Myocardial perfusion in cardiac amyloidosis.

AIMS: Cardiac involvement is the main driver of clinical outcomes in systemic amyloidosis and preliminary studies support the hypothesis that myocardial ischaemia contributes to cellular damage. The aims of this study were to assess the presence and mechanisms of myocardial ischaemia using cardiovascular magnetic resonance (CMR) with multiparametric mapping and histopathological assessment. METHODS AND RESULTS: Ninety-three patients with cardiac amyloidosis (CA) (light-chain amyloidosis n = 42, transthyretin amyloidosis n = 51) and 97 without CA (three-vessel coronary disease [3VD] n = 47, unobstructed coronary arteries n = 26, healthy volunteers [HV] n = 24) underwent quantitative stress perfusion CMR with myocardial blood flow (MBF) mapping. Twenty-four myocardial biopsies and three explanted hearts with CA were analysed histopathologically. Stress MBF was severely reduced in patients with CA with lower values than patients with 3VD, unobstructed coronary arteries and HV (CA: 1.04 ± 0.51 ml/min/g, 3VD: 1.35 ± 0.50 ml/min/g, unobstructed coronary arteries: 2.92 ± 0.52 ml/min/g, HV: 2.91 ± 0.73 ml/min/g; CA vs. 3VD p = 0.011, CA vs. unobstructed coronary arteries p < 0.001, CA vs. HV p < 0.001). Myocardial perfusion abnormalities correlated with amyloid burden, systolic and diastolic function, structural parameters and blood biomarkers (p < 0.05). Biopsies demonstrated abnormal vascular endothelial growth factor staining in cardiomyocytes and endothelial cells, which may be related to hypoxia conditions. Amyloid infiltration in intramural arteries was associated with severe lumen reduction and severe reduction in capillary density. CONCLUSION: Cardiac amyloidosis is associated with severe inducible myocardial ischaemia demonstrable by histology and CMR stress perfusion mapping. Histological evaluation indicates a complex pathophysiology, where in addition to systolic and diastolic dysfunction, amyloid infiltration of the epicardial arteries and disruption and rarefaction of the capillaries play a role in contributing to myocardial ischaemia.

Impact of core laboratory assessment on treatment decisions and clinical outcomes using combined fractional flow reserve and coronary flow reserve measurements - DEFINE-FLOW core laboratory sub-study.

OBJECTIVE: The role of combined FFR/CFR measurements in decision-making on coronary revascularization remains unclear. DEFINE-FLOW prospectively assessed the relationship of FFR/CFR agreement with 2-year major adverse cardiac event (MACE) and target vessel failure (TVF) rates, and uniquely included core-laboratory analysis of all pressure and flow tracings. We aimed to document the impact of core-laboratory analysis on lesion classification, and the relationship between core-laboratory fractional flow reserve (FFR) and coronary flow reserve (CFR) values with clinical outcomes and angina burden during follow-up. METHODS: In 398 vessels (348 patients) considered for intervention, ≥1 coronary pressure/flow tracing was approved by the core-laboratory. Revascularization was performed only when both FFR(≤0.80) and CFR(<2.0) were abnormal, all others were treated medically. RESULTS: MACE was lowest for concordant normal FFR/CFR, but was not significantly different compared with either discordant group (low FFR/normal CFR: HR:1.63; 95%CI:0.61-4.40; P = 0.33; normal FFR/low CFR: HR:1.81; 95%CI:0.66-4.98; P = 0.25). Moreover, MACE did not differ between discordant groups treated medically and the concordant abnormal group undergoing revascularization (normal FFR/low CFR: HR:0.63; 95%CI:0.23-1.73;P = 0.37; normal FFR/low CFR: HR:0.70; 95%CI:0.22-2.21;P = 0.54). Similar findings applied to TVF. CONCLUSIONS: Patients with concordantly normal FFR/CFR have very low 2-year MACE and TVF rates. Throughout follow-up, there were no differences in event rates between patients in whom revascularization was deferred due to preserved CFR despite reduced FFR, and those in whom PCI was performed due to concordantly low FFR and CFR. These findings question the need for routine revascularization in vessels showing low FFR but preserved CFR. CLINICAL TRIAL REGISTRATION: http://ClinicalTrials.govNCT02328820.

Treatment Strategies and Outcomes of Emergency Left Main Percutaneous Coronary Intervention.

