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10 10 Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus Warfarin in Patients with Atrial Fibrillation. N. Engl. J. Med. 2013, 369 (22), 2093–2104.
11 11 Kandzari DE, Mauri L, Koolen JJ, et al. Ultrathin, bioresorbable polymer sirolimus‐eluting stents versus thin, durable polymer everolimus‐eluting stents in patients undergoing coronary revascularisation (BIOFLOW V): a randomised trial. The Lancet 2017, 390 (10105), 1843–1852.
12 12 Windecker S, Haude M, Neumann FJ, et al. Comparison of a novel biodegradable polymer sirolimus‐eluting stent with a durable polymer everolimus‐eluting stent: Results of the randomized BIOFLOW‐II trial. Circ. Cardiovasc. Interv. 2015, 8 (2).
13 13 Saito S, Tölg R, Witzenbichler B, et al. BIOFLOW‐IV, a randomised, intercontinental, multicentre study to assess the safety and effectiveness of the Orsiro sirolimus‐eluting stent in the treatment of subjects with de novo coronary artery lesions: Primary outcome target vessel failure at 12 months. EuroIntervention 2019, 15 (11), E1006–E1013.
14 14 Reardon MJ, Van Mieghem NM, Popma JJ, et al. Surgical or Transcatheter Aortic‐Valve Replacement in Intermediate‐Risk Patients. N. Engl. J. Med. 2017, 376 (14), 1321–1331.
15 15 Van Mieghem NM, Popma JJ, Deeb GM, et al. Complete 2‐Year Results Confirm Bayesian Analysis of the SURTAVI Trial. JACC Cardiovasc. Interv.2020, 13 (3), 323–331.
CHAPTER 7
Physiologic Assessment and Guidance in the Cardiac Catheterization Laboratory
Allen Jeremias, Sukhjinder Nijjer, Justin Davies, and Carlo DiMario
Why to use physiology
The purpose of angiography and revascularization is to improve blood flow and thereby reduce myocardial ischemia. However, angiographic assessment of coronary stenosis has limited value in determining the degree of ischemia imposed and the viability of the subtended myocardium. Angiographic parameters also have limited predictive value of clinical outcome measures, and often, even mild and moderate stenoses can be important and underappreciated [1]. Furthermore, while many patients undergo non‐invasive functional testing prior to angiography, the findings can be at odds with the coronary appearances.
International guidelines recommend coronary physiology for angiographically moderate coronary stenoses (diameter stenosis 50–90%) where non‐invasive functional information is lacking [2,3]. Additionally, in many cases, invasive physiology provides additive information over and above non‐invasive functional testing. Intracoronary pressure wires offer an established and rapid solution for assessing the significance of coronary disease, while also assessing myocardial viability and offering insights into the best treatment strategies [4]. Pressure wires provide greater spatial localization of ischemia, not only to the vessel but also to the lesion level. This is particularly pertinent in multi‐vessel disease where relative perfusion changes can be matched leading to underestimation of ischemia.
There are complex pressure‐flow relationships that determine the measurable pressure gradient across a stenosis (Figures 7.1–7.3) [5], however these can be simplified to produce pressure‐only measurements that are simple to use in the cardiac catheterization laboratory. Multiple research studies have validated these pressure‐only measures of coronary physiology against non‐invasive ischemia testing [6–10] and major international outcomes studies have demonstrated that stenoses of all severities can be managed efficiently by pressure‐only indices such as instantaneous wave‐free ratio (iFR) or Fractional Flow Reserve (FFR) (Figure 7.4) [11–18]. These are now included in international guidelines both in North America and Europe [2,19–21]. Safe deferral of lesions that are non‐ischemic will reduce stent related events. In patients with confirmed ischemia, the pressure wire can determine interventional approaches and, following PCI, can be assessed to validate the hemodynamic success of the intervention [22,23] and identify those at higher risk of later events [24–38].
Figure 7.1 Behavior of resting and hyperemic flow in relation to stenosis severity. Resting flow is remarkably preserved despite worsening stenosis severity – upto 85% diameter stenosis by formal measurement. Hyperemic flow starts falling when stenoses are 30% but falls significantly once stenoses are 50%. Adapted from Gould, Lipscomb and Hamilton 1974.
Figure 7.2 The flow of blood across a coronary stenosis. Pressure gradients across stenoses are due to both viscous and separation losses. Pressure is lost owing to viscous friction along the stenosis (Poiseuille’s law). Flow also accelerates as it passess through the narrowed segment, causing pressure loss as pressure is converted into kinetic energy (Bernoulli’s law). Flow separation and the formation of eddies prevent complete pressure recovery at the exit of the stenosis. Measurement of intracoronary haemodynamics includes proximal perfusion pressure (Pa), coronary pressure and flow velocity distal to the stenosis (Pd and Vd, respectively), and the venous pressure (Pv), which is typically assumed to be negligible. ΔP is the difference between Pd and Pa. Normal diameter (Dn), stenosis diameter (Ds), proximal velocity (Vn), and stenosis velocity (Vs) are indicated. From van de Hoef et al (2013).
Figure 7.3 The curvilinear relationship between pressure and flow is unique for each stenosis. Pressure drop across a stenosis is determined by ΔP = Fv + Sv2 (where F is friction losses and S is separation losses). This produces curvilinear relationship unique to any stenosis; the steepness of the curve reflects the severity of the lesion (eg. Reference vessel, stenosis A, B, C). Increasing the flow velocity across a stenosis will alter the pressure gradient observed. In stenosis A, there is a large resting pressure gradient that is accentuated during hyperemia with little increase in flow. In stenosis B, increasing the concentration of hyperemic agent (depicted as arrows) will increase flow velocity to generate a larger gradient; since resting flow is unchanged, CFR and FFR will move in opposite directions. In even milder stenoses, such as A, large escalations of flow velocity from a relatively low resting value could create a large pressure gradient; in these situations, pressure does not reflect the change in flow. Adapted from van de Hoef et al (2013).
