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Item does not contain fulltext BACKGROUND: Coronary blood flow in humans is known to be predominantly diastolic. Small studies in animals and humans suggest that this is less pronounced or even reversed in the right coronary artery (RCA). AIMS: This study aimed to characterise the phasic patterns of coronary flow in the left versus right coronary arteries of patients undergoing invasive physiological assessment. METHODS: We analysed data from the Iberian-Dutch-English Collaborators (IDEAL) study. A total of 482 simultaneous pressure and flow measurements from 301 patients were included in our analysis. RESULTS: On average, coronary flow was higher in diastole both at rest and during hyperaemia in both the RCA and LCA (mean diastolic-to-systolic velocity ratio [DSVR] was, respectively, 1.85±0.70, 1.76±0.58, 1.53±0.34 and 1.58±0.43 for LCA(rest), LCA(hyp), RCA(rest) and RCA(hyp), p

The main aims of therapy in chronic stable angina are to reduce the risk of myocardial infarction and death and improve symptoms and quality of life (QoL). Unblinded trials have shown that revascularization does not reduce the risk of myocardial infarction or death but does appear to improve symptoms. However, symptoms are susceptible to the placebo effect which can bias therapies to appear more effective than they are. To assess the true physical impact of a treatment on symptoms, placebo-controlled trials with patients and medical and research teams blinded to treatment allocation are necessary. Symptoms and QoL can be reported directly by the patient or indirectly by the physician. Patient-reported outcome measures in angina trials can include angina frequency, frequency of nitrate use, exercise capacity, and questionnaires such as the Seattle Angina Questionnaire (SAQ) and the generic EuroQOL-5D-5L (EQ-5D-5L) QoL questionnaire. Physician-assessed outcome measures include Canadian Cardiovascular Society Class. The Objective Randomised Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina (ORBITA) trial was the first blinded placebo-controlled study investigating the role of percutaneous coronary intervention (PCI) in chronic stable angina. The trial showed a smaller than expected and not statistically significant effect of placebo-controlled PCI on the primary endpoint of change in exercise time at 6 weeks follow-up in single-vessel coronary artery disease. There was also no significant placebo-controlled treatment effect of PCI for the prespecified secondary endpoints of SAQ or EQ-5D-5L, although PCI did result in 20% more patients becoming free from angina than placebo in a non-prespecified secondary analysis. ORBITA has demonstrated the need for symptomatic and QoL effects of PCI to be studied using placebo control. Here, we describe ways of measuring QoL, the impact of the unblinded and blinded trials to date, what we have learned from ORBITA, and what is next for this common and complex condition.

This review article summarizes key landmark trials that have shaped understanding of the role of percutaneous coronary intervention (PCI) in stable coronary artery disease (CAD). The relationship between stenosis, ischemia, and angina is more complex than first imagined. Anginal relief remains the primary indication for PCI in stable CAD. The first placebo-controlled PCI trial showed a surprisingly small effect size, suggesting a significant placebo effect. PCI in stable CAD has not been shown to improve mortality or overall myocardial infarction rates, even in the presence of significant ischemia. Rather, risk reduction medical therapy remains the main intervention for improving outcomes.

Ischemia and no obstructive coronary arteries (INOCA) is a common clinical presentation, with a variety of causes that are often not fully investigated in routine clinical practice. The goal of our study was to characterize a real-world population of patients with INOCA, with a deeper focus on symptoms and stress test findings. The study population consisted of 435 patients who underwent diagnostic coronary angiography for anginal symptoms and/or evidence of myocardial ischemia at non-invasive imaging. In all patients angiography demonstrated nonobstructive coronary artery disease (CAD, less than 30% luminal diameter stenosis or fractional flow reserve > 0.8 and/or instantaneous wave-free ratio > 0.89). Fifty-four percent of the patients were women. Atypical clinical presentation was more common in women (59.5 vs. 49.5%, p = 0.037). Women were more likely to have normal coronary arteries than men (41.8 vs. 16.2%, p

Background The placebo effect is a well described phenomenon in blinded studies evaluating anti-anginal therapeutics, although its impact on clinical research metrics remains unknown. We conducted a systematic review and meta-analysis to quantify the impact of placebo on endpoints of symptoms, life-quality and functional outcomes in randomized placebo-controlled trials (RCTs) of symptomatic stable coronary artery disease. Methods We systematically reviewed MEDLINE, EMBASE, and the Cochrane database for double-blind RCTs of anti-angina therapeutics. Patients randomized to the placebo-arm were the study population. Main outcomes were the changes in exercise performance (exercise treadmill test [ETT] parameters), quality of life (Seattle Angina Questionnaire domains), symptoms (Canadian Cardiovascular Society angina class) and drug usage (nitroglycerin tabs/week) between baseline and following placebo. The primary outcome was ETT total duration time. Data were pooled with a random effect model. Results Seventy-eight RCTs (83% drug-controlled, 17% procedure-controlled) were included encompassing 4,925 patients randomized to placebo. ETT total duration time was significantly improved following placebo as compared to baseline (mean [95% confidence interval]: 29.2 [20.6-37.8] seconds) with evidence of high heterogeneity (I 2 = 98%) At subgroup analysis, crossover design was associated with a smaller placebo effect on ETT performance than parallel study design (p for interaction=0.001). A significant placebo effect was observed for all secondary outcomes with overall high heterogeneity. Conclusion A substantial placebo effect was present in angina RCTs across a variety of functional and life-quality metrics. High variability in placebo effect size was present, mostly unexplained by differences in study and patient characteristics (PROSPERO CRD42019132797).

Objectives-\ud 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.\ud Methods-\ud 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.\ud Results-\ud 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).\ud Conclusions-\ud 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.

