Long-Term Results of Bioresorbable Vascular Scaffolds in Patients With In-Stent Restenosis: The RIBS VI Study.

BACKGROUND: In patients with in-stent restenosis (ISR) bioresorbable vascular scaffolds (BVS) provide similar results to drug-coated balloons (DCBs) but are inferior to drug-eluting stents (DES) at 1 year. However, the long-term efficacy of BVS in these patients remains unknown. OBJECTIVES: This study sought to assess the long-term safety and efficacy of BVS in patients with ISR. METHODS: RIBS VI (Restenosis Intrastent: Bioresorbable Vascular Scaffolds Treatment; NCT02672878) and RIBS VI Scoring (Restenosis Intrastent: Bioresorbable Vascular Scaffolds Treatment With Scoring Balloon; NTC03069066) are prospective multicenter studies designed to evaluate the results of BVS in patients with ISR (N = 220). The inclusion and exclusion criteria were identical to those used in the RIBS IV (ISR of DES) (Restenosis Intra-stent of Drug-eluting Stents: Drug-eluting Balloon vs Everolimus-eluting Stent; NCT01239940) and RIBS V (ISR of bare-metal stents) (Restenosis Intra-stent of Bare Metal Stents: Paclitaxel-eluting Balloon vs Everolimus-eluting Stent; NCT01239953) randomized trials (including 249 ISR patients treated with DCBs and 249 ISR patients treated with DES). A prespecified comparison of the long-term results obtained with these treatment modalities (ie, DES, DCBs, and BVS) was performed. RESULTS: Clinical follow-up at 3 years was obtained in all (100%) 718 patients. The 3-year target lesion revascularization rate after BVS was 14.1% (vs 12.9% after DCBs [not significant], and 5.2% after DES [HR: 2.80; 95% CI: 1.47-5.36; P = 0.001]). In a landmark analysis (>1 year), the target lesion revascularization rate after BVS was higher than after DES (adjusted HR: 3.41; 95% CI: 1.15-10.08) and DCBs (adjusted HR: 3.33; 95% CI: 1.14-9.70). Very late vessel thrombosis was also more frequent with BVS (BVS: 1.8%, DCBs: 0.4%, DES: 0%; P = 0.03). CONCLUSIONS: In patients with ISR, late clinical results of DES are superior to those obtained with DCBs and BVS. Beyond the first year, DCBs are safer and more effective than BVS.

Diaphragmatic Paralysis After Heterotopic Bicaval Stenting.

Heterotopic bicaval stenting offers an alternative therapeutic approach for indirectly addressing the systemic effects of tricuspid regurgitation (TR) in patients with severe symptomatic TR, despite optimal medical therapy. In this report, we describe 2 cases of procedure-related unilateral diaphragmatic paralysis, a clinically important complication not previously documented in the literature.

Increased Incidence of Adverse Events in Diabetes Mellitus Patients with Combined Multiple Vulnerable Plaque Features. New Insights From the COMBINE OCT-FFR trial.

AIMS: To evaluate the individual as well as combined impact of OCT-detected vulnerability features (OCT-VFs) in the prediction of major adverse cardiovascular events (MACE) in non-ischemic lesions in patients with diabetes mellitus (DM). METHODS AND RESULTS: The COMBINE OCT-FFR (NCT02989740) was a prospective, double-blind, international, natural history study that included patients with DM having ≥1 lesions with a fractional flow reserve >0.80, undergoing systematic OCT assessment. Pre-specified OCT-VFs included TCFA, r-MLA, h-PB, and CP. The primary endpoint (MACE) was a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or hospitalization for unstable angina up to 5 years, analyzed according to the presence of these OCT-VFs, both individually and in combination. TCFA, r-MLA, h-PB and CP were identified in 98 (25.1%), 159 (40.8%), 56 (14.4%), and 116 (29.8%) patients, respectively. The primary endpoint rate increased progressively from 6.9% to 50.0% (HR=10.10; 95%CI, 3.37 to 30.25, p<0.001) in patients without OCT-VFs compared to those with concomitant h-PB, r-MLA, CP, and TCFA. Importantly, while TCFA, h-PB, r-MLA and CP were individually associated with the primary endpoint, the presence of two or more OCT-VFs significantly increased the likelihood of adverse events at 5 years. CONCLUSIONS: In patients with DM and non-ischemic lesions, TCFA, h-PB, r-MLA and CP were predictors of adverse events. However, the presence of two or more OCT-VFs significantly increased the likelihood of MACE at 5 years. Further studies are warranted to confirm these findings and their potential clinical implications in a randomized fashion.