Emergency percutaneous coronary intervention of the left main (LM ePCI) coronary artery necessitated by acute coronary syndrome is associated with a high risk of mortality. However, optimal treatment strategies and related outcomes remain undefined in this group. We undertook a multi-center, retrospective, observational cohort study of consecutive patients requiring LM ePCI between 2011 and 2018 and reported the coronary anatomy, treatment strategies, outcomes, and predictors of mortality. A total of 116 consecutive cases were included. Patients were predominantly male (85%) with a median age of 68.0 years; 12 patients (10%) had previous coronary artery bypass grafting. ST-elevation was noted in 76 (66%); 30 (26%) presented with an out-of-hospital cardiac arrest (OOHCA) and 47 (41%) with cardiogenic shock. The most frequent pattern of disease was Medina 1,1,1, seen in 59 patients (51%). The commonest revascularization strategy was provisional stenting (95 cases, 82%) with improved or thrombolysis in myocardial infarction 3 flow seen in 85 cases (73%). All-cause mortality was 35% at 30 days, rising to 58% at 5 years. Adverse predictors of 30-day mortality included presentation with cardiogenic shock (p = 0.018) and OOHCA (p = 0.020), whereas improved flow and/or thrombolysis in myocardial infarction 3 flow in both circumflex and left anterior descending artery afforded a better prognosis (p = 0.028). In conclusion, patients who underwent LM ePCI are a high-risk subgroup and commonly present with cardiogenic shock and OOHCA. Provisional stenting appears to be the preferred option with the successful restoration of coronary flow in most cases despite complex anatomy. High 30-day mortality is driven by the presence of cardiogenic shock, OOHCA, and failure to restore or improve coronary flow.

Subclinical Hypertrophic Cardiomyopathy in Elite Athletes: Knowledge Gaps Persist.

Subclinical hypertrophic cardiomyopathy (HCM) is a phenotypic entity that has emerged from the increased use of cardiovascular magnetic resonance imaging in the evaluation and family screening of patients with HCM. We describe the case of a competitive athlete with a sarcomere gene mutation and family history of HCM who was found to exhibit the subclinical HCM phenotype on cardiovascular magnetic resonance imaging in the absence of left ventricular hypertrophy. We discuss the clinical uncertainties in her management. (Level of Difficulty: Advanced.).

The influence of biological age and sex on long-term outcome after percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: Outcome following ST-segment elevation myocardial infarction (STEMI) is thought to be worse in women than in age-matched men. We assessed whether such differences occur in the UK Pan-London dataset and if age, and particularly menopause, influences upon outcome. METHODS: We undertook an observational cohort study of 26,799 STEMI patients (20,633 men, 6,166 women) between 2005-2015 at 8 centres across London, UK. Patient details were recorded at the time of the procedure into local databases using the British Cardiac Intervention Society (BCIS) PCI dataset. Primary outcome was all-cause mortality at a median follow-up of 4.1 years (IQR: 2.2-5.8 years). RESULTS: Kaplan-Meier analysis demonstrated a higher mortality rate in women versus men (15.6% men vs. 25.3% women, P<0.0001). Univariate Cox analysis revealed that female sex was a predictor of all-cause mortality (HR: 1.69 95% CI: 1.59-1.82). However, after multivariate adjustment, this effect of female sex diminished (HR: 1.05 95% CI: 0.90-1.25). In a sub-group analysis, we compared the sexes separated by age into the ≤55 and the >55 year olds. Age-stratified Cox analysis revealed that female sex was a univariate predictor of all-cause mortality (HR: 1.60 95% CI: 1.25-2.05) in the ≤55 group and in the >55 group (HR: 1.38 95% CI: 1.28-1.47). However, after regression adjustment incorporating the propensity score into a proportional hazard model as a covariate, whilst female sex was not a significant predictor of all-cause mortality in the ≤55 group it was a predictor in the >55 group. Moreover, whilst age did not influence outcome in <55 group, this effect in the >55 group was correlated with age. CONCLUSIONS: Overall women have a worse all-cause mortality following primary PCI for STEMI compared to men. However, this effect was driven predominantly by women >55 years of age since after adjusting for co-morbidities the risk in younger women did not differ significantly from that in men. These observations support the view that as women advance past the menopausal years their risk of further events following revascularization increases substantially and we suggest that routine assessment of hormonal status may improve clinical decision-making and ultimately outcome for women post-PCI.

Quantitative cardiovascular magnetic resonance myocardial perfusion mapping to assess hyperaemic response to adenosine stress.

