Javier Escaned - Academia.edu (original) (raw)
Papers by Javier Escaned
Journal of interventional cardiology, Jan 23, 2018
Instantaneous free-wave ratio (iFR) has been recently demonstrated non-inferior to fractional flo... more Instantaneous free-wave ratio (iFR) has been recently demonstrated non-inferior to fractional flow reserve (FFR) to drive coronary revascularization; however, no study has compared iFR versus coronary angiography (CA). We performed a network meta-analysis to evaluate efficacy and safety of iFR- versus CA-guided strategy. We searched for randomized trials and studies with propensity score matching in The Cochrane Collaboration Central Register of Controlled Trials, EMBASE, and MEDLINE/Pubmed. CA, FFR, and iFR were the three competitive arms, MACE (a composite endpoint of death, myocardial infarction [MI], and target vessel revascularization [TVR]) was the primary endpoint, while its single components the secondary ones. Subgroup analysis was performed for patients presenting with stable coronary artery disease. Eight studies were selected: 4126 patients were evaluated with FFR, 2160 with iFR, and 2214 with CA, acute coronary syndrome (ACS) was the most frequent admission diagnosis. A...
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](Archivos de cardiología de México
One of the most important limitations of coronary angiography is the inability to characterize th... more One of the most important limitations of coronary angiography is the inability to characterize the physiological significance of an intermediate coronary stenosis. Measuring coronary blood flow and pressure provides unique information that complements anatomic evaluation and facilitates decision-making in the cardiac catheterization unit. This review discusses the fundamental concepts of coronary physiology, methodology, and clinical applications of coronary and flow measurements.
Revista Española de Cardiología, 2002
Candell-Riera J, et al. Valoración fisiológica de la circulación coronaria Papel de las técnicas ... more Candell-Riera J, et al. Valoración fisiológica de la circulación coronaria Papel de las técnicas invasivas y no invasivas 105
Journal of Diagnostic Medical Sonography, 1994
JACC. Cardiovascular interventions, Jan 26, 2017
The study sought to determine the coronary flow characteristics of angiographically intermediate ... more The study sought to determine the coronary flow characteristics of angiographically intermediate stenoses classified as discordant by fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). Discordance between FFR and iFR occurs in up to 20% of cases. No comparisons have been reported between the coronary flow characteristics of FFR/iFR discordant and angiographically unobstructed vessels. Baseline and hyperemic coronary flow velocity and coronary flow reserve (CFR) were compared across 5 vessel groups: FFR+/iFR+ (108 vessels, n = 91), FFR-/iFR+ (28 vessels, n = 24), FFR+/iFR- (22 vessels, n = 22), FFR-/iFR- (208 vessels, n = 154), and an unobstructed vessel group (201 vessels, n = 153), in a post hoc analysis of the largest combined pressure and Doppler flow velocity registry (IDEAL [Iberian-Dutch-English] collaborators study). FFR disagreed with iFR in 14% (50 of 366). Baseline flow velocity was similar across all 5 vessel groups, including the unobstructed vessel g...
European heart journal, Dec 13, 2017
Techniques for identifying specific microcirculatory structural changes are desirable. As such, c... more Techniques for identifying specific microcirculatory structural changes are desirable. As such, capillary rarefaction constitutes one of the earliest changes of cardiac allograft vasculopathy (CAV) in cardiac allograft recipients, but its identification with coronary flow reserve (CFR) or intracoronary resistance measurements is hampered because of non-selective interrogation of the capillary bed. We therefore investigated the potential of wave intensity analysis (WIA) to assess capillary rarefaction and thereby predict CAV. Fifty-two allograft patients with unobstructed coronary arteries and normal left ventricular (LV) function were assessed. Adequate aortic pressure and left anterior descending artery flow measurements at rest and with intracoronary adenosine were obtained in 46 of which 2 were lost to follow-up. In a subgroup of 15 patients, simultaneous RV biopsies were obtained and analysed for capillary density. Patients were followed up with 1-3 yearly screening angiography....
Journal of the American College of Cardiology, 2017
In this review, the authors reflect upon the role of coronary physiology in the modern management... more In this review, the authors reflect upon the role of coronary physiology in the modern management of coronary artery disease. They critically appraise the scientific background of the instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR), from early experimental studies to validation studies against indexes of ischemia, to clinical trials assessing outcome. At this important juncture for the field, the authors make predictions for the future of physiological stenosis assessment, outlining developments for both iFR and FFR in new clinical domains beyond the confines of stable angina. With a focus on the evolving future of iFR and FFR, the authors describe how physiological assessment with iFR may advance its application from simply justifying to guiding revascularization.
