Long-term effect of biodegradable vs durable polymer everolimus-eluting stents on neoatherosclerosis in ST-segment elevation myocardial infarction: the CONNECT trial.

BACKGROUND AND AIMS: Neoatherosclerosis is a leading cause of late (>1 year) stent failure following drug-eluting stent implantation. The role of biodegradable (BP) versus durable polymer (DP) drug-eluting stents on long-term occurrence of neoatherosclerosis remains unclear. Superiority of biodegradable against durable polymer current generation thin-strut everolimus-eluting stent (EES) was tested by assessing the frequency of neoatherosclerosis 3 years after primary percutaneous coronary intervention (pPCI) among patients with ST-segment elevation myocardial infarction (STEMI). METHODS: The randomized controlled, multicentre (Japan and Switzerland) CONNECT trial (NCT03440801) randomly (1:1) assigned 239 STEMI patients to pPCI with BP-EES or DP-EES. The primary endpoint was the frequency of neoatherosclerosis assessed by optical coherence tomography (OCT) at 3 years. Neoatherosclerosis was defined as fibroatheroma or fibrocalcific plaque or macrophage accumulation within the neointima. RESULTS: Among 239 STEMI patients randomized, 236 received pPCI with stent implantation (119 BP-EES; 117 DP-EES). A total of 178 patients (75%; 88 in the BP-EES group and 90 in the DP-EES group) underwent OCT assessment at 3 years. Neoatherosclerosis did not differ between the BP-EES (11.4%) and DP-EES (13.3%; odds ratio 0.83, 95% confidence interval 0.33-2.04, p=0.69). There were no differences in the frequency of fibroatheroma (BP-EES 9.1% vs DP-EES 11.1%, p=0.66) or macrophage accumulation (BP-EES 4.5% vs DP-EES 3.3%, p=0.68), and no fibrocalcific neoatherosclerosis was observed. Rates of target lesion failure did not differ between groups (BP-EES 5.9% vs DP-EES 6.0%, p=0.97). CONCLUSIONS: Use of BP-EES for primary PCI in patients presenting with STEMI was not superior to DP-EES regarding frequency of neoatherosclerosis at 3 years.

Global use of angiotensin receptor neprilysin inhibitor in heart failure and reduced, below normal and supranormal ejection fraction.

BACKGROUND: The global use of angiotensin receptor neprilysin inhibitor (ARNI) in clinical practice, especially in patients with heart failure and below-normal ejection fraction (HFbnEF), has not been thoroughly evaluated. We aimed to investigate the characteristics, outcomes, and adverse events in patients treated with ARNI for HF with reduced (HFrEF), below-normal (HFbnEF), and supranormal left ventricular EF (HFsnEF). METHODS: This observational study analyzed data from the electronic healthcare records (EHR) of patients with HF treated with ARNI between 2015 and 2022 in North and South America, Europe, the Middle East, Africa, and Asia-Pacific. Based on the left ventricular EF, patients were categorized as HFrEF (< 40%), HFbnEF (40-60%), and HFsnEF (> 60%). Mortality and the incidence of adverse events were investigated. RESULTS: Of the 11,141 patients analyzed, HFrEF, HFbnEF and HFsnEF accounted for 74%, 22%, and 4%, respectively. Patients with a higher EF were more likely to be older, female, and obese. Hypertension and atrial fibrillation were the most common in HFsnEF. Systolic blood pressure was lower and natriuretic peptide levels were higher in the lower EF groups. Mortality was lowest in HFbnEF (7.7 per 100 patient-years follow-up in HFrEF, 5.8 in HFmrEF, and 6.0 in HFsnEF). Similarly, hypotension and acute kidney injury were the least frequent in HFbnEF. Incidence of elevated serum potassium levels was similar between the groups. CONCLUSIONS: In this analysis of large-scale EHR, ARNI was mainly used in HFrEF and HFbnEF, consistent with previous randomized trials and pooled analyses. Adverse events were less common in HFbnEF.

Association Between Late Gadolinium Enhancement with or Without Reverse Remodeling and Prognosis.

