Effects of haemodynamically atrio-ventricular optimized His bundle pacing on heart failure symptoms and exercise capacity: the His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) randomized, double-blind, cross-over trial.

AIMS: Excessive prolongation of PR interval impairs coupling of atrio-ventricular (AV) contraction, which reduces left ventricular pre-load and stroke volume, and worsens symptoms. His bundle pacing allows AV delay shortening while maintaining normal ventricular activation. HOPE-HF evaluated whether AV optimized His pacing is preferable to no-pacing, in a double-blind cross-over fashion, in patients with heart failure, left ventricular ejection fraction (LVEF) ≤40%, PR interval ≥200 ms and either QRS ≤140 ms or right bundle branch block. METHODS AND RESULTS: Patients had atrial and His bundle leads implanted (and an implantable cardioverter-defibrillator lead if clinically indicated) and were randomized to 6 months of pacing and 6 months of no-pacing utilizing a cross-over design. The primary outcome was peak oxygen uptake during symptom-limited exercise. Quality of life, LVEF and patients' holistic symptomatic preference between arms were secondary outcomes. Overall, 167 patients were randomized: 90% men, 69 ± 10 years, QRS duration 124 ± 26 ms, PR interval 249 ± 59 ms, LVEF 33 ± 9%. Neither peak oxygen uptake (+0.25 ml/kg/min, 95% confidence interval [CI] -0.23 to +0.73, p = 0.3) nor LVEF (+0.5%, 95% CI -0.7 to 1.6, p = 0.4) changed with pacing but Minnesota Living with Heart Failure quality of life improved significantly (-3.7, 95% CI -7.1 to -0.3, p = 0.03). Seventy-six percent of patients preferred His bundle pacing-on and 24% pacing-off (p < 0.0001). CONCLUSION: His bundle pacing did not increase peak oxygen uptake but, under double-blind conditions, significantly improved quality of life and was symptomatically preferred by the clear majority of patients. Ventricular pacing delivered via the His bundle did not adversely impact ventricular function during the 6 months.

Comparing invasive hemodynamic responses in adenosine hyperemia versus physical exercise stress in chronic coronary syndromes.

OBJECTIVES: Adenosine hyperemia is an integral component of the physiological assessment of obstructive coronary artery disease in patients with chronic coronary syndrome (CCS). The aim of this study was to compare systemic, coronary and microcirculatory hemodynamics between intravenous (IV) adenosine hyperemia versus physical exercise stress in patients with CCS and coronary stenosis. METHODS: Twenty-three patients (mean age, 60.6 ± 8.1 years) with CCS and single-vessel coronary stenosis underwent cardiac catheterization. Continuous trans-stenotic coronary pressure-flow measurements were performed during: i) IV adenosine hyperemia, and ii) physical exercise using a catheter-table-mounted supine ergometer. Systemic, coronary and microcirculatory hemodynamic responses were compared between IV adenosine and exercise stimuli. RESULTS: Mean stenosis diameter was 74.6% ± 10.4. Median (interquartile range) FFR was 0.54 (0.44-0.72). At adenosine hyperemia versus exercise stress, mean aortic pressure (Pa, 91 ± 16 mmHg vs 99 ± 15 mmHg, p < 0.0001), distal coronary pressure (Pd, 58 ± 21 mmHg vs 69 ± 24 mmHg, p < 0.0001), trans-stenotic pressure ratio (Pd/Pa, 0.63 ± 0.18 vs 0.69 ± 0.19, p < 0.0001), microvascular resistance (MR, 2.9 ± 2.2 mmHg.cm-1.sec-1 vs 4.2 ± 1.7 mmHg.cm-1.sec-1, p = 0.001), heart rate (HR, 80 ± 15 bpm vs 85 ± 21 bpm, p = 0.02) and rate-pressure product (RPP, 7522 ± 2335 vs 9077 ± 3200, p = 0.0001) were all lower. Conversely, coronary flow velocity (APV, 23.7 ± 9.5 cm/s vs 18.5 ± 6.8 cm/s, p = 0.02) was higher. Additionally, temporal changes in Pa, Pd, Pd/Pa, MR, HR, RPP and APV during IV adenosine hyperemia versus exercise were all significantly different (p < 0.05 for all). CONCLUSIONS: In patients with CCS and coronary stenosis, invasive hemodynamic responses differed markedly between IV adenosine hyperemia versus physical exercise stress. These differences were observed across systemic, coronary and microcirculatory hemodynamics.