The international journal of cardiovascular imaging, Jan 28, 2017
The vasodilator capacity of the coronary circulation is an important diagnostic and prognostic ch... more The vasodilator capacity of the coronary circulation is an important diagnostic and prognostic characteristic, and its accurate assessment is therefore an important frontier. The coronary flow capacity (CFC) concept was introduced to overcome the limitations associated with the use of coronary flow reserve (CFR) for this purpose, which are related to the sensitivity of CFR to physiological alterations in systemic and coronary hemodynamics. CFC was developed from positron emission tomography, and was subsequently extrapolated to invasive coronary physiology. These studies suggest that CFC is a robust framework for the identification of clinically relevant coronary flow abnormalities, and improves identification of patients at risk for adverse events over the use of CFR alone. This Review will discuss the concept of CFC, its promises in the setting of ischaemic heart disease, and its challenges both in theoretical and practical terms.
Cardiovascular diabetology, Jan 19, 2017
In diabetic patients a predisposed coronary microcirculation along with a higher risk of distal p... more In diabetic patients a predisposed coronary microcirculation along with a higher risk of distal particulate embolization during primary percutaneous intervention (PCI) increases the risk of peri-procedural microcirculatory damage. However, new antiplatelet agents, in particular Ticagrelor, may protect the microcirculation through its adenosine-mediated vasodilatory effects. PREDICT is an original, prospective, randomized, multicenter controlled study designed to investigate the protective effect of Ticagrelor on the microcirculation during PCI in patient with diabetes mellitus type 2 or pre-diabetic status. The primary endpoints of this study aim to test (i) the decrease in microcirculatory resistance with antiplatelet therapy (Ticagrelor > Clopidogrel; mechanistic effect) and (ii) the relative microcirculatory protection of Ticagrelor compared to Clopidogrel during PCI (Ticagrelor < Clopidogrel; protective effect). PREDICT will be the first multicentre clinical trial to test ...
Journal of the American Heart Association, Jan 22, 2016
Coronary microcirculatory dysfunction portends a poor cardiovascular outcome. Invasive assessment... more Coronary microcirculatory dysfunction portends a poor cardiovascular outcome. Invasive assessment of microcirculatory dysfunction by coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) is affected by coronary artery disease (CAD). In this study we propose minimal microvascular resistance (mMR) as a new measure of microcirculatory dysfunction and aim to determine whether mMR is influenced by CAD. We obtained 482 simultaneous measurements of intracoronary Doppler flow velocity and pressure. The mMR is defined as the ratio between distal coronary pressure and flow velocity during the hyperemic wave-free period. Measurements were divided into 2 cohorts. Cohort 1 was a paired analysis involving 81 pairs with a vessel with and without CAD to investigate whether HMR, CFR, and mMR are modulated by CAD. CFR was lower, and HMR was higher, in vessels with CAD than in vessels without CAD: 2.12±0.79 versus 2.56±0.63 mm Hg·cm(-1)·s, P<0.001, and 2.61±1.22 versus 2.31±0.89 ...
JACC. Cardiovascular interventions, 2015
This study sought to understand the physiological basis of baseline distal-to-aortic pressure rat... more This study sought to understand the physiological basis of baseline distal-to-aortic pressure ratio (Pd/Pa) and fractional flow reserve (FFR) agreement and discordance, using coronary flow reserve (CFR), stenosis resistance, and microcirculatory resistance measurements, and form there, to investigate the potential value of combining Pd/Pa with FFR in the diagnostic rationale. Pd/Pa is always available before FFR assessment, and emerging data supports the notion that baseline indices can determine the ischemic potential of coronary stenosis in selected subsets. A total of 467 stenosed vessels from 363 patients were investigated with pressure and flow sensors during baseline and hyperemia: 168 vessels (135 patients) with thermodilution-derived flow, and 299 vessels (228 patients) with Doppler-derived flow. Pd/Pa correlated more strongly with CFR than FFR (ρ difference = 0.129; p for ρ comparison <0.001). Although Pd/Pa and FFR were closely correlated (ρ = 0.798; 95% confidence inte...
Circulation. Cardiovascular interventions, 2015
The index of microcirculatory resistance (IMR) is a quantitative and specific index for coronary ... more The index of microcirculatory resistance (IMR) is a quantitative and specific index for coronary microcirculation. However, the distribution and determinants of IMR have not been fully investigated in patients with ischemic heart disease (IHD). Consecutive patients who underwent elective measurement of both fractional flow reserve (FFR) and IMR were enrolled from 8 centers in 5 countries. Patients with acute myocardial infarction were excluded. To adjust for the influence of collateral flow, IMR values were corrected with Yong's formula (IMRcorr). High IMR was defined as greater than the 75th percentile in each of the major coronary arteries. FFR≤0.80 was defined as an ischemic value. 1096 patients with 1452 coronary arteries were analyzed (mean age 61.1, male 71.2%). Mean FFR was 0.84 and median IMRcorr was 16.6 U (Q1, Q3 12.4 U, 23.0 U). There was no correlation between IMRcorr and FFR values (r=0.01, P=0.62), and the categorical agreement of FFR and IMRcorr was low (kappa val...
