Infective Endocarditis Hospitalizations and Outcomes in Patients With End-Stage Kidney Disease: A Nationwide Data-Linkage Study.

Background We investigated the clinical features, microbiology, and short- and long-term outcomes of incident infective endocarditis (IE) hospitalizations in patients with end-stage kidney disease (ESKD) requiring dialysis or with a kidney transplant over 25 years in Scotland. Methods and Results In this retrospective, population-based cohort study linking national hospitalization and mortality data, we identified patients with a history of ESKD and hospitalized with IE in Scotland between January 1, 1990 and December 31, 2014. From January 1, 2008, individual IE hospitalizations were additionally linked to national microbiology data. Multivariable logistic regression, adjusting for patient demographics and comorbidities, evaluated the association between ESKD and all-cause death at 1 and 3 years. Of 7638 incident IE hospitalizations between 1990 and 2014, 2.8% (216/7638) occurred in 210 patients with ESKD and 97.2% (7422/7638) occurred in 7303 patients without ESKD. Positive findings from blood cultures were identified in 42% (950/2267) of incident IE hospitalizations from 2008. Staphylococcus aureus was isolated in 25.9% (21/81) and 12.8% (280/2186) of patients with and without ESKD, respectively (P=0.002). ESKD was associated with an increased odds of death at 1 (44.9% versus 31.4%; adjusted odds ratio [aOR], 2.47, 95% CI, 1.85-3.30;, P<0.001) and 3 years (63.9% versus 42.8%; aOR, 3.77; 95% CI, 2.79-5.12; P<0.001). Conclusions IE is associated with a poor prognosis in patients with ESKD, especially in the longer term. Compared with patients without ESKD, patients with ESKD were twice as likely to die within 1 year, and 3 times as likely to die within 3 years of IE hospitalization.

Native Aortic Valve Disease Progression and Bioprosthetic Valve Degeneration in Patients With Transcatheter Aortic Valve Implantation.

BACKGROUND: Major uncertainties remain regarding disease activity within the retained native aortic valve, and regarding bioprosthetic valve durability, after transcatheter aortic valve implantation (TAVI). We aimed to assess native aortic valve disease activity and bioprosthetic valve durability in patients with TAVI in comparison with subjects with bioprosthetic surgical aortic valve replacement (SAVR). METHODS: In a multicenter cross-sectional observational cohort study, patients with TAVI or bioprosthetic SAVR underwent baseline echocardiography, computed tomography angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography. Participants (n=47) were imaged once with 18F-NaF positron emission tomography/computed tomography either at 1 month (n=9, 19%), 2 years (n=22, 47%), or 5 years (16, 34%) after valve implantation. Patients subsequently underwent serial echocardiography to assess for changes in valve hemodynamic performance (change in peak aortic velocity) and evidence of structural valve dysfunction. Comparisons were made with matched patients with bioprosthetic SAVR (n=51) who had undergone the same imaging protocol. RESULTS: In patients with TAVI, native aortic valves demonstrated 18F-NaF uptake around the outside of the bioprostheses that showed a modest correlation with the time from TAVI (r=0.36, P=0.023). 18F-NaF uptake in the bioprosthetic leaflets was comparable between the SAVR and TAVI groups (target-to-background ratio, 1.3 [1.2-1.7] versus 1.3 [1.2-1.5], respectively; P=0.27). The frequencies of imaging evidence of bioprosthetic valve degeneration at baseline were similar on echocardiography (6% versus 8%, respectively; P=0.78), computed tomography (15% versus 14%, respectively; P=0.87), and positron emission tomography (15% versus 29%, respectively; P=0.09). Baseline 18F-NaF uptake was associated with a subsequent change in peak aortic velocity for both TAVI (r=0.7, P<0.001) and SAVR (r=0.7, P<0.001). On multivariable analysis, 18F-NaF uptake was the only predictor of peak velocity progression (P<0.001). CONCLUSIONS: In patients with TAVI, native aortic valves demonstrate evidence of ongoing active disease. Across imaging modalities, TAVI degeneration is of similar magnitude to bioprosthetic SAVR, suggesting comparable midterm durability. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02304276.

Incidence, Microbiology, and Outcomes in Patients Hospitalized With Infective Endocarditis.

