Maximal Hyperemia Research Articles

TU‐G‐204‐01: BEST IN PHYSICS (IMAGING): Dynamic CT Myocardial Perfusion Measurement and Its Comparison to Fractional Flow Reserve

Purpose:To evaluate a first pass analysis (FPA) technique for CT perfusion measurement in a swine animal and its validation using fractional flow reserve (FFR) as a reference standard.Methods:Swine were placed under anesthesia and relevant physiologic parameters were continuously recorded. Intra‐coronary adenosine was administered to induce maximum hyperemia. A pressure wire was advanced distal to the first diagonal branch of the left anterior descending (LAD) artery for FFR measurements and a balloon dilation catheter was inserted over the pressure wire into the proximal LAD to create varying levels of stenosis. Images were acquired with a 320‐row wide volume CT scanner. Three main coronary perfusion beds were delineated in the myocardium using arteries extracted from CT angiography images using a minimum energy hypothesis. The integrated density in the perfusion bed was used to calculate perfusion using the FPA technique. The perfusion in the LAD bed over a range of stenosis severity was measured. The measured fractional perfusion was compared to FFR and linear regression was performed.Results:The measured fractional perfusion using the FPA technique (P_FPA) and FFR were related as P_FPA = 1.06FFR – 0.06 (r2 = 0.86). The perfusion measurements were calculated with only three to five total CT volume scans, which drastically reduces the radiation dose as compared with the existing techniques requiring 15–20 volume scans.Conclusion:The measured perfusion using the first pass analysis technique showed good correlation with FFR measurements as a reference standard. The technique for perfusion measurement can potentially make a substantial reduction in radiation dose as compared with the existing techniques.

Vascular flow reserve immediately after infrapopliteal intervention as a predictor of wound healing in patients with foot tissue loss.

The purpose of this study was to verify whether the concept of coronary blood flow reserve can be applied to patients with critical limb ischemia who are undergoing endovascular treatment (EVT) for isolated infrapopliteal lesions. Forty patients diagnosed with critical limb ischemia (Rutherford category 5) who were undergoing EVT for isolated infrapopliteal lesions were prospectively enrolled. All lesions were treated with conventional balloon angioplasty without stent placement. After successful EVT, a pressure/temperature sensor-tipped guidewire was positioned in the proximal popliteal artery. Using the thermodilution technique, the mean transit time (Tmn) was determined after bolus injections of 3-mL saline at baseline and at the onset of intra-arterial papaverine induced maximum hyperemia. Vascular flow reserve (VFR) was calculated as resting Tmn divided by hyperemic Tmn. Complete epithelialization of the reference wound (wound healing) was completely closed by either surgical or secondary intervention within 3 months after EVT. Wound healing was achieved in 22 patients after EVT (healing group) but was not achieved in 18 patients (nonhealing group). Postprocedural VFR was significantly lower in the nonhealing group than in the healing group (2.40; interquartile range, 2.00-3.08 versus 4.05; interquartile range, 3.60-4.60; P<0.0001). Receiver operating characteristic analysis revealed postprocedural VFR >3.6 as the best threshold value for complete wound healing after EVT. Univariate analysis revealed that postprocedural VFR >3.6 was a predictor of wound healing (P=0.0002). Advanced lower limb clinical setting may be caused by a poor capability of microvasculature. VFR, which is easily assessable, is useful in clinical risk stratification for patients with critical limb ischemia after EVT in the catheterization laboratory. URL: http://www.umin.ac.jp/ctr. Unique identifier: UMIN000009313.

Fractional flow reserve: physiological basis, advantages and limitations, and potential gender differences.

