Organizational index mapping to identify focal sources during persistent atrial fibrillation.

INTRODUCTION: Localized rotors have been implicated in the mechanism of persistent atrial fibrillation (AF). Although regions of highest dominant frequency (DF) on spectral analysis of the left atrium (LA) have been said to identify rotors, other mechanisms such as wavefront collisions will sporadically also generate an inconsistent distribution of high DF. We hypothesized that if drivers of AF were present, their distinctive spectral characteristics would result more from their temporal stability than their high frequency. METHODS AND RESULTS: Ten patients with persistent AF underwent LA noncontact mapping. Following subtraction of far-field ventricular components, noncontact electrograms at 256 sites underwent fast Fourier transform. Mean absolute difference in DF between 5 sequential 7-second segments of AF was defined as the DF variability (DFV) at each site. Mean ratio of the DF and its harmonics to the total power of the spectrum was defined as the organizational index (OI). Mean DFV was significantly lower in organized areas (OI > 1 SD above mean) than at all sites (0.34 ± 0.04 vs 0.46 ± 0.04 Hz; P < 0.001). When organized areas were ablated during wide-area circumferential ablation, AF organized in remote regions (LA appendage ΔOI ablated vs unablated: +0.21 [0.06-0.41] vs -0.04 [-0.14-0.05]; P = 0.005). CONCLUSIONS: At sites of organized activation, the activation frequency was also significantly more stable over time. This observation is consistent with the existence of focal sources, and inconsistent with a purely random activation pattern. Ablation of such regions is technically feasible, and was associated with organization of AF in remote atrial regions.

Maximizing efficiency of alternation algorithms for hemodynamic optimization of the AV delay of cardiac resynchronization therapy.

BACKGROUND: During optimization of the atrioventricular (AV) delay of cardiac resynchronization therapy (CRT), it is not known exactly which windows of time around the transition are most informative for identification of the optimum. METHOD AND RESULTS: IN 22 patients with CRT, we performed AV delay optimization using continuous noninvasive hemodynamics. We used signal-to-noise ratio to determine the most efficient averaging window location and width. We found that it is most efficient to position the averaging windows immediately before and immediately after the transition in AV delay. For example, skipping five beats after the transition decreases signal-to-noise ratio by 17.5% (P < 0.0001). Similarly, skipping five beats immediately before the transition reduces signal-to-noise ratio by 11.7% (P < 0.0001). The best choice of "fixed" averaging window width was found to be six beats, with signal-to-noise ratio falling by, for example, 41% for a one-beat window (P = 0.0002). However, even better was to set the window width for each patient to match one respiratory cycle. We observed that the pre- and posttransition signal-to-noise ratio traces begin to diverge three beats after the transition in AV delay. We believe this represents the time taken for the peripheral response to pacing-induced changes in stroke volume to occur. CONCLUSIONS: THE most efficient way to use alternating transitions for the hemodynamic optimization of CRT is to use an averaging window of one respiratory cycle, and not to skip any beats between the pretransition and posttransition averaging windows.

The atrioventricular delay of cardiac resynchronization can be optimized hemodynamically during exercise and predicted from resting measurements.

BACKGROUND: Atrioventricular (AV) optimization of cardiac resynchronization therapy (CRT) is typically calculated at rest. However, patients often become symptomatic during exercise. OBJECTIVE: In this study, we use acute noninvasive hemodynamics to optimize the AV delay of CRT during exercise and investigate whether this exercise optimum can be predicted from a three-phase resting model. METHODS: In 20 patients with CRT, we adjusted the sensed AV delay while the patient exercised on a treadmill up to a heart rate of 100 bpm to identify the hemodynamically optimal value. Separately, at rest, by pacing with three different configurations and calculating the sensed-paced difference, we calculated an "expected" value for the exercise optimum. RESULTS: It was possible to perform AV delay optimization while a patient exercised. The resting three-phase model correlated well with the actual exercise optimal AV delay (r = 0.85, mean difference +/- standard deviation [SD] = 3.7 +/- 17 ms). Simply using measurements made at rest during atrial-sensed pacing showed a poorer correlation with exercise (r = 0.64, mean difference +/- SD = 2.2 +/- 24 ms). The three-phase resting model allows improved exercise hemodynamics to be achieved. Programming according to the three-phase resting model yields an exercise blood pressure of only 0.5 mmHg (+/-1.4 mmHg; P = NS) less than the true exercise optimum, whereas programming the resting sensed optimum yields an exercise blood pressure of 1.4 mmHg (+/-2.2 mmHg, P = .02) less than the true optimum. CONCLUSIONS: Using acute noninvasive hemodynamics and a protocol of alternations, it is possible to optimize the AV delay of cardiac resynchronization devices even while a patient exercises. In clinical practice, the exercise optimum AV delay could be determined from three phases of resting measurements, without performing exercise.