Circulation. Cardiovascular interventions, 2015
Percutaneous coronary intervention (PCI) aims to increase coronary blood flow by relieving epicar... more Percutaneous coronary intervention (PCI) aims to increase coronary blood flow by relieving epicardial obstruction. However, no study has objectively confirmed this and assessed changes in flow over different phases of the cardiac cycle. We quantified the change in resting and hyperemic flow velocity after PCI in stenoses defined physiologically by fractional flow reserve and other parameters. Seventy-five stenoses (67 patients) underwent paired flow velocity assessment before and after PCI. Flow velocity was measured over the whole cardiac cycle and the wave-free period. Mean fractional flow reserve was 0.68±0.02. Pre-PCI, hyperemic flow velocity is diminished in stenoses classed as physiologically significant compared with those classed nonsignificant (P<0.001). In significant stenoses, flow velocity over the resting wave-free period and hyperemic flow velocity did not differ statistically. After PCI, resting flow velocity over the wave-free period increased little (5.6±1.6 cm/s...
Journal of the American College of Cardiology, 2015
Background: We acquired a large dataset of combined intracoronary pressure and flow velocity meas... more Background: We acquired a large dataset of combined intracoronary pressure and flow velocity measurements, to better understand the relationships between flow, transstenotic gradient (TG) and microvascular resistance (MVR), and help clarify the rationale of resting stenosis assessment. methods: 567 simultaneous intracoronary pressure and flow velocity measurements were acquired. Flow, TG and MVR were determined during whole cycle resting and hyperemic conditions, and during the wave-free period at rest. Linear regression analysis was done to estimate trends and P-values, according to strata of progressive functional stenosis severity indicated by the fractional flow reserve (FFR). results: With progressive strata of stenosis severity from reference to FFR≤0.50, flow at rest was unchanged (18±8.2 cm/s; P=0.40), but gradually decreased from 45 to 19 cm/s at hyperemia (P<0.01). TG increased from 1.5 to 46 mmHg at rest, and from 3.5 to 55 mmHg at hyperemia (P<0.01 for both). MVR declined from 6.2 to 4.2 at rest (P<0.01), but remained unchanged at hyperemia (2.3±1.1; P=0.19). Phasic analysis during the wave-free period, yielded similar trends as whole cycle analysis. Conclusion: With progressive stenosis severity, an increased TG at rest is observed, while stable coronary flow is maintained by compensatory reduction of MVR owing to coronary autoregulation. This explains why resting pressure, but not resting myocardial perfusion assessment, permits detection of hemodynamic stenosis significance.
Circulation. Cardiovascular interventions, 2013
We studied the hemodynamic response to intravenous adenosine on calculation of fractional flow re... more 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. 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 ΔPa and ΔPd were decreased (ΔPa, -10.2±10.5 mm Hg; ΔPd, -18.2±10.8 mm Hg; P<0.001 for both). The fall in Pa closely correlated with the reduction in peripheral Pr (ΔPr, -1...
Circulation: Cardiovascular Interventions, 2015
Background— A total of 40% to 50% of patients with ST-segment–elevation myocardial infarction dev... more Background— A total of 40% to 50% of patients with ST-segment–elevation myocardial infarction develop microvascular injury (MVI) despite angiographically successful primary percutaneous coronary intervention (PCI). We investigated whether hyperemic microvascular resistance (HMR) immediately after angiographically successful PCI predicts MVI at cardiovascular magnetic resonance and reduced myocardial blood flow at positron emission tomography (PET). Methods and Results— Sixty patients with ST-segment–elevation myocardial infarction were included in this prospective study. Immediately after successful PCI, intracoronary pressure–flow measurements were performed and analyzed off-line to calculate HMR and indices derived from the pressure–velocity loops, including pressure at zero flow. Cardiovascular magnetic resonance and H 2 15 O PET imaging were performed 4 to 6 days after PCI. Using cardiovascular magnetic resonance, MVI was defined as a subendocardial recess of myocardium with low...