Aim: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) forms a significant component of oxidised LDL. The effects of exercise on levels of MDA-LDL and anti-MDA-LDL antibodies are not well-understood. Furthermore, it is not known whether these can be modified in patients with coronary artery disease by percutaneous coronary intervention (PCI).Methods: The Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina (ORBITA) trial was the first blinded, multi-centre randomised trial of PCI vs. placebo procedure for angina relief. Serum samples were available at four time-points: pre-randomisation pre- (P1) and post- (P2) exercise and post-randomisation (6-weeks following the PCI or placebo procedure), pre- (P3) and post- (P4) exercise. ELISAs were performed using laboratory-developed assays for MDA-LDL (adjusted for Apolipoprotein B) and anti-MDA-LDL antibodies.Results: One hundred ninety-six of the 200 patients (age 66.1 [SD 8.99] years, 28% female) with severe single vessel coronary artery disease suitable for PCI enrolled in the ORBITA trial had blood available for analysis. With exercise at pre-randomisation (P2–P1) there was no significant change in adjusted MDA-LDL (−0.001, 95% CI −0.004 to 0.001; p = 0.287); however, IgG and IgM anti-MDA-LDL significantly declined (−0.022, 95% CI −0.029 to −0.014, p < 0.0001; −0.016, 95% CI −0.024 to −0.008, p = 0.0002, respectively). PCI did not have a significant impact on either the pre-exercise values (P3 controlling for P1) of MDA-LDL (p = 0.102), IgG (p = 0.444) or IgM anti-MDA-LDL (p = 0.909). Nor did PCI impact the exercise induced changes in these markers (P4 controlling for P1, P2, and P3) for MDA-LDL (p = 0.605), IgG (p = 0.725) or IgM anti-MDA-LDL (p = 0.171). Pre-randomisation ischaemia on stress echo did not impact these interactions.Conclusions: Exercise results in an acute reduction in anti-oxLDL antibodies in patients with severe single vessel coronary disease, possibly indicating an induction in homoeostatic clearance via the innate immune system. However, PCI did not ameliorate this effect.

Supplemental Digital Content is available in the text., Background: Physiological assessment with pressure wire pullback can characterize coronary artery disease (CAD) with a focal or diffuse pattern. However, the clinical relevance of this distinction is unknown. We use data from the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) to test if the pattern of CAD predicts the placebo-controlled efficacy of percutaneous coronary intervention (PCI) on stress echocardiography ischemia and symptom end points. Methods: One hundred sixty-four patients in ORBITA underwent blinded instantaneous wave-free ratio (iFR) pullback assessment before randomization. Focal disease was defined as a ≥0.03 iFR unit drop within 15 mm, rather than over a longer distance. Analyses were performed using regression modeling. Results: In the PCI arm (n=85), 48 were focal and 37 were diffuse. In the placebo arm (n=79), 35 were focal and 44 were diffuse. Focal stenoses were associated with significantly lower fractional flow reserve (FFR) and iFR values than diffusely diseased vessels (mean FFR and iFR, focal 0.60±0.15 and 0.65±0.24, diffuse 0.78±0.10 and 0.88±0.08, respectively, P

Item does not contain fulltext OBJECTIVES: This study sought to evaluate sex differences in procedural characteristics and clinical outcomes of instantaneous wave-free ratio (iFR)- and fractional flow reserve (FFR)-guided revascularization strategies. BACKGROUND: An iFR-guided strategy has shown a lower revascularization rate than an FFR-guided strategy, without differences in clinical outcomes. METHODS: This is a post hoc analysis of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate stenosis to guide Revascularization) study, in which 601 women and 1,891 men were randomized to iFR- or FFR-guided strategy. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization. RESULTS: Among the entire population, women had a lower number of functionally significant lesions per patient (0.31 +/- 0.51 vs. 0.43 +/- 0.59; p < 0.001) and less frequently underwent revascularization than men (42.1% vs. 53.1%; p < 0.001). There was no difference in mean iFR value according to sex (0.91 +/- 0.09 vs. 0.91 +/- 0.10; p = 0.442). However, the mean FFR value was lower in men than in women (0.83 +/- 0.09 vs. 0.85 +/- 0.10; p = 0.001). In men, an FFR-guided strategy was associated with a higher rate of revascularization than an iFR-guided strategy (57.1% vs. 49.3%; p = 0.001), but this difference was not observed in women (41.4% vs. 42.6%; p = 0.757). There was no difference in MACE rates between iFR- and FFR-guided strategies in both women (5.4% vs. 5.6%, adjusted hazard ratio: 1.10; 95% confidence interval: 0.50 to 2.43; p = 0.805) and men (6.6% vs. 7.0%, adjusted hazard ratio: 0.98; 95% confidence interval: 0.66 to 1.46; p = 0.919). CONCLUSIONS: An FFR-guided strategy was associated with a higher rate of revascularization than iFR-guided strategy in men, but not in women. However, iFR- and FFR-guided strategies showed comparable clinical outcomes, regardless of sex. (Functional Lesion Assessment of Intermediate Stenosis to guide Revascularization [DEFINE-FLAIR]; NCT02053038).

Based on 12‑lead electrocardiogram (ECG) findings, myocardial infarction (MI) patients are dichotomized to ST-elevation MI (STEMI) and non ST-elevation MI (NSTEMI) in terms of management strategy. NSTEMI patients are increasing in numbers worldwide, among which an approximately 30% are associated with a total occlusion of a coronary artery. This review summarizes recent evidence in epidemiology, clinical, laboratory, ECG and prognostic characteristics of this NSTEMI sub-group. Patients with a diagnosis of NSTEMI and a total occluded coronary artery (TOCA) represent a sub-group of NSTEMI patients with total occlusion of coronary arteries and associated high-risk that are frequently not managed according to a STEMI-like pathway. The present review echoes a call for action in changing our everyday clinical practice. Therefore, we propose a new triage algorithm by which recognition of high-risk features in NSTEMI patients is central in order to identify STEMI ‘equivalents’ among NSTEMI patients in terms of similar pathology and high-risk who may benefit from immediate invasive strategy (

ObjectivesThe 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.MethodsWe 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.ResultsMean 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%, pConclusionHypertension, 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.