Late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR) prevents left ventricular reverse remodeling (LVRR), resulting in a poor prognosis. However, the prognosis of patients who have LGE and achieve LVRR and patients who do not have LGE and do not achieve LVRR remains unknown. This study aimed to answer this question by sorting patients with heart failure based on the presence of LGE and LVRR and comparing their prognoses. Another aim was to identify useful factors for predicting LVRR.All patients were followed-up for 24 months. LVRR was defined as a ≥ 10% increase at the last follow-up at 12 ± 6 months from baseline, on echocardiography. The primary endpoint was a composite of cardiovascular death and hospitalization due to worsening heart failure within 18 ± 6 months. Baseline data and data from each outpatient visit were collected and analyzed. We enrolled 80 consecutive patients with heart failure and reduced left ventricular ejection fraction (< 50%) who underwent CMR.LGE was positive in 40 patients (50.0%) and LVRR was observed in 50 patients (63%). The incidence of the primary endpoint was significantly lower in the group that achieved LVRR, regardless of LGE status (LGE-positive group, P = 0.01; LGE-negative group, P = 0.02). In the multivariate analysis, the percentage change in NT-pro BNP levels at 3 months, NT-pro BNP levels at 6 months, and age were independent predictors of LVRR.LGE-positive patients may have a better prognosis if they achieve LVRR. Serial NT-pro BNP testing may be a valuable predictor of LVRR.

Effect of dapagliflozin on ventricular repolarization in patients with heart failure with reduced ejection fraction.

Whether sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduce ventricular arrhythmias and sudden cardiac death is controversial. Ventricular repolarization heterogeneity is associated with ventricular arrhythmias; however, the effect of SGLT2is on ventricular repolarization in patients with heart failure with reduced ejection fraction (HFrEF) has not been fully investigated. We prospectively evaluated 31 HFrEF patients in sinus rhythm who were newly started on dapagliflozin 10 mg/day. Changes in QT interval, corrected QT interval (QTc), QT dispersion (QTD), corrected QTD (QTcD), T peak to T end (TpTe), TpTe/QT ratio, and TpTe/QTc ratio were evaluated at 1-year follow-up. QT interval, QTc interval, QTD, QTcD, TpTe, and TpTe/QTc ratio decreased significantly at 1-year follow-up (427.6 ± 52.6 ms vs. 415.4 ± 35.1 ms; p = 0.047, 437.1 ± 37.3 ms vs. 425.6 ± 22.7 ms; p = 0.019, 54.1 ± 11.8 ms vs. 47.6 ± 14.7 ms; p = 0.003, 56.0 ± 11.2 ms vs. 49.4 ± 12.3 ms; p = 0.004, 98.0 ± 15.6 ms vs. 85.5 ± 20.9 ms; p = 0.018, and 0.225 ± 0.035 vs. 0.202 ± 0.051; p = 0.044, respectively). TpTe/QT ratio did not change significantly (0.231 ± 0.040 vs. 0.208 ± 0.054; p = 0.052). QT interval, QTD, and TpTe were significantly reduced 1 year after dapagliflozin treatment in patients with HFrEF. The beneficial effect of dapagliflozin on the heterogeneity of ventricular repolarization may contribute to the suppression of ventricular arrhythmias.Registry information https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000049428 . Registry number: UMIN000044902.

Diuretic and renal effects of angiotensin receptor-neprilysin inhibitor in patients hospitalized for acute heart failure.

In patients hospitalized for acute decompensation of heart failure (HF), the impact of angiotensin receptor-neprilysin inhibitor (ARNI) on diuresis and renal function has not been fully investigated. Patients with HF and reduced ejection fraction who were hospitalized for acute decompensation and newly initiated ARNI after hemodynamic stabilization were enrolled. Changes in urine volume (UV), body weight, estimated glomerular filtration rate (eGFR), and urine N-acetyl-beta-d-glucosaminidase (uNAG) levels before and after ARNI initiation were investigated. Changes in the diuretic response [DR, calculated as urine volume/(intravenous furosemide volume/40 mg)], N-terminal pro-brain natriuretic peptide (NT-proBNP), hematocrit, and plasma volume (PV) were also evaluated. A total of 60 patients were enrolled. ARNI was initiated at a median of 6 [5, 7] days after hospitalization. After initiation of ARNI, body weight, NT-proBNP, and PV decreased. UV and DR increased only on the day of ARNI initiation (delta UV 400 ± 957 ml and delta DR 1100 ± 3107 ml/40 mg furosemide) and then decreased to baseline levels. In the multivariable linear regression analysis, younger age, higher BMI, and higher NT-proBNP levels were significantly associated with greater UV after ARNI initiation. eGFR and uNAG did not significantly change after the initiation of ARNI [delta eGFR -1.7 ± 12.0 mL/min/1.73 m2 and delta uNAG 2.0 (-5.6, 6.9) IU/L]. In patients hospitalized for HF, the initiation of ARNI was associated with a small and transient increase in UV and DR, and was not associated with worsening of renal function or tubular injury.