Fractional flow reserve (FFR) is a physiological index of the severity of a stenosis in an epicardial coronary artery, based on the pressure differential across the stenosis. Clinicians are increasingly relying on this method because it is independent of baseline flow, relatively simple, and cost effective. The accurate measurement of FFR is predicated on maximal hyperemia being achieved by pharmacological dilation of the downstream resistance vessels (arterioles). When the stenosis causes FFR to be impaired by > 20%, it is considered to be significant and to justify revascularization. A diminished hyperemic response due to microvascular dysfunction can lead to a false normal FFR value, and a misguided clinical decision. The blunted vasodilation could be the result of defects in the signaling pathways modulated (activated or inhibited) by the drug. This might involve a downregulation or reduced number of vascular receptors, endothelial impairment, or an increased activity of an opposing vasoconstricting mechanism, such as the coronary sympathetic nerves or endothelin. There are data to suggest that microvascular dysfunction is more prevalent in post-menopausal women, perhaps due to reduced estrogen levels. The current review discusses the historical background and physiological basis for FFR, its advantages and limitations, and the phenomenon of microvascular dysfunction and its impact on FFR measurements. The question of whether it is warranted to apply gender-specific guidelines in interpreting FFR measurements is addressed.

Day‐to‐day Variability in Arterial Diameter and Brachial Artery Flow‐Mediated Dilation in Sedentary Young Men and Women

Brachial artery flow‐mediated dilation (FMD), an index of endothelial function, is predictive of cardiovascular disease risk. A wide range of FMD day‐to‐day variability has been reported, but whether this variability differs between men and women is unknown. We examined potential sex‐based differences in FMD and its day‐to‐day variability. Sedentary but otherwise healthy men (N=10, age: 22±3 years) and women (N=7, age: 21±2 years) completed two brachial FMD tests 24 hours apart. Women were tested during the mid‐follicular phase of their menstrual cycle (days 7‐12). Baseline arterial diameter (ADBL) and maximum reactive hyperemia diameter (ADRH) were determined, and relative FMD was calculated as FMD% = (ADRH–ADBL)/ADBL. Day 1 measures and between‐day differences were assessed with independent t‐tests. Day‐to‐day variability was assessed with the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Compared to men, women had smaller arterial diameters (p&lt;0.05), but a similar FMD response (p=0.828). No sex‐differences were observed in between‐day differences for any measures (p&gt;0.05). Day‐to‐day variability was low for AD in both sexes (CV of 3‐5%), but high for FMD (men: 43%, women: 55%). Similarly, ICCs were substantial to almost perfect for AD in both sexes (ICC of 0.77‐0.92), but poor for FMD (men: 0.01, women: 0.07). These findings suggest that arterial diameter exhibits better day‐to‐day repeatability than relative FMD in both men and women. Despite women having greater FMD variability than men, between‐day differences were not statistically significant. A larger sample size may be required to detect potential sex‐differences.Funded by NSERC, OGS and GSSI.

Factors influencing the functional significance in intermediate coronary stenosis.

ObjectiveTo analyze the influencing factors of the functional significance determined by fractional flow reserve (FFR) in intermediate coronary artery stenosis.MethodsThe study enrolled 143 patients with 203 intermediate coronary lesions. Pressure-derived FFR of these lesions was gained at maximal hyperemia induced by intravenous adenosine infusion. An FFR < 0.80 was considered as abnormal functional significance. Anatomic parameters at the lesion sites were obtained by off-line quantitative coronary angiography analysis (QCA). The predictive value of the demographic characteristics and anatomic parameters for FFR in these intermediate lesions was assessed using multiple linear and binary logistic regression analysis.ResultsOverall, FFR < 0.8 was found in 70 (34%) of the total 203 intermediate coronary lesions. FFR values were positively correlated with QCA-measured minimum lumen diameters (MLD, r = 0.372, P = 0.000) and the reference vessel diameters (RVD, r = 0.217, P = 0.002) were negatively correlated with percent area stenosis (AS, r = −0.251, P = 0.000) and percent diameter stenosis (DS, r = −0.210, P = 0.000). Age, MLD and the lesion location in different coronary arteries were the independent determinants of FFR < 0.8.ConclusionsMLD can predict the functional significance of intermediate coronary stenosis, while age and the lesion location in different coronary arteries should be taken into account as important influencing factors of FFR values.

A novel equitation to predict the pressure derived collateral flow index in multiple sequential coronary stenoses.

