Matthijs Bax

Fractional flow reserve, absolute and relative coronary blood flow velocity reserve in relation to the results of technetium-99m sestamibi single-photon emission computed tomography in patients with two-vessel coronary artery disease.

OBJECTIVES We sought to perform a direct comparison between perfusion scintigraphic results and intracoronary-derived hemodynamic variables (fractional flow reserve [FFR]; absolute and relative coronary flow velocity reserve [CFVR and rCFVR, respectively]) in patients with two-vessel disease. BACKGROUND There is limited information on the diagnostic accuracy of intracoronary-derived variables (CFVR, FFR and rCFVR) in patients with multivessel disease. METHODS Dipyridamole technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT) was performed in 127 patients. The presence of reversible perfusion defects in the region of interest was determined. Within one week, angiography was performed; CFVR, rCFVR and FFR were determined in 161 coronary lesions after intracoronary administration of adenosine. The predictive value for the presence of reversible perfusion defects on MIBI SPECT of CFVR, rCFVR and FFR was evaluated by the area under the curve (AUC) of the receiver operating characteristics curves. RESULTS The mean percentage diameter stenosis was 57% (range 35% to 85%), as measured by quantitative coronary angiography. Using per-patient analysis, the AUCs for CFVR (0.70 +/- 0.052), rCFVR (0.72 +/- 0.051) and FFR (0.76 +/- 0.050) were not significantly different (p = NS). The percentages of agreement with the results of MIBI SPECT were 76%, 78% and 77% for CFVR, rCFVR and FFR, respectively. Per-lesion analysis, using all 161 measured lesions, yielded similar results. CONCLUSIONS The diagnostic accuracy of three intracoronary-derived hemodynamic variables, as compared with the results of perfusion scintigraphy, is similar in patients with two-vessel coronary artery disease. Cut-offvalues of 2.0 for CFVR, 0.65 for rCFVR and 0.75 for FFR can be used for clinical decision-making in this patient cohort. Discordant results were obtained in 23% of the cases that require prospective evaluation for appropriate patient management.

Diagnostic Accuracy of Combined Intracoronary Pressure and Flow Velocity Information During Baseline Conditions Adenosine-Free Assessment of Functional Coronary Lesion Severity

Background— The assessment of functional coronary lesion severity using intracoronary physiological parameters such as coronary flow velocity reserve and the more widely used fractional flow reserve relies critically on the establishment of maximal hyperemia. We evaluated the diagnostic accuracy of the stenosis resistance index during nonhyperemic conditions, baseline stenosis resistance index, compared with established hyperemic intracoronary hemodynamic parameters, because achievement of hyperemia can be cumbersome in daily clinical practice. Methods and Results— A total of 228 patients, including 299 lesions (mean stenosis diameter 55%±11%), underwent myocardial perfusion scintigraphy for documentation of reversible perfusion defects. Distal coronary pressure and flow velocity were assessed with sensor-equipped guidewires during baseline and maximal hyperemia, induced by an intracoronary bolus of adenosine (20–40 µg). We determined stenosis resistance (SR) during baseline and hyperemic conditions as well as fractional flow reserve and coronary flow velocity reserve. The discriminative value for myocardial ischemia on myocardial perfusion scintigraphy of all parameters was compared using receiver-operating-characteristic curves. Baseline SR showed good agreement with myocardial perfusion scintigraphy. The diagnostic performance of baseline SR (area under the curve, 0.77; 95% CI, 0.71–0.83) was as accurate as fractional flow reserve and coronary flow velocity reserve (area under the curve, 0.77; 95% CI, 0.71–0.83 and area under the curve, 0.75; 95% CI, 0.68–0.81 respectively; P>0.05 compared with baseline SR for both). However, hyperemic SR, combining both pressure and flow velocity information during hyperemia, was superior to all other parameters (area under the curve, 0.81; 95% CI, 0.76–0.87; P<0.05 compared with all other parameters). Conclusions— Combined pressure and flow velocity measurements during baseline conditions may provide a useful tool for functional lesion severity assessment without the need for potent vasodilators.