Circulation. Cardiovascular interventions, 2014
Coronary flow reserve has extensive validation as a prognostic marker in coronary disease. Althou... more 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. Invasive pressure and flow velocity were measured in 216 stenoses from 186 patients with coronary disease. The diagnostic relationship between pressure-only indices (iFR and FFR) and coronary flow velocity reserve (CFVR) was compared using correlation coefficient and the area under the receiver operating characteristic curve. iFR showed a stronger correlation with underlying CFVR (iFR-CFVR, ρ=0.68 versus FFR-CFVR, ρ=0.50; P<0.001). iFR also agreed more closely with CFVR in stenosis classification (iFR area under the receiver ...
Circulation: Cardiovascular Interventions, 2014
Background— Intravenous adenosine infusion produces coronary and systemic vasodilatation, general... more Background— Intravenous adenosine infusion produces coronary and systemic vasodilatation, generally leading to systemic hypotension. However, adenosine-induced hypotension during stable hyperemia is heterogeneous, and its relevance to coronary stenoses assessment with fractional flow reserve (FFR) remains largely unknown. Methods and Results— FFR, coronary flow reserve, and index of microcirculatory resistance were measured in 93 stenosed arteries (79 patients). Clinical and intracoronary measurements were analyzed among tertiles of the percentage degree of adenosine-induced hypotension, defined as follows: %ΔP a =–[100–(hyperemic aortic pressure×100/baseline aortic pressure)]. Overall, %ΔP a was –13.6±12.0%. Body mass index was associated with %ΔP a ( r =0.258; P =0.025) and obesity, an independent predictor of profound adenosine-induced hypotension (tertile 3 of %ΔP a ; odds ratio, 3.95 [95% confidence interval, 1.48–10.54]; P =0.006). %ΔP a was associated with index of microcircu...
Revista Española de Cardiología, 2014
Introduccio´n y objetivos: La vasculopatía del aloinjerto cardiaco afecta tanto al compartimento ... more Introduccio´n y objetivos: La vasculopatía del aloinjerto cardiaco afecta tanto al compartimento coronario epicá rdico como al de la microcirculació n. Se ha propuesto el uso de las té cnicas de imagen de perfusió n de la resonancia magné tica como instrumento ú til para la evaluació n de la microcirculació n, principalmente fuera del contexto del trasplante de corazó n. La pendiente de velocidad del flujopresió n diastó lica hiperé mica instantá nea, que es un índice de la fisiología intracoronaria, ha mostrado mejor correlació n con el remodelado microcirculatorio en la vasculopatía del aloinjerto cardiaco que la de otros índices como la reserva de velocidad del flujo coronario. Con objeto de investigar el potencial de las té cnicas de imagen de perfusió n de resonancia magné tica para detectar la presencia de remodelado microcirculatorio en la vasculopatía de aloinjerto cardiaco, se ha comparado los datos de perfusió n de resonancia magné tica con los índices fisioló gicos intracoronarios invasivos, para estudiar la microcirculació n en una població n de pacientes con trasplante de corazó n que presentaban una enfermedad macrovascular no obstructiva demostrada por la ecografía intravascular. Me´todos: Se estudió a 8 pacientes con trasplante de corazó n (media de edad, 61 AE 12 años; el 100% varones) que presentaban una vasculopatía del aloinjerto epicá rdica definida por ecografía intravascular, estenosis coronarias no significativas y una resonancia magné tica de estré s con dobutamina con evaluació n visual del movimiento de la pared/perfusió n negativa. Se determinaron los datos de perfusió n de resonancia magné tica cuantitativa en estré s y en reposo para establecer el índice de reserva de perfusió n miocá rdica, de manera no invasiva, y se determinaron cuatro índices fisioló gicos intracoronarios evaluados de manera invasiva. Resultados: Los datos posprocesados mostraron una media del índice de reserva de perfusió n miocá rdica de 1,22 AE 0,27, mientras que la reserva de flujo fraccional, la reserva de velocidad del flujo coronario, la resistencia microvascular hiperé mica y la pendiente de velocidad del flujo-presió n diastó lica hiperé mica instantá nea fueron de 0,98 AE 0,02, 2,34 AE 0,55, 2,00 AE 0,69 y 0,91 AE 0,65 cm/s/mmHg respectivamente. El índice de reserva de perfusió n miocá rdica presentó una correlació n intensa tan solo con la pendiente de velocidad del flujo-presió n diastó lica hiperé mica instantá nea (r = 0,75; p = 0,033). Conclusiones: El índice de reserva de perfusió n miocá rdica obtenido a partir de la resonancia magné tica de estré s con dobutamina completa resulta una té cnica fiable para la detecció n no invasiva de la enfermedad coronaria microcirculatoria asociada a la vasculopatía de aloinjerto cardiaco.
