Adult Kawasaki disease: a rare and challenging diagnosis-a case report.

Background: Kawasaki disease (KD) is an acute systemic vasculitis which predominantly occurs in childhood but rarely in adulthood. Diagnosis relies on the presence of typical clinical features; however, patients may present atypically, increasing the challenge of timely diagnosis for physicians. Case summary: We report a case of a 40-year-old male presenting with persistent fever, rash, and unilateral neck swelling. Initial investigations were suggestive of necrotizing lymphadenitis, with a presumed infective aetiology. However, extensive microbiology and immunological investigations remained negative. Cardiac injury was evident with elevated troponin T and NT-proBNP; however, left ventricular systolic function was normal. After 4 days, clinical features consistent with KD were noted and the results of a lymph node biopsy supported this diagnosis. Despite timely treatment with intravenous immunoglobulins (IVIG) and high-dose aspirin, follow-up computed tomography (CT) coronary angiography demonstrated two sequential aneurysms (max 6 mm) in the right coronary artery, plus one small subtle aneurysm in the proximal left anterior descending artery (4 mm). Discussion: Diagnosis of adult KD remains challenging, as symptoms often present sequentially over time rather than simultaneously and many of the clinical features necessary for diagnosis share commonality with other infectious disease processes.

Morphological characteristics of lesions with thin cap fibroatheroma-a substudy from the COMBINE (OCT-FFR) trial.

AIMS: To study if any qualitative or quantitative optical coherence tomography (OCT) variables in combination with thin cap fibroatheroma (TCFA) patients could improve the identification of lesions at risk for future major adverse cardiac events (MACEs). METHODS AND RESULTS: From the combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) trial database (NCT02989740), we performed a detailed assessment OCT qualitative and quantitative variables in TCFA carrying diabetes mellitus (DM) patients with vs. without MACE during follow-up. MACEs were defined as a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and hospitalization for unstable angina. From the 390 fractional flow reserve (FFR)-negative DM patients, 98 (25.2%) had ≥1 OCT-detected TCFA, of which 13 (13.3%) had MACE and 85 (86.7%) were event-free (non-MACE). The baseline characteristics were similar between both groups; however, a smaller minimal lumen area (MLA) and lower mean FFR value were observed in MACE group (1.80 vs. 2.50 mm2, P = 0.01, and 0.85 vs. 0.89, P = 0.02, respectively). Prevalence of healed plaque (HP) was higher in the MACE group (53.85 vs. 21.18%, P = 0.01). TCFA were predominantly located proximal to the MLA. TCFA area was smaller in the MACE group, while no difference was observed regarding the lesion area. CONCLUSION: Within TCFA carrying patients, a smaller MLA, lower FFR values, and TCFA location adjacent to a HP were associated with future MACE. Carpet-like measured lesion area surface was similar, while the TCFA area was smaller in the MACE arm, and predominantly located proximal to the MLA.

Long-term outcomes of patients with normal fractional flow reserve and thin-cap fibroatheroma.

BACKGROUND: The long-term prognostic implications of fractional flow reserve (FFR)-negative lesions hosting vulnerable plaques remain unsettled. AIMS: The aim of this study was to evaluate the association of non-ischaemic lesions hosting optical coherence tomography (OCT)-detected thin-cap fibroatheromas (TCFA) with first and recurrent cardiovascular events during follow-up up to 5 years in a diabetes mellitus (DM) patient population. METHODS: COMBINE OCT-FFR is a prospective, international, double-blind, natural history study. Patients with DM and with ≥1 FFR-negative lesion were classified into 2 groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint (PE) is a composite of cardiac mortality, target vessel-related myocardial infarction (TV-MI), clinically driven target lesion revascularisation (TLR), or unstable angina (UA) requiring hospitalisation during follow-up up to 5 years. RESULTS: Among 390 DM patients (age 67.5±9 years; 37% female) with ≥1 FFR-negative lesion, 292 (74.9%) were TCFA-negative while 98 (25.1%) were TCFA-positive. The PE occurred more frequently in TCFA-positive than in TCFA-negative patients (21.4% vs 8.2%, hazard ratio [HR] 2.89, 95% confidence interval [CI]: 1.61-5.20; p<0.001; 6.42 vs 2.46 events per 100 patient-years, rate ratio [RR] 2.61, 95% CI: 1.38-4.90; p=0.002). Furthermore, when TV-MI, TLR, and UA were treated as recurrent components of the PE, TCFA-positive patients experienced a higher risk of recurrent events (HR 2.89, 95% CI; 1.74-4.80; p<0.001; 13.45 vs 2.87 events per 100 patient-years, RR 4.69, 95% CI: 2.86-7.83; p<0.001). A multivariable analysis identified the presence of TCFA as an independent predictor of the PE (HR 2.76, 95% CI: 1.53-4.97; p<0.001). CONCLUSIONS: OCT-detected TCFA-positive lesions, although not ischaemia-generating, are associated with an increased risk of adverse events during long-term follow-up. CLINICALTRIALS: gov: NCT02989740.