COVID-19 and its impact on the cardiovascular system.

OBJECTIVES: The clinical impact of SARS-CoV-2 has varied across countries with varying cardiovascular manifestations. We review the cardiac presentations, in-hospital outcomes and development of cardiovascular complications in the initial cohort of SARS-CoV-2 positive patients at Imperial College Healthcare National Health Service Trust, UK. METHODS: We retrospectively analysed 498 COVID-19 positive adult admissions to our institute from 7 March to 7 April 2020. Patient data were collected for baseline demographics, comorbidities and in-hospital outcomes, especially relating to cardiovascular intervention. RESULTS: Mean age was 67.4±16.1 years and 62.2% (n=310) were male. 64.1% (n=319) of our cohort had underlying cardiovascular disease (CVD) with 53.4% (n=266) having hypertension. 43.2%(n=215) developed acute myocardial injury. Mortality was significantly increased in those patients with myocardial injury (47.4% vs 18.4%, p<0.001). Only four COVID-19 patients had invasive coronary angiography, two underwent percutaneous coronary intervention and one required a permanent pacemaker implantation. 7.0% (n=35) of patients had an inpatient echocardiogram. Acute myocardial injury (OR 2.39, 95% CI 1.31 to 4.40, p=0.005) and history of hypertension (OR 1.88, 95% CI 1.01 to 3.55, p=0.049) approximately doubled the odds of in-hospital mortality in patients admitted with COVID-19 after other variables had been controlled for. CONCLUSION: Hypertension, pre-existing CVD and acute myocardial injury were associated with increased in-hospital mortality in our cohort of COVID-19 patients. However, only a low number of patients required invasive cardiac intervention.

Management of Acute Coronary Syndromes During the Coronavirus Disease 2019 Pandemic: Deviations from Guidelines and Pragmatic Considerations for Patients and Healthcare Workers.

Coronavirus disease 2019 (COVID-19) is forcing cardiology departments to rapidly adapt existing clinical guidelines to a new reality and this is especially the case for acute coronary syndrome pathways. In this focused review, the authors discuss how COVID-19 is affecting acute cardiology care and propose pragmatic guideline modifications for the diagnosis and management of acute coronary syndrome patients, particularly around the appropriateness of invasive strategies as well as length of hospital stay. The authors also discuss the use of personal protective equipment for healthcare workers in cardiology. Based on shared global experiences and growing peer-reviewed literature, it is possible to put in place modified acute coronary syndrome treatment pathways to offer safe pragmatic decisions to patients and staff.

Relative clinical value of coronary computed tomography and stress echocardiography-guided management of stable chest pain patients: a propensity-matched analysis.

AIMS: The European Society of Cardiology recommends coronary computed tomography (CCT) for the assessment of low-risk patients with suspected stable angina. We aimed to assess in a real-life setting the relative clinical value of stress echocardiography (SE)- and CCT-guided management in this population. METHODS AND RESULTS: Patients with stable chest pain and no prior history of coronary artery disease (CAD) who underwent CCT or SE as the initial investigative strategy were propensity-matched (990 patients each group-age: 59 ± 13.2 years, males: 47.9%) to account for baseline differences in cardiovascular risk factors. Inconclusive tests were 6% vs. 3% (P < 0.005) in CCT vs. SE. Severe (≥70% stenosis) on CCT and inducible ischaemia on SE detected obstructive CAD by invasive coronary angiography in 63% vs. 57% patients (P = 0.33). Over the follow-up period (median 717, interquartile range 93-1069 days) more patients underwent invasive coronary angiography (21.5% vs. 7.3%, P < 0.005), revascularization (7.3% vs. 3.5%, P < 0.005), further functional testing 33.4% vs. 8.7% (P < 0.005), but more patients were prescribed statins 8.8% vs. 3.8% (P < 0.005) in the CCT vs. the SE arm, respectively. Combined all-cause mortality and acute myocardial infarction was low-CCT-2.3% and SE-3.3%-with no significant difference (P = 0.16). CONCLUSION: Initial SE-guided management was similar for the detection of obstructive CAD, demonstrated better resource utilization, but was associated with reduced prescription of statins although with no difference in medium-term outcome compared to CCT in this very low-risk population. However, a randomized study with longer follow-up is needed to confirm the clinical value of our findings.

