Simultaneous 18-FDG PET and MR imaging in lower extremity arterial disease.

Background: Simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) is a novel hybrid imaging method integrating the advances of morphological tissue characterization of MRI with the pathophysiological insights of PET applications. Aim: This study evaluated the use of simultaneous 18-FDG PET/MR imaging for characterizing atherosclerotic lesions in lower extremity arterial disease (LEAD). Methods: Eight patients with symptomatic stenoses of the superficial femoral artery (SFA) under simultaneous acquisition of 18-FDG PET and contrast-enhanced MRI using an integrated whole-body PET/MRI scanner. Invasive plaque characterization of the SFA was performed by intravascular imaging using optical coherence tomography. Histological analysis of plaque specimens was performed after directional atherectomy. Results: MRI showed contrast enhancement at the site of arterial stenosis, as assessed on T2-w and T1-w images, compared to a control area of the contralateral SFA (0.38 ± 0.15 cm vs. 0.23 ± 0.11 cm; 1.77 ± 0.19 vs. 1.57 ± 0.15; p-value <0.05). On PET imaging, uptake of 18F-FDG (target-to-background ratio TBR > 1) at the level of symptomatic stenosis was observed in all but one patient. Contrast medium-induced MR signal enhancement was detected in all plaques, whereas FDG uptake in PET imaging was increased in lesions with active fibroatheroma and reduced in fibrocalcified lesions. Conclusion: In this multimodal imaging study, we report the feasibility and challenges of simultaneous PET/MR imaging of LEAD, which might offer new perspectives for risk estimation.

Outcomes of endovascular treatment for popliteal artery disease.

Background: Finding the appropriate endovascular revascularization strategy for patients with peripheral artery disease and a popliteal artery lesion remains particulary challenging. Data regarding predictors for a beneficial outcome are scarce. Patients and methods: All endovascular procedures of popliteal artery lesions (n=227) performed in 197 patients between February 2009 and May 2018 at our institution were retrospectively analyzed. Hemodynamically relevant restenosis represented the primary endpoint. Results: The overall technical success rate was 98% and yielded 99% for stenoses (n=145) and 97% for occlusions (n=82). In a median follow-up of 10 months, the overall rate of restenosis was 23%. After 1 and 2 years, the primary patency rates were 76% and 55% and the secondary patency rate was 100%, respectively. The estimated probability of restenosis was significantly higher in stented lesions (stent vs. no stent; 36.0% vs. 19.1%; p=0.030). Multivariate analysis identified stent implantation (hazard ratio: 2.4; overall P=0.010) and diabetes (hazard ratio 2.0; P=0.023) as significant predictors for the development of restenosis. Conclusions: Endovascular therapy for popliteal artery disease was associated with high technical success rates and accompanied with a promising mid-term outcome, particularly in lesions treated with balloon angioplasty alone.

Ten-year outcomes after percutaneous coronary intervention of in-stent restenosis in saphenous vein grafts.

BACKGROUND: Only few data is available for long-term outcomes of patients being treated for in-stent restenosis (ISR) in saphenous vein grafts (SVG). AIMS: Thus, the aim of this observational, retrospective study was to close this lack of evidence. METHODS: Between January 2007 and February 2021 a total of 163 patients with 186 ISR lesions located in SVG were treated at two large-volume centers in Munich, Germany. Endpoints of interest were all-cause mortality, target lesion revascularization (TLR) and target vessel myocardial infarction (TVMI). Furthermore, recurrent ISR were assessed. Outcomes are presented as Kaplan-Meier event rates. RESULTS: Mean age was 72.6 ± 8.6 years, 90.8% were male, 36.8% were diabetics and 42.3% presented an acute coronary syndrome. ISR were treated with DES in 64.0% and with balloon angioplasty (BA) in 36.0%. After 10 years, the rates for all-cause mortality, TVMI and TLR were 58.2%, 15.4%, and 22.6%, respectively. No statistically relevant differences were found between the types of treatment (DES or BA) regarding all-cause mortality (55.7% vs. 63.2%, p = 0.181), TVMI (13.8% vs. 18.6%, p = 0.215) and TLR (21.8% vs. 25.0%, p = 0.764). Median time between first and recurrent ISR was 270.8 days. Recurrent ISR were treated with DES in a comparable proportion as during first ISR (p = 0.075). Independent predictor of TLR is patient age (p = 0.034). The median follow-up duration was 5.1 years (75% CI 2.8; 8.5). CONCLUSIONS: Clinical event rates after intervention of ISR located in SVG are high without statistically relevant differences regarding the type of treatment. However, further studies are needed.