Coronary collateral circulation is an alternative source of blood supply to the myocardium when the original blood flow is not sufficient. The pressure derived collateral flow index (CFI) calculated with (P w-P v)/(P a-P v) can be measured during angioplasty and predicts the outcome of the patients with ischemic heart disease. However, the necessity of occluding the coronary artery at maximum hyperemia hampers the wide spread use. We mathematically derived a new equation which calculates CFI in sequential stenoses. The present study aimed to validate the equation in an in vitro model of coronary circulation. The predicted CFI is calculated from the following equation: CFI=(FFRpre-FFRpost(1-∆FFR))/(FFRpre+∆FFR-FFRpost). FFRpre/post is the FFR before and after the angioplasty. ∆FFR is the FFR gradient across the target stenosis. The experimental system consisted of a pump, systemic circulation, coronary circulation, and 5 constrictors placed in the coronary artery. A total of 30 different sequential coronary stenoses were randomly created and 30 different pressure data were obtained. The predicted CFI was compared with the true CFI. A close positive correlation (r=0.90, p<0.0001) was found between the predicted CFI and the true CFI. The accuracy of the equation was demonstrated in an in vitro model of coronary circulation.

Fractional flow reserve: Current applications and overview of the available data.

Flow fractional reserve (FFR) allows to evaluate the functional significance of coronary artery lesions, through the ratio of the mean coronary artery pressure after the stenosis to the mean aortic pressure during maximum hyperemia. The actual widely accepted cut-off value is 0.80. Below this value a coronary lesion is considered significant and therefore it requires invasive revascularization. Several studies [in particular Fractional Flow Reserve vs Angiography for Multivessel Evaluation 1 (FAME-1) and FAME-2] have shown the relationship between FFR measurement and hard end-points (death, myocardial infarction, and urgent revascularization). Consequently, FFR evaluation represents the cornerstone in the decision-making in intermediate coronary lesions. Recent studies paved the way for further applications of FFR evaluation in complex and tricky clinical settings. In this paper, we perform an overview of the data regarding contemporary application of FFR. In particular, we review the use of FFR in: left main intermediate stenoses, serial stenoses, evaluation after stenting, guidance in coronary artery bypass surgery, and acute coronary syndrome. All the data presented in our overview confirm the essential role of FFR assessment in the daily clinical practice. The shift from "operator-dependent" to "FFR-dependent" evaluation in intermediate coronary artery stenosis is of paramount importance in order to improve the prognosis of our patients, through the discrimination of the functional role of every single coronary stenosis.

Is Hyperaemia Essential for Accurate Functional Assessment of Coronary Stenosis Severity?

Fractional flow reserve (FFR) requires the use of maximal hyperaemia as described in the original preclinical and clinical validation studies and subsequent practice changing randomized controlled trials. A perception that the need for hyperaemia (usually induced with adenosine) was one of the obstacles to more widespread adoption of FFR has led to interest in the use of resting non-hyperaemic indices to assess the functional significance of coronary stenoses. We examine the current evidence base and conclude that resting indices agree with FFR in only 80 % of lesions when a binary cut-off is employed but closer to 90 % when hybrid strategies utilising both resting indices and FFR are utilised. It seems counter intuitive to sacrifice diagnostic accuracy when in most patients and healthcare systems the induction of hyperaemia with adenosine is safe and emminently affordable.

Abstract 14685: Efficacy of Combined Administration of Intracoronary Papaverine and Intravenous Adenosine 5’-Triphosphate in Assessment of Fractional Flow Reserve

