Plaque burden is associated with minimal intimal coverage following drug-eluting stent implantation in an adult familial hypercholesterolemia swine model.

Safety and efficacy of coronary drug-eluting stents (DES) are often preclinically tested using healthy or minimally diseased swine. These generally show significant fibrotic neointima at follow-up, while in patients, incomplete healing is often observed. The aim of this study was to investigate neointima responses to DES in swine with significant coronary atherosclerosis. Adult familial hypercholesterolemic swine (n = 6) received a high fat diet to develop atherosclerosis. Serial OCT was performed before, directly after, and 28 days after DES implantation (n = 14 stents). Lumen, stent and plaque area, uncovered struts, neointima thickness and neointima type were analyzed for each frame and averaged per stent. Histology was performed to show differences in coronary atherosclerosis. A range of plaque size and severity was found, from healthy segments to lipid-rich plaques. Accordingly, neointima responses ranged from uncovered struts, to minimal neointima, to fibrotic neointima. Lower plaque burden resulted in a fibrotic neointima at follow-up, reminiscent of minimally diseased swine coronary models. In contrast, higher plaque burden resulted in minimal neointima and more uncovered struts at follow-up, similarly to patients' responses. The presence of lipid-rich plaques resulted in more uncovered struts, which underscores the importance of advanced disease when performing safety and efficacy testing of DES.

The Prognostic Value of a Validated and Automated Intravascular Ultrasound-Derived Calcium Score.

BACKGROUND: Coronary calcification has been linked to cardiovascular events. We developed and validated an algorithm to automatically quantify coronary calcifications on intravascular ultrasound (IVUS). We aimed to assess the prognostic value of an IVUS-calcium score (ICS) on patient-oriented composite endpoint (POCE). METHODS: We included patients that underwent coronary angiography plus pre-procedural IVUS imaging. The ICS was calculated per patient. The primary endpoint was a composite of all-cause mortality, stroke, myocardial infarction, and revascularization (POCE). RESULTS: In a cohort of 408 patients, median ICS was 85. Both an ICS ≥ 85 and a 100 unit increase in ICS increased the risk of POCE at 6-year follow-up (adjusted hazard ratio (aHR) 1.51, 95%CI 1.05-2.17, p value = 0.026, and aHR 1.21, 95%CI 1.04-1.41, p value = 0.014, respectively). CONCLUSIONS: The ICS, calculated by a validated automated algorithm derived from routine IVUS pullbacks, was strongly associated with the long-term risk of POCE.

Two decades after coronary radiation therapy: A single center longitudinal clinical study.

OBJECTIVES: The aim of this study was to evaluate the very long-term clinical outcome after radioactive stent (RS) implantation and intracoronary ß radiation brachytherapy (IRBT). BACKGROUND: Radioactive stents (RS) and intracoronary ß radiation brachytherapy (IRBT) were introduced to prevent restenosis after percutaneous coronary intervention (PCI). Both techniques were associated with a higher incidence of major adverse cardiac events (MACE) in the short and intermediate-term follow up as compared to conventional PCI. METHODS: One hundred and thirty-three patients received radioactive stents (32 P) and 301 patients were treated with IRBT adjunctive to PCI. These groups were propensity matched to respectively 266 and 602 control patients who were treated with routine PCI during the same inclusion period. Endpoints were all-cause mortality and MACE, defined as all-cause death, any myocardial infarction or any revascularization. RESULTS: Median follow-up duration was 17 years. All-cause mortality rates were similar in all groups. Adjusted hazard ratios for MACE and mortality in the RS cohort were 1.55 (95% CI 1.20-2.00) and 0.92 (95% CI 0.63-1.34), respectively. Adjusted hazard ratios for MACE and all-cause mortality in the IRBT cohort were 1.41 (95% CI 1.18-1.67) and 0.95 (95% CI 0.74-1.21), respectively. The difference in MACE rates was predominantly driven by coronary revascularizations in both groups, with a higher MI rate in the IRBT group as well. CONCLUSIONS: Coronary radiation therapy was associated with early increased MACE rates, but the difference in MACE rates decreased beyond 2 years, resulting in a comparable long-term clinical outcome. Importantly, no excess in mortality was observed.

