Fractional Flow Reserve/ Instantaneous Wave-Free Ratio Discordance in Angiographically Intermediate Coronary Stenoses: An Analysis Using Doppler-Derived Coronary Flow Measurements

OBJECTIVES 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). BACKGROUND 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. METHODS Baseline and hyperemic coronary flow velocity and coronary flow reserve (CFR) were compared across 5 vessel groups: FFRþ/iFRþ (108 vessels, n 1�4 91), FFR–/iFRþ (28 vessels, n 1�4 24), FFRþ/iFR– (22 vessels, n 1�4 22), FFR–/iFR– (208 vessels, n 1�4 154), and an unobstructed vessel group (201 vessels, n 1�4 153), in a post hoc analysis of the largest combined pressure and Doppler flow velocity registry (IDEAL [Iberian-Dutch-English] collaborators study). RESULTS FFRdisagreedwithiFRin14%(50of366).Baselineflowvelocitywassimilaracrossall5vesselgroups,includingthe unobstructed vessel group (p 1�4 0.34 for variance). In FFRþ/iFR– discordants, hyperemic flow velocity and CFR were similar to both FFR–/iFR– and unobstructed groups; 37.6 (interquartile range [IQR]: 26.1 to 50.4) cm/s vs. 40.0 [IQR: 29.7 to 52.3] cm/s and 42.2 [IQR: 33.8 to 53.2] cm/s and CFR 2.36 [IQR: 1.93 to 2.81] vs. 2.41 [IQR: 1.84 to 2.94] and 2.50 [IQR: 2.11 to 3.17], respectively (p > 0.05 for all). In FFR–/iFRþ discordants, hyperemic flow velocity, and CFR were similar to the FFRþ/iFRþ group; 28.2 (IQR: 20.5 to 39.7) cm/s versus 23.5 (IQR: 16.4 to 34.9) cm/s and CFR 1.44 (IQR: 1.29 to 1.85) versus 1.39 (IQR: 1.06 to 1.88), respectively (p > 0.05 for all). CONCLUSIONS FFR/iFR disagreement was explained by differences in hyperemic coronary flow velocity. Furthermore, coronary stenoses classified as FFRþ/iFR– demonstrated similar coronary flow characteristics to angiographically unobstructed vessels

Comprehensive assessment of ischaemic heart disease with invasive pressure and flow measurements

This thesis sought to provide some novel insights on the complexity of the invasive assessment of ischaemic heart disease (IHD). Undoubtedly, focal coronary stenosis play a pivotal role in the genesis and prognosis of this entity. Furthermore, therapy guided by the functional assessment of such focal stenosis has shown to improve patient outcomes, as compared to therapy guided by their angiographic appearance alone. However, wealth of consistent data currently show how does this stenosiscentred diagnostic and therapeutical approach, relying only on the fractional flow reserve (FFR), is not perfect, since many patients with non-physiologically significant epicardial stenosis still suffer from angina and cardiovascular events, and conversely, a significant proportion of patients with FFR-significant stenosis do well at medium term. These leaves, consequently, room for further refinement. This thesis pursued to contribute to this refinement, and for these, followed a two-fold pathway. Firstly, it explored the diagnostic consequences of a simpler physiological approach, focused only on the pressure-lone assessment of focal stenosis under non-hyperaemic conditions. Secondly, it explored a more complex-yet comprehensive approach, that included, in addition to the FFR, the available indices to explore coronary microcirculation. In the following paragraphs, the salient findings of the different parts of the present thesis will be discussed in perspective

Coronary pressure and flow relationships in humans: phasic analysis of normal and pathological vessels and the implications for stenosis assessment: a report from the Iberian-Dutch-English (IDEAL) collaborators

Our understanding of human coronary physiological behaviour is derived from animal models. We sought to describe physiological behaviour across a large collection of invasive pressure and flow velocity measurements, to provide a better understanding of the relationships between these physiological parameters and to evaluate the rationale for resting stenosis assessment.Five hundred and sixty-seven simultaneous intracoronary pressure and flow velocity assessments from 301 patients were analysed for coronary flow velocity, trans-stenotic pressure gradient (TG), and microvascular resistance (MVR). Measurements were made during baseline and hyperaemic conditions. The whole cardiac cycle and the diastolic wave-free period were assessed. Stenoses were assessed according to fractional flow reserve (FFR) and quantitative coronary angiography DS%. With progressive worsening of stenoses, from unobstructed angiographic normal vessels to those with FFR ≤ 0.50, hyperaemic flow falls significantly from 45 to 19 cm/s, Ptrend 0.05 for all). Trans-stenotic pressure gradient rose with stenosis severity for both rest and hyperaemic measures (Ptrend < 0.001 for both). Microvascular resistance declines with stenosis severity under resting conditions (Ptrend < 0.001), but was unchanged at hyperaemia (2.3 ± 1.1 mmHg/cm/s; Ptrend = 0.19).With progressive stenosis severity, TG rises. However, while hyperaemic flow falls significantly, resting coronary flow is maintained by compensatory reduction of MVR, demonstrating coronary auto-regulation. These data support the translation of coronary physiological concepts derived from animals to patients with coronary artery disease and furthermore, suggest that resting pressure indices can be used to detect the haemodynamic significance of coronary artery stenoses

Pressure-derived estimations of coronary flow reserve are inferior to flow-derived coronary flow reserve as diagnostic and risk stratification tools

Background: Pressure-derived coronary flow reserve (CFRpres) and pressure-bounded CFR (CFRpb) enable simple estimation of CFR from routine pressure measurements, but have been inadequately validated. We sought to compare CFRpres and CFRpb against flow-derived CFR (CFRflow) in terms of diagnostic accuracy, as well as regarding their comparative prognostic relevance. Methods: We evaluated 453 intermediate coronary lesions with intracoronary pressure and flow measurements. CFR was defined as hyperemic flow/baseline flow. The lower bound (CFRpres) and upper bound of CFRpb were defined as √[(ΔPhyperemia) / (ΔPrest)] and [(ΔPhyperemia) / (ΔPrest)], respectively. Long-term follow-up (median: 11.8-years) was performed in 153 lesions deferred from treatment to document the occurrence of major adverse cardiac events (MACE) defined as a composite of cardiac death, myocardial infarction and target vessel revascularization. CFR < 2.0 was considered abnormal. Results: CFRpb was normal or abnormal in 56.7% of stenoses, and indeterminate in 43.3% of stenoses. There was a poor diagnostic agreement between CFRpres and CFRpb with CFRflow (overall agreement: 45.5% and 71.6% of vessels, respectively). There was equivalent risk for long-term MACE for lesions with abnormal versus normal CFRpres (Breslow p = 0.562), whereas vessels with abnormal CFRflow were significantly associated with increased long-term MACE (Breslow p < 0.001). For vessels where CFRpb was abnormal or normal, there was equivalent risk for long-term MACE for vessels with abnormal versus normal CFRpb (Breslow p = 0.194), whereas vessels with abnormal CFRflow were associated with increased MACE rates over time (Breslow p < 0.001). Conclusions: Pressure-derived estimations of CFR poorly agree with flow-derived measurements of CFR, which may explain the inferior association with long-term MACE as compared to flow-derived CFR