Optimization in First-Passage Resetting

We investigate classic diffusion with the added feature that a diffusing particle is reset to its starting point each time the particle reaches a specified threshold. In an infinite domain, this process is non-stationary and its probability distribution exhibits rich features. In a finite domain, we define a non-trivial optimization in which a cost is incurred whenever the particle is reset and a reward is obtained while the particle stays near the reset point. We derive the condition to optimize the net gain in this system, namely, the reward minus the cost.Comment: 4 pages, 3 figures, revtex 4-1 format. Version 1 contains changes in response to referee comments. Version 2: A missing factor of 2 in an inline formula has been correcte

Repeatability of fractional flow reserve despite variations in systemic and coronary hemodynamics

Objectives This study classified and quantified the variation in fractional flow reserve (FFR) due to fluctuations in systemic and coronary hemodynamics during intravenous adenosine infusion. Background Although FFR has become a key invasive tool to guide treatment, questions remain regarding its repeatability and stability during intravenous adenosine infusion because of systemic effects that can alter driving pressure and heart rate. Methods We reanalyzed data from the VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice) study, which enrolled consecutive patients who were infused with intravenous adenosine at 140 μg/kg/min and measured FFR twice. Raw phasic pressure tracings from the aorta (Pa) and distal coronary artery (Pd) were transformed into moving averages of Pd/Pa. Visual analysis grouped Pd/Pa curves into patterns of similar response. Quantitative analysis of the Pd/Pa curves identified the “smart minimum” FFR using a novel algorithm, which was compared with human core laboratory analysis. Results A total of 190 complete pairs came from 206 patients after exclusions. Visual analysis revealed 3 Pd/Pa patterns: “classic” (sigmoid) in 57%, “humped” (sigmoid with superimposed bumps of varying height) in 39%, and “unusual” (no pattern) in 4%. The Pd/Pa pattern repeated itself in 67% of patient pairs. Despite variability of Pd/Pa during the hyperemic period, the “smart minimum” FFR demonstrated excellent repeatability (bias −0.001, SD 0.018, paired p = 0.93, r2 = 98.2%, coefficient of variation = 2.5%). Our algorithm produced FFR values not significantly different from human core laboratory analysis (paired p = 0.43 vs. VERIFY; p = 0.34 vs. RESOLVE). Conclusions Intravenous adenosine produced 3 general patterns of Pd/Pa response, with associated variability in aortic and coronary pressure and heart rate during the hyperemic period. Nevertheless, FFR – when chosen appropriately – proved to be a highly reproducible value. Therefore, operators can confidently select the “smart minimum” FFR for patient care. Our results suggest that this selection process can be automated, yet comparable to human core laboratory analysis

Phasic pressure measurements for coronary and valvular interventions using fluid-filled catheters: Errors, automated correction, and clinical implications.

We sought to develop an automatic method for correcting common errors in phasic pressure tracings for physiology-guided interventions on coronary and valvular stenosis. Effective coronary and valvular interventions rely on accurate hemodynamic assessment. Phasic (subcycle) indexes remain intrinsic to valvular stenosis and are emerging for coronary stenosis. Errors, corrections, and clinical implications of fluid-filled catheter phasic pressure assessments have not been assessed in the current era of ubiquitous, high-fidelity pressure wire sensors. We recruited patients undergoing invasive coronary physiology assessment. Phasic aortic pressure signals were recorded simultaneously using a fluid-filled guide catheter and 0.014″ pressure wire before and after standard calibration as well as after pullback. We included additional subjects undergoing hemodynamic assessment before and after transcatheter aortic valve implantation. Using the pressure wire as reference standard, we developed an automatic algorithm to match phasic pressures. Removing pressure offset and temporal shift produced the largest improvements in root mean square (RMS) error between catheter and pressure wire signals. However, further optimization <1 mmHg RMS error was possible by accounting for differential gain and the oscillatory behavior of the fluid-filled guide. The impact of correction was larger for subcycle (like systole or diastole) versus whole-cycle metrics, indicating a key role for valvular stenosis and emerging coronary pressure ratios. When calibrating phasic aortic pressure signals using a pressure wire, correction requires these parameters: offset, timing, gain, and oscillations (frequency and damping factor). Automatically eliminating common errors may improve some clinical decisions regarding physiology-based intervention

Quantification of valvular regurgitation by cardiac blood pool scintigraphy: correlation with catheterization