Variation in Coronary Atherosclerosis Severity Related to a Distinct LDL (Low-Density Lipoprotein) Profile: Findings From a Familial Hypercholesterolemia Pig Model.

OBJECTIVE: In an adult porcine model of familial hypercholesterolemia (FH), coronary plaque development was characterized. To elucidate the underlying mechanisms of the observed inter-individual variation in disease severity, detailed lipoprotein profiles were determined. Approach and Results: FH pigs (3 years old, homozygous LDLR R84C mutation) received an atherogenic diet for 12 months. Coronary atherosclerosis development was monitored using serial invasive imaging and histology. A pronounced difference was observed between mildly diseased pigs which exclusively developed early lesions (maximal plaque burden, 25% [23%-34%]; n=5) and advanced-diseased pigs (n=5) which developed human-like, lumen intruding plaques (maximal plaque burden, 69% [57%-77%]) with large necrotic cores, intraplaque hemorrhage, and calcifications. Advanced-diseased pigs and mildly diseased pigs displayed no differences in conventional risk factors. Additional plasma lipoprotein profiling by size-exclusion chromatography revealed 2 different LDL (low-density lipoprotein) subtypes: regular and larger LDL. Cholesterol, sphingosine-1-phosphate, ceramide, and sphingomyelin levels were determined in these LDL-subfractions using standard laboratory techniques and high-pressure liquid chromatography mass-spectrometry analyses, respectively. At 3 months of diet, regular LDL of advanced-diseased pigs contained relatively more cholesterol (LDL-C; regular/larger LDL-C ratio 1.7 [1.3-1.9] versus 0.8 [0.6-0.9]; P=0.008) than mildly diseased pigs, while larger LDL contained more sphingosine-1-phosphate, ceramides, and sphingomyelins. Larger and regular LDL was also found in plasma of 3 patients with homozygous FH with varying LDL-C ratios. CONCLUSIONS: In our adult FH pig model, inter-individual differences in atherosclerotic disease severity were directly related to the distribution of cholesterol and sphingolipids over a distinct LDL profile with regular and larger LDL shortly after the diet start. A similar LDL profile was detected in patients with homozygous FH.

Fractional flow reserve guided percutaneous coronary intervention optimization directed by high-definition intravascular ultrasound versus standard of care: Rationale and study design of the prospective randomized FFR-REACT trial.

BACKGROUND: Post percutaneous coronary intervention (PCI) fractional flow reserve (FFR) is a significant predictor of major adverse cardiac events (MACE). The rationale for low post procedural FFR values often remains elusive based on angiographic findings alone, warranting further assessment using an FFR pullback or additional intravascular imaging. It is currently unknown if additional interventions intended to improve the PCI, decrease MACE rates. STUDY DESIGN: The FFR REACT trial is a prospective, single-center randomized controlled trial in which 290 patients with a post PCI FFR <0.90 will be randomized (1:1) to either standard of care (no additional intervention) or intravascular ultrasound (IVUS)-directed optimization of the FFR (treatment arm). Eligible patients are those treated with angiographically successful PCI for (un)stable angina or non-ST elevation myocardial infarction (MI). Assuming 45% of patients will have a post PCI FFR <0.90, approximately 640 patients undergoing PCI will need to be enrolled. Patients with a post PCI FFR ≥ 0.90 will be enrolled in a prospective registry. The primary end point is defined as a composite of cardiac death, target vessel MI and clinically driven target vessel revascularisation (target vessel failure) at 1 year. Secondary end points will consist of individual components of the primary end point, procedural success, stent thrombosis and correlations on clinical outcome, changes in post PCI Pd/Pa and FFR and IVUS derived dimensions. All patients will be followed for 3 years. CONCLUSION: The FFR-REACT trial is designed to explore the potential benefit of HD-IVUS-guided PCI optimization in patients with a post PCI FFR <0.90 (Dutch trial register: NTR6711).

