Intra-arterial Fractional Flow Reserve Measurements Provide an Objective Assessment of the Functional Significance of Peripheral Arterial Stenoses.

OBJECTIVE: Peripheral arterial stenoses (PAS) are commonly investigated with duplex ultrasound (DUS) and angiography, but these are not functional tests. Fractional flow reserve (FFR), a pressure based index, functionally assesses the ischaemic potential of coronary stenoses, but its utility in PAS is unknown. FFR in the peripheral vasculature in patients with limb ischaemia was investigated. METHODS: Patients scheduled for angioplasty and or stenting of isolated iliac and superficial femoral artery stenoses were recruited. Resting trans-lesional pressure gradient (Pd/Pa) and FFR were measured after adenosine provoked hyperaemia using an intra-arterial 0.014 inch flow and pressure sensing wire (ComboWire XT, Philips). Prior to revascularisation, exercise ABPI (eABPI) and DUS derived peak systolic velocity ratio (PSVR) of the index lesion were determined. Calf muscle oxygenation was measured using blood oxygenation level dependent cardiovascular magnetic resonance prior to and after revascularisation. RESULTS: Forty-one patients (32, 78%, male, mean age 65 ± 11 years) with 61 stenoses (iliac 32; femoral 29) were studied. For lesions < 80% stenosis, resting Pd/Pa was not influenced by the degree of stenosis (p = .074); however, FFR was discriminatory, decreasing as the severity of stenosis increased (p = .019). An FFR of < 0.60 was associated with critical limb threatening ischaemia (area under the curve [AUC] 0.87; 95% CI 0.75 - 0.95), in this study performing better than angiographic % stenosis (0.79; 0.63 - 0.89), eABPI (0.72; 0.57 - 0.83), and PSVR (0.65; 0.51 - 0.78). FFR correlated strongly with calf oxygenation (rho, 0.76; p < .001). A greater increase in FFR signalled resolution of symptoms and signs (ΔFFR 0.25 ± 0.15 vs. 0.13 ± 0.09; p = .009) and a post-angioplasty and stenting FFR of > 0.74 predicted successful revascularisation (combined sensitivity and specificity of 95%; AUC 0.98; 0.91 - 1.00). CONCLUSION: This pilot study demonstrates that FFR can objectively measure the functional significance of PAS that compares favourably with visual and DUS based assessments. Its role as a quality control adjunct that confirms optimal vessel patency after angioplasty and or stenting also merits further investigation.

Coronary Microvascular Dysfunction Is Associated With Myocardial Ischemia and Abnormal Coronary Perfusion During Exercise.

BACKGROUND: Coronary microvascular dysfunction (MVD) is defined by impaired flow augmentation in response to a pharmacological vasodilator in the presence of nonobstructive coronary artery disease. It is unknown whether diminished coronary vasodilator response correlates with abnormal exercise physiology or inducible myocardial ischemia. METHODS: Patients with angina and nonobstructive coronary artery disease had simultaneous coronary pressure and flow velocity measured using a dual sensor-tipped guidewire during rest, supine bicycle exercise, and adenosine-mediated hyperemia. Microvascular resistance (MR) was calculated as coronary pressure divided by flow velocity. Wave intensity analysis quantified the proportion of accelerating wave energy (perfusion efficiency). Global myocardial blood flow and subendocardial:subepicardial perfusion ratio were quantified using 3-Tesla cardiac magnetic resonance imaging during hyperemia and rest; inducible ischemia was defined as hyperemic subendocardial:subepicardial perfusion ratio <1.0. Patients were classified as having MVD if coronary flow reserve <2.5 and controls if coronary flow reserve ≥2.5, with researchers blinded to the classification. RESULTS: Eighty-five patients were enrolled (78% female, 57±10 years), 45 (53%) were classified as having MVD. Of the MVD group, 82% had inducible ischemia compared with 22% of controls (P<0.001); global myocardial perfusion reserve was 2.01±0.41 and 2.68±0.49 (P<0.001). In controls, coronary perfusion efficiency improved from rest to exercise and was unchanged during hyperemia (59±11% vs 65±14% vs 57±18%; P=0.02 and P=0.14). In contrast, perfusion efficiency decreased during both forms of stress in MVD (61±12 vs 44±10 vs 42±11%; both P<0.001). Among patients with a coronary flow reserve <2.5, 62% had functional MVD, with normal minimal MR (hyperemic MR<2.5 mmHg/cm/s), and 38% had structural MVD with elevated hyperemic MR. Resting MR was lower in those with functional MVD (4.2±1.0 mmHg/cm/s) than in those with structural MVD (6.9±1.7 mmHg/cm/s) or controls (7.3±2.2 mmHg/cm/s; both P<0.001). During exercise, the structural group had a higher systolic blood pressure (188±25 mmHg) than did those with functional MVD (161±27 mmHg; P=0.004) and controls (156±30 mmHg; P<0.001). Functional and structural MVD had similar stress myocardial perfusion and exercise perfusion efficiency values. CONCLUSION: In patients with angina and nonobstructive coronary artery disease, diminished coronary flow reserve characterizes a cohort with inducible ischemia and a maladaptive physiological response to exercise. We have identified 2 endotypes of MVD with distinctive systemic vascular responses to exercise; whether endotypes have a different prognosis or require different treatments merits further investigation.

