Tim Lockie

Hemodynamic Response to Intravenous Adenosine and Its Effect on Fractional Flow Reserve Assessment Results of the Adenosine for the Functional Evaluation of Coronary Stenosis Severity (AFFECTS) Study

Background—We studied the hemodynamic response to intravenous adenosine on calculation of fractional flow reserve (FFR). Intravenous adenosine is widely used to achieve conditions of stable hyperemia for measurement of FFR. However, intravenous adenosine affects both systemic and coronary vascular beds differentially. Methods and Results—A total of 283 patients (310 coronary stenoses) underwent coronary angiography with FFR using intravenous adenosine 140 mcg/kg per minute via a central femoral vein. Offline analysis was performed to calculate aortic (Pa), distal intracoronary (Pd), and reservoir (Pr) pressure at baseline, peak, and stable hyperemia. Seven different hemodynamic patterns were observed according to Pa and Pd change at peak and stable hyperemia. The average time from baseline to stable hyperemia was 68.2±38.5 seconds, when both &Dgr;Pa and &Dgr;Pd were decreased (&Dgr;Pa, −10.2±10.5 mm Hg; &Dgr;Pd, −18.2±10.8 mm Hg; P<0.001 for both). The fall in Pa closely correlated with the reduction in peripheral Pr (&Dgr;Pr, −12.9±15.7 mm Hg; P<0.001; r=0.9; P<0.001). &Dgr;Pa and &Dgr;Pd were closely related under conditions of peak (r=0.75; P<0.001) and stable hyperemia (r=0.83; P<0.001). On average, 56% (10.2 mm Hg) of the reduction in Pd was because of fall in Pa. FFR lesion classification changed in 9% using an FFR threshold of ⩽0.80 and 5.2% with FFR threshold <0.75 when comparing Pd/Pa at peak and stable hyperemia. Conclusions—Intravenous adenosine results in variable changes in systemic blood pressure, which can lead to alterations in FFR lesion classification. Attention is required to ensure FFR is measured under conditions of stable hyperemia, although the FFR value at this point may be numerically higher.

Synergistic Adaptations to Exercise in the Systemic and Coronary Circulations That Underlie the Warm-Up Angina Phenomenon

Background— The mechanisms of reduced angina on second exertion in patients with coronary arterial disease, also known as the warm-up angina phenomenon, are poorly understood. Adaptations within the coronary and systemic circulations have been suggested but never demonstrated in vivo. In this study we measured central and coronary hemodynamics during serial exercise. Methods and Results— Sixteen patients (15 male, 61±4.3 years) with a positive exercise ECG and exertional angina completed the protocol. During cardiac catheterization via radial access, they performed 2 consecutive exertions (Ex1, Ex2) using a supine cycle ergometer. Throughout exertions, distal coronary pressure and flow velocity were recorded in the culprit vessel using a dual sensor wire while central aortic pressure was recorded using a second wire. Patients achieved a similar workload in Ex2 but with less ischemia than in Ex1 (P<0.01). A 33% decline in aortic pressure augmentation in Ex2 (P<0.0001) coincided with a reduction in tension time index, a major determinant of left ventricular afterload (P<0.001). Coronary stenosis resistance was unchanged. A sustained reduction in coronary microvascular resistance resulted in augmented coronary flow velocity on second exertion (both P<0.001). These changes were accompanied by a 21% increase in the energy of the early diastolic coronary backward-traveling expansion, or suction, wave on second exercise (P<0.05), indicating improved microvascular conductance and enhanced left ventricular relaxation. Conclusions— On repeat exercise in patients with effort angina, synergistic changes in the systemic and coronary circulations combine to improve vascular–ventricular coupling and enhance myocardial perfusion, thereby potentially contributing to the warm-up angina phenomenon.

Coronary Wave Energy A Novel Predictor of Functional Recovery After Myocardial Infarction