Very long-term outlook of acute coronary syndromes after percutaneous coronary intervention with implantation of polymer-free versus durable-polymer new-generation drug-eluting stents.

BACKGROUND: Detailed long-term follow-up data on patients with acute coronary syndromes (ACS) in general, and those with ST-elevation myocardial infarction (STEMI) in particular, are limited. We aimed to appraise the long-term outlook of patients undergoing percutaneous coronary intervention (PCI) with state-of-the-art coronary stents for STEMI, other types of ACS and stable coronary artery disease (CAD), and also explore the potential beneficial impact of new-generation polymer-free drug-eluting stents (DES) in this setting. METHODS: Baseline, procedural and very long-term outcome data on patients undergoing PCI and randomized to implantation of new-generation polymer-free vs. durable polymer DES were systematically collected, explicitly distinguishing subjects with admission diagnosis of STEMI, non-ST-elevation ACS (NSTEACS), and stable CAD. Outcomes of interest included death, myocardial infarction, revascularization (i.e. patient-oriented composite endpoints [POCE]), major adverse cardiac events (MACE), and device-oriented composite endpoints (DOCE). RESULTS: A total of 3002 patients were included, 1770 (59.0%) with stable CAD, 921 (30.7%) with NSTEACS, and 311 (10.4%) with STEMI. At long-term follow-up (7.5±3.1 years), all clinical events were significantly more common in the NSTEACS group and, to a lesser extent, in the stable CAD group (e.g. POCE occurred in, respectively, 637 [44.7%] vs. 964 [37.9%] vs. 133 [31.5%], P<0.001). While these differences were largely attributable to adverse coexisting features in patients with NSTEACS (e.g. advanced age, insulin-dependent diabetes, and extent of CAD), the unfavorable outlook of patients presenting with NSTEACS persisted even after multivariable adjustment including several prognostically relevant factors (hazard ratio [HR] of NSTEACS vs. stable CAD 1.19 [95% confidence interval 1.03-1.38], P=0.016). Notably, even after encompassing all prognostically impactful features, no difference between polymer-free and permanent polymer drug-eluting stents appeared (HR=0.96 [0.84-1.10], P=0.560). CONCLUSIONS: Unstable coronary artery disease, especially when presenting without ST-elevation, represents an informative marker of adverse long-term prognosis in current state-of-the-art invasive cardiology practice. Even considering admission diagnosis, and despite of using no polymer, polymer-free DES showed similar results with regards to safety and efficacy when compared with DES with permanent polymer.

Prevalence and patterns of in-stent neoatherosclerosis in lower extremity artery disease.

BACKGROUND: In-stent restenosis (ISR) is responsible for a rapid decline of vessel patency after stenting. To date, little is known about the role of in-stent neoatherosclerosis (NA) in stent failure in lower limb arteries. AIMS: This study aimed to determine the prevalence and patterns of in-stent NA in patients with symptomatic ISR of the lower extremity vasculature using intravascular optical coherence tomography (OCT) imaging. METHODS: Patients underwent endovascular revascularisation for ISR including angiography and OCT imaging. NA was defined as the presence of at least 1 fibroatheroma or fibrocalcific plaque within the neointima of a stented segment. RESULTS: Using OCT, we imaged 24 symptomatic patients with lower extremity artery disease (LEAD), with a total of 30 ISR in the lower limbs, prior to their scheduled endovascular interventions. NA formation was observed in 23 (76.7%) lesions, while all stents with an implant duration >5 years (n=8) showed signs of NA. The time from stent implantation to OCT was significantly increased in lesions with NA (p=0.002). Lesions without NA had a significantly shorter duration from index procedure to OCT than those with ≥50 percent (n=9; p=0.003) or <50 percent (n=14; p=0.015) of frames exhibiting signs of NA. NA was predominantly characterised by fibroatheroma with thick fibrous caps with or without calcification. CONCLUSIONS: In-stent NA is frequently identified by OCT imaging after endovascular therapy in lower limb arteries; this increased both in frequency and extent the longer the duration since implantation. Our findings indicate an active atherosclerotic process that may need tailored mitigation strategies.

