Pityriasis rubra pilaris treatment options: A retrospective case series from a tertiary hospital.

Pityriasis rubra pilaris (PRP) is a group of uncommon chronic inflammatory skin conditions with unclear pathophysiology and etiology. To date there is limited published literature and no clinical guidelines for the management of PRP. Infliximab, alone or in combination, is the most widely published successful treatment for adults and etanercept for pediatric populations. We present a case series of patients diagnosed with PRP. Retrospective data were collected from a tertiary Australian dermatology department between January 2010 and December 2019 on patients with PRP. Electronic medical records and pathology database were searched. A total of 13 patients were included. Twelve of the 13 patients used topical agents and three patients attempted narrow-band ultraviolet B phototherapy. All patients received acitretin as first line systemic agent with the dose varying from 10 to 50 mg daily. Six patients treated with acitretin reported adverse events, requiring dose reduction or cessation. Of the nine patients who did not receive a biologic agent, complete clearance of PRP was achieved in five cases. At least one biologic agent was used in four cases with two experiencing a marked improvement. Overall, complete clearance was achieved in six patients. PRP continues to be a challenge to treat with many treatment options used with variable efficacy.

Adalimumab for nail psoriasis: Efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial.

BACKGROUND: Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point. OBJECTIVE: This phase 3 trial evaluated the safety and efficacy of adalimumab in patients with moderate-to-severe fingernail psoriasis and moderate-to-severe plaque psoriasis. METHODS: Patients were randomized 1:1 to 40 mg adalimumab every other week or placebo. The primary efficacy end point was at least 75% improvement in total-fingernail modified Nail Psoriasis Severity Index (NAPSI75) response rate at week 26. Ranked secondary end point scores evaluated at week 26 were total-fingernail NAPSI and modified NAPSI, nail pain, Nail Psoriasis Physical Functioning Severity, Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index, and Physician's Global Assessment (fingernail psoriasis). RESULTS: Of the 217 randomized patients (108 received placebo and 109 received adalimumab), 188 (86.6%) completed 26 weeks of treatment (period A) or escaped early to the open-label period. The study met the primary end point (response rate of 3.4% with placebo vs 46.6% with adalimumab [P < .001]) and all ranked secondary end points. The serious adverse event rates (placebo vs adalimumab) in period A were 4.6% versus 7.3%; the serious infections rates were 1.9% versus 3.7%. LIMITATIONS: Patients with less than 5% BSA involvement were not eligible for enrollment. CONCLUSIONS: After 26 weeks of adalimumab treatment, significant improvements were seen in the primary and all ranked secondary end points and in signs and symptoms of moderate-to-severe nail psoriasis versus with placebo and no new safety risks were identified.

Aortic Stenosis in Dialysis Patients.

Aortic valve stenosis occurs 10-20 years earlier in patients on dialysis compared with the general population. This is likely related to the exposure of the valve to a milieu that predisposes to calcification as well as increased shear stress across the valve. Objective assessment of stenosis severity is largely made using echocardiography though accurate interpretation requires an understanding of the potential pitfalls of the technique and the influence of cardiac output upon the gradient measured across the valve. Timing of valve replacement in severe aortic stenosis is predominantly guided by exercise-induced symptoms (breathlessness, chest pain and [pre] syncope), which are often difficult to assess in the dialysis population who may have limited exercise capacity and symptoms due to renal failure and other comorbidities. Finally, treatment of aortic stenosis remains a constantly evolving area with advances in both conventional surgery and percutaneous techniques.

Legal considerations of consent and privacy in the context of clinical photography in Australian medical practice.

Clinical photography has become integral to clinical practice, especially in visually oriented specialties. Where a clinical photograph forms part of a patient's medical record, clinicians have a legal obligation to keep that photograph for several years, as determined by federal privacy legislation and various state legislation. Patients may be able to access their own clinical photographs in the context of freedom of information legislation. Consent to take clinical photographs must be informed consent, and clinicians have a legal requirement to only use the photograph for the purpose defined by that consent.

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.

The impact of an acute chest pain pathway on the investigation and management of cardiac chest pain.