Thin-Cap Fibroatheroma Rather Than Any Lipid Plaques Increases the Risk of Cardiovascular Events in Diabetic Patients: Insights From the COMBINE OCT-FFR Trial.

BACKGROUND: Autopsy studies have established that thin-cap fibroatheromas (TCFAs) are the most frequent cause of fatal coronary events. In living patients, optical coherence tomography (OCT) has sufficient resolution to accurately differentiate TCFA from thick-cap fibroatheroma (ThCFA) and not lipid rich plaque (non-LRP). However, the impact of OCT-detected plaque phenotype of nonischemic lesions on future adverse events remains unknown. Therefore, we studied the natural history of OCT-detected TCFA, ThCFA, and non-LRP in patients enrolled in the prospective multicenter COMBINE FFR-OCT trial (Combined Optical Coherence Tomography Morphologic and Fractional Flow Reserve Hemodynamic Assessment of Non-Culprit Lesions to Better Predict Adverse Event Outcomes in Diabetes Mellitus Patients). METHODS: In the COMBINE FFR-OCT trial, patients with diabetes and ≥1 lesion with a fractional flow reserve >0.80 underwent OCT evaluation and were clinically followed for 18 months. A composite primary end point of cardiac death, target vessel-related myocardial infarction, target-lesion revascularization, and hospitalization for unstable angina was evaluated in relation to OCT-based plaque morphology. RESULTS: A total of 390 patients (age 67.5±9 years; 63% male) with ≥1 nonischemic lesions underwent OCT evaluation: 284 (73%) had ≥1 LRP and 106 (27%) non-LRP lesions. Among LRP patients, 98 (34.5%) had ≥1 TCFA. The primary end point occurred in 7% of LRP patients compared with 1.9% of non-LRP patients (7.0% versus 1.9%; hazard ratio [HR], 3.9 [95% CI, 0.9-16.5]; P=0.068; log rank-P=0.049). However, within LRP patients, TCFA patients had a much higher risk for primary end point compared with ThCFA (13.3% versus 3.8%; HR, 3.8 [95% CI, 1.5-9.5]; P<0.01), and to non-LRP patients (13.3% versus 1.9%; HR, 7.7 [95% CI, 1.7-33.9]; P<0.01), whereas ThCFA patients had risk similar to non-LRP patients (3.8% versus 1.9%; HR, 2.0 [95% CI, 0.42-9.7]; P=0.38). Multivariable analyses identified TCFA as the strongest independent predictor of primary end point (HR, 6.79 [95% CI, 1.50-30.72]; P=0.013). CONCLUSIONS: Among diabetes patients with fractional flow reserve-negative lesions, patients carrying TCFA lesions represent only one-third of LRP patients and are associated with a high risk of future events while patients carrying LRP-ThCFA and non-LRP lesions portend benign outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02989740.

Thin-cap fibroatheroma predicts clinical events in diabetic patients with normal fractional flow reserve: the COMBINE OCT-FFR trial.

