Effects of exenatide on coronary stent's endothelialization in subjects with type 2 diabetes: a randomized controlled trial. The Rebuild study.

BACKGROUND: Subjects with type 2 diabetes (T2D) have a higher risk of in-stent restenosis and stent thrombosis. The activation of the glucagon-like peptide-1 receptor (GLP-1R) has been suggested to induce several effects on the vasculature that may reduce the risk of stent failure following an angioplasty. The aim of this study is to evaluate the effect of the GLP-1R agonist exenatide on endothelialization of a modern drug-eluting stent (DES) in subjects with T2D. METHODS: 38 subjects with T2D who were eligible for revascularization with implantation of DES were randomized to treatment with exenatide (once weekly) plus standard treatment, or to standard treatment alone. After 12 weeks, a new coronary angiography was performed to evaluate the percentage of strut coverage (primary endpoint) and the presence of neo-atherosclerosis by optical coherence tomography. This study was approved by the Stockholm's Ethical Review Board. RESULTS: The two groups were well balanced regarding baseline clinical characteristics. Strut coverage was 95% (88.7-98.5%) in the exenatide group and 91.4% (88.8-98.5%) in the control group (p = 0.692). There were no significant differences between groups neither in the thickness of neo-intima (0.2 mm in both groups, p = 0.471), nor the maximal in-stent obstruction by neo-intima (15.5% in exenatide group vs 14.7% in control group, p = 0.801). No significant differences were detected in the rate of target lesion revascularization between groups (p = 0.224). CONCLUSION: Twelve weeks treatment with exenatide did not lead to a significantly better stent coverage in people with T2D. No significant differences in the occurrence of neo-atherosclerosis were detected between groups. TRIAL REGISTRATION: The study was registered at www. CLINICALTRIALS: gov (Rebuild Study, NCT02621489).

Fractional Flow Reserve-Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease: 3-Year Follow-Up of the FAME 3 Trial.

BACKGROUND: Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI. METHODS: FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke. RESULTS: A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P=0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P=0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P=0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P=0.02). CONCLUSIONS: At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.

OCT or Angiography Guidance for PCI in Complex Bifurcation Lesions.

BACKGROUND: Imaging-guided percutaneous coronary intervention (PCI) is associated with better clinical outcomes than angiography-guided PCI. Whether routine optical coherence tomography (OCT) guidance in PCI of lesions involving coronary-artery branch points (bifurcations) improves clinical outcomes as compared with angiographic guidance is uncertain. METHODS: We conducted a multicenter, randomized, open-label trial at 38 centers in Europe. Patients with a clinical indication for PCI and a complex bifurcation lesion identified by means of coronary angiography were randomly assigned in a 1:1 ratio to OCT-guided PCI or angiography-guided PCI. The primary end point was a composite of major adverse cardiac events (MACE), defined as death from a cardiac cause, target-lesion myocardial infarction, or ischemia-driven target-lesion revascularization at a median follow-up of 2 years. RESULTS: We assigned 1201 patients to OCT-guided PCI (600 patients) or angiography-guided PCI (601 patients). A total of 111 patients (18.5%) in the OCT-guided PCI group and 116 (19.3%) in the angiography-guided PCI group had a bifurcation lesion involving the left main coronary artery. At 2 years, a primary end-point event had occurred in 59 patients (10.1%) in the OCT-guided PCI group and in 83 patients (14.1%) in the angiography-guided PCI group (hazard ratio, 0.70; 95% confidence interval, 0.50 to 0.98; P = 0.035). Procedure-related complications occurred in 41 patients (6.8%) in the OCT-guided PCI group and 34 patients (5.7%) in the angiography-guided PCI group. CONCLUSIONS: Among patients with complex coronary-artery bifurcation lesions, OCT-guided PCI was associated with a lower incidence of MACE at 2 years than angiography-guided PCI. (Funded by Abbott Vascular and others; OCTOBER ClinicalTrials.gov number, NCT03171311.).

Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery.

BACKGROUND: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking. METHODS: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed. RESULTS: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group. CONCLUSIONS: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.).

Risk of stent failure in patients with diabetes treated with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors: A nationwide observational study.

BACKGROUND: Incretins are a group of glucose-lowering drugs with favourable cardiovascular (CV) effects against neoatherosclerosis. Incretins' potential effect in stent failure is unknown. The aim of this study is to determine if incretin treatment decreases the risk of stent-thrombosis (ST), and/or in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) with implanted drug-eluting stents (DES). METHODS: Observational study including all diabetes patients who underwent PCI with DES in Sweden from 2007 to 2017. By merging 5 national registers, the information on patient characteristics, outcomes and drug dispenses was retrieved. Cox regression analysis with estimated hazard ratios (HRs) adjusted for confounders with 95% confidence intervals (CIs) was used to analyse for the occurrence of ST/ISR, and major adverse cardiovascular events (MACE). A subgroup analysis for the type of incretin treatment was performed. RESULTS: In total 18,505 diabetes patients (30% women) underwent PCI, and 32,463 DES were implanted. Of those, 10% (3449 DES in 1943 patients) were treated with incretins. Median follow-up time was 995 days (Control Group) vs. 771 days (Incretin Group). No significant difference in the risk of ST/ISR was found neither for the main study group (HR:0.98 95% CI:0.80-1.19) nor for the subgroups. No reduction of the risk of MACE (HR:0.96 95% CI:0.88-1.06) was observed. There was a 26% lower risk for CV death in favour of incretin treated patients (HR:0.74 95% CI:0.57-0.95). CONCLUSION: In diabetes patients who underwent PCI incretin treatment was not associated with lower risk of stent failure, but with lower risk of CV death.