Frequency of subclavian artery stenosis in patients with mammarian artery coronary bypass and suspected coronary artery disease progression.

We retrospectively analyzed patient records of all patients with a history of internal mammarian artery (IMA) coronary bypass undergoing coronary angiography at two cardiovascular centers between January 1st 1999 and December 31st 2019. A total of 11,929 coronary angiographies with or without percutaneous coronary intervention were carried out in 3921 patients. Our analysis revealed 82 (2%) patients with documented subclavian artery stenosis. Of these, 8 (10%) patients were classified as having mild, 18 (22%) moderate, and 56 (68%) severe subclavian artery stenosis. In 7 (9%) patients with subclavian artery stenosis, angiography revealed occlusion of the IMA graft. 26 (32%) patients with severe subclavian artery stenosis underwent endovascular or surgical revasculararization of the subclavian artery. In this retrospective multicenter study, subclavian artery stenosis was a relevant finding in patients with an internal mammarian artery coronary bypass graft undergoing coronary angiography. The development of dedicated algorithms for screening and ischemia evaluation in affected individuals may improve treatment of this potentially underdiagnosed and undertreated condition.

Value of PET ECG gating in a cross-validation study of cardiac function assessment by PET/MR imaging.

BACKGROUND: This work investigated the impact of different cardiac gating methods on the assessment of cardiac function by FDG-PET in a cross-validation PET/MR study. METHODS AND RESULTS: MR- and PET-based left ventricular end-diastolic, end-systolic volumes, and ejection fraction (EDV, ESV, and EF) were delineated in 30 patients with a PET/MR examination. Cardiac PET imaging was performed using three ECG gating methods: fixed number of gates per beat (STD), STD with a beat acceptance window (STD-BR), and fixed gate duration (FW). High MR-PET correlations were found in all the values. ESVs correlated better than EDVs and EFs: Pearson's r coefficient [0.92, 0.92, 0.92] in ESV vs [0.75, 0.81, 0.80] in EDV and [0.79, 0.91, 0.87] in EF, for each method [STD, STD-BR, FW]. Biases with respect to MRI for all the evaluated PET methods were less than 13% in EDV, 5% in ESV, and 14% in EF, but with wide limits of agreements, in the range (59-68)% in EDV, (65-70)% in ESV, and (49-71)% in EF. STD showed the strongest disagreement, while there were no marked differences between STD-BR and FW. CONCLUSION: Based on these findings, PET- and MR-based cardiac function parameters were highly correlated but in substantial disagreement with variabilities introduced by the selected PET ECG gating method. The most significant differences were associated with the ECG gating method susceptible to highly irregular beats, while similar performance was observed in the methods using uniform adjustment of gates width per beat with the beat acceptance window, and fixed gate width along all the beats. Thus, strict quality controls of R peak detection are needed to minimize its impact on the function assessment.

Coronary plaque characterization assessed by delayed enhancement dual-layer spectral CT angiography and optical coherence tomography.