Purpose: Inducing maximal coronary hyperemia is important to measure fractional flow reserve (FFR) accurately. Administration of intracoronary (IC) papaverine and intravenous (IV) adenosine 5’-triphosphate (ATP) have been used to achieve maximal hyperemia in the assessment of FFR. However, they may not induce maximal hyperemia in all patients. We aimed to evaluate combined effect of IC papaverine and IV ATP on FFR measurements. Methods: FFR measurements using administration of IC papaverine (12 mg in the left coronary artery and 8 mg in the right coronary artery), IV ATP (140 μg/kg/min), and the combination of IC papaverine plus IV ATP (additional IC bolus infusion of papaverine during IV ATP) were performed in 57 lesions of 52 consecutive patients. FFR values, symptoms, development of atrioventricular block (AVB), and ventricular arrhythmia were recorded. Results: Mean FFR values with IC papaverine, IV ATP, and the combination of IC papaverine and IV ATP were comparable (0.75 ± 0.13 vs. 0.76 ± 0.13 vs. 0.75 ± 0.13, p = 0.87). The proportion of lesions with a positive FFR (FFR ≤0.80) were not significantly different between the 3 methods (54.4% vs. 47.4% vs. 64.9%, p = 0.17). IC papaverine and IV ATP detected 25 lesions and 32 lesions with a negative FFR (FFR &gt; 0.80), respectively. Of these, 7 (28%) and 11 lesions (34%) showed positive FFR with the combination of IC papaverine and IV ATP. Within the region of physiologically intermediate FFR values (0.75 to 0.85 obtained by IV ATP), there were significant differences in the FFR values (0.81 ± 0.02 vs. 0.79 ± 0.03, p = 0.01) and the proportion of positive FFR (48.3% vs. 66.7%, p &lt; 0.01) between IV ATP and the combination of IC papaverine and IV ATP. IC papaverine increased ventricular premature contraction in 2%. IV ATP caused flushing in 48%, chest oppression in 27%, shortness of breath in 10%, and transient 2nd degree AVB in 3%. The combination of IC papaverine and IV ATP caused transient 2nd degree AVB in 2%. Conclusions: The hyperemic efficacy of IC papaverine or IV ATP alone is suboptimal in some patients. Combined administration of IC papaverine and IV ATP can achieve optimal hyperemia in such patients and has the potential to assist in making clinical decisions on patients with physiologically intermediate lesions.

Abstract 19059: Thermodilution-derived Coronary Blood Flow Pattern Immediately After Coronary Intervention as a Predictor of Long-term Clinical Outcomes in Patients With ST-segment Elevation Myocardial Infarction

Background: We reported that coronary blood flow (CBF) can be evaluated by analyzing thermodilution curve that is measured with a single pressure sensor/thermistor-tipped guidewire in the cardiac catheterization laboratory during percutaneous coronary intervention (PCI). Bimodal shape of thermodilution curve was associated with microvascular damage and predictors of left ventricular functional recovery after ST-segment elevation myocardial infarction (STEMI). However it is unknown whether the bimodal shape of thermodilution curve predicts mortality and re-hospitalization for heart failure in long term period for patients experiencing STEMI. Methods: Between September 2009 and August 2012, 97 consecutive patients with a first STEMI were prospectively enrolled in this study. Using a pressure sensor/thermistor-tipped guidewire, CBF pattern was assessed from the thermodilution-curves after successful PCI at maximum hyperemia. CBF pattern was classified into 3 groups according to the shape of thermodilution curve: a narrow unimodal (a rapid fall and rise of temperature-time curves) (n=47), a wide unimodal (a gradual fall and rise of temperature-time curves) (n=33), or bimodal (two populations with valley deeper than 20% of peak temperature drop) (n=17). Major adverse cardiac events (MACE) were defined as cardiac death and/or heart failure re-hospitalization within this study period. Results: Median follow-up period was 2.4 years. Although patients in the narrow-unimodal group and the wide unimodal group had a significantly lower incidence of MACE, patients in bimodal group had a higher risk of MACE during this study period (71, 15, 21%, p&lt;0.001). Multivariate analysis revealed that bimodal shape of the thermodilution-curve was the only independent predictor of MACE after STEMI (hazard ratio, 8.38; 95% confidence interval, 2.13-33.00; P=0.0023). Conclusions: A bimodal shape of the thermodilution curve is associated with the poor long-term clinical outcomes. This easily assessable coronary flow pattern is useful in clinical risk stratification for STEMI patients in the cardiac catheterization laboratory immediately after PCI.

