Michael S. Cunnington

Collateral Donor Artery Physiology and the Influence of a Chronic Total Occlusion on Fractional Flow Reserve

Background—The presence of a concomitant chronic total coronary occlusion (CTO) and a large collateral contribution might alter the fractional flow reserve (FFR) of an interrogated vessel, rendering the FFR unreliable at predicting ischemia should the CTO vessel be revascularized and potentially affecting the decision on optimal revascularization strategy. We tested the hypothesis that donor vessel FFR would significantly change after percutaneous coronary intervention of a concomitant CTO. Methods and Results—In consecutive patients undergoing percutaneous coronary intervention of a CTO, coronary pressure and flow velocity were measured at baseline and hyperemia in proximal and distal segments of both nontarget vessels, before and after percutaneous coronary intervention. Hemodynamics including FFR, absolute coronary flow, and the coronary flow velocity–pressure gradient relation were calculated. After successful percutaneous coronary intervention in 34 of 46 patients, FFR in the predominant donor vessel increased from 0.782 to 0.810 (difference, 0.028 [0.012 to 0.044]; P=0.001). Mean decrease in baseline donor vessel absolute flow adjusted for rate pressure product: 177.5 to 139.9 mL/min (difference −37.6 [−62.6 to −12.6]; P=0.005), mean decrease in hyperemic flow: 306.5 to 272.9 mL/min (difference, −33.5 [−58.7 to −8.3]; P=0.011). Change in predominant donor vessel FFR correlated with angiographic (%) diameter stenosis severity (r=0.44; P=0.009) and was strongly related to stenosis severity measured by the coronary flow velocity–pressure gradient relation (r=0.69; P<0.001). Conclusions—Recanalization of a CTO results in a modest increase in the FFR of the predominant collateral donor vessel associated with a reduction in coronary flow. A larger increase in FFR is associated with greater coronary stenosis severity.

Microvascular dysfunction in the immediate aftermath of chronic total coronary occlusion recanalization

The aim of this study was to compare microvascular resistance under both baseline and hyperemic conditions immediately after percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) with an unobstructed reference vessel in the same patient

Cardiogoniometry Compared to Fractional Flow Reserve at Identifying Physiologically Significant Coronary Stenosis: The CARDIOFLOW Study

Cardiogoniometry (CGM) is method of 3-dimensional electrocardiographic assessment which has been shown to identify patients with angiographically defined, stable coronary artery disease (CAD). However, angiographic evidence of CAD, does not always correlate to physiologically significant disease. The aim of our study was to assess the ability of CGM to detect physiologically significant coronary stenosis defined by fractional flow reserve (FFR). In a tertiary cardiology centre, elective patients with single vessel CAD were enrolled into a prospective double blinded observational study. A baseline CGM recording was performed at rest. A second CGM recording was performed during the FFR procedure, at the time of adenosine induced maximal hyperaemia. A significant CGM result was defined as an automatically calculated ischaemia scoreu2009<u20090u2009and a significant FFR ratio was defined asu2009<u20090.80. Measures of diagnostic performance (including sensitivity and specificity) were calculated for CGM at rest and during maximal hyperaemia. Forty-five patients were included (aged 61.1u2009±u200911.0; 60.0% male), of which eighteen (40%) were found to have significant CAD when assessed by FFR. At rest, CGM yielded a sensitivity of 33.3% and specificity of 63.0%. At maximal hyperaemia the sensitivity and specificity of CGM was 71.4 and 50.0% respectively. The diagnostic performance of CGM to detect physiologically significant stable CAD is poor at rest. Although, the diagnostic performance of CGM improves substantially during maximal hyperaemia, it does not reach sufficient levels of accuracy to be used routinely in clinical practice.