This study aimed to prospectively evaluate delayed enhancement imaging by spectral computed tomography using soluble iodine containing contrast media to improve the in vivo characterization of coronary plaque types based on the quantification of delayed iodine enhancement. Patients with known or suspected coronary artery disease (CAD) underwent spectral coronary CT-angiography (SCCTA). Absolute delayed iodine enhancement in all visible coronary plaques was assessed. Patients with significant CAD (> 50% stenosis) further underwent invasive coronary angiography (ICA) including optical coherence tomography (OCT). We identified 50 non-calcified coronary plaques in 72 patients undergoing SCCTA. 17 patients with significant CAD underwent further ICA including OCT imaging. In those, we were able to match 35 plaques by both SCCTA and OCT. Based on OCT imaging, 22/35 matched plaques (63%) were characterized as high-risk coronary plaques (thin-cap fibroatheroma n = 2, fibroatheroma n = 20), whereas 13/35 (37%) were characterized as low-risk plaques (fibrocalcific lesion n = 3, fibrous plaques n = 9, and early-onset fibroatheroma n = 1). All plaques showed similar HU's and could not be classified into high-risk or low-risk plaques by conventional CT measures. Minimal delayed iodine enhancement within plaques as quantified by SCCTA demonstrated significantly lower values in high-risk as compared to low-risk coronary plaques (1.0 ± 1.5 mg/ml vs. 2.2 ± 1.1 mg/ml, p = 0.021) which allowed estimation of high-risk plaques with high sensitivity and moderate specificity (77% and 56%). Measurement of delayed enhancement iodine uptake within stable coronary artery plaques using dual-layer SCCTA might contribute to a more precise estimation of plaque vulnerability surpassing conventional CT techniques.

Diabetes mellitus and femoropopliteal in-stent restenosis.

Background: The influence of diabetes mellitus (DM) on recurrent in-stent restenosis (ISR) of femoropopliteal arteries remains understudied. We investigated whether DM has an impact on recurrent restenosis after femoropopliteal stenting in patients included in the dRug-coatEd balloon angioPlasty for femoropopliteAl In-stent Restenosis (REPAIR) cooperation. Patients and methods: The REPAIR cooperation pooled the patient-level data from 3 randomized trials in which patients with ISR of femoropopliteal arteries received either drug-coated balloon (DCB) or plain balloon angioplasty. For this analysis, patients were divided in two groups based on whether they had or had not a DM diagnosis at the time of enrollment. The primary outcome was target lesion revascularization (TLR). The main secondary outcome was recurrent ISR. Other outcomes of interest were death, Rutherford class improvement and ankle-brachial index at follow-up. Results: 256 patients (DM, n=99 vs. non-DM, n=157) with 12-month follow-up were included in the analysis. Compared to non-DM patients, DM patients displayed no difference in terms of TLR [adjusted hazard ratio (95% Confidence intervals): 0.96 (0.55, 1.69), p=0.89] and recurrent ISR [1.04 (0.61, 1.77), p=0.88], whilst mortality was higher [9.38 (1.06, 83.11), p=0.044]. There were no differences between groups with respect to other secondary outcomes. The percutaneous treatment with DCB as compared to plain balloon angioplasty significantly reduced the risk of TLR and recurrent ISR without an excess risk of death irrespective of DM (p for interaction ≥0.70). Conclusions: In patients with femoropopliteal ISR, diabetes has a neutral effect on the risk of recurrence, but increases mortality at 12-month follow-up. DCB as compared to plain balloon angioplasty is associated with superior efficacy without trade-off in safety, regardless of diabetes.

Ten-Year Clinical Outcomes in Patients With Acute Coronary Syndrome Treated With Biodegradable, Permanent-Polymer or Polymer-Free Drug-Eluting Stents.

OBJECTIVES: This study aimed to compare 10-year clinical outcomes in patients with acute coronary syndrome (ACS) treated with new-generation biodegradable-polymer (BP-DES), polymer-free (PF-DES), and permanent-polymer drug-eluting stents (PPDES). METHODS: We analyzed 10-year clinical outcomes for 2042 patients with ACS enrolled in the ISAR-TEST 4 and ISAR-TEST 5 randomized controlled trials. Patients were divided into 3 groups: new-generation PP-DES, BP-DES, and PF-DES. Endpoints of interest included a device-oriented composite endpoint (DOCE) and a patient-oriented composite endpoint (POCE) at 10 years. RESULTS: BP-DES as compared with PP-DES demonstrated a lower DOCE frequency, but this did not meet statistical significance (BP-DES vs PP-DES, 35.4% vs 41.5%, respectively; adjusted hazard ratio (HR), 0.83; 95% confidence interval [CI], 0.68-1.00; P=.05). There was a significantly lower POCE frequency in patients treated with BP-DES compared with PP-DES (65.3% vs 69.0%, respectively; HR, 0.86; 95% CI, 0.75-0.99; P=.04). The relative frequency of the DOCE (41.4% vs 41.5%; HR, 0.97; 95% CI, 0.83-1.15; P=.76) and the POCE (66.8% vs 69.0%; HR, 0.99; 0.87-1.12; P=.82) were comparable in patients treated with PF-DES and PP-DES. CONCLUSION: In patients with ACS, BP-DES were associated with a lower relative frequency of a POCE compared with new-generation PP-DES at 10 years. The relative frequencies of both device- and patient-related outcomes were comparable in patients treated with PF-DES and PP-DES at 10 years.