Abstract 12019: Differential Effect of Ticagrelor versus Clopidogrel on Coronary Microvascular Function in Patients With Coronary Aertery Disease

Introduction: Differential Effect of Ticagrelor Versus Clopidogrel on Coronary Microvascular Function in Patients with Coronary Aertery Disease Background and Objectives: Ticagrelor is a new antiplatelet drug directly blocking P2Y12-adenosine diphosphate (ADP) receptors, which show a better clinical profile compared to clopidogrel in patients with acute coronary syndrome. Ticagrelor inhibits adenosine reuptake and increases coronary blood flow by a direct dilation of the microcirculation. We aimed to evaluate the effect of ticagrelor on coronary mircrovascular function in patient with coronary artery disease (CAD) in comparison with clopidogrel. Subjects and Methods: Twenty four patient with CAD were randomized to receive a single dose of ticagrelor (180 mg) or clopidogrel (300mg or on treatment state). Coronary microvascular function was invasively measured by using the index of microvascular resistance (IMR) and coronary flow reserve (CFR). The IMR was calculated from the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of mean hyperemic transit time (hTmn). The CFR was calculated dividing the hTmn by baseline mean transit time. Results: There were no significant differences in baseline clinical and angiographic characteristics.CFR was not significantly different in both groups. (median: 4.00 [interquartile range(IQR) 2.30 to 4.92] vs 5.10 [IQR: 3.72 to 7.90], p = 0.24) However, IMR was significantly lower in ticagrelor than clopidogrel treated patients at 140 μg/kg per minute adenosine infusion rate. (median: 10.74 [interquartile range (IQR) 8.02 to 12.31] vs 15.56 [IQR: 10.77 to 29.74], p =0.05). Conclusions: In patients with CAD, ticagrelor might improves coronary microvascular functionel. These results suggest that ticagrelor could contribute to better clinical outcomes in CAD patients.

Abstract 20015: Value of Quantitative Atherosclerotic Plaque Assessment Using CCTA to Predict Lesion-specific Ischemia, Data from 407 Coronary Lesions

Introduction: While coronary computed tomographic angiography (CCTA) demonstrates high diagnostic performance for identification and exclusion of high-grade anatomic stenosis, it is unable to effectively discriminate coronary lesions that causes ischemia. Hypothesis: To study whether quantitative assessment of CCTA offer incremental information for discrimination of lesion ischemia beyond stenosis measures. Methods: 252 consecutive patients with suspected or known coronary artery disease (CAD) from 17 centers in 5 countries were enrolled (mean age 63±9 years, 71% male). Patients underwent CCTA and invasive coronary angiography (ICA), with 407 coronary lesions interrogated by invasive fractional flow reserve (FFR) at the time of maximum hyperemia. For these coronary lesions, we evaluated % diameter stenosis (%DS), % area stenosis (%AS), minimal luminal diameter (MLD, mm), minimal luminal area (MLA, mm 2 ), and plaque burden at MLA by CCTA. Plaque burden (PB, %) was defined as (vessel area–lumen area)/vessel areaх100. Lesion-specific ischemia by FFR was defined as a value ≤0.8. Results: In quantitative analysis area under the receiver operating characteristic curves (AUC) value of %DS, %AS, MLD, MLA, and PB for prediction of ischemia were 0.72 (95% confidence interval (CI) 0.68-0.77, p&lt;0.001), 0.73 (95% CI 0.68-0.77, p&lt;0.001), 0.75 (95% CI 0.70-0.79, p&lt;0.001), 0.75 (95% CI 0.70-0.79, p&lt;0.001), and 0.77 (95% CI 0.73-0.81, p&lt;0.001), respectively. PB showed significantly improved AUC when compared to % area stenosis (p=0.002). However, PB didn’t show incremental power over MLA (p=0.213). There also was no significant difference in AUC between MLA and % area stenosis (p=0.330) Conclusions: Quantitative plaque assessment using CCTA could predict lesion-specific ischemia with good discrimination. Plaque burden showed incremental value over % area stenosis for ischemia prediction.

Assessment of lower limb flow and adequate intra-arterial papaverine doses to achieve maximal hyperemia in elder subjects.