Vulnerable plaque features and adverse events in patients with diabetes mellitus: a post hoc analysis of the COMBINE OCT-FFR trial.

BACKGROUND: Thin-cap fibroatheroma (TCFA) lesions are associated with a high risk of future major adverse cardiovascular events. However, the impact of other optical coherence tomography-detected vulnerability features (OCT-VFs) and their interplay with TCFA in predicting adverse events remains unknown. AIMS: We aimed to evaluate the individual as well as the combined prognostic impact of OCT-VFs in predicting the incidence of the lesion-oriented composite endpoint (LOCE) in non-ischaemic lesions in patients with diabetes mellitus (DM). METHODS: COMBINE OCT-FFR (ClinicalTrials.gov: NCT02989740) was a prospective, double-blind, international, natural history study that included DM patients with ≥1 non-culprit lesions with a fractional flow reserve>0.80 undergoing systematic OCT assessment. OCT-VFs included the following: TCFA, reduced minimal lumen area (r-MLA), healed plaque (HP), and complicated plaque (CP). The primary endpoint, LOCE - a composite of cardiac mortality, target vessel myocardial infarction, or clinically driven target lesion revascularisation up to 5 years - was analysed according to the presence of these OCT-VFs, both individually and in combination. RESULTS: TCFA, r-MLA, HP and CP were identified in 98 (25.3%), 190 (49.0%), 87 (22.4%), and 116 (29.9%) patients, respectively. The primary endpoint rate increased progressively from 6.3% to 55.6% (hazard ratio 15.2, 95% confidence interval: 4.53-51.0; p<0.001) in patients without OCT-VFs as compared to patients with concomitant HP, r-MLA, CP, and TCFA. The coexistence of TCFA with other OCT-VFs resulted in an increased risk of the LOCE at 5 years. CONCLUSIONS: In DM patients with non-ischaemic lesions, TCFA was the strongest predictor of future LOCE events. However, lesions that present additional OCT-VFs are associated with a higher risk of adverse events than OCT-detected TCFA alone. Further randomised studies are warranted to confirm these findings and their potential clinical implications.

Calcified Nodule: A Rare Clinical Diagnosis in Patients Presenting With ST-Segment Elevation Myocardial Infarction.

Calcified nodules (CNs) represent the least common cause of acute coronary syndrome. Furthermore, case reports describing CNs as the underlying cause for ST-segment elevation myocardial infarction are exceptional. We present a patient with ST-segment elevation myocardial infarction caused by a CN and outline the corresponding diagnostic angiographic and intracoronary imaging findings.

Lithotripsy for calcified in-stent restenosis. The "rock strata peeling pattern": A novel fracture pattern detected by optical coherence tomography.

Calcified neoatherosclerosis represents a particularly challenging scenario in patients with in-stent restenosis (ISR), frequently associated with worse angiographic and optical coherence tomography (OCT) results compared with other patients with typical ISR. Intravascular lithotripsy (IVL) has emerged as a safe and effective technology to circumferentially modify calcium in heavily calcified coronary lesions. Preliminary data also suggest its usefulness in calcified neoatheroscerosis. This case report aims to describe a novel fracture pattern after IVL identified by OCT (the "rock strata peeling pattern") in patients presenting with ISR due to calcified neoatherosclerosis.

CD69 expression on regulatory T cells protects from immune damage after myocardial infarction.