Testing a Patient-Specific In-Silico Model to Noninvasively Estimate Central Blood Pressure.

PURPOSE: To show some preliminary results about the possibility to exploit a cardiovascular mathematical model-made patient-specific by noninvasive data routinely measured during ordinary clinical examinations-in order to obtain sufficiently accurate central blood pressure (BP) estimates. METHODS: A closed-loop multiscale (0D and 1D) model of the cardiovascular system is made patient-specific by using as model inputs the individual mean heart rate and left-ventricular contraction time, weight, height, age, sex and mean/pulse brachial BPs. The resulting framework is used to determine central systolic, diastolic, mean and pulse pressures, which are compared with the beat-averaged invasive pressures of 12 patients aged 72 ± 6.61 years. RESULTS: Errors in central systolic, diastolic, mean and pulse pressures by the model are 4.26 ± 2.81, 5.86 ± 4.38, 4.98 ± 3.95 and 3.51±2.38 mmHg, respectively. CONCLUSION: The proposed modeling approach shows a good patient-specific response and appears to be potentially useful in clinical practice. However, this approach needs to be evaluated in a larger cohort of patients and could possibly be improved through more accurate oscillometric BP measurement methods.

Performing elective cardiac invasive procedures during the COVID-19 outbreak: a position statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

The rearrangement of healthcare services required to face the coronavirus disease 2019 (COVID-19) pandemic led to a drastic reduction in elective cardiac invasive procedures. We are already facing a "second wave" of infections and we might be dealing during the next months with a "third wave" and subsequently new waves. Therefore, during the different waves of the COVID-19 pandemic we have to face the problems of how to perform elective cardiac invasive procedures in non-COVID patients and which patients/procedures should be prioritised. In this context, the interplay between the pandemic stage, the availability of healthcare resources and the priority of specific cardiac disorders is crucial. Clear pathways for "hot" or presumed "hot" patients and "cold" patients are mandatory in each hospital. Depending on the local testing capacity and intensity of transmission in the area, healthcare facilities may test patients for SARS-CoV-2 infection before the interventional procedure, regardless of risk assessment for COVID-19. Pre-hospital testing should always be conducted in the presence of symptoms suggestive of SARS-CoV-2 infection. In cases of confirmed or suspected COVID-19 positive patients, full personal protective equipment using FFP 2/N95 masks, eye protection, gowning and gloves is indicated during cardiac interventions for healthcare workers. When patients have tested negative for COVID-19, medical masks may be sufficient. Indeed, individual patients should themselves wear medical masks during cardiac interventions and outpatient visits.

Long-term effect of remote ischemic conditioning on infarct size and clinical outcomes in patients with anterior ST-elevation myocardial infarction.

BACKGROUND: Conflicting evidence exists concerning the cardioprotective efficacy of remote ischemic conditioning as an adjunct to primary percutaneous intervention (PCI) in ST-elevation myocardial infarction (STEMI) and data on long-term outcomes are scarce. We evaluated final infarct size by cardiac magnetic resonance (CMR) performed 6 months after anterior STEMI treated with remote ischemic conditioning and clinical outcomes up to 3 years after the event. METHODS: One hundred and fifteen patients with anterior STEMI were randomized to remote ischemic per-postconditioning (RIperpostC) or sham procedure as adjunct to primary PCI. The primary outcome was myocardial salvage index (MSI) on CMR 6 months after the event. Secondary outcomes were absolute infarct size, left ventricular function, cardiac mortality, major adverse cardiac and cerebrovascular events (MACCE-composite of all-cause mortality, myocardial infarction, readmission for heart failure, ischemic stroke, and target lesion revascularization) and all the individual components of MACCE. RESULTS: There was no difference in MSI or left ventricular function between the RIperpostC and the control group after 6 months. Nor did clinical outcomes at 6 months or 3 years differ between the groups. CONCLUSIONS: RIperpostC as an adjunct to PCI in anterior STEMI did not result in better MSI or left ventricular function 6 months after the event. Furthermore, clinical outcomes at 6 months and 3 years were not altered.

Changes in 24-h ambulatory blood pressure following restoration of sinus rhythm in patients with atrial fibrillation.