Previous studies reported that invasive physiological assessment for significance of the lesions in the patients with claudication under the condition of pharmacological hyperemia was important to identify the patients who will benefit from revascularization. However, the maximal hyperemic response in lower limb and the method to induce maximum dilatation of vascular bed in lower limb were not well established. The aim of this study was to investigate the range of maximal hyperemic response in lower limb of the normal subjects and to identify the ideal lower limb vasodilatory stimulation. Twelve limbs without stenotic lesions from 12 subjects (average age: 72±6years) were analyzed. Thermodilution-derived mean transit time (Tmn) was obtained at baseline and during pharmacological hyperemia with incremental dose of intra-arterial papaverine (10, 20, 30, and 40mg) using a 0.014-inch pressure/temperature sensor-tipped wire in the superficial femoral artery (SFA). Percent increase in blood flow (%IBF) of lower limb was defined as the ratio between baseline Tmn and hyperemic Tmn. Mean ankle brachial index score of the subjects was 1.14±0.09. The %IBF values were enhanced by papaverine in a dose-dependent manner. A dose of 30mg of intra-arterial papaverine was sufficient to achieve maximum hyperemia (%IBF: range 219-769%). In conclusion, the increase in blood flow of lower limb during maximal hyperemia varied between individuals and maximal hyperemia can be achieved with 30mg of papaverine for the SFA lesion.

Intracoronary and intravenous administration of adenosine achieve comparable maximal hyperemia and stenosis pressure gradient-flow velocity relations

Intracoronary and intravenous administration of adenosine achieve comparable maximal hyperemia and stenosis pressure gradient-flow velocity relations

Multiple composite grafts (k, π or double-Y) in coronary artery surgery: a choice or a necessity?

Composite grafts allow complete arterial revascularization with minimal aortic manipulations. The Y-T configuration supplies all distal branches adequately, whereas it is unclear whether complex composite configurations (K, Π or double-Y) are equally at rest or when challenged by maximal requirements. Forty-seven patients who underwent off-pump coronary artery revascularization by multiple arterial composite grafts (K, Π or double-Y) were retrospectively evaluated. Indication for this surgical option was porcelain aorta or conduit unavailability. Composite systems were evaluated by intraoperative flow measurements and perioperative transthoracic Doppler ultrasonography, 12 months later also by exercise test, sestamibi scintigraphy at rest and during induced hyperaemia and by 64-slice multidetector CT angiography. A total of 141 distal anastomoses were implanted as composite grafts. Perioperative flow measurements and 12-month Doppler ultrasonography were adequate at rest. At stress test, chest pain and/or induced ECG evidence of ischaemia are found in 16 patients (39%). During dipyridamole-induced hyperaemia, single-photon emission computed tomography image revealed that mean summed stress score was 7.2 ± 5.7, summed difference score 5.3 ± 4.2 and coronary flow reserve 1.7 ± 0.2. Multiple composite grafts, albeit adequate at rest, were unable to meet flow requirements during maximal hyperaemia. In daily practice, their use must be not a choice but rather a necessity in those patients without alternative options.

Effects of intravenous caffeine on fractional flow reserve measurements in coronary artery disease

BackgroundIntravenous adenosine is used to minimise the coronary micro-resistance to achieve maximal hyperaemia along with nitrates for optimal fractional flow reserve (FFR) measurements. We hypothesise that caffeine, being a competitive...

Y grafts with the left internal mammary artery and radial artery. Mid-term functional and angiographic results. Cohort study

Background. This retrospective cohort study investigated the functional and haemodynamic mid-term results over 3-years follow up of the left internal mammary artery (LIMA) conduit in composite Y-graft configuration with radial artery (RA) in a population of patients who underwent off-pump coronary artery bypass grafting (CABG). Methods. 148 patients who underwent off-pump CABG with composite Y-graft, were evaluated over 3-year follow up. Two-day dipyridamole induced maximal hyperaemia/rest 99mTc-sestamibi was scheduled preoperatively and 36 months after surgery for functional evaluation. Morphological evaluation was performed by 64 slice multidetector computed tomography (CT) 36 months after surgery. Results. Clinical adverse events were rare within 3 years follow up. Minimal to severe scintigraphic evidence of stress induced ischaemia occurred in 24 patients. Left ventricular (LV) hypertrophy (HR 3.1; 95% CI, 1.5–9.3; p = 0.01) and poor coronary run off (HR 4.1; 95% CI, 2.1–10.8; p = 0.005) were significant multivariate predictors of reversible stress induced ischaemia. 64 slice multidetector CT showed that the main stem of Y composite grafts was patent in all patients, while distal LIMA or RA was stenosed or occluded in 9 patients. Conclusion. Composite Y-graft was adequate to meet the flow requirements of target coronary artery either at rest or during maximal hyperaemia. The use of Y-graft should be carefully evaluated in patients with LV hypertrophy and/or poor coronary run-off.