Increasing evidence has pointed to the important function of T cells in controlling immune homeostasis and pathogenesis after myocardial infarction (MI), although the underlying molecular mechanisms remain elusive. In this study, a broad analysis of immune markers in 283 patients revealed significant CD69 overexpression on Tregs after MI. Our results in mice showed that CD69 expression on Tregs increased survival after left anterior descending (LAD) coronary artery ligation. Cd69-/- mice developed strong IL-17+ γδT cell responses after ischemia that increased myocardial inflammation and, consequently, worsened cardiac function. CD69+ Tregs, by induction of AhR-dependent CD39 ectonucleotidase activity, induced apoptosis and decreased IL-17A production in γδT cells. Adoptive transfer of CD69+ Tregs into Cd69-/- mice after LAD ligation reduced IL-17+ γδT cell recruitment, thus increasing survival. Consistently, clinical data from 2 independent cohorts of patients indicated that increased CD69 expression in peripheral blood cells after acute MI was associated with a lower risk of rehospitalization for heart failure (HF) after 2.5 years of follow-up. This result remained significant after adjustment for age, sex, and traditional cardiac damage biomarkers. Our data highlight CD69 expression on Tregs as a potential prognostic factor and a therapeutic option to prevent HF after MI.

Structure-Based Modulation of the Ligand Sensitivity of a Tomato Dimeric Abscisic Acid Receptor Through a Glu to Asp Mutation in the Latch Loop.

The binding of the plant phytohormone Abscisic acid (ABA) to the family of ABA receptors (PYR/PYL/RCAR) triggers plant responses to abiotic stress. Thus, the implementation of genetic or chemical strategies to modulate PYR/PYL activity might be biotechnologically relevant. We have employed the available structural information on the PYR/PYL receptors to design SlPYL1, a tomato receptor, harboring a single point mutation that displays enhanced ABA dependent and independent activity. Interestingly, crystallographic studies show that this mutation is not directly involved in ABA recognition or in the downstream phosphatase (PP2C) inhibitory interaction, rather, molecular dynamic based ensemble refinement restrained by crystallographic data indicates that it enhances the conformational variability required for receptor activation and it is involved in the stabilization of an active form of the receptor. Moreover, structural studies on this receptor have led to the identification of niacin as an ABA antagonist molecule in vivo. We have found that niacin blocks the ABA binding site by mimicking ABA receptor interactions, and the niacin interaction inhibits the biochemical activity of the receptor.

Outcomes of leadless pacemaker implantation in patients with mechanical heart valves.

INTRODUCTION: Device infections constitute a major complication of transvenous pacemakers. Mechanical heart valves (MHV) increase the risk of infective endocarditis (IE) and pacemaker infection, requiring lifelong vitamin K-antagonists (VKA), which may affect patient management. Leadless pacemakers (LP) are associated with low infection rates, posing an attractive option in MHV patients requiring permanent pacing. This study describes outcomes following LP implantation in patients with MHV. METHODS: This is a multicenter, observational, retrospective study including consecutive patients implanted with an LP at 5 centers between June 2015 and January 2020. Procedural outcomes, antithrombotic management, complications, performance during follow-up and episodes of bacteremia and IE were compared between patients with and without an MHV (MHV and non-MHV groups). RESULTS: Four hundred fifty-nine patients were included (74 in the MHV group, 16.1%, and 385 in the non-MHV group, 83.9%). Procedural outcomes and acute electrical performance were comparable between groups. Vascular complications and cardiac perforation occurred in 2.7 versus 2.3% (p = 1) and 0% versus 0.8% (p = 1) in the MHV group and non-MHV group. One case of IE occurred in the MHV group and 2 in the non-MHV group. In MHV patients, uninterrupted VKA was used in 83.8%, whereas 16.2% were heparin-bridged. Vascular complication or tamponade occurred in 1 (8.3%) MHV heparin-bridged patient versus 1 (1.6%) MHV uninterrupted VKA patient (p = .3). CONCLUSION: LP implantation outcomes in MHV patients are comparable to the general LP population. Device-related infections are rare following LP implantation, including in patients with MHV. In the MHV group, periprocedural anticoagulation management was not associated with significantly different rates of tamponade or vascular complication.