AIMS: Assessment of hyperaemia during adenosine stress cardiovascular magnetic resonance (CMR) remains a clinical challenge with lack of a gold-standard non-invasive clinical marker to confirm hyperaemic response. This study aimed to validate maximum stress myocardial blood flow (SMBF) measured using quantitative perfusion mapping for assessment of hyperaemic response and compare this to current clinical markers of adenosine stress. METHODS AND RESULTS: Two hundred and eighteen subjects underwent adenosine stress CMR. A derivation cohort (22 volunteers) was used to identify a SMBF threshold value for hyperaemia. This was tested in a validation cohort (37 patients with suspected coronary artery disease) who underwent invasive coronary physiology assessment on the same day as CMR. A clinical cohort (159 patients) was used to compare SMBF to other physiological markers of hyperaemia [splenic switch-off (SSO), heart rate response (HRR), and blood pressure (BP) fall]. A minimum SMBF threshold of 1.43 mL/g/min was derived from volunteer scans. All patients in the coronary physiology cohort demonstrated regional maximum SMBF (SMBFmax) >1.43 mL/g/min and invasive evidence of hyperaemia. Of the clinical cohort, 93% had hyperaemia defined by perfusion mapping compared to 71% using SSO and 81% using HRR. There was no difference in SMBFmax in those with or without SSO (2.58 ± 0.89 vs. 2.54 ± 1.04 mL/g/min, P = 0.84) but those with HRR had significantly higher SMBFmax (2.66 1.86 mL/g/min, P < 0.001). HRR >15 bpm was superior to SSO in predicting adequate increase in SMBF (AUC 0.87 vs. 0.62, P < 0.001). CONCLUSION: Adenosine-induced increase in myocardial blood flow is accurate for confirmation of hyperaemia during stress CMR studies and is superior to traditional, clinically used markers of adequate stress such as SSO and BP response.

A practical risk score for early prediction of neurological outcome after out-of-hospital cardiac arrest: MIRACLE2.

AIMS: The purpose of this study was to develop a practical risk score to predict poor neurological outcome after out-of-hospital cardiac arrest (OOHCA) for use on arrival to a Heart Attack Centre. METHODS AND RESULTS: From May 2012 to December 2017, 1055 patients had OOHCA in our region, of whom 373 patients were included in the King's Out of Hospital Cardiac Arrest Registry (KOCAR). We performed prediction modelling with multivariable logistic regression to identify predictors of the primary outcome to derive a risk score. This was externally validated in two independent cohorts comprising 473 patients. The primary endpoint was poor neurological outcome at 6-month follow-up (Cerebral Performance Category 3-5). Seven independent predictors of outcome were identified: missed (unwitnessed) arrest, initial non-shockable rhythm, non-reactivity of pupils, age (60-80 years-1 point; >80 years-3 points), changing intra-arrest rhythms, low pH <7.20, and epinephrine administration (2 points). The MIRACLE2 score had an area under the curve (AUC) of 0.90 in the development and 0.84/0.91 in the validation cohorts. Three risk groups were defined-low risk (MIRACLE2 ≤2-5.6% risk of poor outcome); intermediate risk (MIRACLE2 of 3-4-55.4% of poor outcome); and high risk (MIRACLE2 ≥5-92.3% risk of poor outcome). The MIRACLE2 score had superior discrimination than the OHCA [median AUC 0.83 (0.818-0.840); P < 0.001] and Cardiac Arrest Hospital Prognosis models [median AUC 0.87 (0.860-0.870; P = 0.001] and equivalent performance with the Target Temperature Management score [median AUC 0.88 (0.876-0.887); P = 0.092]. CONCLUSIONS: The MIRACLE2 is a practical risk score for early accurate prediction of poor neurological outcome after OOHCA, which has been developed for simplicity of use on admission.

Complete Versus Culprit only Revascularisation in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction: Incidence and Outcomes from the London Heart Attack Group.