Recent randomised controlled trials, such as ISCHEMIA and ORBITA, have overturned most of what we were taught in medical school about hospital procedures considered necessary for patients with stable coronary artery disease. In this article, we discuss what these trials mean for physicians and patients considering revascularisation procedures with the hope of reducing the risk of death or alleviating angina.

Background In stable coronary artery disease, medications are used for 2 purposes: cardiovascular risk reduction and symptom improvement. In clinical trials and clinical practice, medication use is often not optimal. The ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trial was the first placebo‐controlled trial of percutaneous coronary intervention. A key component of the ORBITA trial design was the inclusion of a medical optimization phase, aimed at ensuring that all patients were treated with guideline‐directed truly optimal medical therapy. In this study, we report the medical therapy that was achieved. Methods and Results After enrollment into the ORBITA trial, all 200 patients entered a 6‐week period of intensive medical therapy optimization, with initiation and uptitration of risk reduction and antianginal therapy. At the prerandomization stage, the median number of antianginals established was 3 (interquartile range, 2–4). A total of 195 patients (97.5%) reached the prespecified target of ≥2 antianginals; 136 (68.0%) did not stop any antianginals because of adverse effects, and the median number of antianginals stopped for adverse effects per patient was 0 (interquartile range, 0–1). Amlodipine and bisoprolol were well tolerated (stopped for adverse effects in 4/175 [2.3%] and 9/167 [5.4%], respectively). Ranolazine and ivabradine were also well tolerated (stopped for adverse effects in 1/20 [5.0%] and 1/18 [5.6%], respectively). Isosorbide mononitrate and nicorandil were stopped for adverse effects in 36 of 172 (20.9%) and 32 of 141 (22.7%) of patients, respectively. Statins were well tolerated and taken by 191 of 200 (95.5%) patients. Conclusions In the 12‐week ORBITA trial period, medical therapy was successfully optimized and well tolerated, with few drug adverse effects leading to therapy cessation. Truly optimal medical therapy can be achieved in clinical trials, and translating this into longer‐term clinical practice should be a focus of future study. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02062593.

Introduction: Improvement in exercise capacity is a therapeutic goal of percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD). Cardiopulmonary exercise testing (CPET) provides an accurate quantification of cardio-respiratory fitness through analysis of ventilatory gas exchange (VGE). The aim of this secondary analysis from the ORBITA trial is to determine the placebo-controlled effect of PCI on VGE parameters and determine if pre-randomisation exercise capacity predicts the placebo-controlled efficacy of PCI. Methods: Following a 6-week medication optimisation phase, patients with severe single vessel CAD underwent pre-randomisation treadmill CPET using the smoothed modified Bruce protocol. Patients were then randomly assigned to PCI or a placebo procedure. At the end of the 6-week follow up period, patients underwent repeat CPET before being unblinded to treatment allocation. Results: CPET data was available for 195 patients (mean age 66.1 ± 9.1, 73.3% male). At baseline, peak oxygen uptake (VO 2 ) was 21.5±6.7ml/kg/min in the PCI arm (n=102) and 20.6±6.6ml/kg/min in the placebo arm (n=93). At follow up, there was no significant benefit from PCI over a placebo procedure for any ventilatory gas exchange (peak VO 2 , p=0.826; O 2 -pulse plateau, p=0.638) or haemodynamic parameter (rate-pressure product, p=0.215). Although PCI resulted in significantly improved patient-reported freedom from angina (OR, 2.58 [95% CI, 1.35-14.92] p=0.004) and angina frequency score (OR, 1.73 [95% CI, 1.02 to 2.96], p=0.0432), there was no detectable interaction between peak VO 2 and these endpoints (P interaction(int) =0.715 and P int =0.588 respectively). Similarly, pre-randomisation peak VO 2 did not predict the placebo-controlled benefit of PCI on physical limitation (P int =0.293), quality of life (P int =0.380), EuroQOL 5 visual analogue score (P int =0.695), Canadian Cardiovascular Society angina class (P int =0.120) or exercise time (P int =0.897). Conclusions: When assessed against placebo, PCI does not improve VGE or exercise capacity, assessed by CPET. Furthermore, pre-randomisation exercise capacity does not predict the placebo-controlled effect of PCI on symptom relief, even in patients with lower functional capacity.

Introduction: Cardiopulmonary exercise testing (CPET) provides a non-invasive evaluation of exercise physiology via ventilatory gas exchange (VGE). We do not know how these assessments correlate with myocardial ischemia or angina symptoms in patients with stable single-vessel coronary artery disease (CAD). In this analysis, we use randomised, blinded data from the ORBITA trial to investigate the association between VGE, ischemia and symptoms in patients with severe single-vessel CAD. Methods: Patients underwent treadmill CPET using the smoothed-modified Bruce protocol, after a 6-week medical optimisation phase during which antianginals were uptitrated. Symptoms were assessed using the Seattle Angina Questionnaire (SAQ), EuroQOL 5 and Canadian Cardiovascular Society (CCS) angina class. Ischemia was quantified using fractional flow reserve (FFR), instantaneous wave-free ratio (iFR) and dobutamine stress echocardiography (DSE). Results: We assessed 195 patients [mean age 66.1±9.1, 143 (73.3%) male]. We found a significant association between peak oxygen uptake (VO 2 ) and minute ventilation to carbon dioxide (VE/VCO 2 ) slope, and physician assessed CCS class [P correlation(cor) cor cor cor cor cor =0.0001) and EuroQOL 5 visual analogue score (P cor = 0.0011, P cor =0.0019). There was no detectable relationship between peak VO 2 or VE/VCO 2 slope, and FFR, iFR or DSE (p>0.05, for all). Patients with an oxygen pulse plateau however, had higher dobutamine stress echo score compared to those without (+0.71; 95%CI 0.22-1.21, p=0.0049). Conclusions: The association between VGE and angina symptoms is stronger than its ability to detect severity of myocardial ischemia. This analysis highlights the complexity of the relationship between symptoms, functional capacity and myocardial ischemia.