AIMS: The aim of this study was to understand the impact of optical coherence tomography (OCT)-detected thin-cap fibroatheroma (TCFA) on clinical outcomes of diabetes mellitus (DM) patients with fractional flow reserve (FFR)-negative lesions. METHODS AND RESULTS: COMBINE OCT-FFR study was a prospective, double-blind, international, natural history study. After FFR assessment, and revascularization of FFR-positive lesions, patients with ≥1 FFR-negative lesions (target lesions) were classified in two groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint compared FFR-negative TCFA-positive patients with FFR-negative TCFA-negative patients for a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or unstable angina requiring hospitalization at 18 months. Among 550 patients enrolled, 390 (81%) patients had ≥1 FFR-negative lesions. Among FFR-negative patients, 98 (25%) were TCFA positive and 292 (75%) were TCFA negative. The incidence of the primary endpoint was 13.3% and 3.1% in TCFA-positive vs. TCFA-negative groups, respectively (hazard ratio 4.65; 95% confidence interval, 1.99-10.89; P < 0.001). The Cox regression multivariable analysis identified TCFA as the strongest predictor of major adverse clinical events (MACE) (hazard ratio 5.12; 95% confidence interval 2.12-12.34; P < 0.001). CONCLUSIONS: Among DM patients with ≥1 FFR-negative lesions, TCFA-positive patients represented 25% of this population and were associated with a five-fold higher rate of MACE despite the absence of ischaemia. This discrepancy between the impact of vulnerable plaque and ischaemia on future adverse events may represent a paradigm shift for coronary artery disease risk stratification in DM patients.

A dorsal-ventral gradient of Wnt3a/ß-catenin signals controls mouse hindgut extension and colon formation.

Despite the importance of Wnt signaling for adult intestinal stem cell homeostasis and colorectal cancer, relatively little is known about its role in colon formation during embryogenesis. The development of the colon starts with the formation and extension of the hindgut. We show that Wnt3a is expressed in the caudal embryo in a dorsal-ventral (DV) gradient across all three germ layers, including the hindgut. Using genetic and lineage-tracing approaches, we describe novel dorsal and ventral hindgut domains, and show that ventrolateral hindgut cells populate the majority of the colonic epithelium. A Wnt3a-ß-catenin-Sp5/8 pathway, which is active in the dorsal hindgut endoderm, is required for hindgut extension and colon formation. Interestingly, the absence of Wnt activity in the ventral hindgut is crucial for proper hindgut morphogenesis, as ectopic stabilization of ß-catenin in the ventral hindgut via gain- or loss-of-function mutations in Ctnnb1 or Apc, respectively, leads to severe colonic hyperplasia. Thus, the DV Wnt gradient is required to coordinate growth between dorsal and ventral hindgut domains to regulate the extension of the hindgut that leads to colon formation.

Late Erosion of Percutaneous ASD Occlusion Device.

Percutaneous closure of atrial septal defects (ASDs) is an ever more common treatment modality in selected patients. Device erosion is a rare but often fatal complication of this therapy, which usually presents early in the post-procedure course. We describe the case of a patient presenting with chest pain and shock in whom early recognition and intervention prevented a negative outcome. Awareness of this potentially lethal complication is important as the population of patients undergoing percutaneous procedures for structural heart disease continues to grow. LEARNING POINTS: As the number of patients undergoing percutaneous atrial septal defect closure increases, so too will the volume presenting with late complications.Early recognition and intervention in cases of device erosion is critical to prevent death.

Impact of elevated HbA1c on long-term mortality in patients presenting with acute myocardial infarction in daily clinical practice: insights from a 'real world' prospective registry of the Zwolle Myocardial Infarction Study Group.

BACKGROUND: Long-term clinical outcome is less well known in up to presentation persons unknown with diabetes mellitus who present with acute myocardial infarction and elevated glycosylated haemoglobin (HbA1c) levels on admission. We aimed to study the prognostic impact of deranged HbA1c at presentation on long-term mortality in patients not known with diabetes, presenting with acute myocardial infarction. METHODS: A single-centre, large, prospective observational study in patients with and without known diabetes admitted to our hospital for ST-segment elevation myocardial infarction (STEMI) and non-STEMI. Newly diagnosed diabetes mellitus was defined as HbA1c of 48 mmol/l or greater and pre-diabetes mellitus was defined as HbA1c between 39 and 47 mmol/l. The primary endpoint was all-cause mortality at short (30 days) and long-term (median 52 months) follow-up. RESULTS: Out of 7900 acute myocardial infarction patients studied, 1314 patients (17%) were known diabetes patients. Of the 6586 patients without known diabetes, 3977 (60%) had no diabetes, 2259 (34%) had pre-diabetes and 350 (5%) had newly diagnosed diabetes based on HbA1c on admission. Both short-term (3.9% vs. 7.4% vs. 6.0%, p<0.001) and long-term mortality (19% vs. 26% vs. 35%, p<0.001) for both pre-diabetes patients as well as newly diagnosed diabetes patients was poor and comparable to known diabetes patients. After multivariate analysis, newly diagnosed diabetes was independently associated with long-term mortality (hazard ratio 1.72, 95% confidence interval 1.27-2.34, P=0.001). CONCLUSIONS: In the largest study to date, newly diagnosed or pre-diabetes was present in 33% of acute myocardial infarction patients and was associated with poor long-term clinical outcome. Newly diagnosed diabetes (HbA1c ⩾48 mmol/mol) is an independent predictor of long-term mortality. More attention to early detection of diabetic status and initiation of blood glucose-lowering treatment is necessary.