Pre-admission antiplatelet therapy and treatment effect of ticagrelor vs. prasugrel in patients with acute coronary syndromes-a subgroup analysis of the ISAR-REACT 5 trial.

AIMS: To assess whether the efficacy and safety of ticagrelor vs. prasugrel in patients with acute coronary syndromes (ACSs) are influenced by pre-admission treatment with aspirin and/or clopidogrel. METHODS AND RESULTS: Patients (n = 4018) were categorized into two groups: pre-admission aspirin and/or clopidogrel group (n = 1455) and no pre-admission aspirin or clopidogrel group (n = 2563). The primary endpoint was the composite of all-cause death, myocardial infarction, or stroke; the secondary safety endpoint was Bleeding Academic Research Consortium (BARC) type 3-5 bleeding, both at 1 year. Patients in the pre-admission aspirin and/or clopidogrel group had a higher risk of ischaemic events, but a similar risk of bleeding to patients in the no pre-admission aspirin or clopidogrel group (cumulative incidences 10.5% vs. 6.7%, and 5.7% vs. 5.7%, respectively). The primary endpoint occurred in 81/717 patients assigned to ticagrelor and 69/738 patients assigned to prasugrel in the pre-admission aspirin and/or clopidogrel group [11.5% vs. 9.5%; hazard ratio (HR) = 1.23; 95% confidence interval (CI) 0.89-1.69], and in 103/1295 patients assigned to ticagrelor and 68/1268 patients assigned to prasugrel in the no pre-admission aspirin or clopidogrel group [8.0% vs. 5.4%; HR = 1.50 (1.10-2.03); Pint = 0.38]. BARC type 3-5 bleeding events did not differ between ticagrelor and prasugrel in patients in the pre-admission aspirin and/or clopidogrel (6.2% vs. 4.5%) or no pre-admission aspirin or clopidogrel (5.3% vs. 5.1%) group (Pint = 0.54). CONCLUSION: In patients with ACS, pre-admission therapy with aspirin and/or clopidogrel has no influence on the relative efficacy and safety of ticagrelor and prasugrel.

Prediction of risk for bleeding, myocardial infarction and mortality after percutaneous coronary intervention in patients with acute coronary syndromes.

BACKGROUND: Whether bleeding and myocardial infarction (MI) improve the performance of risk prediction models for mortality in patients with acute coronary syndromes (ACS) treated with percutaneous coronary intervention (PCI) remains unknown. METHODS: This study included 3377 patients with ACS who underwent PCI in the setting of the ISAR-REACT 5 trial. Patients with bleeding, MI or those dying at 1 year after PCI were characterized in terms of baseline characteristics, risk estimates and C-statistic of the risk prediction models for these outcomes. RESULTS: Major bleeding (Bleeding Academic Research Consortium types 3-5), MI and mortality occurred in 195 patients (5.8%), 143 patients (4.3%) and 143 patients (4.3%), respectively. After adjustment, bleeding [hazard ratio = 5.08; 95% confidence interval (CI), 3.03-8.53; P < 0.001] and MI [hazard ratio = 5.90; 95% CI, (3.00-11.65); P < 0.001) remained independently associated with the risk for 1-year mortality. The C-statistic (with 95% CI) of the model for bleeding, MI and mortality was, 0.755 (0.722-0.786), 0.752 (0.717-0.789) and 0.868 (0.837-0.896), respectively. The inclusion of bleeding [C-statistic: 0.892 (0.867-0.913); delta C-statistic 0.024 (-0.014 to 0.065); P = 0.200] or MI [C-statistic: 0.878 (0.851-0.903); delta C-statistic 0.011 (-0.030 to 0.053); P = 0.635] in the risk prediction models for mortality alongside baseline demographical and clinical variables did not improve prediction for mortality. CONCLUSIONS: In patients with ACS treated with PCI, mortality is the most accurately predicted outcome. Bleeding and MI did not improve risk discrimination for mortality when added in the risk prediction models for mortality suggesting that these outcomes do not provide incremental prognostic information on top of baseline demographical and clinical data.