Introduction The ORBITA trial of percutaneous coronary intervention (PCI) versus a placebo procedure for patients with stable angina was conducted across six sites in the United Kingdom via home monitoring and telephone consultations. Patients underwent detailed assessment of medication adherence which allowed us to measure the efficacy of the implementation of the optimization protocol and interpretation of the main trial endpoints. Methods Prescribing data were collected throughout the trial. Self‐reported adherence was assessed, and urine samples collected at pre‐randomization and at follow‐up for direct assessment of adherence using high‐performance liquid chromatography with tandem mass spectrometry (HPLC MS/MS). Results Self‐reported adherence was >96% for all drugs in both treatment groups at both stages. The percentage of samples in which drug was detected at pre‐randomization and at follow‐up in the PCI versus placebo groups respectively was: clopidogrel, 96% versus 90% and 98% versus 94%; atorvastatin, 95% versus 92% and 92% versus 91%; perindopril, 95% versus 97% and 85% versus 100%; bisoprolol, 98% versus 99% and 96% versus 97%; amlodipine, 99% versus 99% and 94% versus 96%; nicorandil, 98% versus 96% and 94% versus 92%; ivabradine, 100% versus 100% and 100% versus 100%; and ranolazine, 100% versus 100% and 100% versus 100%. Conclusions Adherence levels were high throughout the study when quantified by self‐reporting methods and similarly high proportions of drug were detected by urinary assay. The results indicate successful implementation of the optimization protocol delivered by telephone, an approach that could serve as a model for treatment of chronic conditions, particularly as consultations are increasingly conducted online., Medical therapy for patients with stable angina optimised over 6 weeks of tele‐ health clinic visits. Treatment titrated to home blood pressure and heart rate measurements. Medication adherence confirmed using HPLC MS/MS and patient self‐reporting. Patients subsequently randomised to PCI or placebo procedure in the ORBITA trial. Adherence reassessed at final follow‐up. Self‐reported adherence was >96% for all drugs in both treatment groups at both stages. Proportion of expected drug detected was >90% for all first‐choice, protocol‐directed medicines at both stages. No significant between group differences at pre‐ randomisation or at follow‐up and medication taking patterns did not change following treatment with PCI. The study uses a simple model for optimisation of medical therapy in clinical practice using a telehealth approach with high levels of adherence.

Introduction The ORBITA trial of PCI versus a placebo procedure for patients with stable angina was conducted across 6 sites in the United Kingdom via home monitoring and telephone consultations. Patients underwent detailed assessment of medication adherence which allowed us to measure the efficacy of the implementation of the optimisation protocol and interpretation of the main trial endpoints. Methods Prescribing data were collected throughout the trial. Self-reported adherence was assessed, and urine samples collected at pre-randomisation and at follow-up for direct assessment of adherence using HPLC MS/MS. Results Self-reported adherence was >96% for all drugs in both treatment groups at both stages. The percentage of samples in which drug was detected at pre-randomisation and at follow-up in the PCI vs. OMT groups respectively was: clopidogrel, 96% vs. 90% and 98% vs. 94%; atorvastatin, 95% vs. 92% and 92% vs. 91%; perindopril, 95% vs. 97% and 85% vs. 100%; bisoprolol, 98% vs. 99% and 96% vs. 97%; amlodipine, 99% vs. 99% and 94% vs. 96%; nicorandil, 98% vs. 96% and 94% vs. 92%; ivabradine, 100% vs. 100% and 100% vs. 100%; and ranolazine, 100% vs. 100% and 100% vs. 100%. Conclusions Adherence levels were high throughout the study when quantified by self-reporting methods and similarly high proportions of drug were detected by urinary assay. The results indicate successful implementation of the optimisation protocol delivered by telephone, an approach that could serve as a model for treatment of chronic conditions, particularly as consultations are increasingly conducted online.

Objectives The aim of this study was to assess the long-term clinical outcomes of patients with left main coronary artery (LM) stenosis in whom treatment strategy was based on the instantaneous wave-free ratio (iFR). Background The overall safety of iFR to guide revascularization decision making in patients with stable coronary artery disease has been established. However, no study has examined the safety of deferral of revascularization of LM disease on the basis of iFR. Methods This multicenter observational study included 314 patients in whom LM stenosis was deferred (n = 163 [51.9%]) or revascularized (n = 151 [48.1%]) according to the iFR cutoff ≤0.89. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were each individual component of the primary endpoint and also cardiac death. Results At a median follow-up period of 30 months, the primary endpoint occurred in 15 patients (9.2%) in the deferred group and 22 patients (14.6%) in the revascularized group (hazard ratio: 1.45; 95% confidence interval: 0.75 to 2.81; p = 0.26), indicating no evidence of a significant difference between the 2 groups. For the secondary endpoints, findings in the iFR-based deferral and revascularization groups were as follows: all-cause death, 3.7% versus 4.6%; cardiac death, 1.2% versus 2.0%; nonfatal myocardial infarction, 2.5% versus 5.3%; and target lesion revascularization, 4.3% versus 5.3% (p > 0.05 for all). Conclusions Deferral of revascularization of LM stenosis on the basis of iFR appears to be safe, with similar long-term outcomes to those in patients in whom LM revascularization was performed according to iFR values.