Emergency department (ED) presentation with chest pain accounts for approximately 20% of acute hospital admissions, and delays in the investigation and management of these patients increase the pressure on emergency and medical departments. We implemented a pathway within our trust to improve the efficiency of acute chest pain management. This included the development of a chest pain management algorithm, a short-stay heart assessment centre and a policy to immediately transfer acute coronary syndrome patients to cardiology. The introduction of the chest pain pathway resulted in fewer admissions from the ED with chest pain (34.2% vs 19.0%; p<0.0001), a reduction in time from ED attendance to cardiology transfer (9.3 hours vs 5.7 hours; p<0.0001) and a reduction in time to angiography (62.5 hours vs 26.6 hours; p<0.0001). Length of stay was reduced for cardiology patients (4.7 days vs 2.4 days, p<0.001) and mean length of stay for all patients attending ED with chest pain was reduced by 8.3 hours (27.5 hours vs 19.1 hours; p<0.0001). The changes have significantly improved the management of acute chest pain within our trust and we would suggest that adoption of these changes in other trusts could significantly improve the quality of the care for these patients throughout the NHS.

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.

Three-Dimensional Printing and Cell Therapy for Wound Repair.

Significance: Skin tissue damage is a major challenge and a burden on healthcare systems, from burns and other trauma to diabetes and vascular disease. Although the biological complexities are relatively well understood, appropriate repair mechanisms are scarce. Three-dimensional bioprinting is a layer-based approach to regenerative medicine, whereby cells and cell-based materials can be dispensed in fine spatial arrangements to mimic native tissue. Recent Advances: Various bioprinting techniques have been employed in wound repair-based skin tissue engineering, from laser-induced forward transfer to extrusion-based methods, and with the investigation of the benefits and shortcomings of each, with emphasis on biological compatibility and cell proliferation, migration, and vitality. Critical issues: Development of appropriate biological inks and the vascularization of newly developed tissues remain a challenge within the field of skin tissue engineering. Future Directions: Progress within bioprinting requires close interactions between material scientists, tissue engineers, and clinicians. Microvascularization, integration of multiple cell types, and skin appendages will be essential for creation of complex skin tissue constructs.

Occurrence of regional left ventricular dysfunction in patients undergoing standard and biofeedback dialysis.

BACKGROUND: Cardiac failure and cardiovascular death are extremely prevalent in dialysis patients. Recurrent subclinical myocardial ischemia is important in the genesis of heart failure in nondialysis patients. We examined whether this phenomenon occurs in response to the stress of hemodialysis (HD). METHODS: Eight patients prone to intradialytic hypotension were recruited for a randomized crossover study to compare the development of left ventricular regional wall motion abnormalities during standard (HD) and biofeedback dialysis. Patients underwent serial echocardiography with quantitative analysis to assess ejection fraction and regional left ventricular systolic function during both types of dialysis. Blood pressure and hemodynamic variables also were measured by using continuous pulse wave analysis. RESULTS: Forty-two new regional wall motion abnormalities developed in all 8 patients during HD compared with 23 regional wall motion abnormalities that developed in 7 patients during biofeedback dialysis (odds ratio, 1.8; 95% confidence interval, 1.1 to 3.0). The majority of regional wall motion abnormalities showed improvement in function by 30 minutes postdialysis. Overall mean regional function was significantly more impaired during HD (P = 0.022). At peak stress, ejection fraction (measured by percentage of change from baseline) was significantly lower during HD (P = 0.043). Blood pressure was higher during biofeedback dialysis, with significantly fewer episodes of hypotension (odds ratio, 2.0; 95% confidence interval, 1.01 to 4.4). Significantly smaller decreases in stroke volume and cardiac output and a greater increment in pulse rate were observed during biofeedback dialysis. CONCLUSION: This study shows that reversible left ventricular wall motion abnormalities develop during dialysis with ultrafiltration. We also show that this phenomenon can be ameliorated by the improved hemodynamic stability of biofeedback dialysis and therefore is a potential target for intervention.

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.

A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study.

OBJECTIVES: This study was designed to test a rapid protocol of intravenous acetylcysteine for prevention of radiocontrast-induced nephropathy (RCIN). BACKGROUND: Oral acetylcysteine (NAC) may provide better prophylaxis against RCIN than intravenous (i.v.) hydration alone. Current protocols preclude prophylaxis of same-day or emergency patients owing to the need for prolonged pretreatment. METHODS: We prospectively randomized 80 patients with stable renal dysfunction undergoing cardiac catheterization/intervention to a rapid protocol of i.v. NAC (150 mg/kg in 500 ml N/saline over 30 min immediately before contrast followed by 50 mg/kg in 500 ml N/saline over 4 h, n = 41, 67 +/- 10 years, 90% men) or i.v. hydration (1 ml/kg/h N/saline for 12 h pre- and post-contrast, n = 39, 71 +/- 8.8 years, 85% men). RESULTS: Radiocontrast-induced nephropathy occurred in 2 of the 41 patients in the NAC group (5%) and in 8 of the 39 patients in the hydration group (21%; p = 0.045; relative risk: 0.28; 95% confidence interval 0.08 to 0.98). In the NAC group, mean serum creatinine fell from 1.85 +/- 0.59 to 1.77 +/- 0.73 and 1.79 +/- 0.73 mg/dl 48 h and four days post-contrast (p = 0.02 and 0.023 vs. baseline, respectively). In the hydration group, serum creatinine increased from 1.75 +/- 0.41 to 1.81 +/- 0.6 48 h and 1.80 +/- 0.50 mg/dl four days post-contrast (p = 0.99 and 0.23, respectively). NAC infusion was ceased after the bolus in three patients (7%) due to flushing, itching, or a transient rash. CONCLUSIONS: Administration of i.v. NAC should be considered in all patients at risk of RCIN before contrast exposure when time constraints preclude adequate oral prophylaxis, provided the patient is able to tolerate this degree of volume loading.