Large-bore Vascular Closure: New Devices and Techniques.

Endovascular aneurysm repair, transcatheter aortic valve implantation and percutaneous mechanical circulatory support systems have become valuable alternatives to conventional surgery and even preferred strategies for a wide array of clinical entities. Their adoption in everyday practice is growing. These procedures require large-bore access into the femoral artery. Their use is thus associated with clinically significant vascular bleeding complications. Meticulous access site management is crucial for safe implementation of large-bore technologies and includes accurate puncture technique and reliable percutaneous closure devices. This article reviews different strategies for obtaining femoral access and contemporary percutaneous closure technologies.

Explanation of Postprocedural Fractional Flow Reserve Below 0.85.

BACKGROUND: Fractional flow reserve (FFR) after percutaneous coronary intervention is a predictor of adverse cardiovascular events during follow-up. However, the rationale for low post procedural FFR values remains often elusive based on angiographic findings alone. METHODS AND RESULTS: FFR SEARCH (Stent Evaluated at Rotterdam Cardiology Hospital) is a prospective single-center registry in which post-percutaneous coronary intervention FFR was assessed in 1000 consecutive all-comer patients. FFR measurements were performed with a microcatheter ±20 mm distal to the most distal stent edge. In 100 vessels with a post procedural FFR ≤0.85, and 20 vessels >0.85 high definition intravascular ultrasound analysis was performed. In 100 vessels with a post-percutaneous coronary intervention FFR ≤0.85, mean post procedural FFR was 0.79±0.05. Minimal lumen area was 2.19 (1.81-3.19) mm2, mean lumen area was 5.95 (5.01-7.03) mm2, and minimal stent area was 4.01 (3.09-5.21) mm2. Significant residual focal proximal lesions were found in 29% of the assessed vessels whereas, focal distal lesions were found in 30% of the vessels. Stent underexpansion and malapposition were found in 74% and 22% of vessels, respectively. Clear focal signs of luminal narrowing were found in 54% of the vessels analyzed. Although incidences of focal lesions, underexpansion, and malapposition were similar between both cohorts, minimal stent area was significantly smaller in vessels with a post-percutaneous coronary intervention FFR ≤0.85 as compared with those with an FFR >0.85. CONCLUSIONS: In patients with a post procedural FFR ≤0.85, intravascular ultrasound revealed focal signs of luminal narrowing in a significant number of cases.

SYNTAX score II predicts long-term mortality in patients with one- or two-vessel disease.

OBJECTIVE: SYNTAX score II (SSII) is a long-term mortality prediction model to guide the decision making of the heart-team between coronary artery bypass grafting or percutaneous coronary intervention (PCI) in patients with left main or three-vessel coronary artery disease. This study aims to investigate the long-term predictive value of SSII for all-cause mortality in patients with one- or two-vessel disease undergoing PCI. METHODS: A total of 628 patients (76% men, mean age: 61±10 years) undergoing PCI due to stable angina pectoris (43%) or acute coronary syndrome (57%), included between January 2008 and June 2013, were eligible for the current study. SSII was calculated using the original SYNTAX score website (www.syntaxscore.com). Cox regression analysis was used to assess the association between continuous SSII and long-term all-cause mortality. The area under the receiver-operating characteristic curve was used to assess the performance of SSII. RESULTS: SSII ranged from 6.6 to 58.2 (median: 20.4, interquartile range: 16.1-26.8). In multivariable analysis, SSII proved to be an independent significant predictor for 4.5-year mortality (hazard ratio per point increase: 1.10; 95% confidence interval: 1.07-1.13; p<0.001). In terms of discrimination, SSII had a concordance index of 0.77. CONCLUSION: In addition to its established value in patients with left main and three-vessel disease, SSII may also predict long-term mortality in PCI-treated patients with one- or two-vessel disease.

Neoatherosclerosis development following bioresorbable vascular scaffold implantation in diabetic and non-diabetic swine.