Background: In patients presenting with ST-segment–elevation myocardial infarction, percutaneous coronary intervention (PCI) reduces mortality when compared with fibrinolysis. In other forms of coronary artery disease (CAD), however, it has been controversial whether PCI reduces mortality. In this meta-analysis, we examine the benefits of PCI in (1) patients post–myocardial infarction (MI) who did not receive immediate revascularization; (2) patients who have undergone primary PCI for ST-segment–elevation myocardial infarction but have residual coronary lesions; (3) patients who have suffered a non–ST-segment–elevation acute coronary syndrome; and (4) patients with truly stable CAD with no recent infarct. This analysis includes data from the recently presented International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) and Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI (COMPLETE) trials. Methods and Results: We systematically identified all randomized trials of PCI on a background of medical therapy for the treatment of CAD. The ISCHEMIA trial, presented in November 2019, was eligible for inclusion. Data were combined using a random-effects meta-analysis. The primary end point was all-cause mortality. Forty-six trials, including 37 757 patients, were eligible. In the 3 unstable scenarios, PCI had the following effects on mortality: unrevascularized post-MI relative risk (RR) 0.68 (95% CI, 0.45–1.03); P =0.07; multivessel disease following ST-segment–elevation myocardial infarction (RR, 0.84 [95% CI, 0.69–1.04]; P =0.11); non–ST-segment–elevation acute coronary syndrome (RR, 0.84 [95% CI, 0.72–0.97]; P =0.02). Overall, in these unstable scenarios PCI was associated with a significant reduction in mortality (RR, 0.84 [95% CI, 0.75–0.93]; P =0.02). In unstable CAD, PCI also reduced cardiac death (RR, 0.69 [95% CI, 0.53–0.90]; P =0.007) and MI (RR, 0.74 [95% CI, 0.62–0.90]; P =0.002). For stable CAD, PCI did not reduce mortality (RR, 0.98 [95% CI, 0.87–1.11]), cardiac death (RR, 0.89 [95% CI, 0.71–1.12]; P =0.33), or MI (RR, 0.96 [95% CI, 0.86–1.08]; P =0.54). Conclusions: PCI prevents death, cardiac death, and MI in patients with unstable CAD. For patients with stable CAD, PCI shows no evidence of an effect on any of these outcomes.

The adverse consequences of stable coronary artery disease (CAD) are death, myocardial infarction (MI) and angina. Trials in stable CAD show that percutaneous coronary intervention (PCI) does not reduce mortality. PCI does appear to reduce spontaneous MI rates but at the expense of causing some periprocedural MI. Therefore, the main purpose of PCI is to relieve angina. Indeed, patients and physicians often choose PCI rather than first attempting to control symptoms with anti-anginal medications as recommended by guidelines. Nevertheless, it is unclear how effective PCI is at relieving angina. This is because, whereas anti-anginal medications are universally required to be tested against placebo, there is no such requirement for procedural interventions such as PCI. The first placebo-controlled trial of PCI showed a surprisingly small effect size. This may be because it is overly simplistic to assume that the presence of a stenosis and inducible ischaemia in a patient means that the clinical chest pain they report is caused by ischaemia. In this article, we review the evidence base and argue that if we as a medical specialty wish to lead the science of procedures for symptom control, we should recognise the special merit of placebo-controlled experiments.

Summary Background Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. Methods ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593. Findings ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI −8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group. Interpretation In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy. Funding NIHR Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, Philips Volcano, NIHR Barts Biomedical Research Centre.

Background: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina). Methods: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling. Results: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score ( P interaction =0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina ( P interaction =0.116), physical limitation ( P interaction =0.461), quality of life ( P interaction =0.689), EuroQOL 5 quality-of-life score ( P interaction =0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class ( P interaction =0.693), and treadmill exercise time ( P interaction =0.426). Conclusions: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02062593.

Background: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) disagree on the hemodynamic significance of a coronary lesion in ≈20% of cases. It is unknown whether the physiological pattern of disease is an influencing factor for this. This study assessed whether the physiological pattern of coronary artery disease influences discordance between FFR and iFR measurement. Methods and Results: Three-hundred and sixty intermediate coronary lesions (345 patients; mean age, 64.4±10.3 years; 76% men) with combined FFR, iFR, and iFR pressure-wire pullback were included for analysis from an international multicenter registry. Cut points for hemodynamic significance were FFR ≤0.80 and iFR ≤0.89, respectively. Lesions were classified into FFR+/iFR+ (n=154; 42.7%), FFR−/iFR+ (n=38; 10.6%), FFR+/iFR− (n=41; 11.4%), and FFR−/iFR− (n=127; 35.3%) groups. The physiological pattern of disease was classified according to the iFR pullback recordings as predominantly physiologically focal (n=171; 47.5%) or predominantly physiologically diffuse (n=189; 52.5%). Median FFR and iFR were 0.80 (interquartile range, 0.75–0.85) and 0.89 (interquartile range, 0.86–0.92), respectively. FFR disagreed with iFR in 22% (79 of 360). The physiological pattern of disease was the only influencing factor relating to FFR/iFR discordance: predominantly physiologically focal was significantly associated with FFR+/iFR− (58.5% [24 of 41]), and predominantly physiologically diffuse was significantly associated with FFR−/iFR+ (81.6% [31 of 38]; P Conclusions: The physiological pattern of coronary artery disease was an important influencing factor for FFR/iFR discordance.

Background: Patients with severe aortic stenosis (AS) often have coronary artery disease. Both the aortic valve and the coronary disease influence the blood flow to the myocardium and its ability to respond to stress; leading to exertional symptoms. In this study, we aim to quantify the effect of severe AS on the coronary microcirculation and determine if this is influenced by any concomitant coronary disease. We then compare this to the effect of coronary stenoses on the coronary microcirculation. Methods: Group 1: 55 patients with severe AS and intermediate coronary stenoses treated with transcatheter aortic valve implantation (TAVI) were included. Group 2: 85 patients with intermediate coronary stenoses and no AS treated with percutaneous coronary intervention were included. Coronary pressure and flow were measured at rest and during hyperemia in both groups, before and after TAVI (group 1) and before and after percutaneous coronary intervention (group 2). Results: Microvascular resistance over the wave-free period of diastole increased significantly post-TAVI (pre-TAVI, 2.71±1.4 mm Hg·cm·s −1 versus post-TAVI 3.04±1.6 mm Hg·cm·s −1 [ P =0.03]). Microvascular reserve over the wave-free period of diastole significantly improved post-TAVI (pre-TAVI 1.88±1.0 versus post-TAVI 2.09±0.8 [ P =0.003]); this was independent of the severity of the underlying coronary stenosis. The change in microvascular resistance post-TAVI was equivalent to that produced by stenting a coronary lesion with an instantaneous wave-free ratio of ≤0.74. Conclusions: TAVI improves microcirculatory function regardless of the severity of underlying coronary disease. TAVI for severe AS produces a coronary hemodynamic improvement equivalent to the hemodynamic benefit of stenting coronary stenoses with instantaneous wave-free ratio values