Revista Española de Cardiología (English Edition), 2014
Journal of interventional cardiology, Jan 23, 2018
Instantaneous free-wave ratio (iFR) has been recently demonstrated non-inferior to fractional flo... more Instantaneous free-wave ratio (iFR) has been recently demonstrated non-inferior to fractional flow reserve (FFR) to drive coronary revascularization; however, no study has compared iFR versus coronary angiography (CA). We performed a network meta-analysis to evaluate efficacy and safety of iFR- versus CA-guided strategy. We searched for randomized trials and studies with propensity score matching in The Cochrane Collaboration Central Register of Controlled Trials, EMBASE, and MEDLINE/Pubmed. CA, FFR, and iFR were the three competitive arms, MACE (a composite endpoint of death, myocardial infarction [MI], and target vessel revascularization [TVR]) was the primary endpoint, while its single components the secondary ones. Subgroup analysis was performed for patients presenting with stable coronary artery disease. Eight studies were selected: 4126 patients were evaluated with FFR, 2160 with iFR, and 2214 with CA, acute coronary syndrome (ACS) was the most frequent admission diagnosis. A...
Archivos de cardiología de México
One of the most important limitations of coronary angiography is the inability to characterize th... more One of the most important limitations of coronary angiography is the inability to characterize the physiological significance of an intermediate coronary stenosis. Measuring coronary blood flow and pressure provides unique information that complements anatomic evaluation and facilitates decision-making in the cardiac catheterization unit. This review discusses the fundamental concepts of coronary physiology, methodology, and clinical applications of coronary and flow measurements.
Revista Española de Cardiología, 2002
Candell-Riera J, et al. Valoración fisiológica de la circulación coronaria Papel de las técnicas ... more Candell-Riera J, et al. Valoración fisiológica de la circulación coronaria Papel de las técnicas invasivas y no invasivas 105
Journal of Diagnostic Medical Sonography, 1994
JACC. Cardiovascular interventions, Jan 26, 2017
The study sought to determine the coronary flow characteristics of angiographically intermediate ... more The study sought to determine the coronary flow characteristics of angiographically intermediate stenoses classified as discordant by fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). Discordance between FFR and iFR occurs in up to 20% of cases. No comparisons have been reported between the coronary flow characteristics of FFR/iFR discordant and angiographically unobstructed vessels. Baseline and hyperemic coronary flow velocity and coronary flow reserve (CFR) were compared across 5 vessel groups: FFR+/iFR+ (108 vessels, n = 91), FFR-/iFR+ (28 vessels, n = 24), FFR+/iFR- (22 vessels, n = 22), FFR-/iFR- (208 vessels, n = 154), and an unobstructed vessel group (201 vessels, n = 153), in a post hoc analysis of the largest combined pressure and Doppler flow velocity registry (IDEAL [Iberian-Dutch-English] collaborators study). FFR disagreed with iFR in 14% (50 of 366). Baseline flow velocity was similar across all 5 vessel groups, including the unobstructed vessel g...
European heart journal, Dec 13, 2017
Techniques for identifying specific microcirculatory structural changes are desirable. As such, c... more Techniques for identifying specific microcirculatory structural changes are desirable. As such, capillary rarefaction constitutes one of the earliest changes of cardiac allograft vasculopathy (CAV) in cardiac allograft recipients, but its identification with coronary flow reserve (CFR) or intracoronary resistance measurements is hampered because of non-selective interrogation of the capillary bed. We therefore investigated the potential of wave intensity analysis (WIA) to assess capillary rarefaction and thereby predict CAV. Fifty-two allograft patients with unobstructed coronary arteries and normal left ventricular (LV) function were assessed. Adequate aortic pressure and left anterior descending artery flow measurements at rest and with intracoronary adenosine were obtained in 46 of which 2 were lost to follow-up. In a subgroup of 15 patients, simultaneous RV biopsies were obtained and analysed for capillary density. Patients were followed up with 1-3 yearly screening angiography....
Journal of the American College of Cardiology, 2017
In this review, the authors reflect upon the role of coronary physiology in the modern management... more In this review, the authors reflect upon the role of coronary physiology in the modern management of coronary artery disease. They critically appraise the scientific background of the instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR), from early experimental studies to validation studies against indexes of ischemia, to clinical trials assessing outcome. At this important juncture for the field, the authors make predictions for the future of physiological stenosis assessment, outlining developments for both iFR and FFR in new clinical domains beyond the confines of stable angina. With a focus on the evolving future of iFR and FFR, the authors describe how physiological assessment with iFR may advance its application from simply justifying to guiding revascularization.