Malnutrition, hemodynamics and inflammation in heart failure with reduced, mildly reduced and preserved ejection fraction.

In patients with heart failure (HF) with reduced ejection fraction (HFrEF), malnutrition can be associated with intestinal congestion and systemic inflammation. These relationships have not been fully investigated in HF with mildly reduced EF (HFmrEF) and with preserved EF (HFpEF). We analyzed 420 patients with HF who underwent right heart catheterization. The relationships between hemodynamic parameters, C-reactive protein, and the controlling nutritional (CONUT) score were investigated in HFrEF, HFmrEF and HFpEF. The CONUT score of all patients was 2 [1, 4] (median [interquartile range]), and was not significantly different between the left ventricular EF (LVEF) categories (2 [1, 3] for HFrEF, 2 [1, 3] for HFmrEF, and 3 [1, 4] for HFpEF, p = 0.279). In multivariate linear regression analyses, there was a significant association between CRP and the CONUT score in HFmrEF and HFpEF, while brain natriuretic peptide and right atrial pressure were significantly associated with the CONUT score in HFrEF. Higher CONUT scores predicted a higher incidence of the composite endpoint of death or HF hospitalization within 12 months without an interaction with LVEF (p = 0.980). The CONUT score was an independent predictor of the composite endpoint, death, and HF hospitalization after adjustment for confounders in the multivariate analysis. In conclusion, inflammation was associated with malnutrition in HFmrEF and HFpEF, while congestion was an independent predictor of malnutrition in HFrEF. Malnutrition predicted worse outcomes regardless of LVEF.

Clinical Differences of Recent Myocardial Infarction Compared With Acute Myocardial Infarction　- Insights From the Tokyo CCU Network Multicenter Registry.

BACKGROUND: Characteristics and treatment outcomes of acute myocardial infarction (AMI) patients have been studied; however, those of recent myocardial infarction (RMI) patients remain unclear. This study aimed to clarify characteristics, treatment strategy, and in-hospital outcomes of RMI patients in the Tokyo CCU network database.Methods and Results:In total, 1,853 RMI and 12,494 AMI patients from the Tokyo CCU network database during 2013-2016 were compared. Both RMI and AMI were redefined by onset times of 2-28 days and ≤24 h, respectively. The RMI group had a higher average age (70.4±12.9 vs. 68.0±13.4 years, P<0.001), more women (27.6% vs. 23.6%, P<0.001), lower proportion of patients with chest pain as the chief complaint (75.2% vs. 83.6%, P<0.001), higher prevalence of diabetes mellitus (35.9% vs. 31.0%, P<0.001), and higher mechanical complication incidence (3.0% vs. 1.5%, P<0.001) than did the AMI group. Thirty-day mortality was comparable (5.3% vs. 5.8%, P=0.360); major causes of death were cardiogenic shock and mechanical complications in the AMI and RMI groups, respectively. Death from mechanical complications (not onset time) in the AMI group plateaued almost 1 week after hospitalization, whereas it continued to increase in the RMI group. CONCLUSIONS: Both RMI and AMI patients have distinctive clinical features, sequelae, and causes of death. Although treatment of RMI patients adhered to guidelines, it was insufficient, and death from mechanical complications continues to increase.

Malignant Findings in Candidates for Transcatheter Aortic Valve Implantation.

BACKGROUND: In candidates for transcatheter aortic valve implantation (TAVI), preoperative computed tomography (CT) may detect clinically relevant non-cardiac findings. In particular, when malignant findings are detected, patients may be less likely to undergo the procedure. Additionally, they might require further examinations, which may prolong their time to treatment. We investigated how malignant findings affect candidacy for TAVI. METHODS: In this single-center retrospective study, 98 patients with severe aortic stenosis who had undergone preoperative CT between September 2013 and October 2016 were evaluated for malignant findings. RESULTS: Seven patients (7.1%) had malignant findings. 74 of 91 patients who did not have malignant findings underwent TAVI, SAVR, or balloon aortic valvuloplasty (81.3%). All patients who had malignant findings underwent TAVI or SAVR, and they underwent the procedure sooner after CT than the rest of the patients (mean time to TAVI or SAVR: 24.6 ± 16.8 versus 48.5 ± 45.4 days; P = .003). All 5 patients who had malignant findings without metastatic cancer and who underwent TAVI were still alive during the follow-up period (the mean duration of the follow-up period was 22.3 ± 8.8 months). However, 1 patient who had a malignant finding with metastatic cancer died 7 months after CT. CONCLUSION: Our outcomes indicated that the mean duration before TAVI or SAVR was reduced when malignant findings were detected by CT; and TAVI may be a safe and effective treatment for patients with aortic stenosis and a malignant tumor.