The double injection technique to improve visualization of severe coronary lesions with optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) is a high-resolution imaging modality that provides a precise evaluation of coronary anatomy. However, the presence of severe coronary lesions can prevent the required adequate distal contrast flushing resultting in inadequate blood clearance and poor image quality or complete blood shadowing of the underlying vessel wall. OBJECTIVES: The aim of this prospective study was to evaluate the feasibility and safety of a novel "double injection technique" (DIT) to overcome the limitations of the conventional technique (CT) in patients with severely stenotic lesions. METHODS: Twenty-three patients with severe angiographic lesions were sequentially imaged before intervention with OCT with the CT and then with DIT. A total of 5125 OCT frames were carefully matched and analyzed by an independent central core lab. A semiquantitative image quality score was used to grade the number of quadrants (0-4) with vessel wall visualization. RESULTS: Optimal OCT visualization (Grades 3-4) significantly improved by the DIT (68% vs. 38% of frames, p < 0.001). The DIT also improved the mean score (3.1 ± 0.6 vs. 2.0 ± 0.8; p < 0.05; mean improvement of 1.1 ± 0.5 per patient). There were no complications associated with the DIT. CONCLUSION: The DIT significantly improved preintervention image quality of OCT in severe coronary lesions.

Magnesium-based resorbable scaffold vs permanent metallic sirolimus-eluting stent in patients with ST-segment elevation myocardial infarction: 3-year results of the MAGSTEMI randomised controlled trial.

BACKGROUND: The long-term safety and performance of magnesium-based bioresorbable scaffolds (MgBRS) in ST-segment-elevation myocardial infarction (STEMI) patients are uncertain. AIMS: The aim of this study was to report the 3-year clinical outcomes of the MAGSTEMI trial. METHODS: This investigator-driven, multicentre, randomised, single-blind, controlled trial randomised STEMI patients 1:1 to MgBRS or to permanent metallic sirolimus-eluting stents (SES) at 11 academic centres. The main secondary endpoints included device-oriented composite endpoints (DoCE) and patient-oriented composite endpoints (PoCE), their individual components, any bleeding, and device thrombosis rate. All endpoints were defined according to the Academic Research Consortium. Events were adjudicated by an independent committee. RESULTS: Three-year clinical follow-up was obtained in 142 (90.0%) patients. At 3-year follow-up, MgBRS were associated with a higher rate of DoCE than SES (13 [17.6%] vs 5 [6.6%], diff -11.0 [95% CI: -21.3 to -0.7]; p=0.038). This difference was driven by an increased incidence of DoCE within the first year of follow-up. In the landmark analysis, there was no difference between 1 and 3 years (0 [0.0%] vs 1 [1.4%]; p=1.000). The difference in the rate of DoCE was driven by a higher incidence of target lesion revascularisation (TLR) in the MgBRS group compared to SES (12 [16.2%] vs 4 [5.3%]; diff -10.9% [95% CI: -20.7 to -1.2]; p=0.030). The difference in TLR was observed during the first year, with no further differences observed between 1 and 3 years (0 [0.0%] vs 1 [1.4%]; p=1.000). CONCLUSIONS: At 3-year follow-up, MgBRS were associated with a higher rate of TLR, which was clustered within the first year, compared to SES.

Treatment of in-stent restenosis with sirolimus-eluting magnesium bioresorbable scaffolds: optical coherence tomography insights.

OBJECTIVES: To assess the value of sirolimus-eluting magnesium bioresorbable scaffolds (MgS) in the treatment of patients with in-stent restenosis (ISR). The better option for the treatment of patients with ISR remains unsettled. Bioresorbable vascular scaffolds represent an interesting strategy in this setting to avoid another permanent metal layer. The novel MgS is an attractive option to treat these challenging patients. METHODS: We present the results of the first prospective series of consecutive patients with ISR treated with MgS under optical coherence tomography (OCT) guidance. RESULTS: A total of 14 patients (15 lesions) were prospectively included. The mean age was 67 ± 9 years and six patients (40%) presented with an acute coronary syndrome. In 10 patients (67%), underlying neoatherosclerosis was disclosed by OCT. An excellent MgS expansion was obtained in all but two patients who showed persistent suboptimal expansion in heavily calcified vessels. Minor residual malapposition ( n = 5) and angiographically silent minor edge dissections ( n = 8) were readily recognized by OCT. After a median clinical follow-up of 30 (range, 20-54) months, no patient required repeated revascularization, suffered a myocardial infarction or device thrombosis. CONCLUSIONS: These preliminary results suggest a potential role for the MgS in selected patients presenting with ISR.