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.

Measurement precision in the optimization of cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy improves morbidity and mortality in appropriately selected patients. Whether atrioventricular (AV) and interventricular (VV) pacing interval optimization confers further clinical improvement remains unclear. A variety of techniques are used to estimate optimum AV/VV intervals; however, the precision of their estimates and the ramifications of an imprecise estimate have not been characterized previously. METHODS AND RESULTS: An objective methodology for quantifying the precision of estimated optimum AV/VV intervals was developed, allowing physiologic effects to be distinguished from measurement variability. Optimization using multiple conventional techniques was conducted in individual sessions with 20 patients. Measures of stroke volume and dyssynchrony were obtained using impedance cardiography and echocardiographic methods, specifically, aortic velocity-time integral, mitral velocity-time integral, A-wave truncation, and septal-posterior wall motion delay. Echocardiographic methods yielded statistically insignificant data in the majority of patients (62%-82%). In contrast, impedance cardiography yielded statistically significant results in 84% and 75% of patients for AV and VV interval optimization, respectively. Individual cases demonstrated that accepting a plausible but statistically insignificant estimated optimum AV or VV interval can result in worse cardiac function than default values. CONCLUSIONS: Consideration of statistical significance is critical for validating clinical optimization data in individual patients and for comparing competing optimization techniques. Accepting an estimated optimum without knowledge of its precision can result in worse cardiac function than default settings and a misinterpretation of observed changes over time. In this study, only impedance cardiography yielded statistically significant AV and VV interval optimization data in the majority of patients.

Identification of hemodynamically unstable arrhythmias using subcutaneous photoplethysmography.

INTRODUCTION: Determination of hemodynamic status is central to arrhythmia management in the inpatient setting. In contrast, therapy decisions in implantable cardioverter defibrillators (ICDs) are based exclusively on the arrhythmia's electrical signature. Hemodynamic sensing in ICDs would allow tailoring of therapy according to perfusion status. Subcutaneous photoplethysmography (PPG) is an attractive technology for this application because it responds to changes in arterial pressure and can be readily incorporated into the housing of implanted devices. This study evaluated the accuracy of PPG in identifying hemodynamically unstable simulated arrhythmias in an animal model. METHODS AND RESULTS: Rapid atrial and ventricular pacing was used to simulate arrhythmias in an acute preparation of 7 healthy dogs. Aortic pressure and subcutaneous PPG were simultaneously recorded. Simulated arrhythmias were defined as hemodynamically unstable if aortic pressure decreased by >or=15 mmHg, marginally unstable if pressure decreased by 5-15 mmHg, and hemodynamically stable if pressure either increased or decreased by no more than 5 mmHg. An average of 56 arrhythmias were simulated in each animal. Changes in pressure and PPG output were highly correlated, with correlation coefficient of 0.7-0.9. Subcutaneous PPG identified hemodynamically unstable episodes with a sensitivity of 100% for 6 subjects and 80% for 1 subject. Specificity was more than 90% for 6 subjects and was 50% for 1 subject. CONCLUSIONS: Subcutaneous PPG detects hemodynamically unstable simulated arrhythmias in an acute canine preparation. If successfully validated in humans, this technology may allow ICD therapy to be specifically tailored according to the hemodynamic status of the arrhythmia.

A general framework for dose optimization.

Dose optimization is a ubiquitous challenge in clinical practice and includes both pharmacologic and non-pharmacologic interventions. Methods for the statistical assessment of optimum dosing are lacking. We developed a generic framework for dose titration and demonstrated its application in two domains. Optimum warfarin dose was estimated from clinical titration data. In addition, cardiac pacemaker interval optimization was conducted using three conventional techniques. For both data types, optima were obtained from mathematical functions fit to the raw data. The precision of the estimated optima was quantified using bootstrapping. In pacing optimization, the observed precision varied significantly among the techniques, suggesting that impedance cardiography is superior to commonly used echocardiographic methods. The average 95% confidence interval of the estimated optimum warfarin dose was +/-18%, suggesting that titration within this range is of limited utility. By identifying statistically ineffective interventions, objective analysis of optimization data may both improve outcomes and reduce healthcare costs.

Hemodynamic sensing using subcutaneous photoplethysmography.

Pacemakers and implantable defibrillators presently operate without access to hemodynamic information. If available, such data would allow tailoring of delivered therapy according to perfusion status, optimization of device function, and enhancement of disease monitoring and management. A candidate method for hemodynamic sensing in these devices is photoplethysmography (PPG), which uses light to noninvasively detect changes in blood volume. The present study tested the hypotheses that PPG can function in a subcutaneous location, that the acute changes in blood volume it detects are directly proportional to changes in arterial pressure, and that optimum pacing intervals identified by it are concordant with those determined by arterial pressure. Aortic pressure and PPG were simultaneously recorded in 10 dogs under general anesthesia during changes in atrioventricular (AV) delay and bursts of rapid pacing to simulate tachyarrhythmias. Direct proportionality between transient changes in pressure and PPG waveforms was tested using regression analysis. Scatter plots had a linear appearance, with correlation coefficients of 0.95 (SD 0.03) and 0.72 (SD 0.24) for rapid-pacing and AV delay protocols, respectively. The data were well described by a directly proportional relationship. Optimum AV delays estimated from the induced changes in aortic pressure and PPG waveforms were concordant. This preliminary canine study demonstrates that PPG can function subcutaneously and that it may serve as a surrogate for acute changes in arterial pressure.