Association Between Physiological Stenosis Severity and Angina-Limited Exercise Time in Patients With Stable Coronary Artery Disease.

Importance: Physiological stenosis assessment is recommended to guide percutaneous coronary intervention (PCI) in patients with stable angina. Objective: To determine the association between all commonly used indices of physiological stenosis severity and angina-limited exercise time in patients with stable angina. Design, Setting, and Participants: This cohort study included data (without follow-up) collected over 1 year from 2 cardiac hospitals. Selected patients with stable angina and physiologically severe single-vessel coronary artery disease presenting for clinically driven elective PCI were included. Exposures: Fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), hyperemic stenosis resistance (HSR), and coronary flow reserve (CFR) were measured invasively. Immediately after this, patients maximally exercised on a catheter-table-mounted supine ergometer until they developed rate-limiting angina. Subsequent PCI was performed in most patients, followed by repeat maximal supine exercise testing. Main Outcomes and Measures: Associations between FFR, iFR, HSR, CFR, and angina-limited exercise time were assessed using linear regression and Pearson correlation coefficients. Additionally, the associations between the post-PCI increment in exercise time and baseline FFR, iFR, HSR, and CFR were assessed. Results: Twenty-three patients (21 [91.3%] of whom were male; mean [SD] age, 60.6 [8.1] years) completed the pre-PCI component of the study protocol. Mean (SD) stenosis diameter was 74.6% (10.4%). Median (interquartile range [IQR]) values were 0.54 (0.44-0.72) for FFR, 0.53 (0.38-0.83) for iFR, 1.67 (0.84-3.16) for HSR, and 1.35 (1.11-1.63) for CFR. Mean (SD) angina-limited exercise time was 144 (77) seconds. Anatomical stenosis characteristics were not significantly associated with angina-limited exercise time. Conversely, FFR (R2 = 0.27; P = .01), iFR (R2 = 0.46; P < .001), HSR (R2 = 0.39; P < .01), and CFR (R2 = 0.16; P < .05) were all associated with angina-limited exercise time. Twenty-one patients (19 [90.5%] of whom were male; mean [SD] age, 60.1 [8.2] years) competed the full protocol of PCI, post-PCI physiological assessment, and post-PCI maximal exercise. After PCI, the median (IQR) FFR rose to 0.91 (0.85-0.96), median (IQR) iFR to 0.98 (0.94-0.99), and median (IQR) CFR to 2.73 (2.50-3.12), while the median (IQR) HSR fell to 0.16 (0.06-0.37) (P < .001 for all). The post-PCI increment in exercise time was most significantly associated with baseline iFR (R2 = 0.26; P = .02). Conclusions and Relevance: In a selected group of patients with severe, single-vessel stable angina, FFR, iFR, HSR, and CFR were all modestly correlated with angina-limited exercise time to varying degrees. Notwithstanding the limited sample size, no clear association was demonstrated between anatomical stenosis severity and angina-limited exercise time.

Impact of Percutaneous Revascularization on Exercise Hemodynamics in Patients With Stable Coronary Disease.