BACKGROUND: DM remains a risk factor for poor outcome after stent-implantation, but little is known if and how DM affects the vascular response to BVS. AIM: The aim of our study was to examine coronary responses to bioresorbable vascular scaffolds (BVS) in swine with and without diabetes mellitus fed a 'fast-food' diet (FF-DM and FF-NDM, respectively) by sequential optical coherence tomography (OCT)-imaging and histology. METHODS: Fifteen male swine were evaluated. Eight received streptozotocin-injection to induce DM. After 9 months (M), 32 single BVS were implanted in epicardial arteries with a stent to artery (S/A)-ratio of 1.1:1 under quantitative coronary angiography (QCA) and OCT guidance. Lumen, scaffold, neointimal coverage and composition were assessed by QCA, OCT and near-infrared spectroscopy (NIRS) pre- and/or post-procedure, at 3M and 6M. Additionally, polarization-sensitive (PS)-OCT was performed in 7 swine at 6M. After sacrifice at 3M and 6M, histology and polymer degradation analysis were performed. RESULTS: Late lumen loss was high (~60%) within the first 3M after BVS-implantation (P<0.01 FF-DM vs. FF-NDM) and stabilized between 3M and 6M (<5% change in FF-DM, ~10% in FF-NDM; P>0.20). Neointimal coverage was highly heterogeneous in all swine (DM vs. NDM P>0.05), with focal lipid accumulation, irregular collagen distribution and neointimal calcification. Likewise, polymer mass loss was low (~2% at 3M, ~5% at 6M;P>0.20) and not associated with DM or inflammation. CONCLUSION: Scaffold coverage showed signs of neo-atherosclerosis in all FF-DM and FF-NDM swine, scaffold polymer was preserved and the vascular response to BVS was not influenced by diabetes.

Percutaneous coronary interventions during ST-segment elevation myocardial infarction: current status and future perspectives.

The present article focuses on recent innovations and possible future perspectives in the reperfusion treatment of ST-segment elevation myocardial infarction (STEMI). Among these, the shift from the femoral to the radial vascular access, the recent availability of bioresorbable coronary scaffolds, other innovative forms of stent specifically designed for STEMI patients, the use of cardioprotective strategies, as well as the possibility of including autologous bone marrow stem cell transplantation as part of the treatment of patients with STEMI are described and commented on as a glance into the future.

In vivo detection of high-risk coronary plaques by radiofrequency intravascular ultrasound and cardiovascular outcome: results of the ATHEROREMO-IVUS study.

AIMS: Acute coronary syndromes (ACS) are mostly caused by plaque rupture. This study aims to investigate the prognostic value of in vivo detection of high-risk coronary plaques by intravascular ultrasound (IVUS) in patients undergoing coronary angiography. METHODS AND RESULTS: Between November 2008 and January 2011, IVUS of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for ACS (n = 318) or stable angina (n = 263). Primary endpoint was major adverse cardiac events (MACEs) defined as mortality, ACS, or unplanned coronary revascularization. Culprit lesion-related events were not counted. Cumulative Kaplan-Meier incidence of 1-year MACE was 7.8%. The presence of IVUS virtual histology-derived thin-cap fibroatheroma (TCFA) lesions (present 10.8% vs. absent 5.6%; adjusted HR: 1.98, 95% CI: 1.09-3.60; P = 0.026) and lesions with a plaque burden of ≥70% (present 16.2% vs. absent 5.5%; adjusted HR: 2.90, 95% CI: 1.60-5.25; P < 0.001) were independently associated with a higher MACE rate. Thin-cap fibroatheroma lesions were also independently associated with the composite of death or ACS only (present 7.5% vs. absent 3.0%; adjusted HR: 2.51, 95% CI: 1.15-5.49; P = 0.021). Thin-cap fibroatheroma lesions with a plaque burden of ≥70% were associated with a higher MACE rate within (P = 0.011) and after (P < 0.001) 6 months of follow-up, while smaller TCFA lesions were only associated with a higher MACE rate after 6 months (P = 0.033). CONCLUSION: In patients undergoing coronary angiography, the presence of IVUS virtual histology-derived TCFA lesions in a non-culprit coronary artery is strongly and independently predictive for the occurrence of MACE within 1 year, particularly of death and ACS. Thin-cap fibroatheroma lesions with a large plaque burden carry higher risk than small TCFA lesions, especially on the short term.