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.

Absolute quantification of myocardial blood flow with H(2)(15)O and 3-dimensional PET: an experimental validation.

UNLABELLED: The purpose of this study was to assess a 3-dimensional (3D)-only PET scanner (ECAT EXACT3D) for its use in the absolute quantification of myocardial blood flow (MBF) using H(2)(15)O. METHODS: Nine large white pigs were scanned with H(2)(15)O and C(15)O before and after partially occluding the circumflex (n = 4) or the left anterior descending (n = 5) coronary artery at rest and during hyperemia induced by intravenous dipyridamole. Radioactive microspheres labeled with either (57)Co or (46)Sc were injected during each of the H(2)(15)O scans, which allowed comparison between microsphere and PET measurements of regional MBF. PET analyses of 3D acquisition data were performed using filtered backprojection reconstruction and region-of-interest definition by factor and cluster analysis techniques and single-compartment model quantification. RESULTS: The Hanning filter applied in image reconstruction resulted in a left atrial blood volume recovery factor of 0.84 +/- 0.06. Differences between repeated measurements of recovery were small (mean, -0.8%; range, -6.6% to 3.6%). In 256 paired measurements of MBF ranging from 0.05 to 4.4 mL. g(- 1). min(-1), microsphere and PET measurements were fairly well correlated. The mean difference between the 2 methods was - 0.11 mL. g(-1). min(-1) and the limits of agreement (+2 SD) were -0.82 and 0.60 mL. g(-1). min(-1) (Bland-Altman plot). CONCLUSION: Dynamic measurements with H(2)(15)O using a 3D-only PET tomograph provide reliable and accurate measurements of absolute regional MBF over a wide flow range. The 3D acquisition technique can reduce the radiation dose to the subject while maintaining adequate counting statistics.

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.

Hemodynamic response to intravenous adenosine and its effect on fractional flow reserve assessment: results of the Adenosine for the Functional Evaluation of Coronary Stenosis Severity (AFFECTS) study.

BACKGROUND: We studied the hemodynamic response to intravenous adenosine on calculation of fractional flow reserve (FFR). Intravenous adenosine is widely used to achieve conditions of stable hyperemia for measurement of FFR. However, intravenous adenosine affects both systemic and coronary vascular beds differentially. METHODS AND RESULTS: A total of 283 patients (310 coronary stenoses) underwent coronary angiography with FFR using intravenous adenosine 140 mcg/kg per minute via a central femoral vein. Offline analysis was performed to calculate aortic (Pa), distal intracoronary (Pd), and reservoir (Pr) pressure at baseline, peak, and stable hyperemia. Seven different hemodynamic patterns were observed according to Pa and Pd change at peak and stable hyperemia. The average time from baseline to stable hyperemia was 68.2±38.5 seconds, when both ΔPa and ΔPd were decreased (ΔPa, -10.2±10.5 mm Hg; ΔPd, -18.2±10.8 mm Hg; P<0.001 for both). The fall in Pa closely correlated with the reduction in peripheral Pr (ΔPr, -12.9±15.7 mm Hg; P<0.001; r=0.9; P<0.001). ΔPa and ΔPd were closely related under conditions of peak (r=0.75; P<0.001) and stable hyperemia (r=0.83; P<0.001). On average, 56% (10.2 mm Hg) of the reduction in Pd was because of fall in Pa. FFR lesion classification changed in 9% using an FFR threshold of ≤0.80 and 5.2% with FFR threshold <0.75 when comparing Pd/Pa at peak and stable hyperemia. CONCLUSIONS: Intravenous adenosine results in variable changes in systemic blood pressure, which can lead to alterations in FFR lesion classification. Attention is required to ensure FFR is measured under conditions of stable hyperemia, although the FFR value at this point may be numerically higher.

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.

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.