103 The ability of cardiogoniogmetry compared to flow fractional reserve at identifying physiologically significant coronary stenosis: the cardioflow study

Introduction Cardiogoniometry (CGM) is method of 3-dimensional electrocardiographic assessment which has been previously shown to identify patients with angiographically defined, stable coronary artery disease (CAD). However, angiographic evidence of CAD, does not always correlate to physiologically significant CAD. The aim of our study was to assess the ability of CGM to detect physiologically significant coronary stenosis defined by fractional flow reserve (FFR). Methods In a tertiary cardiology centre, patients with single vessel CAD were enrolled into a prospective double blinded observational study. A baseline CGM recording was performed at rest. A second CGM recording was then performed during the FFR procedure, at the time of maximal hyperaemia. A significant CGM result was defined as an automatically calculated ischaemia score<0u2009and a significant FFR ratio defined as<0.8. After enrolment, CGM and FFR results were compared and markers of diagnostic performance (sensitivity, specificity, positive predictive value and negative predictive value) were calculated at rest and during maximal hyperaemia. Statistical agreement between CGM and FFR was calculated by the Kappa statistic. Results Forty patients were included (aged 61.1±11.0; 60.0% male), of which sixteen (40%) were found to have significant CAD when assessed by FFR. Markers of diagnostic performance of CGM are shown in the table. Conclusion The diagnostic performance of CGM to detect physiologically significant stable CAD is poor at rest. Although, the diagnostic performance of CGM improves substantially during maximal hyperaemia, it does not reach sufficient levels of accuracy to be used routinely in clinical practice. Abstract 103 Table 1 CGM at rest (n= 40) CGM during maximal hyperaemia (n= 40) Sensitivity 31.3% 68.8% Specificity 62.5% 54.2% Positive predictive value 35.7% 50.0% Negative predictive value 57.7% 72.2% Kappa statistic for agreement −0.06, p=0.64 0.21, p=0.15

TCT-220 Is Inhibition of Platelet Aggregation by Endogenous Endothelial Platelet Antagonists Enhanced by Oral Ticagrelor Mediated P2Y12 Blockade in Patients With Coronary Artery Disease?

P2Y12 receptor antagonists inhibit ADP-induced platelet aggregation and have an important role in the managment of acute coronary syndromes. Nitric oxide and prostacyclin (PGI2) are endogenous endothelial inhibitors of platelet activation. This study evaluated the interaction between P2Y12

Biomarkers of coronary endothelial health: correlation with invasive measures of collateral function, flow and resistance in chronically occluded coronary arteries and the effect of recanalization.

ObjectivesIn the presence of a chronically occluded coronary artery, the collateral circulation matures by a process of arteriogenesis; however, there is considerable variation between individuals in the functional capacity of that collateral network. This could be explained by differences in endothelial health and function. We aimed to examine the relationship between the functional extent of collateralization and levels of biomarkers that have been shown to relate to endothelial health. MethodsWe measured four potential biomarkers of endothelial health in 34 patients with mature collateral networks who underwent a successful percutaneous coronary intervention (PCI) for a chronic total coronary occlusion (CTO) before PCI and 6–8 weeks after PCI, and examined the relationship of biomarker levels with physiological measures of collateralization. ResultsWe did not find a significant change in the systemic levels of sICAM-1, sE-selectin, microparticles or tissue factor 6–8 weeks after PCI. We did find an association between estimated retrograde collateral flow before CTO recanalization and lower levels of sICAM-1 (r=0.39, P=0.026), sE-selectin (r=0.48, P=0.005) and microparticles (r=0.38, P=0.03). ConclusionRecanalization of a CTO and resultant regression of a mature collateral circulation do not alter systemic levels of sICAM-1, sE-selectin, microparticles or tissue factor. The identified relationship of retrograde collateral flow with sICAM-1, sE-selectin and microparticles is likely to represent an association with an ability to develop collaterals rather than their presence and extent.

Response to Letter Regarding Article, “Collateral Donor Artery Physiology and the Influence of a Chronic Total Occlusion on Fractional Flow Reserve”

We appreciate the interest and comments from Dr Saito1 on our article.2 It is gratifying that some of the findings of their in vitro work have been borne out by our results. Many of their comments have already been addressed in the article.2 We agree that the mass of collateral dependent myocardium and extent of collateralization are likely to be important factors in the extent of change in donor vessel fractional flow reserve (FFR) …

72 Non-Target Vessel Haemodynamics Prior to Angioplasty of Chronic Total Coronary Occlusions, is There Really Substrate for an Important Change in Haemodynamic Lesion Severity?

