[Show abstract][Hide abstract] ABSTRACT: Aims: Maximum and stable hyperaemia are critical prerequisites for the accurate measurement of fractional flow reserve (FFR). However, in some patients in whom hyperaemia is induced through a central vein (IV) the minimum distal coronary pressure to aortic pressure ratio (Pd/Pa ratio) develops before the stabilisation of hyperaemia. We sought to describe the prevalence, magnitude and clinical implications of this phenomenon. Methods and results: The FFR tracing archive of a single institution was reviewed and a total of 104 high-quality IV-FFR recordings from 90 patients were identified. Whenever the minimum Pd/Pa ratio was found before the onset of stable hyperaemia, a search for the lowest Pd/Pa ratio within the steady-state hyperaemic plateau was performed and labelled as FFRstable. Whilst in most cases the minimum Pd/Pa ratio developed during stable hyperaemia, in 19 cases (prevalence of 18.3% [95% CI: 12.0% to 26.8%]) this value was found before the stabilisation of the hyperaemic state. In such cases, the minimum Pd/Pa ratio stabilised later at a higher level (0.77±0.09 vs. 0.81±0.08, p<0.001) (mean difference, 0.03±0.02, range, 0.01 to 0.10). In terms of dichotomous classification of stenosis severity and if FFRstable had been used to decide on revascularisation, reclassification would have occurred in three (2.9%) cases, all presenting a minimum Pd/Pa ratio ≤0.80 with FFRstable >0.80. Conclusions: During IV adenosine infusion, the minimum Pd/Pa ratio occurs before the stabilisation of hyperaemia in a significant proportion of cases. While the overall difference between the minimum Pd/Pa ratio and its FFRstable counterpart is small, reclassification of stenosis severity might occur, if choosing between the minimum and stable values of FFR within the same trace.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study is to summarize cumulative evidence suggesting that the combination of fractional flow reserve (FFR), coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) might provide a more comprehensive invasive assessment of ischaemic heart disease (IHD).
[Show abstract][Hide abstract] ABSTRACT: Myocardial tissue perfusion remains compromised in 30-40% of patients with ST-segment elevation myocardial infarction (STEMI) despite restored epicardial patency after primary percutaneous coronary intervention (pPCI). This phenomenon is attributed to microvascular dysfunction secondary to numerous pathophysiological mechanisms, including distal embolisation of plaque and thrombus material. Its association with larger post-infarction myocardial necrosis, impaired left ventricular recovery, and worse clinical outcome illustrates the pertinence of a comprehensive armamentarium for the diagnosis, protection and treatment of microvascular dysfunction in STEMI patients. Current strategies to protect the microvasculature during pPCI are based on the assumption that distal embolisation of thrombotic and atheromatous debris is the main mechanism precipitating impaired myocardial tissue perfusion. However, recent findings suggest that this assumption is only true for the border zone of the ischaemic myocardium, whereas the infarct core consists of intramyocardial haemorrhage secondary to microvascular destruction, rather than obstruction. This observation has pertinent implications for contemporary and future adjuvant treatment strategies in STEMI patients. In this review, we provide an overview of the currently available armamentarium to assess the microvasculature, review contemporary strategies in pPCI to protect the myocardium, and discuss novel insights into microvascular pathophysiology that may help guide our focus from the coronary arteries to the microvasculature.
[Show abstract][Hide abstract] ABSTRACT: Aims: We sought to compare the diagnostic accuracy of basal stenosis resistance index (BSR), instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) for stenosis-specific myocardial ischaemia identified by means of a combined reference standard of myocardial perfusion scintigraphy and the hyperaemic stenosis resistance index. Methods and results: BSR and FFR were determined for 299 coronary stenoses, iFR was determined for 85 coronary stenoses (iFR cohort). The discriminative value for stenosis-specific myocardial ischaemia was compared by means of the area under the receiver operating characteristic (ROC) curves (AUC). Classification agreement with the reference standard was determined according to ROC curve-derived ischaemic cut-off values, as well as according to clinical cut-off values, equivalent to the 0.80 FFR cut-off. Across all stenoses, the discriminative value of BSR and FFR was equivalent (AUC: 0.90 and 0.91, respectively, p=0.46). In the iFR cohort, the discriminative value was equivalent for BSR, iFR, and FFR (AUC: 0.88, 0.84, and 0.88, respectively; p≥0.20 for all). At both ischaemic as well as clinical cut-off values, classification agreement with the reference standard was equivalent for BSR and FFR across all stenoses, as well as for BSR, iFR, and FFR in the iFR cohort. Conclusions: BSR, iFR, and FFR have equivalent diagnostic accuracy for the detection of ischaemia-generating coronary stenoses.