BACKGROUND: Despite advances in technology, patients with Cardiogenic Shock (CS) presenting with ST-segment myocardial infarction (STEMI) still have a poor prognosis with high mortality rates. A large proportion of these patients have multi-vessel coronary artery disease, the treatment of which is still unclear. We aimed to assess the trends in management of CS patients with multi-vessel disease (MVD), particularly looking at the incidence and outcomes of complete revascularisation compared to culprit vessel only. METHODS AND RESULTS: We undertook an observational cohort study of 21,210 STEMI patients treated between 2005 and 2015 at the 8 Heart Attack Centres in London, UK. Patients' details were recorded prospectively into local databases using the British Cardiac Intervention Society (BCIS) PCI dataset. 1058 patients presented with CS and MVD. Primary outcome was all-cause mortality. Patients were followed-up for a median of 4.1 years (IQR range: 2.2-5.8 years). 497 (47.0%) patients underwent complete revascularisation during primary PCI for CS with stable rates seen over time. These patients were more likely to be male, hypertensive and more likely to have poor LV function compared to the culprit vessel intervention group. Although crude, in hospital major adverse cardiac events (MACE) rates were similar (40.8% vs. 36.0%, p = 0.558) between the two groups. Kaplan-Meier analysis demonstrated no significant differences in mortality rates between the two groups (53.8% complete revascularisation vs. 46.8% culprit vessel intervention, p = 0.252) during the follow-up period. After multivariate cox analysis (HR 0.69 95% CI (0.44-0.98)) and the use of propensity matching (HR: 0.81 95% CI: 0.62-0.97) complete revascularisation was associated with reduced mortality. A number of co-variates were included in the model, including age, gender, diabetes, hypertension, hypercholesterolaemia, previous PCI, previous MI, chronic renal failure, Anterior infarct, number of treated vessels, pre-procedure TIMI flow, procedural success and GP IIb/IIIA use. CONCLUSION: In a contemporary observational series of CS patients with MVD, complete revascularisation appears to be associated with better outcomes compared to culprit vessel only intervention. This supports on-going clinical trials in this area and provides further evidence of the association of complete revascularisation in STEMI with good outcomes.

Automated Pixel-Wise Quantitative Myocardial Perfusion Mapping by CMR to Detect Obstructive Coronary Artery Disease and Coronary Microvascular Dysfunction: Validation Against Invasive Coronary Physiology.

OBJECTIVES: This study sought to assess the performance of cardiovascular magnetic resonance (CMR) myocardial perfusion mapping against invasive coronary physiology reference standards for detecting coronary artery disease (CAD, defined by fractional flow reserve [FFR] ≤0.80), microvascular dysfunction (MVD) (defined by index of microcirculatory resistance [IMR] ≥25) and the ability to differentiate between the two. BACKGROUND: Differentiation of epicardial (CAD) and MVD in patients with stable angina remains challenging. Automated in-line CMR perfusion mapping enables quantification of myocardial blood flow (MBF) to be performed rapidly within a clinical workflow. METHODS: Fifty patients with stable angina and 15 healthy volunteers underwent adenosine stress CMR at 1.5T with quantification of MBF and myocardial perfusion reserve (MPR). FFR and IMR were measured in 101 coronary arteries during subsequent angiography. RESULTS: Twenty-seven patients had obstructive CAD and 23 had nonobstructed arteries (7 normal IMR, 16 abnormal IMR). FFR positive (epicardial stenosis) areas had significantly lower stress MBF (1.47 ± 0.48 ml/g/min) and MPR (1.75 ± 0.60) than FFR-negative IMR-positive (MVD) areas (stress MBF: 2.10 ± 0.35 ml/g/min; MPR: 2.41 ± 0.79) and normal areas (stress MBF: 2.47 ± 0.50 ml/g/min; MPR: 2.94 ± 0.81). Stress MBF ≤1.94 ml/g/min accurately detected obstructive CAD on a regional basis (area under the curve: 0.90; p < 0.001). In patients without regional perfusion defects, global stress MBF <1.82 ml/g/min accurately discriminated between obstructive 3-vessel disease and MVD (area under the curve: 0.94; p < 0.001). CONCLUSIONS: This novel automated pixel-wise perfusion mapping technique can be used to detect physiologically significant CAD defined by FFR, MVD defined by IMR, and to differentiate MVD from multivessel coronary disease. A CMR-based diagnostic algorithm using perfusion mapping for detection of epicardial disease and MVD warrants further clinical validation.

Angiography Alone Versus Angiography Plus Optical Coherence Tomography to Guide Percutaneous Coronary Intervention: Outcomes From the Pan-London PCI Cohort.