The international journal of cardiovascular imaging, Jan 28, 2017
The vasodilator capacity of the coronary circulation is an important diagnostic and prognostic ch... more The vasodilator capacity of the coronary circulation is an important diagnostic and prognostic characteristic, and its accurate assessment is therefore an important frontier. The coronary flow capacity (CFC) concept was introduced to overcome the limitations associated with the use of coronary flow reserve (CFR) for this purpose, which are related to the sensitivity of CFR to physiological alterations in systemic and coronary hemodynamics. CFC was developed from positron emission tomography, and was subsequently extrapolated to invasive coronary physiology. These studies suggest that CFC is a robust framework for the identification of clinically relevant coronary flow abnormalities, and improves identification of patients at risk for adverse events over the use of CFR alone. This Review will discuss the concept of CFC, its promises in the setting of ischaemic heart disease, and its challenges both in theoretical and practical terms.
Cardiovascular diabetology, Jan 19, 2017
In diabetic patients a predisposed coronary microcirculation along with a higher risk of distal p... more In diabetic patients a predisposed coronary microcirculation along with a higher risk of distal particulate embolization during primary percutaneous intervention (PCI) increases the risk of peri-procedural microcirculatory damage. However, new antiplatelet agents, in particular Ticagrelor, may protect the microcirculation through its adenosine-mediated vasodilatory effects. PREDICT is an original, prospective, randomized, multicenter controlled study designed to investigate the protective effect of Ticagrelor on the microcirculation during PCI in patient with diabetes mellitus type 2 or pre-diabetic status. The primary endpoints of this study aim to test (i) the decrease in microcirculatory resistance with antiplatelet therapy (Ticagrelor > Clopidogrel; mechanistic effect) and (ii) the relative microcirculatory protection of Ticagrelor compared to Clopidogrel during PCI (Ticagrelor < Clopidogrel; protective effect). PREDICT will be the first multicentre clinical trial to test ...
Journal of the American Heart Association, Jan 22, 2016
Coronary microcirculatory dysfunction portends a poor cardiovascular outcome. Invasive assessment... more Coronary microcirculatory dysfunction portends a poor cardiovascular outcome. Invasive assessment of microcirculatory dysfunction by coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) is affected by coronary artery disease (CAD). In this study we propose minimal microvascular resistance (mMR) as a new measure of microcirculatory dysfunction and aim to determine whether mMR is influenced by CAD. We obtained 482 simultaneous measurements of intracoronary Doppler flow velocity and pressure. The mMR is defined as the ratio between distal coronary pressure and flow velocity during the hyperemic wave-free period. Measurements were divided into 2 cohorts. Cohort 1 was a paired analysis involving 81 pairs with a vessel with and without CAD to investigate whether HMR, CFR, and mMR are modulated by CAD. CFR was lower, and HMR was higher, in vessels with CAD than in vessels without CAD: 2.12±0.79 versus 2.56±0.63 mm Hg·cm(-1)·s, P<0.001, and 2.61±1.22 versus 2.31±0.89 ...
JACC. Cardiovascular interventions, 2015
This study sought to understand the physiological basis of baseline distal-to-aortic pressure rat... more This study sought to understand the physiological basis of baseline distal-to-aortic pressure ratio (Pd/Pa) and fractional flow reserve (FFR) agreement and discordance, using coronary flow reserve (CFR), stenosis resistance, and microcirculatory resistance measurements, and form there, to investigate the potential value of combining Pd/Pa with FFR in the diagnostic rationale. Pd/Pa is always available before FFR assessment, and emerging data supports the notion that baseline indices can determine the ischemic potential of coronary stenosis in selected subsets. A total of 467 stenosed vessels from 363 patients were investigated with pressure and flow sensors during baseline and hyperemia: 168 vessels (135 patients) with thermodilution-derived flow, and 299 vessels (228 patients) with Doppler-derived flow. Pd/Pa correlated more strongly with CFR than FFR (ρ difference = 0.129; p for ρ comparison <0.001). Although Pd/Pa and FFR were closely correlated (ρ = 0.798; 95% confidence inte...
Circulation. Cardiovascular interventions, 2015
The index of microcirculatory resistance (IMR) is a quantitative and specific index for coronary ... more The index of microcirculatory resistance (IMR) is a quantitative and specific index for coronary microcirculation. However, the distribution and determinants of IMR have not been fully investigated in patients with ischemic heart disease (IHD). Consecutive patients who underwent elective measurement of both fractional flow reserve (FFR) and IMR were enrolled from 8 centers in 5 countries. Patients with acute myocardial infarction were excluded. To adjust for the influence of collateral flow, IMR values were corrected with Yong's formula (IMRcorr). High IMR was defined as greater than the 75th percentile in each of the major coronary arteries. FFR≤0.80 was defined as an ischemic value. 1096 patients with 1452 coronary arteries were analyzed (mean age 61.1, male 71.2%). Mean FFR was 0.84 and median IMRcorr was 16.6 U (Q1, Q3 12.4 U, 23.0 U). There was no correlation between IMRcorr and FFR values (r=0.01, P=0.62), and the categorical agreement of FFR and IMRcorr was low (kappa val...