[Show abstract][Hide abstract] ABSTRACT: Coronary flow reserve has extensive validation as a prognostic marker in coronary disease. Although pressure-only fractional flow reserve (FFR) improves outcomes compared with angiography when guiding percutaneous coronary intervention, it disagrees with coronary flow reserve classification 30% of the time. We evaluated whether baseline instantaneous wave-free ratio (iFR) could provide an improved pressure-only estimation of underlying coronary flow reserve.
[Show abstract][Hide abstract] ABSTRACT: Discordance between fractional flow reserve (FFR) and coronary flow velocity reserve (CFVR) may reflect important coronary pathophysiology but usually remains unnoticed in clinical practice. We evaluated the physiological basis and clinical outcome associated with FFR/CFVR discordance.
We studied 157 intermediate coronary stenoses in 157 patients, evaluated by FFR and CFVR between April 1997 and September 2006 in which revascularization was deferred. Long-term follow-up was performed to document the occurrence of major adverse cardiac events: cardiac death, myocardial infarction, or target vessel revascularization. Discordance between FFR and CFVR occurred in 31% and 37% of stenoses at the 0.75, and 0.80 FFR cut-off value, respectively, and was characterized by microvascular resistances during basal and hyperemic conditions. Follow-up duration amounted to 11.7 years (Q1-Q3, 9.9-13.3 years). Compared with concordant normal results of FFR and CFVR, a normal FFR with an abnormal CFVR was associated with significantly increased major adverse cardiac events rate throughout 10 years of follow-up, regardless of the FFR cut-off applied. In contrast, an abnormal FFR with a normal CFVR was associated with equivalent clinical outcome compared with concordant normal results: ≤3 years when FFR <0.75 was depicted abnormal and throughout 10 years of follow-up when FFR ≤0.80 was depicted abnormal.
Discordance of CFVR with FFR originates from the involvement of the coronary microvasculature. Importantly, the risk for major adverse cardiac events associated with FFR/CFVR discordance is mainly attributable to stenoses where CFVR is abnormal. This emphasizes the requirement of intracoronary flow assessment in addition to coronary pressure for optimal risk stratification in stable coronary artery disease.
[Show abstract][Hide abstract] ABSTRACT: Aims: It has been argued that hyperaemic microvascular resistance (HMR), defined as the ratio of mean distal coronary pressure to flow velocity, is overestimated in the presence of a coronary stenosis compared to actual microvascular resistance (MR), due to neglecting collateral flow. We aimed to test the hypothesis that HMR allows accurate identification of microvascular functional abnormalities by evaluating the association between high or low HMR and the presence of myocardial ischaemia on non-invasive stress testing. Methods and results: Myocardial perfusion scintigraphy was performed in 228 patients, with 299 lesions to identify reversible myocardial ischaemia. Intracoronary distal pressure and flow velocity were assessed during adenosine-induced hyperaemia (20-40 µg, intracoronary) to determine hyperaemic stenosis resistance (HSR) and HMR. HMR >1.9 mmHg/cm/s was defined as high. The diagnostic odds ratio (OR) for myocardial ischaemia for lesions associated with high compared to low HMR was 2.6 (95% confidence interval [CI]: 1.5-4.4; p<0.001) overall, 3.3 (95% CI: 1.2-9.0; p=0.02) for lesions with HSR >0.8 mmHg/cm/s, and 1.3 (95% CI: 0.6-2.9; p=0.52) for lesions with HSR ≤0.8 mmHg/cm/s. Conclusions: The increased risk of myocardial ischaemia in the presence of high HMR, uncorrected for collateral flow, demonstrates that HMR is reflective of an increase in actual MR, identifying pertinent pathophysiological alterations in the microvasculature.
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 04/2014; 9(12):1423-31. · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fractional flow reserve (FFR) aims to identify the extent of epicardial disease, but may be obscured by involvement of the coronary microvasculature. We documented the impact of hyperaemic stenosis resistance (HSR) and hyperaemic microvascular resistance (HMR) on FFR, and its relationship with myocardial ischaemia in patients with stable coronary artery disease.