OBJECTIVES: The authors sought to evaluate the accuracy of instantaneous wave-Free Ratio (iFR) pullback measurements to predict post-percutaneous coronary intervention (PCI) physiological outcomes, and to quantify how often iFR pullback alters PCI strategy in real-world clinical settings.\ud \ud BACKGROUND: In tandem and diffuse disease, offline analysis of continuous iFR pullback measurement has previously been demonstrated to accurately predict the physiological outcome of revascularization. However, the accuracy of the online analysis approach (iFR pullback) remains untested.\ud \ud METHODS: Angiographically intermediate tandem and/or diffuse lesions were entered into the international, multi-center iFR GRADIENT (Single instantaneous wave-Free Ratio Pullback Pre-Angioplasty Predicts Hemodynamic Outcome Without Wedge Pressure in Human Coronary Artery Disease) registry. Operators were asked to submit their procedural strategy after angiography alone and then after iFR-pullback measurement incorporating virtual PCI and post-PCI iFR prediction. PCI was performed according to standard clinical practice. Following PCI, repeat iFR assessment was performed and the actual versus predicted post-PCI iFR values compared.\ud \ud RESULTS: Mean age was 67+/-12 years (81% male). Paired pre-and post-PCI iFR were measured in 128 patients (134 vessels). The predicted post-PCI iFR calculated online was 0.93+/-0.05; observed actual iFR was 0.92+/-0.06. iFR pullback predicted the post-PCI iFR outcome with 1.4+/-0.5% error. In comparison to angiography-based decision making, after iFR pullback, decision making was changed in 52 (31%) of vessels; with a reduction in lesion number (-0.18+/-0.05 lesion/vessel; p = 0.0001) and length (-4.4+/-1.0 mm/vessel; p < 0.0001).\ud \ud CONCLUSIONS: In tandem and diffuse coronary disease, iFR pullback predicted the physiological outcome of PCI with a high degree of accuracy. Compared with angiography alone, availability of iFR pullback altered revascularization procedural planning in nearly one-third of patients.

OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p amp;lt; 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. Funding Agencies|Philips; Upsala Clinical Research Centre; Volcano; Imperial College; Philips Volcano; Imperial College London; Medical Research Council

The instantaneous wave-free ratio (iFR) is a recently developed invasive index of coronary disease severity that simplifies stenosis assessment by eliminating the need for vasodilator administration [(1–4)][1]. Multiple studies have so far compared iFR with other established invasive modalities

BACKGROUND: Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. METHODS: We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. RESULTS: At 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, -0.2 percentage points; 95% confidence interval [CI], -2.3 to 1.8; P

ObjectivesThe 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.BackgroundSerial 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.MethodsThe 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).ResultsAfter 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).ConclusionsiFR 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.

Fractional flow reserve (FFR) assessment provides anatomical and physiological information that is often used to tailor treatment strategies in coronary artery disease. Whilst robust data validates FFR use in stable ischaemic heart disease, its use in acute coronary syndromes (ACS) is less well investigated. We critically review the current data surrounding FFR use across the spectrum of ACS including culprit and non-culprit artery analysis. With adenosine being conventionally used to induce maximal hyperaemia during FFR assessment, co-existent clinical conditions may preclude its use during acute myocardial infarction. Therefore, we include a current review of instantaneous wave free ratio as a novel vasodilator independent method of assessing lesion severity as an alternative strategy to guide revascularisation in ACS., Highlights • Small studies support the use of FFR in non-culprit vessels during ACS. • FFR demonstrates diagnostic accuracy and reproducibility in AMI, particularly in intermediate lesions. • Microvascular dysfunction observed from earlier work does not appear to hinder FFR calculation, but further studies are required for validation. • Vasodilator independent assessment of coronary stenoses has some preliminary data supporting its use in non culprit arteries during ACS, but ongoing trial results are awaited regarding clinical outcomes.

Objectives To evaluate the first experience of real-time instantaneous wave–free ratio (iFR) measurement by clinicians. Background The iFR is a new vasodilator-free index of coronary stenosis severity, calculated as a trans-lesion pressure ratio during a specific period of baseline diastole, when distal resistance is lowest and stable. Because all previous studies have calculated iFR offline, the feasibility of real-time iFR measurement has never been assessed. Methods Three hundred ninety-two stenoses with angiographically intermediate stenoses were included in this multicenter international analysis. Instantaneous wave–free ratio and fractional flow reserve (FFR) were performed in real time on commercially available consoles. The classification agreement of coronary stenoses between iFR and FFR was calculated. Results Instantaneous wave–free ratio and FFR maintain a close level of diagnostic agreement when both are measured by clinicians in real time (for a clinical 0.80 FFR cutoff: area under the receiver operating characteristic curve [ROCAUC] 0.87, classification match 80%, and optimal iFR cutoff 0.90; for a ischemic 0.75 FFR cutoff: iFR ROCAUC 0.90, classification match 88%, and optimal iFR cutoff 0.85; if the FFR 0.75-0.80 gray zone is accounted for: ROCAUC 0.93, classification match 92%). When iFR and FFR are evaluated together in a hybrid decision-making strategy, 61% of the population is spared from vasodilator while maintaining a 94% overall agreement with FFR lesion classification. Conclusion When measured in real time, iFR maintains the close relationship to FFR reported in offline studies. These findings confirm the feasibility and reliability of real-time iFR calculation by clinicians., Graphical Abstract

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) disagrees on the hemodynamic significance of a coronary lesion in approximately 20% of cases. It is unknown if the physiological pattern of disease is an influencing factor for this discordance. This study assessed whether the

Fractional Flow Reserve (FFR) and instantaneous wave-free ratio (iFR) are the two most commonly used coronary pressure based indices of physiological stenosis severity. FFR is calculated as (Pd - Pw) / (Pa -Pw) during pharmacological hyperemia. Conversely, iFR is calculated as Pd/Pa during the wave