Circulation. Cardiovascular interventions, 2015
Percutaneous coronary intervention (PCI) aims to increase coronary blood flow by relieving epicar... more Percutaneous coronary intervention (PCI) aims to increase coronary blood flow by relieving epicardial obstruction. However, no study has objectively confirmed this and assessed changes in flow over different phases of the cardiac cycle. We quantified the change in resting and hyperemic flow velocity after PCI in stenoses defined physiologically by fractional flow reserve and other parameters. Seventy-five stenoses (67 patients) underwent paired flow velocity assessment before and after PCI. Flow velocity was measured over the whole cardiac cycle and the wave-free period. Mean fractional flow reserve was 0.68±0.02. Pre-PCI, hyperemic flow velocity is diminished in stenoses classed as physiologically significant compared with those classed nonsignificant (P<0.001). In significant stenoses, flow velocity over the resting wave-free period and hyperemic flow velocity did not differ statistically. After PCI, resting flow velocity over the wave-free period increased little (5.6±1.6 cm/s...
Journal of the American College of Cardiology, 2015
Background: We acquired a large dataset of combined intracoronary pressure and flow velocity meas... more Background: We acquired a large dataset of combined intracoronary pressure and flow velocity measurements, to better understand the relationships between flow, transstenotic gradient (TG) and microvascular resistance (MVR), and help clarify the rationale of resting stenosis assessment. methods: 567 simultaneous intracoronary pressure and flow velocity measurements were acquired. Flow, TG and MVR were determined during whole cycle resting and hyperemic conditions, and during the wave-free period at rest. Linear regression analysis was done to estimate trends and P-values, according to strata of progressive functional stenosis severity indicated by the fractional flow reserve (FFR). results: With progressive strata of stenosis severity from reference to FFR≤0.50, flow at rest was unchanged (18±8.2 cm/s; P=0.40), but gradually decreased from 45 to 19 cm/s at hyperemia (P<0.01). TG increased from 1.5 to 46 mmHg at rest, and from 3.5 to 55 mmHg at hyperemia (P<0.01 for both). MVR declined from 6.2 to 4.2 at rest (P<0.01), but remained unchanged at hyperemia (2.3±1.1; P=0.19). Phasic analysis during the wave-free period, yielded similar trends as whole cycle analysis. Conclusion: With progressive stenosis severity, an increased TG at rest is observed, while stable coronary flow is maintained by compensatory reduction of MVR owing to coronary autoregulation. This explains why resting pressure, but not resting myocardial perfusion assessment, permits detection of hemodynamic stenosis significance.
Circulation. Cardiovascular interventions, 2013
We studied the hemodynamic response to intravenous adenosine on calculation of fractional flow re... more 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. 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 ΔPa and ΔPd were decreased (ΔPa, -10.2±10.5 mm Hg; ΔPd, -18.2±10.8 mm Hg; P<0.001 for both). The fall in Pa closely correlated with the reduction in peripheral Pr (ΔPr, -1...
Circulation: Cardiovascular Interventions, 2015
Background— A total of 40% to 50% of patients with ST-segment–elevation myocardial infarction dev... more Background— A total of 40% to 50% of patients with ST-segment–elevation myocardial infarction develop microvascular injury (MVI) despite angiographically successful primary percutaneous coronary intervention (PCI). We investigated whether hyperemic microvascular resistance (HMR) immediately after angiographically successful PCI predicts MVI at cardiovascular magnetic resonance and reduced myocardial blood flow at positron emission tomography (PET). Methods and Results— Sixty patients with ST-segment–elevation myocardial infarction were included in this prospective study. Immediately after successful PCI, intracoronary pressure–flow measurements were performed and analyzed off-line to calculate HMR and indices derived from the pressure–velocity loops, including pressure at zero flow. Cardiovascular magnetic resonance and H 2 15 O PET imaging were performed 4 to 6 days after PCI. Using cardiovascular magnetic resonance, MVI was defined as a subendocardial recess of myocardium with low...