Long-term mortality and prehospital tirofiban treatment in patients with ST elevation myocardial infarction.

OBJECTIVE: We undertook a subgroup analysis of the On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2), a placebo-controlled, double-blind, randomised trial, in order to evaluate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and long-term (5 years) mortality and to investigate the effect of prehospital tirofiban administration on mortality in relation to NT-proBNP levels. METHODS: A total of 984 patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) were randomised to either in ambulance tirofiban or placebo. NT-proBNP levels were evaluated on admission before angiography (baseline) and 18-96 hours thereafter (post PCI). RESULTS: There were 918 (93.3%) patients with NT-proBNP values available at baseline and 865 (87.9%) post PCI. Patients with baseline NT-proBNP values above the median (137 pg/mL) had higher 30-day (5.1% vs 0.2%, p<0.001), 1-year (7.0% vs 0.7%, p<0.001) and 5-year (20.3% vs 4.9%, p<0.001) mortality as compared with patients with values below the median. Using multivariate Cox analysis, NT-proBNP above the median was an independent predictor for 5-year mortality (HR 2.73, 95% CI 1.47 to 5.06; p=0.002). Patients with values above the median who received early tirofiban treatment had significant lower mortality compared with patients treated with placebo at 30 days (2.7% vs 7.5%, p=0.021) and 1 year (4.5% vs 9.4%, p=0.043). At 5 years, a lower but non-significant mortality rate was maintained in the treatment group (18% vs 22.4%, p=0.265). CONCLUSIONS: In patients with STEMI, baseline NT-proBNP level independently predicts long-term mortality. In patients with baseline NT-proBNP levels above the median, early prehospital treatment with tirofiban significantly reduced 30-day and 1-year mortality, suggesting that high-risk patients may derive particular benefit. This finding should be confirmed in other studies. TRIAL REGISTRATION NUMBER: ISRCTN06195297.

A prospective, randomized, open-label trial of 6-month versus 12-month dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction: Rationale and design of the "DAPT-STEMI trial".

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with second-generation drug eluting stents (DESs) is unclear. Because prolonged DAPT is associated with higher bleeding risk and health care costs, establishing optimal DAPT duration is of paramount importance. No other randomized controlled trials have evaluated the safety of shorter DAPT duration in ST-elevation myocardial infarction (STEMI) patients treated with second-generation DESs and latest P2Y12 platelet receptor inhibitors. HYPOTHESIS: Six months of DAPT after Resolute Integrity stent implantation in STEMI patients is not inferior to 12 months of DAPT in clinical outcomes. STUDY DESIGN: The Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation In ST-elevation Myocardial Infarction (DAPT-STEMI) trial is a randomized, multicenter, international, open-label trial designed to examine the safety (noninferiority) of 6-month DAPT after Resolute Integrity stent implantation in STEMI patients compared with 12-month DAPT. Event-free patients on DAPT at 6month will be randomized (1:1 fashion) between single (aspirin only) versus DAPT for an additional 6 months and followed until 2 years after primary percutaneous coronary intervention. The primary end point is a patient-oriented composite endpoint of all-cause mortality, any myocardial infarction, any revascularization, stroke, and major bleeding (net adverse clinical events [NACE]) at 18 months after randomization. To achieve a power of 85% for a noninferiority limit of 1.66, a total of 1100 enrolled patients are required. SUMMARY: The DAPT-STEMI trial aims to assess in STEMI patients treated with second-generation DESs whether discontinuation of DAPT after 6 months of event-free survival is noninferior to routine 12-month DAPT.