What you need to know Stable angina refers to chest discomfort that is classically retrosternal, triggered by exertion, and relieved by rest or nitrates within minutes. Unstable symptoms, such as those occurring at rest or persisting when activity stops, suggest an acute coronary syndrome and will not be discussed here.1 More than one million people in the United Kingdom live with stable coronary artery disease (CAD), with an annual mortality rate of 1.5%.2 3 It is associated with long term morbidity and has serious effects on quality of life.4 Treatment options include medical therapy, coronary angioplasty with or without stenting (percutaneous coronary intervention; PCI), and coronary artery bypass surgery (CABG), for which guidelines from the UK’s National Institute for Health and Care Excellence (NICE) and European Society of cardiology (ESC) exist.5 6 However, patients’ and doctors’ expectations of potentials benefits of PCI in stable CAD are often overstated.7 This article focuses on the limited evidence base and indications for PCI in stable angina. #### Sources and selection criteria We searched Medline and the Cochrane Library using terms from a previous systematic review of treatment of stable angina (“stable angina”, “percutaneous coronary intervention”, and “medical therapy”),8 updated to March 2015. We also drew on our experience of coronary angioplasty and medical treatment of patients with stable coronary artery disease and our knowledge of NICE and ESC guidance. ### The two main goals are risk factor modification and symptomatic relief ### Risk factor modification

Aim: There are limited data on the mid-term safety following the use of the guided-subintimal tracking and re-entry (guided-STAR) technique for the treatment of chronic total occlusions (CTO) and concerns have arisen about a potential increased risk of stent thrombosis (ST). Objectives: The aim of this study was to evaluate the mid-term safety in terms of cardiac death and ST after recanalization using the contrast guided-STAR technique when compared to conventional anterograde CTO recanalization (CA-CTO). Methods and Results: This retrospective study analyzed 355 consecutive patients with successful angiographic recanalization (residual stenosis

Background There is strong evidence of FFR guided treatment in multi-vessel disease. The presence of a concomitant CTO may influence the FFR measurement in donor vessel as suggested in previous studies and reports. This has an important implication on clinical decision making for complete revascularisation in patients with chronic total occlusion. We sought to investigate the influence of collateral regression after successful CTO recanalisation on donor vessel pressure-derived indices. Methods The study participants were patients with angina who had RCA CTO. 28 out of 34 consecutive patients underwent successful PCI to RCA CTOs during the study period and completed the follow study (at 3 months post CTO PCI) were included in this analysis. Coronary pressure-derived indices (resting PD/PA, iFR and FFR) were measured pre and post successful RCA CTO PCI in donor vessels and at follow up procedures. Results The mean age was 62.38 years. The mean estimated CTO duration was 238.72 weeks and CTO length was 32.44 mm. 25 patients had ischaemia and or viability in the RCA territory assessed with cardiac MRI. LAD was the major donor vessel in 24 patients and LCX was the minor donor vessel in 4 patients. Percent stenosis on QCA in the major and minor donor vessel were 40.6% and 35.1% respectively. The mean resting Pd/Pa, iFR and FFR pre and post RCA CTO PCI and at follow-up procedures in major donor vessel were (0.893, 0.862, 0.764), (0.907, 0.886, 0.753) and (0.918, 0.901, 0.787) respectively. The mean resting Pd/Pa, iFR and FFR pre and post RCA CTO PCI and at follow-up procedures in minor donor vessel were (0.979, 0.966, 0.890), (0.983, 0.979, 0.880) and (0.981, 0.974, 0.898) respectively. The changes in coronary pressure-derived indices pre and post RCA CTO PCI and at follow up procedures are summarised in table 1. In major donor vessel, there was significant changes in the difference between follow up and pre-CTO PCI values for Pd/Pa, iFR and FFR values (p values 0.006, 0.003 and 0.047 respectively). There was also significant change in the difference between follow up and post-CTO PCI FFR value (P value 0.002). FFR collateral reduced significantly at follow-up (p value 0.000). Conclusion Successful recanalisation of a RCA CTO results in increase in major donor vessel coronary pressure-derived indices at follow up procedure associated with the regression of collateral function. In patients with multi-vessel disease, the expected change and the optimal timing to perform PCI in donor vessel should be considered when planning multi-vessel revascularisation in this setting.

Percutaneous coronary intervention (PCI) to aorto-ostial (AO) lesions is technically demanding and associated with high revascularization rates. The aim of this study was to assess outcomes after bare metal stent (BMS) compared to drug-eluting stent (DES) implantation after PCI to AO lesions. A retrospective cohort analysis was conducted of all consecutive patients who underwent PCI to AO lesions at 2 centers. Angiographic and clinical outcomes in 230 patients with DES from September 2000 to December 2009 were compared to a historical control group of 116 patients with BMS. Comparison of the baseline demographics showed more diabetics (32% vs 16%, p = 0.001), lower ejection fractions (52.3 ± 9.7% vs 55.0 ± 11.5%, p = 0.022), longer stents (17.55 ± 7.76 vs 14.37 ± 5.60 mm, p