Pathology of self-expanding transcatheter aortic valves: Findings from the CoreValve US pivotal trials.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has recently become an alternative to surgical aortic valve replacement for patients with severe aortic stenosis. However, paravalvular leaks, possible leaflet thrombosis, and device durability following TAVR remain unresolved issues. METHODS AND RESULTS: We conducted the first systematic microscopic and macroscopic pathologic analysis of self-expanding CoreValve transcatheter aortic valves removed at autopsy or surgically from the U.S. pivotal trial of extreme- and high-risk patients. Implants were evaluated for histopathologic changes in the valve frame and leaflets. Thrombus/neointima on the leaflets was graded depending on the leaflet thickness and the extent of leaflet involvement. Inflammation, calcification, and structural integrity were also assessed. A total of 21 cases (median age 86.0 years [IQR, 79.0-91.0]), with median duration of implant duration of 17.0 days ranged from 0 to 503 days were evaluated. No valve frame fracture was observed and severe paravalvular gaps were uncommon. Inflammation and thrombus in the valve frame was minimal, but neointimal growth increased overtime. Symptomatic valve thrombosis was observed in one case (5%) and subclinical moderate leaflet thrombus was observed in four additional cases (19%). Inflammation of the leaflets was mild, while structural changes were minimal, and one case had infective endocarditis. Pannus or leaflet calcification were not observed. CONCLUSIONS: This first systematic macroscopic and microscopic pathologic analysis of self-expanding transcatheter aortic valves demonstrates favorable short-term pathologic findings. However, our finding of subclinical leaflet thrombus formation confirms prior observations and warrants further investigation.

Safety of Zilver PTX Drug-Eluting Stent Implantation Following Drug-Coated Balloon Dilation in a Healthy Swine Model.

PURPOSE: To compare the safety of Zilver PTX drug-eluting stents (DES) following drug-coated balloon (DCB) angioplasty or conventional balloon angioplasty (BA) in a healthy porcine iliofemoral artery model. METHODS: DES implantation following DCB (DCB+DES) or BA (BA+DES) was assessed by angiography and histology in the nondiseased iliofemoral arteries of 20 animals, with sacrifice at 1, 3, and 6 months. Safety assessment compared quantitative measures of vessel integrity (eg, preservation of artery geometry, structure, and lumen dimensions; absence of aneurysm; malapposition) and histological parameters (eg, excessive inflammation). The percentage of uncovered struts could not be >30% per section and the endothelial cell loss had to be <50%. The vascular and skeletal muscle changes in the downstream regions were also assessed histologically for evidence of emboli. RESULTS: No significant differences in safety parameters, including inflammation and endothelial cell loss, were observed between the 2 groups at all time points. Percentage of fibrin was significantly higher in DCB+DES at 3 months [20.0% (IQR 11.6, 28.4) vs BA+DES 4.2% (IQR 1.4, 9.6), respectively; p=0.04], with consistent trends between groups at all time points. Medial smooth muscle cell loss peaked at 1 month and was not statistically different between groups at any time point, although the loss was greater in the DCB+DES group. Sections with arterioles exhibiting paclitaxel-associated fibrinoid necrosis in downstream tissues were observed exclusively in the DCB group at 1 month (14.3% of sections) and 3 months (11.5%). CONCLUSION: This preclinical study suggests that Zilver PTX stent implantation is a safe strategy after DCB angioplasty and might be considered for patients who require stenting after DCB treatment.

Biologic Drug Effect and Particulate Embolization of Drug-Eluting Stents versus Drug-Coated Balloons in Healthy Swine Femoropopliteal Arteries.