BACKGROUND: Despite improvements in management, infective endocarditis remains associated with high mortality and morbidity. We describe temporal changes in the incidence, microbiology, and outcomes of infective endocarditis and the effect of changes in national antibiotic prophylaxis guidelines on incident infective endocarditis. METHODS: Using a Scotland-wide, individual-level linkage approach, all patients hospitalized with infective endocarditis from 1990 to 2014 were identified and linked to national microbiology, prescribing, and morbidity and mortality datasets. Linked data were used to evaluate trends in the crude and age- and sex-adjusted incidence and outcomes of infective endocarditis hospitalizations. From 2008, microbiology data and associated outcomes adjusted for patient demographics and comorbidity were also analyzed. An interrupted time series analysis was performed to evaluate incidence before and after changes to national antibiotic prophylaxis guidelines. RESULTS: There were 7638 hospitalizations (65±17 years, 51% females) with infective endocarditis. The estimated crude hospitalization rate increased from 5.3/100 000 (95% CI, 4.8-5.9) to 8.6/100 000 (95% CI, 8.1-9.1) between 1990 and 1995 but remained stable thereafter. There was no change in crude incidence following the 2008 change in antibiotic prophylaxis guidelines (relative risk of change 1.06 [95% CI, 0.94-1.20]). The incidence rate in patients >80 years of age doubled from 1990 to 2014 (17.7/100 000 [95% CI, 13.4-23.3] to 37.9/100 000 [95% CI, 31.5-45.5]). The predicted 1-year age- and comorbidity-adjusted case fatality rate for a 65-year-old patient decreased in women (27.3% [95% CI, 24.6-30.2] to 23.7% [95% CI, 21.1-26.6]) and men (30.7% [95% CI, 27.7-33.8] to 26.8% [95% CI, 24.0-29.7]) from 1990 to 2014. Blood culture data were available from 2008 (n=2267/7638, 30%), with positive blood cultures recorded in 42% (950/2267). Staphylococcus (403/950, 42.4%) and streptococcus (337/950, 35.5%) species were most common. Staphylococcus aureus and enterococcus had the highest 1-year mortality (adjusted odds ratio 4.34 [95% CI, 3.12-6.05] and 3.41 [95% CI, 2.04-5.70], respectively). CONCLUSIONS: Despite changes in antibiotic prophylaxis guidelines, the crude incidence of infective endocarditis has remained stable. However, the incidence rate has doubled in the elderly. Positive blood cultures were observed in less than half of patients, with Staphylococcus aureus and enterococcus bacteremia associated with worse outcomes.

Percutaneous Repair of Ventricular Ruptures.

Acquired ventricular wall ruptures can be life-threatening. Depending on the pathological features and anatomy, surgical repair can be technically challenging and may be associated with high morbidity and mortality. We present 3 successful percutaneous repairs of different ruptures that used a variety of techniques. (Level of Difficulty: Advanced.).

Left Ventricular Thrombus After Primary PCI for ST-Elevation Myocardial Infarction: 1-Year Clinical Outcomes.

BACKGROUND: Left ventricular thrombus formation is a complication of acute myocardial infarction. However, the incidence and risk of systemic thromboembolism in the era of primary angioplasty for ST elevation myocardial infarction (STEMI) is unclear. This study aims to determine clinical outcomes in patients with STEMI treated with primary angioplasty and left ventricular thrombus at 1 year. METHODS: Patients who underwent primary angioplasty for STEMI and had a transthoracic echocardiogram were recruited. The primary endpoint was a composite of all-cause mortality, stroke, and systemic thromboembolism at 1 year. For the primary endpoint, the difference between the presence and absence of left ventricular thrombus was compared using a logistic regression, adjusting for minimization variables including age, diabetes mellitus, hypertension, and previous stroke. RESULTS: Of 2608 patients who underwent primary angioplasty for STEMI, 1645 (63%) patients had a transthoracic echocardiogram performed during the index hospital admission. Forty patients (2.4%) had evidence of left ventricular thrombus on transthoracic echocardiography. Patients with left ventricular thrombus were more likely to develop atrial fibrillation in the immediate postinfarction period (6 [15%] vs 87 [5.4%], P = 0.025). At 1 year, the primary endpoint occurred in 4 (10%) patients with left ventricular thrombus and 146 (9.1%) who did not (logistic regression hazard ratio 0.79, 95% confidence interval 0.23-2.70). CONCLUSIONS: In the contemporary era of mechanical reperfusion for STEMI, echocardiographic detection of left ventricular thrombus was observed in <3% patients. The presence of left ventricular thrombus was not associated with an increased risk of systemic thromboembolism.