Resting Coronary Flow Varies With Normal Cardiac Catheter Laboratory Stimuli.

BACKGROUND: Growing evidence supports physiology-guided revascularization, with Fractional Flow Reserve (FFR) the most commonly used invasive measure of coronary blood flow impairment at the time of diagnostic angiography. Recently, there has been growing interest in stenosis severity indices measured at rest, such as Instantaneous Wave Free Ratio (iFR) and the ratio of distal coronary to aortic pressure at rest (resting Pd/Pa). Their reliability may, theoretically, be more susceptible to changes in microvascular tone and coronary flow. This study aimed to assess variability of resting coronary flow with normal catheter laboratory stimuli. METHODS: Simultaneous intracoronary pressure (Pd) and Doppler Average Peak Flow Velocity (APV) recordings were made at rest and following the verbal warning preceding an intravenous adenosine infusion. RESULTS: 72 patients undergoing elective angiography were recruited (mean age 62 years, 52.7% male) with a wide range of coronary artery disease severity (FFR 0.86 ±â€¯0.09). Average peak flow velocity varied significantly between measurements at rest and just prior to commencement of adenosine, with a mean variation of 10.2% (17.82 ±â€¯9.41 cm/s vs. 19.63 ±â€¯10.44 cm/s, p < 0.001) with an accompanying significant drop in microvascular resistance (6.27 ±â€¯2.73 mm Hg·cm-1·s-1 vs. 5.8 ±â€¯2.92 mm Hg·cm-1·s-1, p < 0.001). These changes occurred without significant change in systemic hemodynamic measures. Whilst there was a trend for an associated change in the resting indices, Pd/Pa and iFR, this was statistically and clinically not significant (0.92 ±â€¯0.08 vs. 0.92 ±â€¯0.08, p = 0.110; and 0.90 ±â€¯0.11 vs. 0.89 ±â€¯0.12, p = 0.073). CONCLUSION: Resting coronary flow and microvascular resistance vary significantly with normal catheter laboratory stimuli, such as simple warnings. The clinical impact of these observed changes on indices of stenosis severity, particularly those measured at rest, needs further assessment within larger cohorts.

Changes in contractility determine coronary haemodynamics in dyssynchronous left ventricular heart failure, not vice versa.