PURPOSE: To compare the drug effect in treated vessels and downstream effects in distal skeletal muscle of drug-coated balloons (DCBs) and drug-eluting stents (DESs) in a healthy preclinical swine model. MATERIALS AND METHODS: Four groups of treated iliofemoral arteries (percutaneous transluminal angioplasty [PTA]+DES, DCB+DES, DCB+bare metal stent [BMS], and DCB alone) of 12 healthy swine were assessed, with euthanasia at 30 days. Biological drug effect was evaluated using smooth muscle cell (SMC) loss score according to both depth and circumference as well as a neointimal fibrin and medial proteoglycan scores which were compared between the 4 groups. Vascular and skeletal muscle changes in regions downstream from the treated site were also assessed histologically for evidence of emboli. RESULTS: DESs showed greater medial SMC loss in the treated arteries irrespective of preceding DCB or PTA treatment in terms of depth (DCB+DES vs PTA+DES vs DCB+BMS vs DCB alone; median, 4.0 mm vs 3.8 mm vs 3.0 mm vs 2.2 mm; P = .009) and circumference (4.0 mm vs 3.5 mm vs 2.0 mm vs 1.2 mm, respectively; P = .007). Sections of skeletal muscles downstream from the treated arteries showed arteriolar changes of fibrinoid necrosis consistent with paclitaxel effect exclusively in the DCB groups (DCB+BMS, 26.9% of sections; DCB+DES, 14.3%; DCB alone, 19.2%; PTA+DES, 0%; P = .02). CONCLUSIONS: In the treated arteries, irrespective of preceding DCB treatment or PTA, DES treatment showed maximum drug effects vs DCB alone or in combination with BMS placement, and there was no detrimental toxic effect in DCB-treated iliofemoral arteries before DES treatment compared with PTA before DES treatment. Downstream vascular changes were exclusively seen in groups treated with DCBs.

Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus.

The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus. Moreover, there is a higher incidence of healed plaque ruptures and positive remodeling in hearts from subjects with type 1 diabetes mellitus and type 2 diabetes mellitus, suggesting a more active atherogenic process. Lesion calcification in the coronary, carotid, and other arterial beds is also more extensive. Although the role of coronary artery calcification in identifying cardiovascular disease and predicting its outcome is undeniable, our understanding of how key hormonal and physiological alterations associated with diabetes mellitus such as insulin resistance and hyperglycemia influence the process of vascular calcification continues to grow. Important drivers of atherosclerotic calcification in diabetes mellitus include oxidative stress, endothelial dysfunction, alterations in mineral metabolism, increased inflammatory cytokine production, and release of osteoprogenitor cells from the marrow into the circulation. Our review will focus on the pathophysiology of type 1 diabetes mellitus- and type 2 diabetes mellitus-associated vascular disease with particular focus on coronary and carotid atherosclerotic calcification.

Prognostic Impact of Computed Tomography-Derived Abdominal Fat Area on Transcatheter Aortic Valve Implantation.

BACKGROUND: Obesity has previously been identified as an indicator of good prognosis in patients undergoing transcatheter aortic valve implantation (TAVI), an association known as the "obesity paradox". We investigated whether abdominal total fat area (TFA), visceral fat area (VFA), or subcutaneous fat area (SFA) are prognostic indicators of long-term clinical outcome in patients undergoing TAVI. Methods and Results: We retrospectively analyzed 100 consecutive patients who underwent TAVI between December 2013 and April 2017. TFA, VFA, and SFA were measured from routine pre-procedural computed tomography (CT). Patients were divided into 2 groups according to median TFA, VFA, or SFA, and we investigated the association of abdominal fat area with adverse clinical events, including all-cause death and re-hospitalization due to worsening heart failure. At a median follow-up of 665 days, patients with higher SFA had significantly lower incidence of the composite outcome and all-cause death compared with patients with lower SFA (15.0% vs. 37.7%, P=0.025; and 8.9% vs. 23.7%, P=0.047, respectively). In contrast, patients with higher TFA or VFA did not show significant reduction in the incidences of the composite outcome or all-cause mortality. CONCLUSIONS: CT-derived SFA had prognostic value in patients undergoing TAVI.

Pathology of balloon-expandable transcatheter aortic valves.