How should I treat impaired systolic function and clinical deterioration after surgery of type A aortic dissection?

BACKGROUND: A 50-year-old male with diagnosis of acute type A aortic dissection underwent surgical repair. Immediately after surgery the patient had transient ECG changes, a raise in serum cardiac markers and physical signs of heart failure. INVESTIGATION: Physical examination, electrocardiography, echocardiography (transthoracic and transoesophageal), coronary angiography, intravascular ultrasound. DIAGNOSIS: Type A aortic dissection. MANAGEMENT: Surgical repair, coronary angiography, percutaneous coronary intervention.

NIRS and IVUS for characterization of atherosclerosis in patients undergoing coronary angiography.

OBJECTIVES: The aim of this study was to compare the findings of near-infrared spectroscopy (NIRS), intravascular ultrasound (IVUS) virtual histology (VH), and grayscale IVUS obtained in matched coronary vessel segments of patients undergoing coronary angiography. BACKGROUND: Intravascular ultrasound VH has been developed to add tissue characterization to the grayscale IVUS assessment of coronary plaques. Near-infrared spectroscopy is a new imaging technique able to identify lipid core-containing coronary plaques (LCP). METHODS: We performed NIRS and IVUS-VH pullbacks in a consecutive series of 31 patients with a common region of interest (ROI) between 2 side branches. For each ROI, we analyzed the chemogram blocks by NIRS, plaque area and plaque burden by grayscale IVUS, and tissue types by IVUS-VH. The chemogram block is a summary metric of a 2-mm vertical slice of the chemogram. The value ranges from 0 to 1 according to the presence of lipids and represents the probability of LCP with a color scale from red (low probability) through orange and tan to yellow (high probability). RESULTS: Plaque area (mm(2)) increases as percentage VH derived-necrotic core (NC) content (4.6 ± 2.7 vs. 7.4 ± 3.5 vs. 8.6 ± 3.4 vs. 7.9 ± 3.3, grouped in percentage NC quartiles, p<0.001) and chemogram block probability color bin thresholds increase (4.9 ± 3.8 red, 7.3 ± 3.6 orange, 8.1 ± 3.4 tan, and 8.7 ± 3.4 yellow, p<0.001). The correlation between the block chemogram detection of lipid core and percentage NC content by VH was weak (r=0.149). Correction for the presence of calcium does not improve this correlation. CONCLUSIONS: Larger plaque area by grayscale IVUS was more often associated with either elevated percentage VH-NC or LCP by NIRS; however, the correlation between the detection of LCP by NIRS and necrotic core by VH is weak.

How should I treat acute valve regurgitation?

BACKGROUND: An 81-year-old male with symptoms of angina and dyspnoea (NYHA 3), a history of coronary bypass surgery, a transaortic peak gradient of 109 mmHg on transthoracic echocardiography and a logistic Euro-SCORE of 21.6 was deemed suboptimal for surgery by a multidisciplinary team and was accepted for TAVI. INVESTIGATION: Preprocedural diameter of the native aortic root was 24.4 mm on transthoracic echocardiography (TTE), 26.9 mm on contrast angiography and 26.8 mm by 30.2 mm on multislice computed tomography (MSCT). DIAGNOSIS: heavy calcification of the aortic root and coronary arteries by MSCT. TREATMENT: Transcatheter aortic calve replacement with an 29 mm CoreValve prosthesis.

Multi-modality intra-coronary plaque characterization: a pilot study.