Objectives The aim of this study was to evaluate the incidence, predictors, management, and clinical outcomes in patients with grade III coronary perforation during percutaneous coronary intervention. Background Grade III coronary perforation is a rare but recognized complication associated with high morbidity and mortality. Methods From 24,465 patients undergoing percutaneous coronary intervention from May 1993 to December 2009, 56 patients had grade III coronary perforation. Results Most lesions were complex: 44.6% type B2, 51.8% type C, and 28.6% chronic total occlusions, and within a small vessel (≤2.5 mm) in 32.1%. Glycoprotein IIb/IIIa inhibitors were administered in 17.9% of patients. The device causing perforation was intracoronary balloon in 50%: 53.6% compliant, 46.4% noncompliant; intracoronary guidewire in 17.9%; rotablation in 3.6%; and directional atherectomy in 3.6%. Following perforation, immediate treatment and success rates, respectively, were prolonged balloon inflation 58.9%, 54.5%; covered stent implantation 46.4%, 84.6%; coronary artery bypass graft surgery (CABG) and surgical repair 16.0%, 44.4%; and coil embolization 1.8%, 100%. Multiple methods were required in 39.3%. During the procedure (n = 56), 19.6% required cardiopulmonary resuscitation and 3.6% died. In-hospital (n = 54), 3.7% required CABG, 14.8% died. The combined procedural and in-hospital myocardial infarction rate was 42.9%, and major adverse cardiac event rate was 55.4%. At clinical follow-up (n = 46) (median: 38.1 months, range 7.6 to 122.8), 4.3% had a myocardial infarction, 4.3% required CABG, and 15.2% died. The target lesion revascularization rate was 13%, with target vessel revascularization in 19.6%, and major adverse cardiac events in 41.3%. Conclusions Grade III coronary perforation is associated with complex lesions and high acute and long-term major adverse cardiac event rates.

Objectives Our aim was to assess clinical outcome after transcatheter aortic valve implantation (TAVI) performed with the 2 commercially available valves with 3 delivery approaches selected in a stepwise fashion. Background Limited data exist on the results of a comprehensive TAVI program using different valves with transfemoral, transapical, and transaxillary approaches for treatment of severe aortic stenosis. Methods We report 30-day and 6-month outcomes of high-risk patients consecutively treated in a single center with either the Medtronic-CoreValve (MCV) (Medtronic, Minneapolis, Minnesota) or Edwards-SAPIEN valve (ESV) (Edwards Lifesciences, Irvine, California) delivered via the transfemoral or transaxillary approaches and ESV via the transapical approach. Results A total of 137 patients underwent TAVI: 107 via transfemoral (46 MCV and 61 ESV), 15 via transaxillary (12 MCV and 3 ESV), and 15 via transapical approach. After the transfemoral approach, the procedural success rate was 93.5%, and major vascular complication rate was 20.6%. No intra-procedural deaths occurred. The procedural success rates of transapical and transaxillary approaches were 86.6% and 93.3%, respectively. The 30-day mortality rate was 0.9% in transfemoral group and 13.3% in transapical, and no deaths occurred after transaxillary access. Cumulative death rate at 6 months was 12.2% in transfemoral, 26.6% in transapical, and 18.2% in transaxillary groups. At multivariable analysis, logistic European System for Cardiac Operative Risk Evaluation, body surface area, and history of cerebrovascular disease were significantly associated with an increased risk of major adverse cardiac and cerebrovascular events. Conclusions Routine TAVI using both MCV and ESV with a selection of approaches is feasible and allows treatment of a wide range of patients with good overall procedural success rates and 30-day and 6-month outcomes.

Coronary physiology is recommended to guide percutaneous coronary intervention (PCI) in stable coronary disease. PCI in such settings aims to relieve angina and improve exercise capacity. The aim of this study was to determine the relationship between instantaneous wave-free ratio (iFR), fractional

AIM: Severe aortic stenosis frequently involves the development of left ventricular hypertrophy (LVH) creating a dichotomous haemodynamic state within the coronary circulation. Whilst the increased force of ventricular contraction enhances its resultant relaxation and thus increases the distal diastolic coronary "suction" force, the presence of LVH has a potentially opposing effect on ventricular-coronary interplay. The aim of this study was to use non-invasive coronary wave intensity analysis (WIA) to separate and measure the sequential effects of outflow tract obstruction relief and then LVH regression following intervention for aortic stenosis. METHODS: Fifteen patients with unobstructed coronary arteries undergoing aortic valve intervention (11 surgical aortic valve replacement [SAVR], 4 TAVI) were successfully assessed before and after intervention, and at 6 and 12 months post-procedure. Coronary WIA was constructed from simultaneously acquired coronary flow from transthoracic echo and pressure from an oscillometric brachial cuff system. RESULTS: Immediately following intervention, a decline in the backward decompression wave (BDW) was noted (9.7 ± 5.7 vs 5.1 ± 3.6 × 103 W/m2 /s, P

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 × 104 W·m−2·s−2, concordance correlation coefficient (CCC): 0.73, P < 0.01; cumulative: −64.4 ± 32.8 vs. −59.4 ± 34.2 × 102 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 × 104 W·m−2·s−2 ( P < 0.01 vs. rest) and cumulative BDW −19.2 ± 12.6 × 103 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.

Wave Intensity Analysis (WIA) has found particular applicability in the coronary circulation where it is able to quantify and qualify the energy affecting blood flow. The most important wave for the regulation of coronary blood flow is the backward-travelling decompression wave (BDW). Until now

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 P 0.80 had a significantly smaller gain (Δ4.6±2.3 cm/s; P 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.

Aims The efficacy of transvenous Cryoablation (Cryo), for the treatment of atrioventricular nodal re-entry tachycardia (AVNRT), when compared with radiofrequency (RF) ablation, requires further investigation. Methods and results We sought to compare the acute- and follow-up results of 71 cases each of Cryo and RF for AVNRT using a retrospective matched case–control study design and aimed at identifying patient and procedural factors that may predict success with each strategy. Primary failure of Cryo (thus necessitating RF at the same sitting) was seen in 11 (15.4%) cases, whereas there were two (2.8%) primary failures with RF (P , 0.01). Patients in the Cryo group had significantly higher arrhythmia recurrence [14 (19.8%)] when compared with the RF group [4 (5.6%)] (P , 0.01). The incidence of recurrence following Cryo was significantly higher if an echo beat was still inducible after ablation than if complete slow pathway block was achieved (7/19, vs. 4/46, P , 0.001). The median number of Cryo lesions was significantly lower in patients who had recurrence compared with those who did not (1.5 vs. 3.0, P ¼ 0.02). Conclusion We have observed a much higher primary failure and recurrence rate with Cryo when compared with RF for AVNRT. It may be possible to decrease this high recurrence rate by aiming to achieve complete slow pathway block and by increasing the number of Cryo lesions.