OBJECTIVES: This study aimed to determine the effect on long-term survival of using optical coherence tomography (OCT) during percutaneous coronary intervention (PCI). BACKGROUND: Angiographic guidance for PCI has substantial limitations. The superior spatial resolution of OCT could translate into meaningful clinical benefits, although limited data exist to date about their effect on clinical endpoints. METHODS: This was a cohort study based on the Pan-London (United Kingdom) PCI registry, which includes 123,764 patients who underwent PCI in National Health Service hospitals in London between 2005 and 2015. Patients undergoing primary PCI or pressure wire use were excluded leaving 87,166 patients in the study. The primary endpoint was all-cause mortality at a median of 4.8 years. RESULTS: OCT was used in 1,149 (1.3%) patients, intravascular ultrasound (IVUS) was used in 10,971 (12.6%) patients, and angiography alone in the remaining 75,046 patients. Overall OCT rates increased over time (p < 0.0001), with variation in rates between centers (p = 0.002). The mean stent length was shortest in the angiography-guided group, longer in the IVUS-guided group, and longest in the OCT-guided group. OCT-guided procedures were associated with greater procedural success rates and reduced in-hospital MACE rates. A significant difference in mortality was observed between patients who underwent OCT-guided PCI (7.7%) compared with patients who underwent either IVUS-guided (12.2%) or angiography-guided (15.7%; p < 0.0001) PCI, with differences seen for both elective (p < 0.0001) and acute coronary syndrome subgroups (p = 0.0024). Overall this difference persisted after multivariate Cox analysis (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.26 to 0.81; p = 0.001) and propensity matching (hazard ratio: 0.39; 95% CI: 0.21 to 0.77; p = 0.0008; OCT vs. angiography-alone cohort), with no difference in matched OCT and IVUS cohorts (HR: 0.88; 95% CI: 0.61 to 1.38; p = 0.43). CONCLUSIONS: In this large observational study, OCT-guided PCI was associated with improved procedural outcomes, in-hospital events, and long-term survival compared with standard angiography-guided PCI.

Contemporary trends in cardiogenic shock: Incidence, intra-aortic balloon pump utilisation and outcomes from the London Heart Attack Group.

BACKGROUND: Cardiogenic shock remains a major cause of morbidity and mortality in patients with ST-segment elevation myocardial infarction. We aimed to assess the current trends in cardiogenic shock management, looking specifically at the incidence, use of intra-aortic balloon pump therapy and outcomes in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. METHODS AND RESULTS: We undertook an observational cohort study of 21,210 ST-segment elevation myocardial infarction patients treated between 2005-2015 at the eight Heart Attack Centres in London, UK. Patients' details were recorded at the time of the procedure into local databases using the British Cardiac Intervention Society percutaneous coronary intervention dataset. There were 1890 patients who presented with cardiogenic shock. The primary outcome was all-cause mortality at a median follow-up of 4.1 years (interquartile range: 2.2-5.8 years). Increasing rates of cardiogenic shock were seen over the course of the study with consistently high mortality rates of 45-70%. A total of 685 patients underwent intra-aortic balloon pump insertion during primary percutaneous coronary intervention for cardiogenic shock with decreasing rates over time. Those patients undergoing intra-aortic balloon pump therapy were younger, more likely to have poor left ventricular function and less likely to have had previous percutaneous coronary intervention compared to the control group. Procedural success rates were similar (86.0% vs 87.1%, p=0.292) although crude, in-hospital major adverse cardiac event rates were higher (43.8% vs 33.7%, p<0.0001) in patients undergoing intra-aortic balloon pump therapy. Kaplan-Meier analysis demonstrated significantly higher mortality rates in patients receiving intra-aortic balloon pump therapy (50.9% intra-aortic balloon pump vs 39.9% control, p<0.0001) during the follow-up period. After multivariate Cox analysis (hazard ratio 1.04, 95% confidence interval 0.62-1.89) and the use of propensity matching (hazard ratio: 1.29, 95% confidence interval: 0.68-1.45) intra-aortic balloon pump therapy was not associated with mortality. CONCLUSION: Cardiogenic shock treated by percutaneous coronary intervention is increasing in incidence and remains a condition associated with high mortality and limited treatment options. Intra-aortic balloon pump therapy was not associated with a long-term survival benefit in this cohort and may be associated with increased early morbidity.

Prospective comparison of novel dark blood late gadolinium enhancement with conventional bright blood imaging for the detection of scar.