Hyperemia-free delineation of epicardial and microvascular impairments using a basal index.

The assessment of functional coronary lesion severity using intracoronary hemodynamic parameters like the pressure-derived fractional flow reserve and the flow-derived coronary flow reserve are known to rely critically on the establishment of maximal hyperemia. We evaluated a hyperemia-free index, basal pressure drop coefficient (bCDP), that combines pressure and velocity for simultaneous assessment of the status of both epicardial and microvascular circulations. In 23 pigs, simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual-sensor tipped guidewire in the settings of both normal and abnormal microcirculation with the presence of epicardial lesions of area stenosis (AS) < 50% and AS > 50%. The bCDP, a parameter based on fundamental fluid dynamics principles, was calculated as the transtenotic pressure-drop divided by the dynamic pressure in the distal vessel, measured under baseline (without hyperemia) conditions. The group mean values of bCDP for normal (84 ± 18) and abnormal (124.5 ± 15.6) microcirculation were significantly different. Similarly, the mean values of bCDP from AS < 50% (72.5 ± 16.1) and AS > 50% (136 ± 17.2) were also significantly different (p < 0.05). The bCDP could significantly distinguish between lesions of AS < 50% to AS > 50% under normal microcirculation (52.1 vs. 85.8; p < 0.05) and abnormal microcirculation (84.9 vs. 172; p < 0.05). Further, the bCDP correlated linearly and significantly with the hyperemic parameters FFR (r = 0.42, p < 0.05) and CDP (r = 0.50, p < 0.05). The bCDP is a promising clinical diagnostic parameter that can independently assess the severity of epicardial stenosis and microvascular impairment. We believe that it has an immediate appeal for detection of coronary artery disease if validated clinically.

Coronary and Microvascular Physiology During Intra-Aortic Balloon Counterpulsation

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

O índice de resistência microcirculação para o estudo invasivo da microcirculação coronária – descrição e validação de um modelo animal

IntroductionThe index of microcirculatory resistance (IMR) enables/provides quantitative, invasive, and real‐time assessment of coronary microcirculation status. AimsThe primary aim of this study was to validate the assessment of IMR in a large animal model, and the secondary aim was to compare two doses of intracoronary papaverine, 5 and 10 mg, for induction of maximal hyperemia and its evolution over time. MethodsMeasurements of IMR were performed in eight pigs. Mean distal pressure (Pd) and mean transit time (Tmn) were measured at rest and at maximal hyperemia induced with intracoronary papaverine, 5 and 10 mg, and after 2, 5, 8 and 10 minutes. Disruption of the microcirculation was achieved by selective injection of 40‐μm microspheres via a microcatheter in the left anterior descending artery. ResultsIn each animal 14 IMR measurements were made. There were no differences between the two doses of papaverine regarding Pd response and IMR values – 11±4.5 U with 5 mg and 10.6±3 U with 10 mg (p=0.612). The evolution of IMR over time was also similar with the two doses, with significant differences from resting values disappearing after five minutes of intracoronary papaverine administration. IMR increased with disrupted microcirculation in all animals (41±16 U, p=0.001). ConclusionsIMR provides invasive and real‐time assessment of coronary microcirculation. Disruption of the microvascular bed is associated with a significant increase in IMR. A 5‐mg dose of intracoronary papaverine is as effective as a 10‐mg dose in inducing maximal hyperemia. After five minutes of papaverine administration there is no significant difference from resting hemodynamic status.