Target and non-target vessel related events at 10 years post percutaneous coronary intervention.

AIMS: To define the incidence of events related to the stented vessel (target vessel related events: TVRE) and events related to non-stented vessels (non-target vessel related events: NTVRE) through to 10-year follow-up in patients post-PCI with newer generation drug eluting stents (DES). METHODS AND RESULTS: The current study is a post-hoc analysis of patient level data from two randomised controlled trials in Germany. Patients older than 18 years with ischemic symptoms or evidence of myocardial ischemia in the presence of ≥ 50% de novo stenosis located in the native coronary vessels were considered eligible. The endpoints of interest were TVRE (a composite of first target vessel myocardial infarction or target vessel revascularization) and NTVRE (a composite of first non-target vessel MI or non-target vessel revascularization) through to 10 years post PCI. We included 4953 patients in this analysis. Through to 10-years post-PCI, TVRE occurred in 1238 of 4953 patients (cumulative incidence: 25.8%) and NTVRE occurred in 1442 of 4953 patients (cumulative incidence: 30.3%). The majority of TVRE and NTVRE were revascularization events. From 0 to 1 years, the cumulative incidence of TVRE was 15.9% and of NTVRE was 12.3%. From 1 to 10 years, the cumulative incidences of TVRE and NTVRE were 11.2% and 22.4%, respectively. CONCLUSION: At 10-year post-PCI with new generation drug eluting stents, events related to remote vessel disease progression account for a higher proportion of events than events related to the stented vessel. TRIAL REGISTRATION: ISAR TEST 4 ClinicalTrials.gov Identifier: NCT00598676. ISAR TEST 5 ClinicalTrials.gov Identifier: NCT00598533.

Efficacy and safety of ECG-synchronized pulsatile extracorporeal membrane oxygenation in the clinical setting: The SynCor Trial.

INTRODUCTION: Mechanical circulatory support (MCS) devices are increasingly used as a treatment option in resuscitation or in patients with cardiogenic shock (CS). Prophylactic implantation in high-risk percutaneous coronary interventions (HRPCI) is another upcoming indication. The i-cor ECG-synchronized cardiac assist device combines the hemodynamic support of a veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with the ability to generate a pulsatile flow and thus decreasing adverse effects of VA-ECMO on myocardial function. Aim of this study was to obtain data concerning feasibility, safety and outcomes in both indications. METHODS: A total of 47 patients (34 HRPCI, 13 CS) were included in nine German centers and participated in this study. Demographic and clinical parameters, procedural as well as follow-up data were prospectively recorded and analyzed. RESULTS: Device implantation and initiation of ECG-synchronized cardiac assist was technical successful in all cases and no failures of the consoles or disposable parts were observed. Furthermore, intended percutaneous coronary interventions and successful weaning from cardiac assist was achieved in 97.1% of HRPCI patients. We observed a 30d-survival of 94.1% in the HRPCI group and 69.2% in the CS group. Main complications in both groups were bleeding events (14.7% HRPCI, 23.1% CS) and critical limb ischemia (2.9% HRPCI, 38.5% CS). CONCLUSION: The i-cor ECG-synchronized cardiac assist device appears safe and feasible showing clinical outcomes comparable to existing data in the setting of high-risk percutaneous coronary interventions and acute cardiogenic shock. Further prospective trials are warranted to identify optimal patient and interventional characteristics that will benefit most of this novel kind of mechanical circulatory support.

Long-term clinical outcomes after drug eluting stent implantation with and without stent overlap.