The diagnosis of valvular regurgitation (R) is usually based on clinical signs. Quantification conventionally requires catheterization (C). We have quantified R with cardiac blood pool scintigraphy (CBPS) and compared the results with those obtained by C. Regurgitant fraction (RF) determined by C was calculated with the technique of Dodge. Forward output was measured by thermodilution or cardiogreen dilution. The RF at CBPS was obtained by the stroke index ratio (SIR) minus 1.2 divided by SIR, where SIR is the ratio of the stroke counts of left venticle over those of the right ventricle. Stroke counts are calculated directly from the time-activity curves. Each time-activity curve was obtained by drawing one region of interest around each diastolic image. The correction factor (1.2) was calculated from a large normal population. 22 patients had aortic R, 7 mitral R, 12 both, 8 patients had no evidence of regurgitation. RF of the patients with R varied from 27 to 71% (x = 42%) at C and from 26 to 74% (Y = 41%) at CBPS. Linear regression shows a good correlation coefficient (r = 0.82). The regression equation is y = 0.93x + 1.8. No correlation was found between RF (CBPS or C) and the severity of R assessed visually from angiography. In conclusion: CBPS, a non-invasive method, allows easy and repeatable determination of RF and correlates well with data obtained at catheterizatio

Ability of FFR-CT to detect the absence of hemodynamically significant lesions in patients with high-risk NSTE-ACS admitted in the emergency department with chest pain, study design and rationale.

In the era of High-sensitive troponin (hs-Tn), up to 50% of patients with a mild increase of hs-Tn will finally have a normal invasive coronary angiogram. Fractional Flow Reserve (FFR) derived from coronary computed tomographic angiography (FFR-CT) has never been used as a non-invasive tool for the diagnosis of coronary artery disease in patients with high-risk acute coronary syndrome without ST segment elevation (NSTE-ACS). The study aims to determine the role of coronary CT angiography and FFR-CT in the setting of high-risk NSTE-ACS. We will conduct a prospective trial, enrolling 250 patients admitted with high-risk NSTE-ACS who will rapidly undergo a coronary CT angiography and then a coronary angiography with FFR measurements. Results of coronary CT, FFR-CT and coronary angiography (± FFR) will be compared. In conclusion, non-invasive identification of patients with high-risk NSTE-ACS who could avoid coronary angiography would reduce procedure related risks and medical costs

Intracoronary EnalaPrilat to Reduce MICROvascular Damage During Percutaneous Coronary Intervention (ProMicro) study.

Intracoronary angiotensin-converting enzyme inhibitors have been shown to relieve myocardial ischemia in stable patients and to improve epicardial flow in patients with ST-segment elevation myocardial infarction. Yet, it is still unclear whether these effects are mediated by a modulation of the coronary microcirculation. Methods We randomly assigned 40 patients to receive either an intracoronary bolus of enalaprilat (50 g) or placebo before elective PCI. The index of microvascular resistance was measured at baseline, 10 minutes after study drug administration, and after PCI. High-sensitivity cardiac troponin T was measured as a marker of myocardial injury. Results Infusion of enalaprilat resulted in a significant reduction in index of microvascular resistance (27 11 at baseline vs. 19 9 after drug vs. 15 8 after PCI), whereas a significant post-procedural increase in index of microvascular resistance levels was observed in the placebo group (24 15 at baseline vs. 24 15 after drug vs. 33 19 after PCI). Index of microvascular resistance levels after PCI were significantly lower in the enalaprilat group (p 0.001). Patients pre-treated with enalaprilat also showed lower peak values (mean: 21.7 ng/ml, range: 8.2 to 34.8 ng/ml vs. mean: 32.3 ng/ml, range: 12.6 to 65.2 ng/ml, p 0.048) and peri-procedural increases of high-sensitivity cardiac troponin T (mean: 9.9 ng/ml, range: 2.7 to 19.0 ng/ml vs. mean: 26.6 ng/ml, range: 6.3 to 60.5 ng/ml, p 0.025). Conclusions Intracoronary enalaprilat improves coronary microvascular function and protects myocardium from procedurerelated injury in patients with coronary artery disease undergoing PCI. Larger studies are warranted to investigate whether these effects of enalaprilat could result into a significant clinical benefit. (J Am Coll Cardiol 2013;61:615–21) © 2013 by the American College of Cardiology Foundatio