BACKGROUND: The risk of rupture and subsequent thrombosis of the atherosclerotic coronary plaques is related to the presence of necrotic core with high lipid content. We conducted an exploratory pilot trial to compare the capability for lipid tissue detection using four intra-coronary diagnostic techniques: greyscale intravascular ultrasound (GS IVUS), IVUS radiofrequency data (IVUS RFD) analysis, optical coherence tomography (OCT) and intravascular magnetic resonance spectroscopy (IVMR). METHODS: Twenty-four matched target plaques were analyzed with the 4 techniques in non-culprit lesions in five patients with stable angina. Following IVUS pullback, OCT and IVMR was performed. Plaque composition was assessed using established criteria of each technology. RESULTS: Atherosclerotic plaques classified as soft by GS IVUS were mainly composed by fibro-fatty (80%) or necrotic core (20%) by IVUS RFD. These soft plaques were classified as "lipid-rich" by OCT in the majority of cases (80%). IVMR confirmed the presence of lipid with a lipid fraction index ranging between 36 and 79 in these soft plaques. Besides this good agreement for soft plaques, GS IVUS, IVUS RFD and OCT had 100% agreement in the identification of calcified plaques. CONCLUSION: The present study explored multi-modality imaging of atherosclerotic plaque in-vivo. Assessing specifically lipid-rich plaques, there was generally good agreement for plaque components identified as soft by traditional GS IVUS with RFD and OCT whereas IVMR showed a varying amount of lipid in these regions. Nevertheless there continues to remain inherent variation, namely as a result of the different imaging resolutions and the lack of common nomenclature and classification.

Incomplete stent apposition and delayed tissue coverage are more frequent in drug-eluting stents implanted during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction than in drug-eluting stents implanted for stable/unstable angina: insights from optical coherence tomography.

OBJECTIVES: The aim of this study was to compare the frequency of incomplete stent apposition (ISA) and struts not covered by tissue at long-term follow-up (as assessed by optical coherence tomography [OCT]) in drug-eluting stents (DES) implanted during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) versus DES implanted for unstable and stable angina. BACKGROUND: Incomplete stent apposition and the absence of strut endothelialization might be linked to stent thrombosis. DES implanted for STEMI might have a higher risk of thrombosis. METHODS: Consecutive patients in whom OCT was performed at least 6 months after DES implantation were included in the study. Stent struts were classified on the basis of the presence or absence of ISA and tissue coverage. RESULTS: Forty-seven lesions in 43 patients (1,356 frames, 10,140 struts) were analyzed (49% stable angina, 17% unstable angina, 34% STEMI). Median follow-up time was 9 (range 7 to 72) months. Drug-eluting stents implanted during primary PCI presented ISA more often than DES implanted in stable/unstable angina patients (75% vs. 25.8%, p = 0.001). The frequency of uncovered struts was also higher in the STEMI group (93.8% vs. 67.7%, p = 0.048). On multivariate analysis, DES implantation in STEMI was the only independent predictor of ISA (odds ratio: 9.8, 95% confidence interval: 2.4 to 40.4, p = 0.002) and the presence of uncovered struts at follow-up (odds ratio: 9.5, 95% confidence interval: 1.0 to 90.3, p = 0.049). CONCLUSIONS: DES implanted for STEMI had a higher frequency of incompletely apposed struts and uncovered struts as assessed by OCT at follow-up. DES implantation during primary PCI in STEMI was an independent predictor of ISA and the presence of uncovered struts at follow-up.

How should I treat a complex Post-CABG patient?

BACKGROUND: A 69 year old man was admitted with unstable angina (Class IIB). He had a history of chronic renal impairment, diabetes mellitus, hypertension and coronary bypass surgery in 1997 (LIMA graft to the LAD anf diagonal branch, saphenous vein grafts to the RCA and first marginal branch of LCx. INVESTIGATION: Coronary angiography. DIAGNOSIS: Unstable angina (Class IIB). Occlusion of the LCx and RCA. Functionally occluded LIMA on the LAD and diagonal branch. Diffuse disease of the LAD with two significant lesions at the LAD-first diagonal and mid-distal LAD. TREATMENT: Revascularisation.