BACKGROUND: Conventional bright blood late gadolinium enhancement (bright blood LGE) imaging is a routine cardiovascular magnetic resonance (CMR) technique offering excellent contrast between areas of LGE and normal myocardium. However, contrast between LGE and blood is frequently poor. Dark blood LGE (DB LGE) employs an inversion recovery T2 preparation to suppress the blood pool, thereby increasing the contrast between the endocardium and blood. The objective of this study is to compare the diagnostic utility of a novel DB phase sensitive inversion recovery (PSIR) LGE CMR sequence to standard bright blood PSIR LGE. METHODS: One hundred seventy-two patients referred for clinical CMR were scanned. A full left ventricle short axis stack was performed using both techniques, varying which was performed first in a 1:1 ratio. Two experienced observers analyzed all bright blood LGE and DB LGE stacks, which were randomized and anonymized. A scoring system was devised to quantify the presence and extent of gadolinium enhancement and the confidence with which the diagnosis could be made. RESULTS: A total of 2752 LV segments were analyzed. There was very good inter-observer correlation for quantifying LGE. DB LGE analysis found 41.5% more segments that exhibited hyperenhancement in comparison to bright blood LGE (248/2752 segments (9.0%) positive for LGE with bright blood; 351/2752 segments (12.8%) positive for LGE with DB; p < 0.05). DB LGE also allowed observers to be more confident when diagnosing LGE (bright blood LGE high confidence in 154/248 regions (62.1%); DB LGE in 275/324 (84.9%) regions (p < 0.05)). Eighteen patients with no bright blood LGE were found to have had DB LGE, 15 of whom had no known history of myocardial infarction. CONCLUSIONS: DB LGE significantly increases LGE detection compared to standard bright blood LGE. It also increases observer confidence, particularly for subendocardial LGE, which may have important clinical implications.

Functional coronary stenosis severity assessed from the mean pressure gradient-velocity relationship obtained by contrast medium-induced submaximal hyperaemia.

AIMS: First, to establish the diagnostic performance of the pressure gradient at a standardised mean velocity (dPv) as derived from the cycle-averaged stenosis pressure gradient-velocity (dP-v) relationship obtained by administration of adenosine and, second, to determine whether dPv can be assessed from contrast medium-induced submaximal hyperaemia. METHODS AND RESULTS: Distal coronary pressure and velocity were simultaneously recorded in 64 patients during the response to intracoronary injection of adenosine. dPv was assessed at velocities between 20 and 50 cm/s. The pressure gradient at a mean flow velocity of 30 cm/s (dPv30) yielded an excellent diagnostic performance against FFR ≤0.8 (area under the curve 0.96; sensitivity 84%; specificity 96%; accuracy 89%). In a subgroup of 21 patients, measurements were repeated throughout contrast medium-induced reactive hyperaemia. Peak velocity and pressure gradient were lower compared to adenosine, but the course of the corresponding dP-v relationships coincided very well over the common velocity range, with no difference in dPv30. CONCLUSIONS: dPv30 reliably detects functionally significant coronary lesions. It derives from stenosis haemodynamics and can be obtained with submaximal hyperaemia, such as following injection of contrast medium, thereby obviating the maximal vasodilation by adenosine required for FFR or other established hyperaemic parameters of functional stenosis severity.

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.

Dynamic damping of the aortic pressure trace during hyperemia: the impact on fractional flow reserve measurement.

We report on two cases that illustrate an important caveat in the measurement of fractional flow reserve (FFR) in coronary arteries. To obtain accurate FFR measurements, two fundamental requirements must be fulfilled. One is to minimize microvascular resistance; the other is that there is no damping of the proximal aortic pressure trace. A problem with either of these requirements can be a source of serious error in the measurement of FFR. In each case we present here, despite a good aortic pressure trace at the start of the procedure, there is dynamic damping of the pressure trace during hyperemia, secondary to axial migration of the guiding catheter into the left main stem (LMS). In both cases, a normal aortic pressure trace (Pa) is present at baseline. After intracoronary adenosine injection, there was a fall in both mean Pa and distal coronary pressure (Pd) concomitant with damping of Pa, evidenced by loss of the dicrotic notch and ventricularization of the pressure trace. The resultant FFR value is underestimated. As hyperemia wears off, both pressure traces return to normal with good articulation of the dicrotic notch. When the procedure was repeated taking care to ensure that the guide did not move into the LMS during hyperemia, the Pa trace remained stable following intracoronary adenosine, while mean Pd decreased as before. In both cases, hemodynamically significant lesions were demonstrated that had been masked by the artifactual drop in Pa during the first attempt.

