Kaleab N. Asrress

Diagnostic classification of the instantaneous wave-free ratio is equivalent to fractional flow reserve and is not improved with adenosine administration. Results of CLARIFY (Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study).

OBJECTIVES This study sought to determine if adenosine administration is required for the pressure-only assessment of coronary stenoses. BACKGROUND The instantaneous wave-free ratio (iFR) is a vasodilator-free pressure-only measure of the hemodynamic severity of a coronary stenosis comparable to fractional flow reserve (FFR) in diagnostic categorization. In this study, we used hyperemic stenosis resistance (HSR), a combined pressure-and-flow index, as an arbiter to determine when iFR and FFR disagree which index is most representative of the hemodynamic significance of the stenosis. We then test whether administering adenosine significantly improves diagnostic performance of iFR. METHODS In 51 vessels, intracoronary pressure and flow velocity was measured distal to the stenosis at rest and during adenosine-mediated hyperemia. The iFR (at rest and during adenosine administration [iFRa]), FFR, HSR, baseline, and hyperemic microvascular resistance were calculated using automated algorithms. RESULTS When iFR and FFR disagreed (4 cases, or 7.7% of the study population), HSR agreed with iFR in 50% of cases and with FFR in 50% of cases. Differences in magnitude of microvascular resistance did not influence diagnostic categorization; iFR, iFRa, and FFR had equally good diagnostic agreement with HSR (receiver-operating characteristic area under the curve 0.93 iFR vs. 0.94 iFRa and 0.96 FFR, p = 0.48). CONCLUSIONS iFR and FFR had equivalent agreement with classification of coronary stenosis severity by HSR. Further reduction in resistance by the administration of adenosine did not improve diagnostic categorization, indicating that iFR can be used as an adenosine-free alternative to FFR.

The intra-observer reproducibility of cardiovascular magnetic resonance myocardial feature tracking strain assessment is independent of field strength

BACKGROUND Cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) is a promising novel method for quantification of myocardial wall mechanics from standard steady-state free precession (SSFP) images. We sought to determine whether magnetic field strength affects the intra-observer reproducibility of CMR-FT strain analysis. METHODS We studied 2 groups, each consisting of 10 healthy subjects, at 1.5 T or 3T Analysis was performed at baseline and after 4 weeks using dedicated CMR-FT prototype software (Tomtec, Germany) to analyze standard SSFP cine images. Right ventricular (RV) and left ventricular (LV) longitudinal strain (Ell(RV) and Ell(LV)) and LV long-axis radial strain (Err(LAX)) were derived from the 4-chamber cine, and LV short-axis circumferential and radial strains (Ecc(SAX), Err(SAX)) from the short-axis orientation. Strain parameters were assessed together with LV ejection fraction (EF) and volumes. Intra-observer reproducibility was determined by comparing the first and the second analysis in both groups. RESULTS In all volunteers resting strain parameters were successfully derived from the SSFP images. There was no difference in strain parameters, volumes and EF between field strengths (p>0.05). In general Ecc(SAX) was the most reproducible strain parameter as determined by the coefficient of variation (CV) at 1.5 T (CV 13.3% and 46% global and segmental respectively) and 3T (CV 17.2% and 31.1% global and segmental respectively). The least reproducible parameter was Ell(RV) (CV 1.5 T 28.7% and 53.2%; 3T 43.5% and 63.3% global and segmental respectively). CONCLUSIONS CMR-FT results are similar with reasonable intra-observer reproducibility in different groups of volunteers at 1.5 T and 3T. CMR-FT is a promising novel technique and our data indicate that results might be transferable between field strengths. However there is a considerable amount of segmental variability indicating that further refinements are needed before CMR-FT can be fully established in clinical routine for quantitative assessment of wall mechanics and strain.

Hybrid iFR-FFR decision-making strategy: implications for enhancing universal adoption of physiology-guided coronary revascularisation.

AIMS Adoption of fractional flow reserve (FFR) remains low (6-8%), partly because of the time, cost and potential inconvenience associated with vasodilator administration. The instantaneous wave-Free Ratio (iFR) is a pressure-only index of stenosis severity calculated without vasodilator drugs. Before outcome trials test iFR as a sole guide to revascularisation, we evaluate the merits of a hybrid iFR-FFR decision-making strategy for universal physiological assessment. METHODS AND RESULTS Coronary pressure traces from 577 stenoses were analysed. iFR was calculated as the ratio between Pd and Pa in the resting diastolic wave-free window. A hybrid iFR-FFR strategy was evaluated, by allowing iFR to defer some stenoses (where negative predictive value is high) and treat others (where positive predictive value is high), with adenosine being given only to patients with iFR in between those values. For the most recent fixed FFR cut-off (0.8), an iFR of <0.86 could be used to confirm treatment (PPV of 92%), whilst an iFR value of >0.93 could be used to defer revascularisation (NPV of 91%). Limiting vasodilator drugs to cases with iFR values between 0.86 to 0.93 would obviate the need for vasodilator drugs in 57% of patients, whilst maintaining 95% agreement with an FFR-only strategy. If the 0.75-0.8 FFR grey zone is accounted for, vasodilator drug requirement would decrease by 76%. CONCLUSION A hybrid iFR-FFR decision-making strategy for revascularisation could increase adoption of physiology-guided PCI, by more than halving the need for vasodilator administration, whilst maintaining high classification agreement with an FFR-only strategy.