BACKGROUND: Recently, the therapeutic benefits of percutaneous coronary intervention (PCI) have been challenged in patients with stable coronary artery disease (SCD). OBJECTIVES: The authors examined the impact of PCI on exercise responses in the coronary circulation, the microcirculation, and systemic hemodynamics in patients with SCD. METHODS: A total of 21 patients (mean age 60.3 ± 8.4 years) with SCD and single-vessel coronary stenosis underwent cardiac catheterization. Pre-PCI, patients exercised on a supine ergometer until rate-limiting angina or exhaustion. Simultaneous trans-stenotic coronary pressure-flow measurements were made throughout exercise. Post-PCI, this process was repeated. Physiological parameters, rate-limiting symptoms, and exercise performance were compared between pre-PCI and post-PCI exercise cycles. RESULTS: PCI reduced ischemia as documented by fractional flow reserve value (pre-PCI 0.59 ± 0.18 to post-PCI 0.91 ± 0.07), instantaneous wave-free ratio value (pre-PCI 0.61 ± 0.27 to post-PCI 0.96 ± 0.05) and coronary flow reserve value (pre-PCI 1.7 ± 0.7 to post-PCI 3.1 ± 1.0; p < 0.001 for all). PCI increased peak-exercise average peak coronary flow velocity (p < 0.0001), coronary perfusion pressure (distal coronary pressure; p < 0.0001), systolic blood pressure (p = 0.01), accelerating wave energy (p < 0.001), and myocardial workload (rate-pressure product; p < 0.01). These changes observed immediately following PCI resulted from the abolition of stenosis resistance (p < 0.0001). PCI was also associated with an immediate improvement in exercise time (+67 s; 95% confidence interval: 31 to 102 s; p < 0.0001) and a reduction in rate-limiting angina symptoms (81% reduction in rate-limiting angina symptoms post-PCI; p < 0.001). CONCLUSIONS: In patients with SCD and severe single-vessel stenosis, objective physiological responses to exercise immediately normalize following PCI. This is seen in the coronary circulation, the microcirculation, and systemic hemodynamics.

Resolving the paradox of randomised controlled trials and observational studies comparing multi-vessel angioplasty and culprit only angioplasty at the time of STEMI.

BACKGROUND: Patients presenting with ST-elevation myocardial infarction commonly have multi-vessel coronary artery disease. After the culprit artery is treated, the optimal treatment strategy for the residual disease is not yet defined. Large observational studies suggest that treatment of residual disease should be deferred but smaller randomised controlled trials (RCTs) suggest multi-vessel primary percutaneous coronary intervention (MV-PPCI) at the time of STEMI is safe. We examine if allocation bias of high-risk patients could explain the conflicting results between observational studies and RCTs and aim to resolve the paradox between the two. METHODS: A meta-analysis of registries comparing culprit-only PPCI to MV-PPCI was performed. We then determined if high-risk patients were more likely to be allocated to MV-PPCI. A meta-regression was performed to determine if any allocation bias of high-risk patients could explain the difference in outcomes between therapies. RESULTS: 47,717 patients (19 studies) were eligible. MV-PPCI had higher mortality than culprit-only PPCI (OR 1.59, 95% CI 1.12 to 2.24, p=0.03). However, higher risk patients were more likely to be allocated to MV-PPCI (OR 1.45, 95% CI 1.18 to 1.78, p=0.0005). When this was accounted for, there was no difference in mortality between culprit-only PPCI and MV-PPCI (OR 0.99, 95% CI 0.69 to 1.41, p=0.94). DISCUSSION: Clinicians preferentially allocate higher-risk patients to MV-PPCI at the time of STEMI, resulting in observational studies reporting higher mortality with this strategy. When this is accounted for, these large observational studies in 'real world' patients support the conclusion of the smaller RCTs in the field: MV-PPCI has equivalent mortality to a culprit-only approach.

Estimation of coronary wave intensity analysis using noninvasive techniques and its application to exercise physiology.

Wave intensity analysis (WIA) has found particular applicability in the coronary circulation where it can quantify traveling waves that accelerate and decelerate blood flow. The most important wave for the regulation of flow is the backward-traveling decompression wave (BDW). Coronary WIA has hitherto always been calculated from invasive measures of pressure and flow. However, recently it has become feasible to obtain estimates of these waveforms noninvasively. In this study we set out to assess the agreement between invasive and noninvasive coronary WIA at rest and measure the effect of exercise. Twenty-two patients (mean age 60) with unobstructed coronaries underwent invasive WIA in the left anterior descending artery (LAD). Immediately afterwards, noninvasive LAD flow and pressure were recorded and WIA calculated from pulsed-wave Doppler coronary flow velocity and central blood pressure waveforms measured using a cuff-based technique. Nine of these patients underwent noninvasive coronary WIA assessment during exercise. A pattern of six waves were observed in both modalities. The BDW was similar between invasive and noninvasive measures [peak: 14.9 ± 7.8 vs. -13.8 ± 7.1 × 10(4) W·m(-2)·s(-2), concordance correlation coefficient (CCC): 0.73, P < 0.01; cumulative: -64.4 ± 32.8 vs. -59.4 ± 34.2 × 10(2) W·m(-2)·s(-1), CCC: 0.66, P < 0.01], but smaller waves were underestimated noninvasively. Increased left ventricular mass correlated with a decreased noninvasive BDW fraction (r = -0.48, P = 0.02). Exercise increased the BDW: at maximum exercise peak BDW was -47.0 ± 29.5 × 10(4) W·m(-2)·s(-2) (P < 0.01 vs. rest) and cumulative BDW -19.2 ± 12.6 × 10(3) W·m(-2)·s(-1) (P < 0.01 vs. rest). The BDW can be measured noninvasively with acceptable reliably potentially simplifying assessments and increasing the applicability of coronary WIA.