The Instantaneous wave-Free Ratio (iFR) pullback: a novel innovation using baseline physiology to optimise coronary angioplasty in tandem lesions.

Coronary intervention is increasingly performed in complex disease with tandem and diffuse disease. Pressure wires enable detailed assessment of the physiological significance of a stenosis but in the presence of tandem disease, predicting the impact of a stenting a given stenosis can be difficult and is impeded by flow interaction between stenoses under hyperemia. In this review, we consider the physiological difficulties posed by flow interaction under hyperemia and consider alternative approaches such as assessment under baseline conditions. Specifically we consider the potential value of the iFR-Pullback approach and its capacity to enable Virtual-PCI, which may assist in planning intervention.

Intra-aortic Balloon Pump Therapy for Acute Myocardial Infarction: A Meta-analysis.

IMPORTANCE: Intra-aortic balloon pump (IABP) therapy is a widely used intervention for acute myocardial infarction with cardiogenic shock. Guidelines, which previously strongly recommended it, have recently undergone substantial change. OBJECTIVE: To assess IABP efficacy in acute myocardial infarction. DATA SOURCES: Human studies found in Pubmed, Embase, and Cochrane libraries through December 2014 and in reference lists of selected articles. Search strings were "myocardial infarction" or "acute coronary syndrome" and "intra-aortic balloon pump" or "counterpulsation." STUDY SELECTION: Randomized clinical trials (RCTs) and observational studies comparing use of IABP with no IABP in patients with acute myocardial infarction. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted the data, and risk of bias in RCTs was assessed using the Cochrane risk of bias tool. We conducted separate meta-analyses of the RCTs and observational studies. Data were quantitatively synthesized using random-effects meta-analysis. MAIN OUTCOMES AND MEASURES: Thirty-day mortality. RESULTS: There were 12 eligible RCTs randomizing 2123 patients. In the RCTs, IABP use had no statistically significant effect on mortality (odds ratio [OR], 0.96 [95% CI, 0.74-1.24]), with no significant heterogeneity among trials (I2 = 0%; P = .52). This result was consistent when studies were stratified by the presence (OR, 0.94 [95% CI, 0.69-1.28]; P = .69, I2 = 0%) or absence (OR, 0.98 [95% CI, 0.57-1.69]; P = .95, I2 = 17%) of cardiogenic shock. There were 15 eligible observational studies totaling 15 530 patients. Their results were mutually conflicting (heterogeneity I2 = 97%; P < .001), causing wide uncertainty in the summary estimate for the association with mortality (OR, 0.96 [95% CI, 0.54-1.70]). A simple index of baseline risk marker imbalance in the observational studies appeared to explain much of the heterogeneity in the observational data (R2meta = 46.2%; P < .001). CONCLUSIONS AND RELEVANCE: Use of IABP was not found to improve mortality among patients with acute myocardial infarction in the RCTs, regardless of whether patients had cardiogenic shock. The observational studies showed a variety of mutually contradictory associations between IABP therapy and mortality, much of which was explained by the differences between studies in the balance of risk factors between IABP and non-IABP groups.

Pre-angioplasty instantaneous wave-free ratio pullback provides virtual intervention and predicts hemodynamic outcome for serial lesions and diffuse coronary artery disease.

OBJECTIVES: The aim of this study was to perform hemodynamic mapping of the entire vessel using motorized pullback of a pressure guidewire with continuous instantaneous wave-free ratio (iFR) measurement. BACKGROUND: Serial stenoses or diffuse vessel narrowing hamper pressure wire-guided management of coronary stenoses. Characterization of functional relevance of individual stenoses or narrowed segments constitutes an unmet need in ischemia-driven percutaneous revascularization. METHODS: The study was performed in 32 coronary arteries with tandem and/or diffusely diseased vessels. An automated iFR physiological map, integrating pullback speed and physiological information, was built using dedicated software to calculate physiological stenosis severity, length, and intensity (ΔiFR/mm). This map was used to predict the best-case post-percutaneous coronary intervention (PCI) iFR (iFRexp) according to the stented location, and this was compared with the observed iFR post-PCI (iFRobs). RESULTS: After successful PCI, the mean difference between iFRexp and iFRobs was small (mean difference: 0.016 ± 0.004) with a strong relationship between ΔiFRexp and ΔiFRobs (r = 0.97, p < 0.001). By identifying differing iFR intensities, it was possible to identify functional stenosis length and quantify the contribution of each individual stenosis or narrowed segment to overall vessel stenotic burden. Physiological lesion length was shorter than anatomic length (12.6 ± 1.5 vs. 23.3 ± 1.3, p < 0.001), and targeting regions with the highest iFR intensity predicted significant improvement post-PCI (r = 0.86, p < 0.001). CONCLUSIONS: iFR measurements during continuous resting pressure wire pullback provide a physiological map of the entire coronary vessel. Before a PCI, the iFR pullback can predict the hemodynamic consequences of stenting specific stenoses and thereby may facilitate the intervention and stenting strategy.