C-reactive protein and coronary events following percutaneous coronary angioplasty

Abstract Purpose We investigated the associations between baseline C-reactive protein levels in patients undergoing percutaneous coronary angioplasty and death, nonfatal myocardial infarction, and repeat revascularization during 14 months of follow-up. Methods In a single-center, prospective, cohort study, plasma levels of C-reactive protein were measured in 1458 consecutive patients undergoing elective or urgent coronary angioplasty. Patients were followed at 12 to 14 months for the occurrence of death, nonfatal myocardial infarction, and repeat revascularization. Results The incidence of death or myocardial infarction was 6.1% (44/716) in patients with an increased C-reactive protein level (>3 mg/L) and 1.5% (11/742) in patients with a normal level (relative risk [RR] = 4.4; 95% confidence interval [CI]: 2.2 to 8.5; P P = 0.0001). The incidence of repeat revascularization was similar in patients with or without an increased C-reactive protein level (23% [168/716] vs. 22% [163/742], P = 0.54). Statin therapy at the time of the procedure was associated with a lower mean (± SD) C-reactive protein level (5.8 ± 9.7 mg/L vs. 7.2 ± 12.1 mg/L, P = 0.02), but was not associated with the risk of death, nonfatal myocardial infarction, and repeat revascularization during follow-up. Conclusion An increased C-reactive protein level is an independent prognostic indicator for the occurrence of death or nonfatal myocardial infarction following coronary angioplasty, but is not associated with the need for repeat revascularization.

Rationale and design of EXPLORE: a randomized, prospective, multicenter trial investigating the impact of recanalization of a chronic total occlusion on left ventricular function in patients after primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

BackgroundIn the setting of primary percutaneous coronary intervention, patients with a chronic total occlusion in a non-infarct related artery were recently identified as a high-risk subgroup. It is unclear whether ST-elevation myocardial infarction patients with a chronic total occlusion in a non-infarct related artery should undergo additional percutaneous coronary intervention of the chronic total occlusion on top of optimal medical therapy shortly after primary percutaneous coronary intervention. Possible beneficial effects include reduction in adverse left ventricular remodeling and preservation of global left ventricular function and improved clinical outcome during future coronary events.Methods/DesignThe Evaluating Xience V and left ventricular function in Percutaneous coronary intervention on occLusiOns afteR ST-Elevation myocardial infarction (EXPLORE) trial is a randomized, prospective, multicenter, two-arm trial with blinded evaluation of endpoints. Three hundred patients after primary percutaneous coronary intervention for ST-elevation myocardial infarction with a chronic total occlusion in a non-infarct related artery are randomized to either elective percutaneous coronary intervention of the chronic total occlusion within seven days or standard medical treatment. When assigned to the invasive arm, an everolimus-eluting coronary stent is used. Primary endpoints are left ventricular ejection fraction and left ventricular end-diastolic volume assessed by cardiac Magnetic Resonance Imaging at four months. Clinical follow-up will continue until five years.DiscussionThe ongoing EXPLORE trial is the first randomized clinical trial powered to investigate whether recanalization of a chronic total occlusion in a non-infarct related artery after primary percutaneous coronary intervention for ST-elevation myocardial infarction results in a better preserved residual left ventricular ejection fraction, reduced end-diastolic volume and enhanced clinical outcome.Trial registrationtrialregister.nl NTR1108.

Impact of Coronary Microvascular Function on Long-Term Cardiac Mortality in Patients With Acute ST-Segment–Elevation Myocardial Infarction