The effects of angiotensin II signaling blockade on platelet activity in subjects with hypertension.

BACKGROUND: To investigate the effects of Angiotensin II receptor blockade (ARB) and angiotensin converting enzyme (ACE) inhibition on platelet reactivity in patients with mild to moderate hypertension. PFA-100 evaluates platelet function (expressed in seconds as closure time, CT) in anti-coagulated whole blood in vitro at high shear rates. The test cartridge is impregnated with either collagen and epinephrine (Col/Epi) or collagen and ADP (Col/ADP). METHODS: 33 patients were randomized to perindopril 4mg (n = 9), valsartan 80mg/d (n = 9) and for lifestyle modification (n = 15) for 4 weeks. Platelet reactivity was measured at baseline and after 4 weeks by PFA-100. Normotensive controls (n = 11) were also tested at baseline to standardize PFA-100 CT. Haematocrit, platelet count and plasma vWF antigen levels were measured. RESULTS: There was no difference in baseline haematocrit, platelet count or vWF antigen level between the groups. The vWF antigen levels measured after 4 weeks showed no significant difference either. Significant blood pressure reduction was seen in the treated group (SBP P = 0.002 and DBP P = 0.005) when compared to the life style modification group (SBP P = 0.06 and DBP P = 0.04) after 4 weeks. There was no significant statistical difference in Col/ADP CT in treated and non-treated groups but increase in CT (P = 0.05) in treated group with Col/Epi seen after 4 weeks. CONCLUSION: In patients with mild to moderate hypertension, valsartan and perindopril compared to life style modification demonstrate a significant decrease in platelet reactivity.

A new method of applying randomised control study data to the individual patient: A novel quantitative patient-centred approach to interpreting composite end points.

BACKGROUND: Modern randomised controlled trials typically use composite endpoints. This is only valid if each endpoint is equally important to patients but few trials document patient preference and seek the relative importance of components of combined endpoints. If patients weigh endpoints differentially, our interpretation of trial data needs to be refined. METHODS AND RESULTS: We derive a quantitative, structured tool to determine the relative importance of each endpoint to patients. We then apply this tool to data comparing angioplasty with drug-eluting stents to bypass surgery. The survey was administered to patients undergoing cardiac catheterisation. A meta-analysis comparing coronary artery bypass grafting (CABG) to percutaneous coronary interventuin (PCI) was then performed using (a) standard MACE and (b) patient-centred MACE. Patients considered stroke worse than death (stroke 102.3 ± 19.6%, p < 0.01), and MI and repeat revascularisation less severe than death (61.9 ± 26.8% and 41.9 ± 25.4% respectively p < 0.01 for both). 7 RCTs (5251 patients) were eligible. Meta-analysis demonstrated that standard MACE occurs more frequently with PCI than surgery (OR 1.44; 95% CI 1.10 to 1.87; p = 0.007). Re-analysis using patient-centred MACE found no significant difference between PCI and CABG (OR 1.22, 95% CI 0.97 to 1.53; p = 0.10). CONCLUSIONS: Patients do not consider the constituent endpoints of MACE equal. We derive a novel patient-centred metric that recognises and quantifies the differences attributed to each endpoint. When patient preference data are applied to contemporary trial results, there is no significant difference between PCI and CABG. Responses from individual patients in clinic could be used to give individual patients a recommendation that is truly personalised.

Change in coronary blood flow after percutaneous coronary intervention in relation to baseline lesion physiology: results of the JUSTIFY-PCI study.