Endothelial Progenitor Cell Biology and Vascular Recovery Following Transradial Cardiac Catheterization.

BACKGROUND: Transradial catheterization is associated with radial artery injury and vasomotor dysfunction and represents an accessible model of acute vascular injury in humans. We characterized vascular injury and functional recovery to understand the role of circulating endothelial progenitor cells in vascular repair. METHODS AND RESULTS: In 50 patients (aged 64±10 years, 70% male) undergoing transradial cardiac catheterization, radial artery injury was assessed by optical coherence tomography and examination of explanted vascular sheaths. Flow- and nitrate-mediated dilatation of the radial artery was assessed in both arms at baseline, at 24 hours, and at 1, 4, and 12 weeks. Circulating endothelial progenitor cell populations were quantified using flow cytometry. Late endothelial outgrowth colonies were isolated and examined in vitro. Optical coherence tomography identified macroscopic injury in 12 of 50 patients (24%), but endothelial cells (1.9±1.2×104 cells) were isolated from all arterial sheaths examined. Compared with the noncatheterized radial artery, flow-mediated vasodilatation was impaired in the catheterized artery at 24 hours (9.9±4.6% versus 4.1±3.1%, P<0.0001) and recovered by 12 weeks (8.1±4.9% versus 10.1±4.9%, P=0.09). Although the number of CD133+ cells increased 24 hours after catheterization (P=0.02), the numbers of CD34+ cells and endothelial outgrowth colonies were unchanged. Migration of endothelial cells derived from endothelial outgrowth colonies correlated with arterial function before catheterization but was not related to recovery of function following injury. CONCLUSIONS: Transradial cardiac catheterization causes endothelial denudation, vascular injury, and vasomotor dysfunction that recover over 12 weeks. Recovery of vascular function does not appear to be dependent on the mobilization or function of endothelial progenitor cells. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02147119.

Progressive breathlessness following transcatheter aortic valve replacement.

: An 84-year-old man presented urgently to the cardiology clinic with rapid onset exertional dyspnoea while walking on the flat. Five months previously, he underwent implantation of a balloon-expandable 26 mm transcatheter heart valve (SAPIEN 3, Edwards Lifesciences) for severe aortic stenosis. On clinical examination, the jugular venous pressure was elevated and a mid-late ejection systolic murmur was audible in the aortic region. ECG demonstrated sinus rhythm with a left ventricular (LV) strain pattern. Transthoracic echocardiography and cardiac CT were performed (figure 1). heartjnl;103/21/1703/F1F1F1Figure 1(A) Transthoracic continuous wave Doppler through the transcatheter AV. ECG-gated cardiac CT oblique reconstruction of the LV outflow tract and aortic root in mid-diastole (B) with axial reconstruction of the transcatheter AV in end-systole (inset). AT, acceleration time; AV, aortic valve; LV, left ventricular. QUESTION: Which aetiology best explains this presentation?Pannus formationTranscatheter bioprosthetic valve endocarditisPatient-prosthesis mismatchTranscatheter bioprosthetic valve leaflet thrombosisStructural valve degeneration.

Computed tomography myocardial perfusion vs 15O-water positron emission tomography and fractional flow reserve.