We evaluated 255 coronary arteries with stenoses of intermediate severity by means of intracoronary pressure and flow measurements to determine FFR, HSR and HMR. Myocardial perfusion scintigraphy (MPS) was performed to identify inducible myocardial ischaemia. In 178 patients, HMR was additionally determined in a reference coronary artery. Target vessel HMR was stratified according to reference vessel HMR tertiles. The diagnostic OR for inducible ischaemia on MPS of a positive compared with a negative FFR was significantly higher only in the presence of a high HMR (at the 0.75 and 0.80 FFR cut-off). Among stenoses with a positive FFR, the prevalence of ischaemia was significantly higher when HMR was high despite equivalent FFR across the HMR groups. This was paralleled by a concomitant significant increase in HSR with increasing HMR across groups. The relation between FFR and HSR (r(2)=0.54, p<0.001) was modulated by the magnitude of HMR, and improved substantially after adjustment for HMR (adjusted-r(2)=0.73, p<0.001), where, for epicardial disease of equivalent severity, FFR increased with increasing HMR.
Identification of epicardial disease severity by FFR is partly obscured by the microvascular resistance, which illustrates the necessity of combined pressure and flow measurements in daily practice.
[Show abstract][Hide abstract] ABSTRACT: Fractional flow reserve (FFR)-guided coronary revascularization is associated with an unequivocal clinical benefit compared with angiographic guidance. However, the well-documented clinical merit of FFR-guided revascularization has resulted in several misunderstandings as to its diagnostic characteristics. Moreover, it has led to the use of FFR as a gold-standard reference test for the identification of stenosis-related inducible myocardial ischemia. Frequently overlooked is the fact that FFR was originally validated against noninvasive stress-testing to document its ability to identify ischemia-generating stenoses, as well as its optimal cut-off value to do so, which illustrates the paradox of using FFR as a gold-standard reference for this purpose. The diagnostic characteristics of FFR are more complex than is widely understood, and its conceptual validity is based on multiple assumptions that are not considered in clinical practice. In contrast, the validity of FFR as a clinical tool is based on empirical evidence derived from multiple large-scale randomized controlled trials. It is, therefore, of great importance to understand the fundamental physiological basis of FFR, and to be aware of the underlying assumptions and their implications, for appropriate application and interpretation of FFR on an individual basis. This review aims to elucidate the assumptions that underlie the concept of FFR, to provide insight into their consequences for daily practice, and to highlight the practical methodology that is critical for its interpretation in clinical practice.
Current Treatment Options in Cardiovascular Medicine 04/2014; 16(4):294.
[Show abstract][Hide abstract] ABSTRACT: 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.
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 12/2013; · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pre-clinical studies aimed at treating ischemic heart disease (i.e. stem cell- and growth factor therapy) often consider restoration of the impaired microvascular circulation as an important treatment goal. However, serial in vivo measurement hereof is often lacking. The purpose of this study was to evaluate the applicability of intracoronary pressure and flow velocity as a measure of microvascular resistance in a large animal model of chronic myocardial infarction (MI). Myocardial infarction was induced in Dalland Landrace pigs (n = 13; 68.9 ± 4.1 kg) by a 75-min. balloon occlusion of the left circumflex artery (LCX). Intracoronary pressure and flow velocity parameters were measured simultaneously at rest and during adenosine-induced hyperemia, using the Combowire (Volcano) before and 4 weeks after MI. Various pressure- and/or flow-derived indices were evaluated. Hyperemic microvascular resistance (HMR) was significantly increased by 28% in the infarct-related artery, based on a significantly decreased peak average peak flow velocity (pAPV) by 20% at 4 weeks post-MI (P = 0.03). Capillary density in the infarct zone was decreased compared to the remote area (658 ± 207/mm(2) versus 1650 ± 304/mm(2) , P = 0.017). In addition, arterioles in the infarct zone showed excessive thickening of the alpha smooth muscle actin (αSMA) positive cell layer compared to the remote area (33.55 ± 4.25 μm versus 14.64 ± 1.39 μm, P = 0.002). Intracoronary measurement of HMR successfully detected increased microvascular resistance that might be caused by the loss of capillaries and arteriolar remodelling in the chronic infarcted pig heart. Thus, HMR may serve as a novel outcome measure in pre-clinical studies for serial assessment of microvascular circulation.