BACKGROUND: Percutaneous coronary intervention (PCI) aims to increase coronary blood flow by relieving epicardial obstruction. However, no study has objectively confirmed this and assessed changes in flow over different phases of the cardiac cycle. We quantified the change in resting and hyperemic flow velocity after PCI in stenoses defined physiologically by fractional flow reserve and other parameters. METHODS AND RESULTS: Seventy-five stenoses (67 patients) underwent paired flow velocity assessment before and after PCI. Flow velocity was measured over the whole cardiac cycle and the wave-free period. Mean fractional flow reserve was 0.68±0.02. Pre-PCI, hyperemic flow velocity is diminished in stenoses classed as physiologically significant compared with those classed nonsignificant (P<0.001). In significant stenoses, flow velocity over the resting wave-free period and hyperemic flow velocity did not differ statistically. After PCI, resting flow velocity over the wave-free period increased little (5.6±1.6 cm/s) and significantly less than hyperemic flow velocity (21.2±3 cm/s; P<0.01). The greatest increase in hyperemic flow velocity was observed when treating stenoses below physiological cut points; treating stenoses with fractional flow reserve ≤0.80 gained Δ28.5±3.8 cm/s, whereas those fractional flow reserve >0.80 had a significantly smaller gain (Δ4.6±2.3 cm/s; P<0.001). The change in pressure-only physiological indices demonstrated a curvilinear relationship to the change in hyperemic flow velocity but was flat for resting flow velocity. CONCLUSIONS: Pre-PCI physiology is strongly associated with post-PCI increase in hyperemic coronary flow velocity. Hyperemic flow velocity increases 6-fold more when stenoses classed as physiologically significant undergo PCI than when nonsignificant stenoses are treated. Resting flow velocity measured over the wave-free period changes at least 4-fold less than hyperemic flow velocity after PCI.

Pre-angioplasty instantaneous wave-free ratio pullback provides virtual intervention and predicts hemodynamic outcome for serial lesions and diffuse coronary artery disease.

OBJECTIVES: The aim of this study was to perform hemodynamic mapping of the entire vessel using motorized pullback of a pressure guidewire with continuous instantaneous wave-free ratio (iFR) measurement. BACKGROUND: Serial stenoses or diffuse vessel narrowing hamper pressure wire-guided management of coronary stenoses. Characterization of functional relevance of individual stenoses or narrowed segments constitutes an unmet need in ischemia-driven percutaneous revascularization. METHODS: The study was performed in 32 coronary arteries with tandem and/or diffusely diseased vessels. An automated iFR physiological map, integrating pullback speed and physiological information, was built using dedicated software to calculate physiological stenosis severity, length, and intensity (ΔiFR/mm). This map was used to predict the best-case post-percutaneous coronary intervention (PCI) iFR (iFRexp) according to the stented location, and this was compared with the observed iFR post-PCI (iFRobs). RESULTS: After successful PCI, the mean difference between iFRexp and iFRobs was small (mean difference: 0.016 ± 0.004) with a strong relationship between ΔiFRexp and ΔiFRobs (r = 0.97, p < 0.001). By identifying differing iFR intensities, it was possible to identify functional stenosis length and quantify the contribution of each individual stenosis or narrowed segment to overall vessel stenotic burden. Physiological lesion length was shorter than anatomic length (12.6 ± 1.5 vs. 23.3 ± 1.3, p < 0.001), and targeting regions with the highest iFR intensity predicted significant improvement post-PCI (r = 0.86, p < 0.001). CONCLUSIONS: iFR measurements during continuous resting pressure wire pullback provide a physiological map of the entire coronary vessel. Before a PCI, the iFR pullback can predict the hemodynamic consequences of stenting specific stenoses and thereby may facilitate the intervention and stenting strategy.

Improvement in coronary haemodynamics after percutaneous coronary intervention: assessment using instantaneous wave-free ratio.