Is ischemia the only factor predicting cardiovascular outcomes in all diabetes mellitus patients?

Diabetes mellitus (DM) is associated with an excess in cardiovascular morbidity and mortality, and is characterized by increased rates of coronary artery disease. Furthermore, once atherosclerosis is established, this is associated with an increased extent, complexity and a more rapid progression than seen in non-DM patients. Ischemia is the single most important predictor of future hard cardiac events and ischemia correction remains the cornerstone of current revascularization strategies. However recent data suggests that, in DM patients, coronary atherosclerosis despite the absence of ischemia, detected by either invasive or non-invasive methods, may not be associated with the same low risk of future cardiac events as seen in non-DM patients. This review seeks to examine the current evidence supporting an ischemia driven revascularization strategy, and to challenge the notion that ischemia is the only clinically relevant factor in the prediction of cardiovascular outcomes in all-comer DM patients. Specifically, we examine whether in DM patients certain characteristics beyond ischemia, such as microvascular disease, coronary atherosclerosis burden, progression and plaque composition, may need to be considered for a more refined risk stratification in these high-risk patients.

Factors associated with deferred lesion failure following fractional flow reserve assessment in patients with diabetes mellitus.

OBJECTIVE: To explore the predictors of deferred lesion failure (DLF) in patients with diabetes mellitus (DM) and lesions with a fractional flow reserve (FFR) >0.80 and to examine whether a predictive relationship between negative FFR values (>0.80-1.00) and DLF exists. BACKGROUND: DM is associated with rapidly progressive atherosclerosis and predictors of DLF in FFR negative lesions in this high-risk group are unknown. METHODS: All DM patients who underwent FFR-assessment between 1/01/2010 and 31/12/2013 were included, and followed until 1/7/2015. Patients carrying ≥1 FFR negative lesion(s) were assessed for DLF, and multivariate models used to identify independent factors associated with DLF. RESULTS: A total of 205 patients with 252 FFR >0.80 lesions were identified. At a mean follow-up of 3.1 ± 1.4 years, DLF occurred in 29/205 (14.1%) patients, 31/252 (12.3%) lesions. Using marginal Cox regression multivariate analysis, insulin requiring DM [HR 2.24 (95%CI; 1.01-4.95), P = 0.046] and prior revascularization [HR 2.70 (95%CI 1.21-6.01), P = 0.015] were identified as being associated with a higher incidence of DLF. Absolute FFR values in FFR negative lesions in DM patients are not predictive of DLF (receiver operating characteristics curve analysis: area under the curve: 0.57 ± 0.06, 95%CI 0.46-0.69). CONCLUSIONS: In DM patients with FFR negative lesions, insulin requiring DM and prior revascularization are predictors for DLF. In contrast to non-DM patients, no predictive relationship between absolute negative FFR values (ranging >0.80-1.00) and the risk of DLF exists in DM patients. © 2017 Wiley Periodicals, Inc.

Impact of TCFA on Unanticipated Ischemic Events in Medically Treated Diabetes Mellitus: Insights From the PROSPECT Study.

OBJECTIVES: This study sought to investigate the relationship between thin-cap fibroatheromas (TCFAs) on major adverse cardiac events (MACEs) arising from medically treated nonculprit lesions (NCLs) in patients with acute coronary syndromes (ACS) with and without diabetes mellitus (DM). BACKGROUND: MACEs occur frequently in patients with DM and ACS. The impact of plaque composition on subsequent MACEs in DM patients with ACS is unknown. METHODS: In the PROSPECT (Providing Regional Observations Study Predictors of Events in the Coronary Tree) study, using 3-vessel radiofrequency intravascular ultrasound, we analyzed the incidence of NCL-MACE in 2 propensity-matched groups according to the presence of DM and TCFA. RESULTS: Among 697 patients, 119 (17.7%) had DM. The 3-year total MACE rate (29.4% vs. 18.8%; p = 0.01) was significantly higher in patients with versus without DM, driven by a higher rate of NCL-MACE in DM (18.7% vs. 10.4%; p = 0.02). Propensity score matching generated 2 balanced groups with and without DM of 82 patients each. Among DM patients, the presence of ≥1 TCFA was associated with higher NCL-MACE at 3 years (27.8% vs. 8.9% in patients without a TCFA, hazard ratio: 3.56; 95% confidence interval: 0.98 to 12.96; p = 0.04). DM patients without a TCFA had a similar 3-year rate of NCL-MACE as patients without DM (8.9% vs. 8.9%; hazard ratio: 1.09; 95% confidence interval: 0.27 to 4.41; p = 0.90). CONCLUSIONS: ACS patients with DM and ≥1 TCFA have a high rate of NCL-MACE at 3 years. In contrast, the prognosis of ACS patients with DM but no TCFAs is favorable and similar to patients without DM.

Combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) prospective study. Rationale and design.

BACKGROUND: Fractional flow reserve (FFR) is a widely used tool for the identification of ischaemia-generating stenoses and to guide decisions on coronary revascularisation. However, the safety of FFR-based decisions in high-risk subsets, such as patients with Diabetes Mellitus (DM) or vulnerable stenoses presenting thin-cap fibro-atheroma (TCFA), is unknown. This study will examine the impact of optical coherence tomography (OCT) plaque morphological assessment and the identification of TCFA, in combination with FFR to better predict clinical outcomes in DM patients. METHODS: COMBINE (OCT-FFR) is a prospective, multi-centre study investigating the natural history of DM patients with ≥1 angiographically intermediate target lesion in three subgroups of patients; patients with FFR negative lesions without TCFA (group A) and patients with FFR negative lesions with TCFA (group B) as detected by OCT and to compare these two groups with each other, as well as to a third group with FFR-positive, PCI-treated intermediate lesions (group C). The study hypothesis is that DM patients with TCFA (group B) have a worse outcome than those without TCFA (group A) and also when compared to those patients with lesions FFR ≤0.80 who underwent complete revascularisation. The primary endpoint is the incidence of target lesion major adverse cardiac events (MACE); a composite of cardiac death, myocardial infarction or rehospitalisation for unstable/progressive angina in group B vs. group A. CONCLUSION: COMBINE (OCT-FFR) is the first prospective study to examine whether the addition of OCT plaque morphological evaluation to FFR haemodynamic assessment of intermediate lesions in DM patients will better predict MACE and possibly lead to new revascularisation strategies. Trial Registration Netherlands Trial Register: NTR5376.

Fractional Flow Reserve-Guided Deferred Versus Complete Revascularization in Patients With Diabetes Mellitus.

To assess the safety and efficacy of deferred versus complete revascularization using a fractional flow reserve (FFR)-guided strategy in patients with diabetes mellitus (DM), we analyzed all DM patients who underwent FFR-guided revascularization from January 1, 2010, to December 12, 2013. Patients were divided into 2 groups: those with ≥1 remaining FFR-negative (>0.80) medically treated lesions [FFR(-)MT] and those with only FFR-positive lesions (≤0.80) who underwent complete revascularization [FFR(+)CR] and were followed until July 1, 2015. The primary end point was the incidence of major adverse cardiovascular events (MACE), a composite of death, myocardial infarction (MI), target lesion (FFR assessed) revascularization, and rehospitalization for acute coronary syndrome. A total of 294 patients, 205 (69.7%) versus 89 (30.3%) in FFR(-)MT and FFR(+)CR, respectively, were analyzed. At a mean follow-up of 32.6 ± 18.1 months, FFR(-)MT was associated with higher MACE rate 44.0% versus 26.6% (log-rank p = 0.02, Cox regression-adjusted hazard ratio [HR] 2.01, 95% confidence interval [CI] 1.21 to 3.33, p <0.01), and driven by both safety and efficacy end points: death/MI (HR 2.02, 95% CI 1.06 to 3.86, p = 0.03), rehospitalization for acute coronary syndrome (HR 2.06, 95% CI 1.03 to 4.10, p = 0.04), and target lesion revascularization (HR 3.38, 95% CI 1.19 to 9.64, p = 0.02). Previous MI was a strong effect modifier within the FFR(-)MT group (HR 1.98, 95% CI 1.26 to 3.13, p <0.01), whereas this was not the case in the FFR(+)CR group (HR 0.66, 95% CI 0.27 to 1.62, p = 0.37). Significant interaction for MACE was present between FFR groups and previous MI (p = 0.03). In conclusion, in patients with DM, particularly those with previous MI, deferred revascularization is associated with poor medium-term outcomes. Combining FFR with imaging techniques may be required to guide our treatment strategy in these patients with high-risk, fast-progressing atherosclerosis.