Background—Microvascular function is increasingly being recognized as an important marker of risk in coronary artery disease, and may be accurately assessed by intracoronary Doppler flow velocity measurements. In the setting of ST-segment–elevation myocardial infarction there are limited data regarding the prognostic value of microvascular function in both infarct-related and reference coronary arteries for long-term clinical outcome. We sought to determine the prognostic value of microvascular function, as assessed by Doppler flow velocity measurements, for cardiac mortality after primary percutaneous coronary intervention for acute ST-segment–elevation myocardial infarction. Methods and Results—Between April 1997 and August 2000, we included 100 consecutive patients with a first anterior wall ST-segment–elevation myocardial infarction. Immediately after primary percutaneous coronary intervention, intracoronary Doppler flow velocity was measured in the infarct-related artery, to determine coronary flow velocity reserve (CFVR), diastolic deceleration time, and the presence of systolic retrograde flow, as well as in a reference vessel to determine reference vessel CFVR. The primary end point was cardiac mortality at 10-year follow-up. Complete follow-up was obtained in 94 patients (94%). At 10-year follow-up, cardiac mortality amounted to 14%. Cardiac mortality amounted to 5% when reference vessel CFVR was normal (≥2.1), in contrast to 31% when abnormal (<2.1; P=0.001). Reference vessel CFVR <2.1 was associated with a 4.09 increase in long-term cardiac mortality hazard after multivariate adjustment for identified predictors for cardiac mortality (hazard ratio, 4.09; 95% confidence interval, 1.18–14.17; P=0.03) Conclusions—Microvascular dysfunction, measured by reference vessel CFVR determined after primary percutaneous coronary intervention for acute anterior wall ST-segment–elevation myocardial infarction is associated with a significantly increased long-term cardiac mortality.

Impaired Coronary Autoregulation is Associated With Long-term Fatal Events in Patients With Stable Coronary Artery Disease

Background—Abnormalities in the coronary microcirculation are increasingly recognized as an elementary component of ischemic heart disease, which can be accurately assessed by coronary flow velocity reserve in reference vessels (refCFVR). We studied the prognostic value of refCFVR for long-term mortality in patients with stable coronary artery disease. Methods and Results—We included patients with stable coronary artery disease who underwent intracoronary physiological evaluation of ≥1 coronary lesion of intermediate severity between April 1997 and September 2006. RefCFVR was assessed if a coronary artery with <30% irregularities was present. RefCFVR >2.7 was considered normal. Patients underwent revascularization of all ischemia-causing lesions. Long-term follow-up was performed to document the occurrence of (cardiac) mortality. RefCFVR was determined in 178 patients. Kaplan–Meier estimates of 12-year all-cause mortality were 16.7% when refCFVR >2.7 and 39.6% when refCFVR ⩽2.7 (P<0.001), whereas Kaplan–Meier estimates for cardiac mortality were 7.7% when refCFVR >2.7 and 31.6% when refCFVR ⩽2.7 (P<0.001). After multivariable adjustment, refCFVR ⩽2.7 was associated with a 2.24-fold increase in all-cause mortality hazard (hazard ratio, 2.24; 95% confidence interval, 1.13–4.44; P=0.020) and a 3.32-fold increase in cardiac mortality hazard (hazard ratio, 3.32; 95% confidence interval, 1.27–8.67; P=0.014). Impairment of refCFVR originated from significantly higher baseline flow velocity in the presence of significantly lower reference vessel baseline microvascular resistance (P<0.001), indicating impaired coronary autoregulation as its cause. Conclusions—In patients with stable coronary artery disease, impaired refCFVR, resulting from increased baseline flow velocity indicating impaired coronary autoregulation, is associated with a significant increase in fatal events at long-term follow-up.

The Doppler flow wire in acute myocardial infarction

Contemporary mechanical reperfusion therapy for acute myocardial infarction is aimed at early and complete restoration of myocardial perfusion. However, successful restoration of epicardial blood flow does not guarantee restoration of flow at the myocardial tissue level. The incidence of inadequate myocardial reperfusion after primary percutaneous coronary intervention (PCI) varies from 15–70%, based upon the diagnostic modality used. The Doppler flow guidewire can be used immediately after primary PCI to identify patients with apparently restored epicardial flow but impaired reperfusion at the myocardial microcirculatory and tissue level. Characteristic findings by intracoronary Doppler flow velocity measurements such as a reduced coronary flow velocity reserve, and, in particular, systolic flow velocity reversal and a short diastolic deceleration time are associated with the presence of microvascular obstruction. Detection of microvascular obstruction by the Doppler flow wire directly after primary PCI can identify patients who may benefit from adjunctive therapy after primary PCI.