OBJECTIVES: Computed tomography (CT) can perform comprehensive cardiac imaging. We compared CT coronary angiography (CTCA) and CT myocardial perfusion (CTP) with 15O-water positron emission tomography (PET) and invasive coronary angiography (ICA) with fractional flow reserve (FFR). METHODS: 51 patients (63 (61-65) years, 80 % male) with known/suspected coronary artery disease (CAD) underwent 320-multidetector CTCA followed by "snapshot" adenosine stress CTP. Of these 22 underwent PET and 47 ICA/FFR. Obstructive CAD was defined as CTCA stenosis >50 % and CTP hypoperfusion, ICA stenosis >70 % or FFR <0.80. RESULTS: PET hyperaemic myocardial blood flow (MBF) was lower in obstructive than non-obstructive territories defined by ICA/FFR (1.76 (1.32-2.20) vs 3.11 (2.44-3.79) mL/(g/min), P < 0.001) and CTCA/CTP (1.76 (1.32-2.20) vs 3.12 (2.44-3.79) mL/(g/min), P < 0.001). Baseline and hyperaemic CT attenuation density was lower in obstructive than non-obstructive territories (73 (71-76) vs 86 (84-88) HU, P < 0.001 and 101 (96-106) vs 111 (107-114) HU, P 0.001). PET hyperaemic MBF corrected for rate pressure product correlated with CT attenuation density (r = 0.579, P < 0.001). There was excellent per-patient sensitivity (96 %), specificity (85 %), negative predictive value (90 %) and positive predictive value (94 %) for CTCA/CTP vs ICA/FFR. CONCLUSION: CT myocardial attenuation density correlates with 15O-water PET MBF. CTCA and CTP can accurately identify obstructive CAD. KEY POINTS: •CT myocardial perfusion can aid the assessment of suspected coronary artery disease. • CT attenuation density from "snapshot" imaging is a marker of myocardial perfusion. • CT myocardial attenuation density correlates with 15 O-water PET myocardial blood flow. • CT attenuation density is lower in obstructive territories defined by invasive angiography. • Diagnostic accuracy of CTCA+CTP is comparable to invasive angiography + fractional flow reserve.

Novel cardioprotective and regenerative therapies in acute myocardial infarction: a review of recent and ongoing clinical trials.

Following the original large-scale randomized trials of aspirin and ß-blockade, there have been a number of major advances in pharmacological and mechanical treatments for acute myocardial infarction. Despite this progress, myocardial infarction remains a major global cause of mortality and morbidity, driving a quest for novel treatments in this area. As the understanding of mitochondrial dynamics and the pathophysiology of reperfusion injury has evolved, the last three decades have seen advances in ischemic conditioning, pharmacological and metabolic cardioprotection, as well as biological and stem-cell therapies. The aim of this review is to provide a synopsis of adjunctive cardioprotective and regenerative therapies currently undergoing or entering early clinical trials in the treatment of patients with acute myocardial infarction.

Prolonged Clopidogrel Use is Associated with Improved Clinical Outcomes Following Drug-Eluting But Not Bare Metal Stent Implantation.

BACKGROUND: Guidelines recommend clopidogrel use for 6-12 months following drug-eluting stent (DES) implantation and 1-12 months following bare metal stent (BMS) implantation. The role of clopidogrel beyond 12 months is unclear. METHODS: We linked hospital administrative, community pharmacy and cardiac revascularization data to determine clopidogrel use and outcomes for all patients (those with acute presentations and those with stable angina) receiving a coronary stent in British Columbia 2004-2006, with follow-up until the end of 2008. Cox proportional hazard regression was performed to evaluate the effect of clopidogrel duration (≤12 vs. >12 months) on outcomes following BMS or DES implantation. Patients who died ≤12 months from index stent placement were excluded. RESULTS: A total of 15,629 patients were included in the study. Of 3599 patients who received at least one DES and 12,030 patients who received only BMS, 1326 (37 %) and 2121 (18 %), respectively, filled a prescription for clopidogrel >12 months from the index procedure. The mean duration of clopidogrel was 406 ± 35 days and 407 ± 37 days in the prolonged use (>12 months) DES and BMS cohorts, respectively, compared with 224 ± 112 days (p < 0.001) and 122 ± 117 days (p < 0.001), respectively, for patients receiving clopidogrel ≤12 months. Clopidogrel use beyond 12 months was associated with a reduction in mortality [hazard ratio (HR) 0.66, 95 % confidence interval (CI) 0.45-0.97] and the composite of mortality and readmission for myocardial infarction (HR 0.72, 95 % CI 0.55-0.94) in patients treated with DES, but not BMS alone. Prolonged clopidogrel use was not associated with bleeding-related mortality. CONCLUSIONS: Clopidogrel use beyond 12 months was associated with a reduction in death and hospitalization for myocardial infarction following DES, but not BMS, implantation. Our findings support a longer duration of clopidogrel therapy for patients treated with DES.

Rotigaptide protects the myocardium and arterial vasculature from ischaemia reperfusion injury.