Introduction Fractional flow reserve (FFR) guided angioplasty has been shown to have a beneficial effect on clinical outcome in patients with multi-vessel coronary disease. However, multi-vessel disease is frequently accompanied by a chronic total occlusion (CTO). We have limited understanding of the effect of the donation of a collateral supply to collateral dependent myocardium on the FFR. Marked changes in non-target vessel FFR post recanalisation of CTOs have been reported, but the consistency of this phenomenon remains uncertain and changes in haemodynamic indices immediately post-angioplasty might be confounded by the effect of the vessel trauma of angioplasty on the microvasculature. If the phenomenon is consistent, we might expect haemodynamics in a vessel donating collaterals to a CTO to be dependent on the extent of angiographic collateral flow originating from it. Methods Prior to CTO angioplasty in 22 patients, simultaneous pressure and flow were measured at rest and during hyperaemia in the distal and proximal segment of each non-target vessel. Absolute coronary flow, coronary flow reserve, hyperaemic microvascular resistance and fractional flow reserve were calculated. Blinded to haemodynamic measurements, the major collateral donor vessel was selected and each vessel was graded by the size of the largest collateral branch which originated from it by collateral connexion (CC) grade (0 = no continuous connexion, 1 = threadlike connexion, 2 = side branch like connexion). Haemodynamic measurements were compared between the major and minor collateral donor vessels using a paired t-test. Results All patients had right dominant coronary anatomy. The target vessel was the left anterior descending artery (LAD) in 9 patients, circumflex artery (LCx) in 2 and right coronary artery (RCA) in 11. All target vessels were filled by a modified Rentrop grade of >2 (2 n = 12, 3 n = 10). Angiographic characteristics are listed in Table 1 and haemodynamic measurements are listed in Table 2. In spite of clearly increased angiographic collateral donation, we did not identify any associated significant difference between haemodynamic indices. Abstract 72 Table 1 Minor Collateral Donorn Major Collateral Donorn CC class (0,1,2) 2 3 11 1 8 11 0 11 0 Vessel LAD 7 6 LCx 15 5 RCA 0 11 Abstract 72 Table 2 Minor Collateral Donor Mean(SD) Major Collateral Donor Mean(SD) Difference (95% CI, p-value) Donor Vessel Duke Jeopardy Score 3.27(1.91) 4.09(1.44) 0.75 (-0.61-2.11, p =. 27) Maximum diameter stenosis (%) 36.9(13.6) 32.6(14.9) -4.3 (-11.5-3.0, p =. 23) Fractional Flow Reserve 0.82(0.11) 0.80(0.10) -0.02 (-0.07-0.04, p =. 55) Hyperaemic Microvascular Resistance (mmHg/cm/s) 2.19(0.87) 2.01(0.95) -0.18 (-0.74-0.38, p =. 51) Coronary Flow Reserve 2.11(0.61) 2.13(0.78) -0.03 (-0.36-0.42, p =. 88) Hyperaemic Absolute Flow (ml/min) 168.8(97.7) 189.4(126.9) 20.6 (-30.7-72.0,p =. 41) Crude Resting Absolute Flow (ml/min) 79.5(43.0) 86.0(37.1) 6.4 (-13.6-26.5,p =. 51) Resting Absolute Flow adjustedfor Rate Pressure Product (ml/min) 105.8(61.3) 111.6(58.7) 5.8 (-21.0-32.6, p =. 66) Conclusion The mechanism for a large rise in non-target vessel FFR post CTO angioplasty must involve one or more of a fall in absolute flow, a fall in coronary flow reserve or an increase in microvascular resistance. One would expect that change to move towards the norm for a vessel donating fewer collateral branches. The absence of a difference in any of these haemodynamic indices between paired non-target vessels with differing CC grades (and therefore different extents of collateral ‘donation’) would suggest thatthe large changes in FFR which have been reported might only represent a publication biassed measurement extreme, rather than the rule.