Journal of Cellular and Molecular Medicine 08/2013; · 4.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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. KAPLANMEIER ESTIMATES OF 12-YEAR ALL-CAUSE MORTALITY WERE 16.7% WHEN REFCFVR 2.7 AND 39.6% WHEN REFCFVR 2.7 (P0.001), WHEREAS KAPLANMEIER ESTIMATES FOR CARDIAC MORTALITY WERE 7.7% WHEN REFCFVR 2.7 AND 31.6% WHEN REFCFVR 2.7 (P0.001). 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, 1.134.44; P=0.020) AND A 3.32-FOLD INCREASE IN CARDIAC MORTALITY HAZARD (HAZARD RATIO, 3.32; 95% CONFIDENCE INTERVAL, 1.278.67; P=0.014). IMPAIRMENT OF REFCFVR ORIGINATED FROM SIGNIFICANTLY HIGHER BASELINE FLOW VELOCITY IN THE PRESENCE OF SIGNIFICANTLY LOWER REFERENCE VESSEL BASELINE MICROVASCULAR RESISTANCE (P0.001), 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.
[Show abstract][Hide abstract] ABSTRACT: Coronary artery disease, CAD, is associated with both narrowing of the epicardial coronary arteries and microvascular disease, thereby limiting coronary flow and myocardial perfusion. CAD accounts for almost 2 million deaths within the European Union on an annual basis. In this paper, we review the physiological and pathophysiological processes underlying clinical decision making in coronary disease as well as the models for interpretation of the underlying physiological mechanisms. Presently, clinical decision making is based on non-invasive magnetic resonance imaging, MRI, of myocardial perfusion and invasive coronary hemodynamic measurements of coronary pressure and Doppler flow velocity signals obtained during catheterization. Within the euHeart project, several innovations have been developed and applied to improve diagnosis-based understanding of the underlying biophysical processes. Specifically, MRI perfusion data interpretation has been advanced by the gradientogram, a novel graphical representation of the spatiotemporal myocardial perfusion gradient. For hemodynamic data, functional indices of coronary stenosis severity that do not depend on maximal vasodilation are proposed and the Valsalva maneuver for indicating the extravascular resistance component of the coronary circulation has been introduced. Complementary to these advances, model innovation has been directed to the porous elastic model coupled to a one-dimensional model of the epicardial arteries. The importance of model development is related to the integration of information from different modalities, which in isolation often result in conflicting treatment recommendations.
Medical & Biological Engineering 07/2013; · 1.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aims: Large intracoronary thrombus in patients with acute coronary syndromes remains a challenge in percutaneous coronary intervention, despite technical advances of manual aspiration catheters and mechanical thrombectomy devices. The Trevo® Pro 4 is a novel self-expanding mechanical thrombus retrieval device, designed for removal of occlusive thrombi in the setting of acute ischaemic stroke. We describe the first use of this novel mechanical thrombus retrieval device in the setting of coronary intervention. Methods and results: In close collaboration with the interventional radiology department, two patients presenting with an acute coronary syndrome, complicated by refractory large intracoronary thrombus, were treated using the Trevo Pro 4. Both patients were treated successfully, resulting in complete removal of refractory thrombus without the occurrence of adverse events. Conclusions: The Trevo Pro 4 can be successfully used in the setting of coronary intervention. It is simple to use, does not require complex preparations, and the handling is straightforward. A larger study to assess the safety and efficacy of this device in the setting of coronary interventions is warranted.
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 06/2013; · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Documentation of inducible myocardial ischaemia, related to the coronary stenosis of interest, is of increasing importance in lesion selection for percutaneous coronary intervention (PCI). Fractional flow reserve (FFR) is an easily understood, routine diagnostic modality that has become part of daily clinical practice, and is used as a surrogate technique for noninvasive assessment of myocardial ischaemia. However, the application of a single, discrete, cut-off value for FFR-guided lesion selection for PCI, and its adoption in contemporary revascularization guidelines, has limited the requirement for a thorough understanding of the physiological basis of FFR. This limitation constitutes an obstacle for the adequate use and interpretation of this technique, and also for the understanding of new and future modalities of physiological functional intracoronary testing. In this Review, we revisit the fundamental elements of coronary physiology in the absence or presence of coronary artery disease. We provide insight into three essential characteristics of FFR as a diagnostic tool in contemporary clinical practice-the theoretical framework of FFR and its associated limitations; the characteristics and role of FFR as a surrogate for noninvasively assessed myocardial ischaemia; and the requirement and associated caveats of potent vasodilatory drugs to induce maximal vasodilatation of the coronary vascular bed.
[Show abstract][Hide abstract] ABSTRACT: 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-SEGMENTELEVATION 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-SEGMENTELEVATION MYOCARDIAL INFARCTION.METHODS AND RESULTS: BETWEEN APRIL 1997 AND AUGUST 2000, WE INCLUDED 100 CONSECUTIVE PATIENTS WITH A FIRST ANTERIOR WALL ST-SEGMENTELEVATION 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, 1.1814.17; 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.