OBJECTIVE: The aim of this study was to investigate the impact of drug eluting stent (DES) overlap on clinical outcomes after percutaneous coronary intervention (PCI). BACKGROUND: While the use of overlapping bare metal stent has been associated with an increased risk of adverse clinical events, the long-term impact of DES overlap on clinical outcomes is not certain at present. Similarly, the effect of different DES generations and polymer types on DES overlap associated clinical outcomes has not previously been comprehensively elucidated. METHODS: We analyzed the angiographic and clinical outcomes of 5605 patients treated with DES in the setting of the ISAR-TEST 4 and ISAR-TEST 5 randomized control trials according to the presence or absence of stent overlap. The clinical endpoints assessed in this study were all-cause death, myocardial infarction (MI), target lesion revascularization (TLR), and definite or probable stent thrombosis at 10-years. We also compared rates of binary angiographic restenosis (BAR) at 6-8 months. RESULTS: At 10 years, all-cause mortality (Hazard ratios [HR] = 1.05 [0.95-1.16]; p = 0.348) did not differ between the stent overlap and no stent overlap groups. MI (8.4% vs. 5.2%; HR = 1.67 [1.35-2.07], p < 0.001) and TLR (23.7% vs. 16.3%; HR = 1.54 [1.36-1.74], p < 0.001) occurred more frequently in the stent overlap group. For MI, landmark analysis demonstrated that this increase in risk was primarily in the first 30 days post PCI. BAR at 6-8 months was also more frequent in the stent overlap group (16.0% vs. 10.3%; HR = 1.65 [1.41-1.92], p < 0.001). CONCLUSION: DES overlap is associated with an increased risk of adverse clinical events post PCI.

Imaging of cardiac fibroblast activation in a patient after acute myocardial infarction using 68Ga-FAPI-04.

Our previous study has demonstrated the feasibility of noninvasive imaging of fibroblast activation protein (FAP)-expression after myocardial infarction (MI) in MI-territory in a rat model with 68Ga-FAPI-04-PET. In the current extended clinical case, we sought to delineate cardiac uptake of 68Ga-FAPI-04 in a patient after MI with clinical indication for the evidence of fibroblast activation. Carcinoma patients without cardiac disease underwent 68Ga-FAPI-04-PET/CT as control. The patient with one-vessel disease underwent dynamic 68Ga-FAPI-04-cardiac-PET/CMR for 60 minutes. Correlation of cardiac 68Ga-FAPI-04 uptake with clinical findings, ECG, echocardiography, coronary-arteriography and enhanced cardiac-MRI with T1 MOLLI and ECV mapping were performed. No uptake was found in normal myocardium and in mature scar. A focal intense 68Ga-FAPI-04 uptake with continuous wash-out in the infarct territory of coronary occlusion correlating with T1 and ECV mapping was observed. The uptake of 68Ga-FAPI-04 extends beyond the actual infarcted area and overestimates the infarct size as confirmed by follow-up CMR.

A case report of RASA1-associated inherited lymphoedema with recurrent life-threatening lymphangitis.

BACKGROUND: Most cases of lymphoedema are secondary to other causes, while cases of primary lymphoedema, in particular that of congenital origin, are uncommon. Limited genetic disorders are so far known to be associated with lymphatic malformation including mutations in RASA1. This clinical case highlights the possible complications of RASA1-associated lymphatic malformation in a female suffering from recurrent life-threatening septic lymphangitis. CASE SUMMARY: A 23-year-old female patient presented with congenital lymphoedema of the lower right extremity. At the age of eight, she first suffered from an episode of lymphangitis. Thereafter, she developed recurrent episodes of lymphangitis predominately occurring during menstruation and culminating into severe and life-threatening septicaemias. Due to the menstrual association, endometriosis was suspected but could not be confirmed. Furthermore, angiography could not detect any sign of arteriovenous fistula. Single-Photon-Emission-Computed-Tomography confirmed absent major lymphatics of the right leg with severely impaired and prolonged dermal lymphatic backflow. Genetic testing identified a disease-causing variant in the RASA1 gene. DISCUSSION: To our knowledge, this is the first case of recurrent septic lymphangitis with close relation to menstruation in a female with RASA1-associated lymphatic malformation. Due to the possible de novo or somatic origin of a pathogenic variant, a genetic disease should be considered in spite of an unremarkable family history or a localized lymphoedema. Although there is no curative therapy available yet, the knowledge of the underlying genetic defect is important for interdisciplinary patient care and might be crucial for individual molecular therapies in the future.