Circulation. Cardiovascular interventions, 2014
Coronary flow reserve has extensive validation as a prognostic marker in coronary disease. Althou... more 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. Invasive pressure and flow velocity were measured in 216 stenoses from 186 patients with coronary disease. The diagnostic relationship between pressure-only indices (iFR and FFR) and coronary flow velocity reserve (CFVR) was compared using correlation coefficient and the area under the receiver operating characteristic curve. iFR showed a stronger correlation with underlying CFVR (iFR-CFVR, ρ=0.68 versus FFR-CFVR, ρ=0.50; P<0.001). iFR also agreed more closely with CFVR in stenosis classification (iFR area under the receiver ...
Circulation: Cardiovascular Interventions, 2014
Background— Intravenous adenosine infusion produces coronary and systemic vasodilatation, general... more Background— Intravenous adenosine infusion produces coronary and systemic vasodilatation, generally leading to systemic hypotension. However, adenosine-induced hypotension during stable hyperemia is heterogeneous, and its relevance to coronary stenoses assessment with fractional flow reserve (FFR) remains largely unknown. Methods and Results— FFR, coronary flow reserve, and index of microcirculatory resistance were measured in 93 stenosed arteries (79 patients). Clinical and intracoronary measurements were analyzed among tertiles of the percentage degree of adenosine-induced hypotension, defined as follows: %ΔP a =–[100–(hyperemic aortic pressure×100/baseline aortic pressure)]. Overall, %ΔP a was –13.6±12.0%. Body mass index was associated with %ΔP a ( r =0.258; P =0.025) and obesity, an independent predictor of profound adenosine-induced hypotension (tertile 3 of %ΔP a ; odds ratio, 3.95 [95% confidence interval, 1.48–10.54]; P =0.006). %ΔP a was associated with index of microcircu...
Revista Española de Cardiología, 2014
Introduccio´n y objetivos: La vasculopatía del aloinjerto cardiaco afecta tanto al compartimento ... more Introduccio´n y objetivos: La vasculopatía del aloinjerto cardiaco afecta tanto al compartimento coronario epicá rdico como al de la microcirculació n. Se ha propuesto el uso de las té cnicas de imagen de perfusió n de la resonancia magné tica como instrumento ú til para la evaluació n de la microcirculació n, principalmente fuera del contexto del trasplante de corazó n. La pendiente de velocidad del flujopresió n diastó lica hiperé mica instantá nea, que es un índice de la fisiología intracoronaria, ha mostrado mejor correlació n con el remodelado microcirculatorio en la vasculopatía del aloinjerto cardiaco que la de otros índices como la reserva de velocidad del flujo coronario. Con objeto de investigar el potencial de las té cnicas de imagen de perfusió n de resonancia magné tica para detectar la presencia de remodelado microcirculatorio en la vasculopatía de aloinjerto cardiaco, se ha comparado los datos de perfusió n de resonancia magné tica con los índices fisioló gicos intracoronarios invasivos, para estudiar la microcirculació n en una població n de pacientes con trasplante de corazó n que presentaban una enfermedad macrovascular no obstructiva demostrada por la ecografía intravascular. Me´todos: Se estudió a 8 pacientes con trasplante de corazó n (media de edad, 61 AE 12 años; el 100% varones) que presentaban una vasculopatía del aloinjerto epicá rdica definida por ecografía intravascular, estenosis coronarias no significativas y una resonancia magné tica de estré s con dobutamina con evaluació n visual del movimiento de la pared/perfusió n negativa. Se determinaron los datos de perfusió n de resonancia magné tica cuantitativa en estré s y en reposo para establecer el índice de reserva de perfusió n miocá rdica, de manera no invasiva, y se determinaron cuatro índices fisioló gicos intracoronarios evaluados de manera invasiva. Resultados: Los datos posprocesados mostraron una media del índice de reserva de perfusió n miocá rdica de 1,22 AE 0,27, mientras que la reserva de flujo fraccional, la reserva de velocidad del flujo coronario, la resistencia microvascular hiperé mica y la pendiente de velocidad del flujo-presió n diastó lica hiperé mica instantá nea fueron de 0,98 AE 0,02, 2,34 AE 0,55, 2,00 AE 0,69 y 0,91 AE 0,65 cm/s/mmHg respectivamente. El índice de reserva de perfusió n miocá rdica presentó una correlació n intensa tan solo con la pendiente de velocidad del flujo-presió n diastó lica hiperé mica instantá nea (r = 0,75; p = 0,033). Conclusiones: El índice de reserva de perfusió n miocá rdica obtenido a partir de la resonancia magné tica de estré s con dobutamina completa resulta una té cnica fiable para la detecció n no invasiva de la enfermedad coronaria microcirculatoria asociada a la vasculopatía de aloinjerto cardiaco.
Revista Española de Cardiología (English Edition), 2014