OBJECTIVE: To determine whether the instantaneous wave-free ratio (iFR) can detect improvement in stenosis significance after percutaneous coronary intervention (PCI) and compare this with fractional flow reserve (FFR) and whole cycle Pd/Pa. DESIGN: A prospective observational study was undertaken in elective patients scheduled for PCI with FFR ≤ 0.80. Intracoronary pressures were measured at rest and during adenosine-mediated vasodilatation, before and after PCI. iFR, Pd/Pa and FFR values were calculated using the validated fully automated algorithms. SETTING: Coronary catheter laboratories in two UK centres and one in the USA. PATIENTS: 120 coronary stenoses in 112 patients were assessed. The mean age was 63 ± 10 years, while 84% were male; 39% smokers; 33% with diabetes. Mean diameter stenosis was 68 ± 16% by quantitative coronary angiography. RESULTS: Pre-PCI, mean FFR was 0.66 ± 0.14, mean iFR was 0.75 ± 0.21 and mean Pd/Pa 0.83 ± 0.16. PCI increased all indices significantly (FFR 0.89 ± 0.07, p<0.001; iFR 0.94 ± 0.05, p<0.001; Pd/Pa 0.96 ± 0.04, p<0.001). The change in iFR after intervention (0.20 ± 0.21) was similar to ΔFFR 0.22 ± 0.15 (p=0.25). ΔFFR and ΔiFR were significantly larger than resting ΔPd/Pa (0.13 ± 0.16, both p<0.001). Similar incremental changes occurred in patients with a higher prevalence of risk factors for microcirculatory disease such as diabetes and hypertension. CONCLUSIONS: iFR and FFR detect the changes in coronary haemodynamics elicited by PCI. FFR and iFR have a significantly larger dynamic range than resting Pd/Pa. iFR might be used to objectively document improvement in coronary haemodynamics following PCI in a similar manner to FFR.

Diagnostic classification of the instantaneous wave-free ratio is equivalent to fractional flow reserve and is not improved with adenosine administration. Results of CLARIFY (Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study).

OBJECTIVES: This study sought to determine if adenosine administration is required for the pressure-only assessment of coronary stenoses. BACKGROUND: The instantaneous wave-free ratio (iFR) is a vasodilator-free pressure-only measure of the hemodynamic severity of a coronary stenosis comparable to fractional flow reserve (FFR) in diagnostic categorization. In this study, we used hyperemic stenosis resistance (HSR), a combined pressure-and-flow index, as an arbiter to determine when iFR and FFR disagree which index is most representative of the hemodynamic significance of the stenosis. We then test whether administering adenosine significantly improves diagnostic performance of iFR. METHODS: In 51 vessels, intracoronary pressure and flow velocity was measured distal to the stenosis at rest and during adenosine-mediated hyperemia. The iFR (at rest and during adenosine administration [iFRa]), FFR, HSR, baseline, and hyperemic microvascular resistance were calculated using automated algorithms. RESULTS: When iFR and FFR disagreed (4 cases, or 7.7% of the study population), HSR agreed with iFR in 50% of cases and with FFR in 50% of cases. Differences in magnitude of microvascular resistance did not influence diagnostic categorization; iFR, iFRa, and FFR had equally good diagnostic agreement with HSR (receiver-operating characteristic area under the curve 0.93 iFR vs. 0.94 iFRa and 0.96 FFR, p = 0.48). CONCLUSIONS: iFR and FFR had equivalent agreement with classification of coronary stenosis severity by HSR. Further reduction in resistance by the administration of adenosine did not improve diagnostic categorization, indicating that iFR can be used as an adenosine-free alternative to FFR.

Hybrid iFR-FFR decision-making strategy: implications for enhancing universal adoption of physiology-guided coronary revascularisation.

AIMS: Adoption of fractional flow reserve (FFR) remains low (6-8%), partly because of the time, cost and potential inconvenience associated with vasodilator administration. The instantaneous wave-Free Ratio (iFR) is a pressure-only index of stenosis severity calculated without vasodilator drugs. Before outcome trials test iFR as a sole guide to revascularisation, we evaluate the merits of a hybrid iFR-FFR decision-making strategy for universal physiological assessment. METHODS AND RESULTS: Coronary pressure traces from 577 stenoses were analysed. iFR was calculated as the ratio between Pd and Pa in the resting diastolic wave-free window. A hybrid iFR-FFR strategy was evaluated, by allowing iFR to defer some stenoses (where negative predictive value is high) and treat others (where positive predictive value is high), with adenosine being given only to patients with iFR in between those values. For the most recent fixed FFR cut-off (0.8), an iFR of <0.86 could be used to confirm treatment (PPV of 92%), whilst an iFR value of >0.93 could be used to defer revascularisation (NPV of 91%). Limiting vasodilator drugs to cases with iFR values between 0.86 to 0.93 would obviate the need for vasodilator drugs in 57% of patients, whilst maintaining 95% agreement with an FFR-only strategy. If the 0.75-0.8 FFR grey zone is accounted for, vasodilator drug requirement would decrease by 76%. CONCLUSION: A hybrid iFR-FFR decision-making strategy for revascularisation could increase adoption of physiology-guided PCI, by more than halving the need for vasodilator administration, whilst maintaining high classification agreement with an FFR-only strategy.