Assessment of Impact of Patient Recruitment Volume on Risk Profile, Outcomes, and Treatment Effect in a Randomized Trial of Ticagrelor Versus Prasugrel in Acute Coronary Syndromes.

BACKGROUND Whether there are differences in the risk profile and treatment effect in patients recruited in a low recruitment center (LRC) versus patients recruited in a high recruitment center (HRC) in a randomized multicenter trial remains unknown. METHODS AND RESULTS This study included 4018 patients with acute coronary syndrome recruited in the ISAR-REACT 5 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5) trial. The primary end point was a composite of all-cause death, myocardial infarction, or stroke. Overall, 3011 patients (75%) were recruited in the HRCs (7 centers recruiting 258 to 628 patients; median, 413 patients) and 1007 patients (25%) were recruited in the LRCs (16 centers recruiting 5 to 201 patients; median, 52 patients). Patients recruited in the LRCs had more favorable cardiovascular risk profiles than patients recruited in the HRCs. The primary end point occurred in 72 patients in the LRCs and 249 patients in the HRCs (cumulative incidence, 7.3% and 8.4%; P=0.267). All-cause mortality was lower among patients recruited in the LRCs (n=29) than among patients recruited in the HRCs (n=134; cumulative incidence 2.9% versus 4.5%; P=0.031). There was no significant interaction between the treatment effect of ticagrelor versus prasugrel and patient recruitment category (LRC versus HRC) regarding the primary efficacy end point (LRC: hazard ratio [HR], 1.42 [95% CI, 0.89-2.28]; HRC: HR, 1.33 [95% CI, 1.04-1.72]; P for interaction=0.800). CONCLUSIONS Patients with acute coronary syndrome recruited in a LRC appear to have more favorable cardiovascular risk profiles and lower 1-year mortality rates compared with patients recruited in a HRC. The recruitment volume did not interact with the treatment effect of ticagrelor versus prasugrel. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

Twelve-month clinical outcomes in patients with acute coronary syndrome undergoing complex percutaneous coronary intervention: insights from the ISAR-REACT 5 trial.

AIMS: Complex percutaneous coronary intervention (PCI) is associated with a higher risk of ischaemic events. However, no study has analysed the effect of PCI complexity on outcomes in a contemporary cohort of acute coronary syndrome (ACS) patients treated with a dual anti-platelet therapy regimen based on potent P2Y12-inhibitors. Therefore, we performed the current analysis. METHODS AND RESULTS: This analysis included all ACS patients treated with PCI in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 5 trial. Complex PCI was defined as at least one of: multi-vessel PCI, ≥3 stents implanted, ≥3 lesions treated, and total stented length >60 mm. The primary endpoint was the composite of all-cause death, myocardial infarction (MI), or stroke at 12 months; the safety endpoint was Bleeding Academic Research Consortium types 3-5 bleeding at 12 months. Overall, 3377 patients were included in this analysis (complex PCI, n = 1429; non-complex PCI, n = 1948). The primary endpoint occurred more frequently in the complex PCI group than the non-complex PCI group [10.1% vs. 7.2%, hazard ratio (HR): 1.44, 95% confidence interval (CI) (1.14-1.82), P = 0.002], driven primarily by a higher risk of MI [HR: 1.62, (1.17-2.26), P = 0.004]. The safety endpoint was not statistically different between patients undergoing complex vs. non-complex PCI, although it was numerically higher in the complex PCI group [6.7% vs. 5.3%, HR: 1.28, (0.97-1.70), P = 0.08]. CONCLUSIONS: Acute coronary syndrome patients undergoing complex PCI have an increased incidence of ischaemic events compared with ACS patients undergoing non-complex PCI. CLINICAL TRIAL REGISTRATION: NCT01944800, Prospective, Randomized Trial of Ticagrelor Vs. Prasugrel in Patients With Acute Coronary Syndrome-Full-Text View-ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01944800.