Does the instantaneous wave-free ratio approximate the fractional flow reserve?

OBJECTIVES This study sought to examine the clinical performance of and theoretical basis for the instantaneous wave-free ratio (iFR) approximation to the fractional flow reserve (FFR). BACKGROUND Recent work has proposed iFR as a vasodilation-free alternative to FFR for making mechanical revascularization decisions. Its fundamental basis is the assumption that diastolic resting myocardial resistance equals mean hyperemic resistance. METHODS Pressure-only and combined pressure-flow clinical data from several centers were studied both empirically and by using pressure-flow physiology. A Monte Carlo simulation was performed by repeatedly selecting random parameters as if drawing from a cohort of hypothetical patients, using the reported ranges of these physiologic variables. RESULTS We aggregated observations of 1,129 patients, including 120 with combined pressure-flow data. Separately, we performed 1,000 Monte Carlo simulations. Clinical data showed that iFR was +0.09 higher than FFR on average, with ±0.17 limits of agreement. Diastolic resting resistance was 2.5 ± 1.0 times higher than mean hyperemic resistance in patients. Without invoking wave mechanics, classic pressure-flow physiology explained clinical observations well, with a coefficient of determination of >0.9. Nearly identical scatter of iFR versus FFR was seen between simulation and patient observations, thereby supporting our model. CONCLUSIONS iFR provides both a biased estimate of FFR, on average, and an uncertain estimate of FFR in individual cases. Diastolic resting myocardial resistance does not equal mean hyperemic resistance, thereby contravening the most basic condition on which iFR depends. Fundamental relationships of coronary pressure and flow explain the iFR approximation without invoking wave mechanics.

The effects of VARC-defined acute kidney injury after transcatheter aortic valve implantation (TAVI) using the Edwards bioprosthesis

AIMS The aim of this study was to identify the incidence and risk factors for acute kidney injury (AKI) after TAVI, a potentially serious complication of transcatheter aortic valve implantation (TAVI) that has been redefined by the Valve Academic Research Consortium (VARC). METHODS AND RESULTS We performed a retrospective analysis of 248 patients undergoing TAVI. AKI was defined as a VARC-modified Risk, Injury, Failure, Loss, and End-stage (RIFLE) kidney disease score ≥ 2. Eighty-nine patients suffered AKI (35.9%) and demonstrated increased mortality at 30 days (13.5% vs. 3.8%) and one year (31.5% vs. 15.0%) (p<0.001). Multivariate regression analysis identified diabetes mellitus (p<0.001), peripheral vascular disease (p=0.007), chronic kidney disease stage (p=0.010) as independently associated risk factors for AKI. CONCLUSIONS More than one third of patients sustain AKI after TAVI using the Edwards bioprosthesis, as defined by the VARC-modified RIFLE score. AKI increased the mortality at both 30 days and at one year. A history of diabetes mellitus, peripheral vascular disease and higher chronic kidney disease stage had the strongest independent associations with post-TAVI AKI.

Coronary and Microvascular Physiology During Intra-Aortic Balloon Counterpulsation

OBJECTIVES This study sought to identify the effect of coronary autoregulation on myocardial perfusion during intra-aortic balloon pump (IABP) therapy. BACKGROUND IABP is the most commonly used circulatory support device, although its efficacy in certain scenarios has been questioned. The impact of alterations in microvascular function on IABP efficacy has not previously been evaluated in humans. METHODS Thirteen patients with ischemic cardiomyopathy (left ventricular ejection fraction: 34 ± 8%) undergoing percutaneous coronary intervention were recruited. Simultaneous intracoronary pressure and Doppler-flow measurements were undertaken in the target vessel following percutaneous coronary intervention, during unassisted and IABP-assisted conditions. Coronary autoregulation was modulated by the use of intracoronary adenosine, inducing maximal hyperemia. Wave intensity analysis characterized the coronary wave energies associated with balloon counterpulsation. RESULTS Two unique diastolic coronary waves were temporally associated with IABP device use; a forward compression wave and a forward expansion wave caused by inflation and deflation, respectively. During basal conditions, IABP therapy increased distal coronary pressure (82.4 ± 16.1 vs. 88.7 ± 17.8 mm Hg, p = 0.03), as well as microvascular resistance (2.32 ± 0.52 vs. 3.27 ± 0.41 mm Hg cm s(-1), p = 0.001), with no change in average peak velocity (30.6 ± 12.0 vs. 26.6 ± 11.3 cm s(-1), p = 0.59). When autoregulation was disabled, counterpulsation caused an increase in average peak velocity (39.4 ± 10.5 vs. 44.7 ± 17.5 cm s(-1), p = 0.002) that was linearly related with IABP-forward compression wave energy (R(2) = 0.71, p = 0.001). CONCLUSIONS Autoregulation ameliorates the effect of IABP on coronary flow. However, during hyperemia, IABP augments myocardial perfusion, principally due to a diastolic forward compression wave caused by balloon inflation, suggesting IABP would be of greatest benefit when microcirculatory reserve is exhausted.