Background—Revascularization after acute coronary syndromes provides prognostic benefit, provided that the subtended myocardium is viable. The microcirculation and contractility of the subtended myocardium affect propagation of coronary flow, which can be characterized by wave intensity analysis. The study objective was to determine in acute coronary syndromes whether early wave intensity analysis-derived microcirculatory (backward) expansion wave energy predicts late viability, defined by functional recovery. Methods and Results—Thirty-one patients (58±11 years) were enrolled after non-ST elevation myocardial infarction. Regional left ventricular function and late-gadolinium enhancement were assessed by cardiac magnetic resonance imaging, before and 3 months after revascularization. The backward-traveling (microcirculatory) expansion wave was derived from wave intensity analysis of phasic coronary pressure and velocity in the infarct-related artery, whereas mean values were used to calculate hyperemic microvascular resistance. Twelve-hour troponin T, left ventricular ejection fraction, and percentage late-gadolinium enhancement mass were 1.35±1.21 µg/L, 56±11%, and 8.4±6.0%, respectively. The infarct-related artery backward-traveling (microcirculatory) expansion wave was inversely correlated with late-gadolinium enhancement infarct mass (r=–0.81; P<0.0001) and strongly predicted regional left ventricular recovery (r=0.68; P=0.001). By receiver operating characteristic analysis, a backward-traveling (microcirculatory) expansion wave threshold of 2.8 W m–2 s–2×105 predicted functional recovery with sensitivity and specificity of 0.91 and 0.82 (AUC 0.88). Hyperemic microvascular resistance correlated with late-gadolinium enhancement mass (r=0.48; P=0.03) but not left ventricular recovery (r=–0.34; P=0.07). Conclusions—The microcirculation-derived backward expansion wave is a new index that correlates with the magnitude and location of infarction, which may allow for the prediction of functional myocardial recovery. Coronary wave intensity analysis may facilitate myocardial viability assessment during cardiac catheterization.

Does left ventricular function continue to influence mortality following contemporary percutaneous coronary intervention

BackgroundLeft ventricular (LV) dysfunction was associated with adverse outcome after percutaneous coronary intervention (PCI) in the balloon-angioplasty and bare-metal stent era. Technological advances have reduced complications after PCI. The impact of left ventricular ejection fraction (LVEF) on outcomes in current clinical practice is unknown, with commonly used risk stratification models not consistently incorporating preprocedural LVEF. MethodsA total of 2328 consecutive patients undergoing PCI in a single centre between April 2005 and July 2009 were analysed. Patients were eligible if LVEF had been categorized before PCI as good (LVEF ≥50%), moderate (LVEF 30–49%) or poor (LVEF <30%). Those in cardiogenic shock were excluded. Mortality data were tracked using the UK Office of National statistics database. Logistic regression analysis was used to predict the risk of mortality at 30-day and long-term follow-up. ResultsOverall all-cause mortality was 1.0% at 30 days and 5% at long-term follow-up. Kaplan–Meier analysis revealed an early divergence in survival curves according to LVEF. Mortality rates stratified by LVEF category were 0.4, 1.3 and 6.3% at 30 days and 3.3, 5.7 and 12.0% in the long term (2.2±1.1 years) (P<0.0001). Multiple regression analysis confirmed that impaired LVEF (⩽50%) independently predicts 30-day [hazard ratio 4.20 (confidence interval 2.50–7.04), P=0.001] and long-term all-cause mortality [hazard ratio 1.67 (1.28–2.19), P=0.001]. ConclusionLV impairment remains a strong predictor of early and late mortality after PCI. LV function assessment is integral in risk stratification and patient optimization and should be recommended, wherever feasible, before PCI.

Functional coronary stenosis severity assessed from the mean pressure gradient-velocity relationship obtained by contrast medium-induced submaximal hyperaemia

AIMS First, to establish the diagnostic performance of the pressure gradient at a standardised mean velocity (dPv) as derived from the cycle-averaged stenosis pressure gradient-velocity (dP-v) relationship obtained by administration of adenosine and, second, to determine whether dPv can be assessed from contrast medium-induced submaximal hyperaemia. METHODS AND RESULTS Distal coronary pressure and velocity were simultaneously recorded in 64 patients during the response to intracoronary injection of adenosine. dPv was assessed at velocities between 20 and 50 cm/s. The pressure gradient at a mean flow velocity of 30 cm/s (dPv30) yielded an excellent diagnostic performance against FFR ≤0.8 (area under the curve 0.96; sensitivity 84%; specificity 96%; accuracy 89%). In a subgroup of 21 patients, measurements were repeated throughout contrast medium-induced reactive hyperaemia. Peak velocity and pressure gradient were lower compared to adenosine, but the course of the corresponding dP-v relationships coincided very well over the common velocity range, with no difference in dPv30. CONCLUSIONS dPv30 reliably detects functionally significant coronary lesions. It derives from stenosis haemodynamics and can be obtained with submaximal hyperaemia, such as following injection of contrast medium, thereby obviating the maximal vasodilation by adenosine required for FFR or other established hyperaemic parameters of functional stenosis severity.