BACKGROUND: The Placement of AoRtic TraNscathetER Valves trials (PARTNER) showed favorable safety and efficacy versus medical or surgical therapy in inoperable, high, and intermediate surgical risk patients with severe aortic stenosis. However, the biological responses to transcatheter aortic valves have not been well characterized. OBJECTIVES: The aim of this study was to perform pathologic assessment of Edwards SAPIEN transcatheter aortic valves removed either at autopsy or surgically during the PARTNER I and II clinical trials. METHODS: Explanted valves and frame were evaluated for pathologic responses including extent of thrombus, inflammation, neointima, and leaflet degeneration/calcification according to semiquantitative grading by implant duration (≤30 days; 31-90 days; >90 days). RESULTS: A total of 22 cases (median age 82.0 years, 45% men) were included, with a duration of implantation that ranged from 0 to 1739 days (median duration 16.5 days [interquartile range, 2.8-68.3]). Valve thrombosis resulting in severe aortic stenosis was observed in one case. Moderate leaflet thrombus was seen in 14% of cases (n = 3) and all were asymptomatic. Calcification was seen in two valves: one with severe leaflet calcification had severe aortic stenosis requiring surgical replacement, while the other showed early calcification. Mild structural leaflet changes were exclusively seen in valve implants >90 days. Valve inflammation and thrombus formation was mild in majority of the cases. CONCLUSIONS: Overall, our study demonstrates moderate thrombus formation in 14% and calcification in only 2 valves, ≥4 years duration. In this short-duration study, acceptable durability and biocompatibility of the Edwards SAPIEN transcatheter valve system was demonstrated; however, further studies are required to confirm the significance and application of our findings.

Comparison of Particulate Embolization after Femoral Artery Treatment with IN.PACT Admiral versus Lutonix 035 Paclitaxel-Coated Balloons in Healthy Swine.

PURPOSE: Different carrier excipients unique to individual drug-coated balloons (DCBs) may influence embolic safety characteristics in peripheral vascular territories through embolization of released particulates. A comparator study of IN.PACT Admiral vs Lutonix 035 balloons in healthy swine was therefore performed to assess which balloon produces more downstream emboli. MATERIALS AND METHODS: Single or overlapping 80-mm IN.PACT and Lutonix 035 DCBs were assessed in the femoral arteries of 21 swine with 28- and 90-day follow-up, with standard balloon angioplasty as a control. Histologic analysis of arterial wall and downstream skeletal muscle and coronary band was performed. This analysis was supported by an analytic measurement of paclitaxel levels. RESULTS: IN.PACT DCBs demonstrated a more pronounced change in medial wall composition, characterized by a paclitaxel-induced loss of medial smooth muscle cells accompanied by increased proteoglycans. The percentage of sections with arterioles exhibiting paclitaxel-associated fibrinoid necrosis in downstream tissues was higher at 90 days with overlapping IN.PACT DBCs compared with Lutonix 035 DCBs (46.2% [interquartile range, 19.2-57.7] vs 0.0% [0.0-11.5]; P = .01), with similar trends noted for 28-day single and overlapping DCBs. Drug analysis in parallel tissues further confirmed higher paclitaxel concentrations in nontarget tissues for IN.PACT than Lutonix 035 balloons for single and overlapping configurations at both time points. Rare embolic crystalline material was observed in downstream tissues, but only for IN.PACT balloons. CONCLUSIONS: There was more fibrinoid necrosis in tissues treated with IN.PACT DCBs compared with Lutonix DCBs, suggesting increased emboli debris with higher paclitaxel levels.

Neoatherosclerosis: overview of histopathologic findings and implications for intravascular imaging assessment.

Despite the reduction in late thrombotic events with newer-generation drug-eluting stents (DES), late stent failure remains a concern following stent placement. In-stent neoatherosclerosis has emerged as an important contributing factor to late vascular complications including very late stent thrombosis and late in-stent restenosis. Histologically, neoatherosclerosis is characterized by accumulation of lipid-laden foamy macrophages within the neointima with or without necrotic core formation and/or calcification. The development of neoatherosclerosis may occur in months to years following stent placement, whereas atherosclerosis in native coronary arteries develops over decades. Pathologic and clinical imaging studies have demonstrated that neoatherosclerosis occurs more frequently and at an earlier time point in DES when compared with bare metal stents, and increases with time in both types of implant. Early development of neoatherosclerosis has been identified not only in first-generation DES but also in second-generation DES. The mechanisms underlying the rapid development of neoatherosclerosis remain unknown; however, either absence or abnormal endothelial functional integrity following stent implantation may contribute to this process. In-stent plaque rupture likely accounts for most thrombotic events associated with neoatherosclerosis, while it may also be a substrate of in-stent restenosis as thrombosis may occur either symptomatically or asymptomatically. Intravascular optical coherence tomography is capable of detecting neoatherosclerosis; however, the shortcomings of this modality must be recognized. Future studies should assess the impact of iterations in stent technology and risk factor modification on disease progression. Similarly, refinements in imaging techniques are also warranted that will permit more reliable detection of neoatherosclerosis.