Classification performance of instantaneous wave-free ratio (iFR) and fractional flow reserve in a clinical population of intermediate coronary stenoses: results of the ADVISE registry.

AIMS: To evaluate the classification agreement between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) in patients with angiographic intermediate coronary stenoses. METHODS AND RESULTS: Three hundred and twelve patients (339 stenoses) with angiographically intermediate stenoses were included in this international clinical registry. The iFR was calculated using fully automated algorithms. The receiver operating characteristic (ROC) curve was used to identify the iFR optimal cut-point corresponding to FFR 0.8. The classification agreement of coronary stenoses as significant or non-significant was established between iFR and FFR and between repeated FFR measurements for each 0.05 quantile of FFR values, from 0.2 to 1. Close agreement was observed between iFR and FFR (area under ROC curve= 86%). The optimal iFR cut-off (for an FFR of 0.80) was 0.89. After adjustment for the intrinsic variability of FFR, the classification agreement (accuracy) between iFR and FFR was 94%. Amongst the stenoses classified as non-significant by iFR (>0.89) and as significant by FFR (≤0.8), 81% had associated FFR values located within the FFR "grey-zone" (0.75-0.8) and 41% within the 0.79-0.80 FFR range. CONCLUSIONS: In a population of intermediate coronary stenoses, the classification agreement between iFR and FFR is excellent and similar to that of repeated FFR measurements in the same sample. Vasodilator-independent assessment of intermediate stenosis seems applicable and may foster adoption of coronary physiology in the catheterisation laboratory.

Development and validation of a new adenosine-independent index of stenosis severity from coronary wave-intensity analysis: results of the ADVISE (ADenosine Vasodilator Independent Stenosis Evaluation) study.

OBJECTIVES: The purpose of this study was to develop an adenosine-independent, pressure-derived index of coronary stenosis severity. BACKGROUND: Assessment of stenosis severity with fractional flow reserve (FFR) requires that coronary resistance is stable and minimized. This is usually achieved by administration of pharmacological agents such as adenosine. In this 2-part study, we determine whether there is a time when resistance is naturally minimized at rest and assess the diagnostic efficiency, compared with FFR, of a new pressure-derived adenosine-free index of stenosis severity over that time. METHODS: A total of 157 stenoses were assessed. In part 1 (39 stenoses), intracoronary pressure and flow velocity were measured distal to the stenosis; in part 2 (118 stenoses), intracoronary pressure alone was measured. Measurements were made at baseline and under pharmacologic vasodilation with adenosine. RESULTS: Wave-intensity analysis identified a wave-free period in which intracoronary resistance at rest is similar in variability and magnitude (coefficient of variation: 0.08 ± 0.06 and 284 ± 147 mm Hg s/m) to those during FFR (coefficient of variation: 0.08 ± 0.06 and 302 ± 315 mm Hg s/m; p = NS for both). The resting distal-to-proximal pressure ratio during this period, the instantaneous wave-free ratio (iFR), correlated closely with FFR (r = 0.9, p < 0.001) with excellent diagnostic efficiency (receiver-operating characteristic area under the curve of 93%, at FFR <0.8), specificity, sensitivity, negative and positive predictive values of 91%, 85%, 85%, and 91%, respectively. CONCLUSIONS: Intracoronary resistance is naturally constant and minimized during the wave-free period. The instantaneous wave-free ratio calculated over this period produces a drug-free index of stenosis severity comparable to FFR. (Vasodilator Free Measure of Fractional Flow Reserve [ADVISE]; NCT01118481).