Coronary wave energy: a novel predictor of functional recovery after myocardial infarction.

BACKGROUND: Revascularization after acute coronary syndromes provides prognostic benefit, provided that the subtended myocardium is viable. The microcirculation and contractility of the subtended myocardium affect propagation of coronary flow, which can be characterized by wave intensity analysis. The study objective was to determine in acute coronary syndromes whether early wave intensity analysis-derived microcirculatory (backward) expansion wave energy predicts late viability, defined by functional recovery. METHODS AND RESULTS: Thirty-one patients (58±11 years) were enrolled after non-ST elevation myocardial infarction. Regional left ventricular function and late-gadolinium enhancement were assessed by cardiac magnetic resonance imaging, before and 3 months after revascularization. The backward-traveling (microcirculatory) expansion wave was derived from wave intensity analysis of phasic coronary pressure and velocity in the infarct-related artery, whereas mean values were used to calculate hyperemic microvascular resistance. Twelve-hour troponin T, left ventricular ejection fraction, and percentage late-gadolinium enhancement mass were 1.35±1.21 µg/L, 56±11%, and 8.4±6.0%, respectively. The infarct-related artery backward-traveling (microcirculatory) expansion wave was inversely correlated with late-gadolinium enhancement infarct mass (r=-0.81; P<0.0001) and strongly predicted regional left ventricular recovery (r=0.68; P=0.001). By receiver operating characteristic analysis, a backward-traveling (microcirculatory) expansion wave threshold of 2.8 W m(-2) s(-2)×10(5) predicted functional recovery with sensitivity and specificity of 0.91 and 0.82 (AUC 0.88). Hyperemic microvascular resistance correlated with late-gadolinium enhancement mass (r=0.48; P=0.03) but not left ventricular recovery (r=-0.34; P=0.07). CONCLUSIONS: The microcirculation-derived backward expansion wave is a new index that correlates with the magnitude and location of infarction, which may allow for the prediction of functional myocardial recovery. Coronary wave intensity analysis may facilitate myocardial viability assessment during cardiac catheterization.

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.

Future Directions for Percutaneous Mechanical Circulatory Support Devices.

Outcomes of patients in cardiogenic shock remain high, but the development of novel percutaneous mechanical circulatory support devices offers additional therapeutic options. Hand in hand with innovations in device technology, however, must also come development of integrated circulatory support networks focusing on rapid assessment of patients, multidisciplinary discussion, and timely therapeutic intervention. This article summarizes some of the recent developments in device technology; potential procedures for patient risk stratification, device selection, and response to therapy; management of vascular access to reduce insertion point complications; and some of the expanding potential roles of percutaneous mechanical circulatory support devices.

Does left ventricular function continue to influence mortality following contemporary percutaneous coronary intervention?

BACKGROUND: Left ventricular (LV) dysfunction was associated with adverse outcome after percutaneous coronary intervention (PCI) in the balloon-angioplasty and bare-metal stent era. Technological advances have reduced complications after PCI. The impact of left ventricular ejection fraction (LVEF) on outcomes in current clinical practice is unknown, with commonly used risk stratification models not consistently incorporating preprocedural LVEF. METHODS: A total of 2328 consecutive patients undergoing PCI in a single centre between April 2005 and July 2009 were analysed. Patients were eligible if LVEF had been categorized before PCI as good (LVEF ≥50%), moderate (LVEF 30-49%) or poor (LVEF <30%). Those in cardiogenic shock were excluded. Mortality data were tracked using the UK Office of National statistics database. Logistic regression analysis was used to predict the risk of mortality at 30-day and long-term follow-up. RESULTS: Overall all-cause mortality was 1.0% at 30 days and 5% at long-term follow-up. Kaplan-Meier analysis revealed an early divergence in survival curves according to LVEF. Mortality rates stratified by LVEF category were 0.4, 1.3 and 6.3% at 30 days and 3.3, 5.7 and 12.0% in the long term (2.2±1.1 years) (P<0.0001). Multiple regression analysis confirmed that impaired LVEF (≤50%) independently predicts 30-day [hazard ratio 4.20 (confidence interval 2.50-7.04), P=0.001] and long-term all-cause mortality [hazard ratio 1.67 (1.28-2.19), P=0.001]. CONCLUSION: LV impairment remains a strong predictor of early and late mortality after PCI. LV function assessment is integral in risk stratification and patient optimization and should be recommended, wherever feasible, before PCI.