Efficiency, reproducibility and agreement of five different hemodynamic measures for optimization of cardiac resynchronization therapy.

BACKGROUND: Several hemodynamic measures have been used for optimization of the AV delay of cardiac resynchronization therapy (CRT), including pulse pressure (PP), systolic blood pressure (SBP) and cardiac output (CO). We aimed to determine whether these measures identify the same optimum and whether they have the same efficiency and reproducibility at identifying this optimum. METHODS AND RESULTS: In 22 patients with cardiac resynchronization therapy, we adjusted the AV delay while atrially pacing at 110 bpm and simultaneously recording SBP, diastolic blood pressure (DBP), PP, mean arterial pressure (MAP) and CO. SBP, PP and CO all had essentially the same signal-to-noise ratios (15.4+/-5.4, 15.5+/-6.4, 15.3+/-7.4 respectively p=NS). In contrast, MAP and DBP had significantly worse signal-to-noise ratios than SBP (14.2+/-5.6, p=0.003 and 12.1+/-4.4, p<0.0001 respectively). The optimal AV delay was very similar between SBP, PP, MAP and DBP. For example, the optima identified by SBP correlated strongly with those identified by PP (r=0.94), MAP (r=0.96) and DBP (r=0.90). In contrast, the optima detected by CO was poorly related to these (e.g. r=0.36 with SBP optima). Reproducibility was best for optima detected by SBP followed by MAP and PP. CONCLUSIONS: Essentially the same AV optimum is identified, regardless of whether the parameter chosen for maximization is SBP, PP, MAP or DBP. We conclude that optimizing the CRT AV delay using SBP gives the best combination of efficiency and reproducibility, with PP and MAP being reasonable alternatives.

Induction of oscillatory ventilation pattern using dynamic modulation of heart rate through a pacemaker.

For disease states characterized by oscillatory ventilation, an ideal dynamic therapy would apply a counteracting oscillation in ventilation. Modulating respiratory gas transport through the circulation might allow this. We explore the ability of repetitive alternations in heart rate, using a cardiac pacemaker, to elicit oscillations in respiratory variables and discuss the potential for therapeutic exploitation. By incorporating acute cardiac output manipulations into an integrated mathematical model, we observed that a rise in cardiac output should yield a gradual rise in end-tidal CO2 and, subsequently, ventilation. An alternating pattern of cardiac output might, therefore, create oscillations in CO2 and ventilation. We studied the effect of repeated alternations in heart rate of 30 beats/min with periodicity of 60 s, on cardiac output, respiratory gases, and ventilation in 22 subjects with implanted cardiac pacemakers and stable breathing patterns. End-tidal CO2 and ventilation developed consistent oscillations with a period of 60 s during the heart rate alternations, with mean peak-to-trough relative excursions of 8.4 +/- 5.0% (P < 0.0001) and 24.4 +/- 18.8% (P < 0.0001), respectively. Furthermore, we verified the mathematical prediction that the amplitude of these oscillations would depend on those in cardiac output (r = 0.59, P = 0.001). Repetitive alternations in heart rate can elicit reproducible oscillations in end-tidal CO2 and ventilation. The size of this effect depends on the magnitude of the cardiac output response. Harnessed and timed appropriately, this cardiorespiratory mechanism might be exploited to create an active dynamic responsive pacing algorithm to counteract spontaneous respiratory oscillations, such as those causing apneic breathing disorders.

Determination of optimal atrioventricular delay for cardiac resynchronization therapy using acute non-invasive blood pressure.

AIMS: In this study, we apply non-invasive blood pressure (BP) monitoring, by continuous finger photoplethysmography (Finometer), to detect directly haemodynamic responses during adjustment of the atrioventricular (AV) delay of cardiac resynchronization therapy (CRT), at different heart rates. METHODS AND RESULTS: Twelve patients were studied with six re-attending for reproducibility assessment. At each AV delay, systolic BP relative to a reference AV delay of 120 ms (SBPrel) was calculated. We found that at higher heart rates, altering the AV delay had a more pronounced effect on BP (average range of SBPrel=17.4 mmHg) compared with resting rates (average range of SBPrel=6.5 mmHg), P<0.0001. Secondly, peak AV delay differed between patients (minimum 120 ms, maximum 200 ms). Thirdly, small changes in AV delay had significant BP effects: programming AV delay 40 ms below the peak AV delay reduced SBPrel by 4.9 mmHg (P<0.003); having it 40 ms above the peak decreased SBPrel by 4.4 mmHg (P<0.0005). Finally, the peak AV delay is highly reproducible both on the same day and at 3 months (Bland-Altman difference: 3+/-8 ms). CONCLUSIONS: Continuous non-invasive arterial pressure monitoring demonstrates that even small changes in AV delay from its haemodynamic peak value have a significant effect on BP. This peak varies between individuals, is highly reproducible, and is more pronounced at higher heart rates than resting rates.