonstrated that <97.7% VP (adjusted HR 1.29; 95% CI 1.14-1.46; p <0.001) and >2% ineffective VP (HR 1.35; 95% CI 1.18-1.54; p<0.001) were both significantly associated with decreased survival. CONCLUSIONS: Ineffective VP is associated with decreased survival. In addition to maximizing the percentage of delivered CRT pacing, every effort should be made to minimize ineffective VP.

Impact of ventricular dyssynchrony on postexercise accommodation of systolic myocardial motion in hypertensive patients with heart failure and a normal ejection fraction: a tissue-Doppler echocardiography study.

BACKGROUND: We hypothesized left ventricular (LV) dyssynchrony would affect postexercise accommodation of regional myocardial motion in patients with heart failure and a normal ejection fraction (HFNEF). METHODS AND RESULTS: Tissue-Doppler echocardiography was studied in 100 hypertensive patients with LV ejection fraction >50%. Among them, 70 HFNEF patients were classified into the systolic dyssynchrony (Dys: >65 ms difference of electromechanical delay between septal and lateral segments) (43 patients) and nondyssynchrony (Ndys: 27 patients) groups, and the other 30 patients were as the control (Ctrl). The systolic myocardial velocities (Sm) of 6-basal LV segments at baseline and after exercise were analyzed. When compared with the Ctrl group, the baseline lower mean Sm of 6 LV segments in the Ndys group could increase to a similar postexercise level as that in the Ctrl group, whereas that in the Dys group remained lower after exercise (7.8 ± 1.3 versus Ndys: 8.6 ± 1.5 and Ctrl: 8.9 ± 1.2 cm/s, P < .05, respectively). This is mainly due to a much higher percentage increase of lateral Sm after exercise in the Ndys group (Ndys: 49 versus Dys: 29%, P < .05). CONCLUSIONS: Dyssynchrony-related regional myocardial contractile abnormality after exercise in HFNEF patients suggested the detrimental impact of electromechanical uncoupling on HF symptoms.

Electrical modalities beyond pacing for the treatment of heart failure.

In this review, we report on electrical modalities, which do not fit the definition of pacemaker, but increase cardiac performance either by direct application to the heart (e.g., post-extrasystolic potentiation or non-excitatory stimulation) or indirectly through activation of the nervous system (e.g., vagal or sympathetic activation). The physiological background of the possible mechanisms of these electrical modalities and their potential application to treat heart failure are discussed.

Heart failure hospitalization reduction and cost savings achieved by improved delivery of effective biventricular pacing: economic implications of the OLE study under the US setting.

Background: The hOLter for Efficacy analysis (OLE) study demonstrated that current device pacing diagnostics overestimate the amount of cardiac resynchronization therapy (CRT) pacing that effectively stimulates the cardiac tissue. Sub-optimal pacing increases mortality, hospitalizations, and associated health-care costs. We sought to estimate the expected number of hospital admissions due to heart failure (HF) and its respective financial impact in patients with maximized effective pacing versus conventional pacing. Methods: A Markov model was developed to project HF hospitalizations and quantify the costs that could be avoided if pacing was maximally effective. OLE data were used to inform the prevalence of ineffective pacing among CRT patients and and average loss of pacing by causes. Adaptive CRT trial data quantified the reduction in underlying hospitalization risk by increasing effective pacing delivered. Survival was informed by a meta-analysis of 5 randomized clinical trials. Costs were analyzed from a US payer perspective. Results: Projected average hospitalizations totaled 4.58 over a lifetime horizon for CRT patients with conventional pacing. Maximizing effective pacing delivery was projected to avoid 1.83 HF admissions/patient over the lifetime. This equates to a savings of 40% (US$22,802) compared with conventional pacing from the Medicare perspective. In a sensitivity analysis, CRT with effective pacing was projected to provide cost savings in all scenarios. Conclusions: Maximized effective pacing leads to a lower number of HF hospitalizations, thus allowing significant cost offsets in the US setting.

Acute electromechanical effects of atrioventricular coupled pacing in patients with heart failure.