Guide extension, unmissable tool in the armamentarium of modern interventional cardiology. A comprehensive review.

Due to the aging population undergoing percutaneous coronary intervention (PCI), interventional cardiologists are confronted daily with treatment of lesions with complex anatomy. Despite improvements in stent devices and PCI techniques, these lesions remain a challenge in terms of procedural success. Guide-extensions (GE) are coaxial "mother and child" catheters employed to facilitate device delivery but they can be used in many different complex scenarios. A comprehensive review of the possible applications of GE and of the GuideLiner™ (GL), the most widely used GE device, is missing. We therefore aim to provide a comprehensive review of all the potential applications of the GL and other GE devices, describe its limitations as well as tips and tricks for successful usage of this GE catheter.

Clinical outcomes of deferred revascularisation using fractional flow reserve in patients with and without diabetes mellitus.

OBJECTIVE: Deferred revascularisation based upon fractional flow reserve (FFR >0.80) is associated with a low incidence of target lesion failure (TLF). Whether deferred revascularisation is also as safe in diabetes mellitus (DM) patients is unknown. METHODS: All DM patients and the next consecutive Non-DM patients who underwent a FFR-assessment between 1/01/2010 and 31/12/2013 were included, and followed until 1/07/2015. Patients with lesions FFR >0.80 were analysed according to the presence vs. absence of DM, while patients who underwent index revascularisation in FFR-assessed or other lesions were excluded. The primary endpoint was the incidence of TLF; a composite of target lesion revascularisation (TLR) and target vessel myocardial infarction (TVMI). RESULTS: A total of 250 patients (122 DM, 128 non-DM) who underwent deferred revascularisation of all lesions (FFR >0.80) were compared. At a mean follow up of 39.8 ± 16.3 months, DM patients compared to non-DM had a higher TLF rate, 18.1 vs 7.5 %, logrank p ≤ 0.01, Cox regression-adjusted HR 3.65 (95 % CI 1.40-9.53, p < 0.01), which was largely driven by a higher incidence of TLR (17.2 vs. 7.5 %, HR 3.52, 95 % CI 1.34-9.30, p = 0.01), whilst a non-significant but numerically higher incidence of TVMI (6.1 vs. 2.0 %, HR 3.34, 95 % CI 0.64-17.30, p = 0.15) was observed. CONCLUSIONS: This study, the largest to directly compare the clinical outcomes of FFR-guided deferred revascularisation in patients with and without DM, shows that DM patients are associated with a significantly higher TLF rate. Whether intravascular imaging, additional invasive haemodynamics or stringent risk factor modification may impact on this higher TLF rate remains unknown.

A new gain-of-function mouse line to study the role of Wnt3a in development and disease.

Wnt/ß-catenin signals are important regulators of embryonic and adult stem cell self-renewal and differentiation and play causative roles in tumorigenesis. Purified recombinant Wnt3a protein, or Wnt3a-conditioned culture medium, has been widely used to study canonical Wnt signaling in vitro or ex vivo. To study the role of Wnt3a in embryogenesis and cancer models, we developed a Cre recombinase activatable Rosa26(Wnt3a) allele, in which a Wnt3a cDNA was inserted into the Rosa26 locus to allow for conditional, spatiotemporally defined expression of Wnt3a ligand for gain-of-function (GOF) studies in mice. To validate this reagent, we ectopically overexpressed Wnt3a in early embryonic progenitors using the T-Cre transgene. This resulted in up-regulated expression of a ß-catenin/Tcf-Lef reporter and of the universal Wnt/ß-catenin pathway target genes, Axin2 and Sp5. Importantly, T-Cre; Rosa26(Wnt3a) mutants have expanded presomitic mesoderm (PSM) and compromised somitogenesis and closely resemble previously studied T-Cre; Ctnnb1(ex3) (ß-catenin(GOF) ) mutants. These data indicate that the exogenously expressed Wnt3a stimulates the Wnt/ß-catenin signaling pathway, as expected. The Rosa26(Wnt3a) mouse line should prove to be an invaluable tool to study the function of Wnt3a in vivo.