A mathematical model of coronary blood flow control: simulation of patient-specific three-dimensional hemodynamics during exercise

This paper presents a new mathematical model of the dynamic control of coronary resistance. It shows a remarkable ability to predict coronary flow in an exercising patient, which would otherwise be impossible, and provides new insight into the purpose and action of the coronary flow control systems. It is applicable as part of a controlled boundary condition at the coronary outlets of a three-dimensional Navier-Stokes simulation of hemodynamics.

Patent foramen ovale: the current state of play

### Learning objectives Patent foramen ovale (PFO) is a common finding, occurring in up to 25% of people.1 ,2 An association between PFO and stroke has consistently been seen in up to 50% of patients without an identifiable cause, that is, the so-called cryptogenic stroke (CS) and only in 20% with an identified cause.3 ,4 Many studies have been published testing the hypothesis that paradoxical emboli through a PFO may be implicated, however the available evidence is mixed and conflicting,5 ,6 perhaps in part due to the low recurrence rate and long-term nature of these events. PFOs are associated with numerous other conditions including migraine with aura, decompression sickness, other venoarterial embolic phenomena and platypnoea orthodeoxia. In this review we will describe the embryological development of the interatrial septum, discuss the diagnosis and clinical associations of PFO, as well as evaluate the available data for and against closure. The embryological development of the interatrial septum and foramen ovale is complex, starting at 4–5 weeks post conception with fusion of ventral and dorsal endocardial cushions. Closure of the atrioventricular canal creates two cavities that develop into atria and ventricles and divide into left and right sides. Initially the septum primum grows from the roof of the atria towards the fused endocardial cushion (figure 1A), while the gap, the ostium primum, allows interatrial flow. Before complete atrial separation, a new communication, the ostium secundum, develops by fenestration of the superior region (figure 1B ), allowing continuous right-to-left shunting of oxygenated blood from the umbilical arteries bypassing the fetal pulmonary circulation (figure 1 …

Physiology of Angina and its Alleviation with Nitroglycerine- Insights from Invasive Catheter Laboratory Measurements During Exercise

Background: The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. Methods: Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. Results: Patients continued to exercise after nitroglycerin administration with less ST-segment depression (P=0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P=0.030) and myocardial oxygen demand were seen (tension-time index, P=0.024; rate-pressure product, P=0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P=0.017). Exercise reduced peripheral arterial wave reflection (P<0.05), which was not further augmented by the administration of nitroglycerin (P=0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity–pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P<0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. Conclusions: The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies.

Doppler Versus Thermodilution-Derived Coronary Microvascular Resistance to Predict Coronary Microvascular Dysfunction in Patients With Acute Myocardial Infarction or Stable Angina Pectoris

Coronary microvascular resistance is increasingly measured as a predictor of clinical outcomes, but there is no accepted gold-standard measurement. We compared the diagnostic accuracy of 2 invasive indices of microvascular resistance, Doppler-derived hyperemic microvascular resistance (hMR) and thermodilution-derived index of microcirculatory resistance (IMR), at predicting microvascular dysfunction. A total of 54 patients (61 ± 10 years) who underwent cardiac catheterization for stable coronary artery disease (n = 10) or acute myocardial infarction (n = 44) had simultaneous intracoronary pressure, Doppler flow velocity and thermodilution flow data acquired from 74 unobstructed vessels, at rest and during hyperemia. Three independent measurements of microvascular function were assessed, using predefined dichotomous thresholds: (1) coronary flow reserve (CFR), the average value of Doppler- and thermodilution-derived CFR; (2) cardiovascular magnetic resonance (CMR) derived myocardial perfusion reserve index; and (3) CMR-derived microvascular obstruction. hMR correlated with IMR (rho = 0.41, p <0.0001). hMR had better diagnostic accuracy than IMR to predict CFR (area under curve [AUC] 0.82 vs 0.58, p <0.001, sensitivity and specificity 77% and 77% vs 51% and 71%) and myocardial perfusion reserve index (AUC 0.85 vs 0.72, p = 0.19, sensitivity and specificity 82% and 80% vs 64% and 75%). In patients with acute myocardial infarction, the AUCs of hMR and IMR at predicting extensive microvascular obstruction were 0.83 and 0.72, respectively (p = 0.22, sensitivity and specificity 78% and 74% vs 44% and 91%). We conclude that these 2 invasive indices of coronary microvascular resistance only correlate modestly and so cannot be considered equivalent. In our study, the correlation between independent invasive and noninvasive measurements of microvascular function was better with hMR than with IMR.