BACKGROUND: Postextrasystolic potentiation (PESP) is a property of cardiac tissue whereby two closely timed depolarizations cause the subsequent contraction to be of increased magnitude. METHODS AND RESULTS: Ten subjects were studied in a single-blind study to evaluate the safety and performance of an atrioventricular coupled pacing (A-VCP) algorithm to produce sustained PESP among subjects with moderate heart failure. The primary end points were algorithm safety, patient perception, and cardiac function. The effects of A-VCP on cardiac function were assessed by comparing echocardiographic parameters before and after 15 to 20 minutes of A-VCP. A-VCP produced no arrhythmic episodes, ejection fraction increased by 8 ejection fraction points (31%) (P < or = .001), end-systolic volume decreased by 10% (P < or = .05), and a trend toward increasing end-diastolic volume was observed (P = .084). Stroke volume increased by 43% (P < or = .001), and the pulse rate decreased by 41% (P < or = .001) during A-VCP. This resulted in decreased cardiac output of 15% (P < or = .05). Six of the 10 subjects felt no effects from A-VCP, and four subjects felt a change with A-VCP turned on. CONCLUSION: Short-term A-VCP was found to be safe and well tolerated in a majority of patients. Hemodynamic effects were mixed with improved ejection fraction and stroke volume but decreased cardiac output.

A novel algorithm increases the delivery of effective cardiac resynchronization therapy during atrial fibrillation: The CRTee randomized crossover trial.

BACKGROUND: Cardiac resynchronization therapy (CRT) requires a high percentage of ventricular pacing (%Vp) to maximize its clinical benefits. Atrial fibrillation (AF) has been shown to reduce %Vp in CRT due to competition with irregular intrinsic atrioventricular (AV) conduction. We report the results of a prospective randomized crossover trial evaluating the amount of effective CRT delivered during AF with a novel algorithm (eCRTAF). OBJECTIVE: The purpose of this study was to determine whether eCRTAF increases the amount of effective CRT delivered during AF compared to a currently available rate regularization algorithm. METHODS: Patients previously implanted with a cardiac resynchronization therapy-defibrillator and with a history of AF and intact AV conduction received up to 4 weeks of control (Conducted AF Response) and up to 4 weeks of eCRTAF in a randomized sequence. The percent effective CRT (%eCRT) pacing, which excludes beats without left ventricular capture, %Vp, and mean heart rate (HR) were recorded during AF and sinus rhythm. RESULTS: The eCRTAF algorithm resulted in a significantly higher %eCRT during AF than control (87.8% ± 7.8% vs 80.8% ± 14.3%; P <.001) and %Vp during AF than control (90.0% ± 5.9% vs 83.2% ± 11.9%; P <.001), with a small but statistically significant increase in mean HR of 2.5 bpm (79.5 ± 9.7 bpm vs 77.0 ± 9.9 bpm; P <.001). CONCLUSION: In a cohort of CRT patients with a history of AF, eCRTAF significantly increased %eCRT pacing and %Vp during AF with a small increase in mean HR. This algorithm may represent a novel noninvasive method of significantly increasing effective CRT delivery during AF, potentially improving CRT response.

Device pacing diagnostics overestimate effective cardiac resynchronization therapy pacing results of the hOLter for Efficacy analysis of CRT (OLÉ CRT) study.

BACKGROUND: A high percentage of biventricular (BiV) or left ventricular (LV) pacing in cardiac resynchronization therapy (CRT) devices has been associated with superior clinical outcomes. However, the percent ventricular (%V) pacing reported by CRT devices simply indicates the number of paces the device has delivered and not the proportion of pacing that has captured the LV effectively. OBJECTIVE: The purpose of this study was to determine whether a beat-by-beat evaluation of effective pacing would provide a more accurate evaluation of CRT delivery. METHODS: An automatic electrogram (EGM)-based algorithm that classifies each LV pace as effective or ineffective based on detection of QS/QS-r morphology on the unipolar LV EGM during pacing was developed and validated. LV EGMs that were recorded by 24-hour Holter from 57 CRT patients were postprocessed. The percent effective CRT (%e-CRT) pacing was calculated by dividing the time spent in e-CRT pacing by the total time of the recording. RESULTS: In this CRT cohort, the average %V pacing (94.8% ± 8%) significantly overestimated the %e-CRT pacing (87.5% ± 23%; P <.001). A significant minority of subjects (18%) had a discrepancy of at least 3 percentage points between %V pacing and %e-CRT pacing (mean 39% ± 41%). CONCLUSION: Current device pacing diagnostics overestimate the amount of CRT pacing actually delivered. The new algorithm quantifies ineffective CRT pacing, which enables clinicians to identify patients with this issue and to address the reasons behind suboptimal CRT delivery.