CORONARY WAVE INTENSITY: A NOVEL INVASIVE TOOL FOR PREDICTING MYOCARDIAL VIABILITY FOLLOWING ACUTE CORONARY SYNDROMES

Wave intensity analysis (WIA) uses simultaneous changes in intracoronary pressure and flow to characterize coronary circulatory energy. In normal hearts, flow is mainly due to microvascular, diastolic backward expansion (BEW) and aortic, systolic forward compression (FCW) waves (Fig 1a). Regional

Three-dimensional analysis of vulnerable segments in the left anterior descending artery

ObjectivesAnalysis of conventional angiograms has suggested that specific anatomic parameters of particular segments of a coronary artery render them prone to vulnerable plaque development, plaque rupture, and consequent thrombosis. This study aimed at performing a three-dimensional analysis of recanalized left anterior descending (LAD) coronary arteries in patients who had suffered an anterior ST-elevation myocardial infarction (STEMI). MethodsCoronary angiograms of 76 consecutive patients with an anterior STEMI and a recanalized LAD were reconstructed in the three-dimensional space, and compared with angiograms of 76 patients with stable coronary artery disease (SCAD) and significant LAD stenosis. ResultsIn both groups the majority of lesions occurred between 20 and 40 mm (P=0.745), but the number of lesions beyond 60 mm from the ostium was significantly higher in SCAD compared with STEMI (P=0.045). Culprit lesions were statistically significantly longer in patients with STEMI compared with SCAD (18.3±7.5 vs. 12.7±6.2 mm, P<0.001). Cut-off point analysis indicated a lesion length of ≥12.5 mm as discriminating threshold between SCAD and STEMI (sensitivity 79% and specificity 63%). Bifurcation branches on the culprit lesion were seen in 79% of the patients with STEMI and 58% of those with SCAD (P=0.026). Lesion angulation was significantly sharper in STEMI compared with SCAD patients in diastole (155±15 vs. 160±14 degrees, P=0.037). Multiple logistic regression model including these parameters had a high discriminating ability with c-statistic 0.78 (95% confidence intervals: 0.71–0.86), sensitivity 72.4%, and specificity 75%. ConclusionSpecific anatomic characteristics of LAD segments predispose to development of plaque rupture and thrombosis.

Contemporary trends in cardiogenic shock: Incidence, intra-aortic balloon pump utilisation and outcomes from the London Heart Attack Group:

Background: Cardiogenic shock remains a major cause of morbidity and mortality in patients with ST-segment elevation myocardial infarction. We aimed to assess the current trends in cardiogenic shock management, looking specifically at the incidence, use of intra-aortic balloon pump therapy and outcomes in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods and results: We undertook an observational cohort study of 21,210 ST-segment elevation myocardial infarction patients treated between 2005–2015 at the eight Heart Attack Centres in London, UK. Patients’ details were recorded at the time of the procedure into local databases using the British Cardiac Intervention Society percutaneous coronary intervention dataset. There were 1890 patients who presented with cardiogenic shock. The primary outcome was all-cause mortality at a median follow-up of 4.1 years (interquartile range: 2.2–5.8 years). Increasing rates of cardiogenic shock were seen over the course of the study with consistently high mortality rates of 45–70%. A total of 685 patients underwent intra-aortic balloon pump insertion during primary percutaneous coronary intervention for cardiogenic shock with decreasing rates over time. Those patients undergoing intra-aortic balloon pump therapy were younger, more likely to have poor left ventricular function and less likely to have had previous percutaneous coronary intervention compared to the control group. Procedural success rates were similar (86.0% vs 87.1%, p=0.292) although crude, in-hospital major adverse cardiac event rates were higher (43.8% vs 33.7%, p<0.0001) in patients undergoing intra-aortic balloon pump therapy. Kaplan-Meier analysis demonstrated significantly higher mortality rates in patients receiving intra-aortic balloon pump therapy (50.9% intra-aortic balloon pump vs 39.9% control, p<0.0001) during the follow-up period. After multivariate Cox analysis (hazard ratio 1.04, 95% confidence interval 0.62–1.89) and the use of propensity matching (hazard ratio: 1.29, 95% confidence interval: 0.68–1.45) intra-aortic balloon pump therapy was not associated with mortality. Conclusion: Cardiogenic shock treated by percutaneous coronary intervention is increasing in incidence and remains a condition associated with high mortality and limited treatment options. Intra-aortic balloon pump therapy was not associated with a long-term survival benefit in this cohort and may be associated with increased early morbidity.

WAVE SPEED IN THE HUMAN CORONARY ARTERY DOES NOT DECREASE WITH VASODILATION: EXTENDING THE LIMITS OF VALIDITY OF THE SINGLE–POINT TECHNIQUE FOR WAVE INTENSITY ANALYSIS

The rapidly expanding technique of wave intensity analysis (WIA) requires that coronary wave speed is known. This study is the first to directly measure coronary wave speed in humans and compare it to the single–point technique (SPc), which is derived from local pressure and velocity signals, but

Physiology of Angina and Its Alleviation With NitroglycerinClinical Perspective: 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.