AIM: Ischaemia-reperfusion injury (IRI) causes impaired endothelial function and is a major component of the adverse effects of reperfusion following myocardial infarction. Rotigaptide increases gap junction conductance via connexin-43. We tested the hypothesis that rotigaptide reduces experimental myocardial infarction size and ameliorates endothelial IRI in humans. METHODS: Myocardial infarction study: porcine myocardial infarction was achieved by catheter-induced occlusion of the left anterior descending artery. In a randomized double-blind study, rotigaptide (n = 9) or placebo (n = 10) was administered intravenously as a 10 min bolus prior to reperfusion and continuously during 2 h of reperfusion. Myocardial infarction size (IS) was assessed as proportion of the area at risk (AAR). Human translational study: forearm IRI was induced in the presence or absence of intra-arterial rotigaptide. In a randomized double-blind study, forearm arterial blood flow was measured at rest and during intra-arterial infusion of acetylcholine (5-20 µg min(-1) ; n = 11) or sodium nitroprusside (2-8 mg min(-1) ; n = 10) before and after intra-arterial infusion of placebo or rotigaptide, and again following IRI. RESULTS: Myocardial infarction study: Rotigaptide treatment was associated with a reduction of infarct size (IS/AAR[%]: 18.7 ± 4.1 [rotigaptide] vs. 43.6 ± 4.2 [placebo], P = 0.006). Human translational study: Endothelium-dependent vasodilatation to acetylcholine was attenuated after ischaemia-reperfusion in the presence of placebo (P = 0.007), but not in the presence of rotigaptide (P = NS). Endothelium-independent vasodilatation evoked by sodium nitroprusside was unaffected by IRI or rotigaptide (P = NS). CONCLUSIONS: Rotigaptide reduces myocardial infarction size in a porcine model and protects from IRI-related endothelial dysfunction in man. Rotigaptide may have therapeutic potential in the treatment of myocardial infarction.

Vascular injury and repair: a potential target for cell therapies.

Whether due to atherosclerotic disease or mechanical intervention, vascular injury is a frequently encountered pathology in cardiovascular medicine. The past decade has seen growing interest in the role of circulating endothelial progenitor cells in vessel recovery postinjury. Despite this, the definition, origin and potential role of endothelial progenitor cells in vascular regeneration remains highly controversial. While animal work has shown early promise, evidence of a therapeutic role for endothelial progenitor cells in humans remains elusive. To date, clinical trials involving direct cell administration, growth factor therapy and endothelial cell capture stents have largely been disappointing, although this may in part reflect limitations in study design. This article will outline the pathophysiological mechanisms of vascular injury with an emphasis on endothelial progenitor cell biology and the potential therapeutic role of this exciting new field.

Optical coherence tomography versus intravascular ultrasound to evaluate stent implantation in patients with calcific coronary artery disease.

AIMS: Stent underexpansion and malapposition are associated with adverse outcomes following percutaneous coronary intervention, but detection and treatment can be challenging in the presence of extensive coronary artery calcification. Frequency domain optical coherence tomography (FD-OCT) is a novel intravascular imaging technique with greater spatial resolution than intravascular ultrasound (IVUS) but its role in the presence of extensive coronary calcification remains unclear. We sought to determine the utility of FD-OCT compared to IVUS imaging to guide percutaneous coronary intervention in patients with severe calcific coronary artery disease. METHODS: 18 matched IVUS and FD-OCT examinations were evaluated following coronary stent implantation in 12 patients (10 male; mean age 70±7 years) undergoing rotational atherectomy for symptomatic calcific coronary artery disease. RESULTS: In-stent luminal areas were smaller (minimum in-stent area 6.77±2.18 vs 7.19±2.62 mm(2), p<0.05), while reference lumen dimensions were similar with FD-OCT compared with IVUS. Stent malapposition was detected in all patients by FD-OCT and in 10 patients by IVUS. The extent of stent malapposition detected was greater (20% vs 6%, p<0.001) with FD-OCT compared to IVUS. Postdilation increased the in-stent luminal area (minimum in-stent area: 8.15±1.90 vs 7.30±1.62 mm(2), p<0.05) and reduced the extent of stent malapposition (19% vs 34%, p<0.005) when assessed by FD-OCT, but not IVUS. CONCLUSIONS: Acute stent malapposition occurs frequently in patients with calcific coronary disease undergoing rotational atherectomy and stent implantation. In the presence of extensive coronary artery calcification, FD-OCT affords enhanced stent visualisation and detection of malapposition, facilitating improved postdilation stent apposition and minimal luminal areas. TRIAL REGISTRATION NUMBER: NCT02065102.

Delay in filling first clopidogrel prescription after coronary stenting is associated with an increased risk of death and myocardial infarction.