Long-term impact of chronic total occlusion recanalisation in patients with ST-elevation myocardial infarction

Background During primary percutaneous coronary intervention (PCI), a concurrent chronic total occlusion (CTO) is found in 10% of patients with ST-elevation myocardial infarction (STEMI). Long-term benefits of CTO-PCI have been suggested; however, randomised data are lacking. Our aim was to determine mid-term and long-term clinical outcome of CTO-PCI versus CTO-No PCI in patients with STEMI with a concurrent CTO. Methods The Evaluating Xience and left ventricular function in PCI on occlusiOns afteR STEMI (EXPLORE) was a multicentre randomised trial that included 302 patients with STEMI after successful primary PCI with a concurrent CTO. Patients were randomised to either CTO-PCI or CTO-No PCI. The primary end point of the current study was occurrence of major adverse cardiac events (MACE): cardiac death, coronary artery bypass grafting and MI. Other end points were 1-year left ventricular function (LVF); LV-ejection fraction and LV end-diastolic volume and angina status. Results The median long-term follow-up was 3.9 (2.1–5.0) years. MACE was not significantly different between both arms (13.5% vs 12.3%, HR 1.03, 95% CI 0.54 to 1.98; P=0.93). Cardiac death was more frequent in the CTO-PCI arm (6.0% vs 1.0%, P=0.02) with no difference in all-cause mortality (12.9% vs 6.2%, HR 2.07, 95% CI 0.84 to 5.14; P=0.11). One-year LVF did not differ between both arms. However, there were more patients with freedom of angina in the CTO-PCI arm at 1 year (94% vs 87%, P=0.03). Conclusions In this randomised trial involving patients with STEMI with a concurrent CTO, CTO-PCI was not associated with a reduction in long-term MACE compared to CTO-No PCI. One-year LVF was comparable between both treatment arms. The finding that there were more patients with freedom of angina after CTO-PCI at 1-year follow-up needs further investigation. Clinical trial registration EXPLORE trial number NTR1108 www.trialregister.nl.

Microvascular dysfunction following ST-elevation myocardial infarction and its recovery over time

AIMS It is unclear whether microvascular dysfunction following ST-elevation myocardial infarction (STEMI) is prognostic for long-term left ventricular function (LVF), and whether recovery of the microvasculature status is associated with LVF improvement. The aim of this study was to assess whether microvascular dysfunction in the infarct-related artery (IRA), as assessed by coronary flow reserve (CFR) within one week after PPCI, was associated with LVF at both four months and two years. METHODS AND RESULTS In 62 patients, CFR and hyperaemic microvascular resistance index (HMRI) in the IRA were assessed by intracoronary Doppler flow measurements within one week and at four months. CMR was performed at the same time points and also at two years. CFR at baseline was associated with left ventricular ejection fraction (LVEF) at four months (β=4.66, SE=2.10; p=0.03) and at two-year follow-up (β=5.84, SE=2.45; p=0.02). HMRI was not associated with LVF. In large infarcts, absolute improvement of CFR in the first four months was associated with LVEF improvement (β=5.09, SE=1.86, p=0.01). CONCLUSIONS Microvascular dysfunction, assessed by CFR, in the subacute phase of STEMI is prognostic for LVEF at four months and two years. This underlines the pivotal role of microvascular dysfunction following STEMI.

Letter by Michiels et al Regarding Article, “Diagnostic Accuracy of Combined Intracoronary Pressure and Flow Velocity Information During Baseline Conditions: Adenosine-Free Assessment of Functional Coronary Lesion Severity”

We read with interest the article by van de Hoef and colleagues about the value of the coronary stenosis pressure drop-flow velocity ratio (ΔP/V) in the evaluation of coronary stenosis.1 We congratulate the authors with this meticulous and well-written investigational report; however, we have a number of comments. Again (as with iFR in the recently published ADVISE study),2 the authors claim in their subtitle that they demonstrate the diagnostic performance of an adenosine-free assessment of functional coronary lesion severity. In recent literature, there seems to be an unjustified quest for proving that on one hand (very) high doses of intracoronary adenosine are necessary to …