BACKGROUND: Biventricular pacing has been shown to increase both cardiac contractility and coronary flow acutely but the causal relationship is unclear. We hypothesised that changes in coronary flow are secondary to changes in cardiac contractility. We sought to examine this relationship by modulating coronary flow and cardiac contractility. METHODS: Contractility and lusitropy were altered by varying the location of pacing in 8 patients. Coronary autoregulation was transiently disabled with intracoronary adenosine. Simultaneous coronary flow velocity, coronary pressure and left ventricular pressure data were measured in the different pacing settings with and without hyperaemia and wave intensity analysis performed. RESULTS: Multisite pacing was effective at altering left ventricular contractility and lusitropy (pos. dp/dtmax -13% to +10% and neg. dp/dtmax -15% to +17% compared to baseline). Intracoronary adenosine decreased microvascular resistance (362.5 mm Hg/s/m to 156.7 mm Hg/s/m, p < 0.001) and increased LAD flow velocity (22 cm/s vs 45 cm/s, p < 0.001) but did not acutely change contractility or lusitropy. The magnitude of the dominant accelerating wave, the Backward Expansion Wave, was proportional to the degree of contractility as well as lusitropy (r = 0.47, p < 0.01 and r = -0.50, p < 0.01). Perfusion efficiency (the proportion of accelerating waves) increased at hyperaemia (76% rest vs 81% hyperaemia, p = 0.04). Perfusion efficiency correlated with contractility and lusitropy at rest (r = 0.43 & -0.50 respectively, p = 0.01) and hyperaemia (r = 0.59 & -0.6, p < 0.01). CONCLUSIONS: Acutely increasing coronary flow with adenosine in patients with systolic heart failure does not increase contractility. Changes in coronary flow with biventricular pacing are likely to be a consequence of enhanced cardiac contractility from resynchronization and not vice versa.

Is heart rate response a reliable marker of adenosine-induced coronary hyperemia?

Introduction Growing evidence supports ischemia-guided management of chest pain, with invasive and non-invasive tests reliant upon achieving adenosine-induced coronary hyperemia (defined as increased blood flow to an organ's perfusion bed). In the non-invasive setting, surrogate markers of hyperemia, such as increases in heart rate, are often used, despite not being formally validated. We tested whether heart rate and other non-invasive indices are reliable markers of coronary hyperemia. Methods The first part involved Doppler flow-based validation of the best pressure-wire markers of hyperemia in 53 patients. Subsequently, using these validated pressure-derived parameters, 265 pressure-wire traces were analysed to determine whether heart rate and other non-invasive parameters correlated with hyperemia. Results In the flow derivation cohort, the best determinant of hyperemia came from having 2 out of 3 of: (1) Ventriculisation of the distal pressure waveform, (2) disappearance of distal dicrotic pressure notch, (3) separation of mean aortic and distal pressures. Within the 244 patients demonstrating hyperemia, non-invasive markers of hyperemia, such as change in heart rate (p = 0.77), blood pressure (p = 0.60) and rate-pressure product (p = 0.86), were poor correlates of coronary hyperemia, with only 37.3% demonstrating a ≥ 10% increase in heart rate that is commonly used to adjudge adenosine-induced hyperemia in the non-invasive setting. Conclusions We demonstrate, by correlation with Doppler-flow data, a validated method of identifying coronary hyperemia within the catheter laboratory using the pressure-wire. We subsequently show that non-invasive parameters, such as heart rate change, are poor predictors of coronary hyperemia during stress imaging protocols that rely upon achieving adenosine-induced hyperemia.

The impact of discussing preoperative fasting with patients.

Patients awaiting surgery are often fasted preoperatively well in excess of the recommended fasting times. Educated perioperative practitioners were asked to discuss preoperative starvation with patients. Preoperative starvation period for clear fluids was significantly reduced from a mean of 8 hours 30 minutes in the original audit, to 6 hours 10 minutes in this study of 113 patients (p < 0.001). Improving patient understanding of preoperative fasting can increase compliance with fasting recommendations.

Preoperative starvation in elective general surgery.

OBJECTIVE: Study preoperative fasting times of adult elective surgical patients. METHODS: Fasting times for food and clear fluids, and the information used by patients to decide when to start fasting were studied. RESULTS: Among 200 patients, median fasting times were 2-4 times the guideline recommendations. Most patients used hospital written instructions but many started fasting substantially earlier than the instructions stipulated. DISCUSSION: Improved communication with patients could improve fasting times.