BACKGROUND: Patients frequently experience difficulties with medication compliance after hospital discharge. We investigated the effect of a delay in filling a first clopidogrel prescription after hospital discharge on clinical outcomes subsequent to coronary stenting. METHODS AND RESULTS: Hospital administrative, community pharmacy, and cardiac revascularization data were determined for all patients receiving a coronary stent in British Columbia 2004-2006 with follow-up out to 2 years. Cox's proportional hazard regression analysis, adjusting for baseline demographics and procedural variables, was performed to examine the effects of delay in filling a clopidogrel prescription after hospital discharge on clinical outcomes.Of 15 629 patients treated with coronary stents, 3599 received at least 1 drug-eluting stent (DES), whereas 12 030 received bare metal stents (BMS) alone. In total, 1064 (30%) and 3758 (31%) patients in the DES and BMS groups, respectively, failed to fill a prescription within 3 days of discharge (median, 1 day; interquartile range [IQR], 1 to 3). After regression analysis, a delay of >3 days was predictive of mortality and recurrent myocardial infarction (MI) irrespective of stent type (DES: hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.7 to 3.4; and HR, 2.0; 95% CI, 1.5 to 2.7, respectively, and BMS: HR, 2.2; 95% CI, 1.9 to 2.6; and HR, 1.8; 95% CI, 1.5 to 2.1, respectively). This excess hazard was greatest in the 30-day period immediately after hospital discharge (mortality: HR, 5.5; 95% CI, 3.5 to 8.6; and MI: HR, 3.1; 95% CI, 2.4 to 4.0, for all patients). CONCLUSIONS: Delays in patients filling their first prescription for clopidogrel after coronary stenting are common and associated with adverse clinical outcomes, irrespective of stent type. Strategies to reduce delays have the potential to improve clinical outcomes.

Displacement of cortisol from human heart by acute administration of a mineralocorticoid receptor antagonist.

CONTEXT: Mineralocorticoid receptor (MR) antagonists have beneficial effects in patients with heart failure and myocardial infarction, often attributed to blocking aldosterone action in the myocardium. However, binding of aldosterone to MR requires local activity of the enzyme 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), which inactivates cortisol to cortisone and thereby prevents receptor occupancy by cortisol. In vivo activity of 11ß-HSD2 and potential occupancy of MR by cortisol in human heart have not been quantified. OBJECTIVE: This study aimed to measure in vivo activity of 11ß-HSD2 and to establish whether cortisol binds MR in human heart. PARTICIPANTS AND INTERVENTIONS: Nine patients without heart failure undergoing diagnostic coronary angiography were infused to steady state with the stable isotope tracers 9,11,12,12-[(2)H]4-cortisol and 1,2-[(2)H]2-cortisone to quantify cortisol and cortisone production. Samples were obtained from the femoral artery and coronary sinus before and for 40 minutes after bolus iv administration of an MR antagonist, potassium canrenoate. Coronary sinus blood flow was measured by venography and Doppler flow wire. RESULTS: There was no detectable production of cortisol or cortisone across the myocardium. After potassium canrenoate administration, plasma aldosterone concentrations increased substantially but aldosterone was not detectably released from the myocardium. In contrast, plasma cortisol concentrations did not change in the systemic circulation but tissue-bound cortisol was released transiently from the myocardium after potassium canrenoate administration. CONCLUSIONS: Human cardiac 11ß-HSD2 activity appears too low to inactivate cortisol to cortisone. Cortisol is displaced acutely from the myocardium by MR antagonists and may contribute to adverse MR activation in human heart.

18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial.

BACKGROUND: The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ((18)F-NaF) and (18)F-fluorodeoxyglucose ((18)F-FDG). METHODS: In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent (18)F-NaF and (18)F-FDG PET-CT, and invasive coronary angiography. (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of (18)F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction. FINDINGS: In 37 (93%) patients with myocardial infarction, the highest coronary (18)F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40-2·25] vs highest non-culprit 1·24 [1·06-1·38], p<0·0001). By contrast, coronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40-2·13] vs 1·58 [1·28-2·01], p=0·34). Marked (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal (18)F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61-2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09-1·19] vs 1·01 [0·94-1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21-29] vs 18% [14-22], p=0·001). INTERPRETATION: (18)F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease. FUNDING: Chief Scientist Office Scotland and British Heart Foundation.