OBJECTIVE: The interplay between atrial fibrillation and blood pressure (BP) is insufficiently studied. In symptomatic patients with persistent atrial fibrillation, electrical cardioversion (ECV) is often used to restore sinus rhythm. In this prospective study, we investigated how restoration of sinus rhythm affected 24-h ambulatory BP. METHODS: Ninety-eight patients with persistent atrial fibrillation were examined with 24-h ambulatory BP monitoring before and approximately a week after ECV. RESULTS: Sixty-two patients remained in sinus rhythm at the time of the second ambulatory BP monitoring (AF-SR group), whereas 36 patients had relapsed into atrial fibrillation (AF-AF group). In the AF-SR group, there was a significant increase in mean systolic 24-h BP (5.6 mmHg), a significant decrease in mean diastolic 24-h BP (-4.7 mmHg) and accordingly, a significant 25% (10.4 mmHg) increase in mean 24-h pulse pressure. CONCLUSION: These findings may reflect the haemodynamic conditions that are prevalent in atrial fibrillation, ambulatory BP measurement bias in atrial fibrillation or a combination of both factors. From a clinical standpoint, our results suggest that an increased attention to BP is needed when sinus rhythm is restored, as underlying hypertension may be masked by BP changes during atrial fibrillation. From a general standpoint, it may be speculated that BP, as indicated by the relatively large difference in pulse pressure, may be inherently different in atrial fibrillation and may therefore not be interpretable in the equivalent manner as BP in sinus rhythm.

EAPCI Core Curriculum for Percutaneous Cardiovascular Interventions (2020): Committee for Education and Training European Association of Percutaneous Cardiovascular Interventions (EAPCI). A branch of the European Society of Cardiology.

The proposed 2020 Core Curriculum for Percutaneous Cardiovascular Interventions aims to provide an updated European consensus that defines the level of experience and knowledge in the field of percutaneous cardiovascular intervention (PCI). It promotes homogenous education and training programmes among countries, and is the cornerstone of the new EAPCI certification, designed to support the recognition of competencies at the European level and the free movement of certified specialists in the European Community. It is based on a thorough review of the ESC guidelines and of the EAPCI textbook on percutaneous interventional cardiovascular medicine. The structure of the current core curriculum evolved from previous EAPCI core curricula and from the "2013 core curriculum of the general cardiologist" to follow the current ESC recommendations for core curricula. In most subject areas, there was a wide - if not unanimous - consensus among the task force members on the training required for the interventional cardiologist of the future. The document recommends that acquisition of competence in interventional cardiology requires at least two years of postgraduate training, in addition to four years devoted to cardiology. The first part of the curriculum covers general aspects of training and is followed by a comprehensive description of the specific components in 54 chapters. Each of the chapters includes statements of the objectives, and is further subdivided into the required knowledge, skills, behaviours, and attitudes.

Clinical outcomes with unselected use of an ultrathin-strut sirolimus-eluting stent: a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

AIMS: The aim of this study was to assess the real-world clinical performance of a sirolimus-eluting ultrathin-strut drug-eluting stent (DES) (Orsiro) in a large nationwide cohort of patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: From the Swedish Coronary Angiography and Angioplasty Registry, the two-year outcomes of 4,561 patients implanted with Orsiro (Orsiro group) and 69,570 receiving other newer-generation DES (n-DES group) were analysed. The rate of definite stent thrombosis was low in both groups (0.67% and 0.83% for Orsiro and n-DES, respectively; adjusted hazard ratio [HR] 0.90, 95% confidence interval [CI]: 0.55-1.46, p-value 0.66). Restenosis was also infrequent (1.5% vs 2.0% with Orsiro and n-DES, adjusted HR 0.81, 95% CI: 0.63-1.03, p-value=0.09). The risk of target lesion revascularisation by PCI was lower in the Orsiro group (1.6% vs 2.3%, adjusted HR 0.75, 95% CI: 0.60-0.94, p-value=0.013). All-cause mortality and myocardial infarction did not show a statistically significant difference between the two groups (mortality of 7.5% in both groups, adjusted HR 0.99, 95% CI: 0.72-1.35, p-value=0.94; 6.0% vs 5.2% for myocardial infarction, adjusted HR 1.19, 95% CI: 1.00-1.43, p-value=0.06). CONCLUSIONS: In a nationwide scenario, the use of a sirolimus-eluting ultrathin-strut DES portended favourable clinical outcomes.

Incidence and outcome of myocardial infarction treated with percutaneous coronary intervention during COVID-19 pandemic.

OBJECTIVE: Most reports on the declining incidence of myocardial infarction (MI) during the COVID-19 have either been anecdotal, survey results or geographically limited to areas with lockdowns. We examined the incidence of MI during the COVID-19 pandemic in Sweden, which has remained an open society with a different public health approach fighting COVID-19. METHODS: We assessed the incidence rate (IR) as well as the incidence rate ratios (IRRs) of all MI referred for coronary angiography in Sweden using the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR), during the COVID-19 pandemic in Sweden (1 March 2020-7 May 2020) in relation to the same days 2015-2019. RESULTS: A total of 2443 MIs were referred for coronary angiography during the COVID-19 pandemic resulting in an IR 36 MIs/day (204 MIs/100 000 per year) compared with 15 213 MIs during the reference period with an IR of 45 MIs/day (254 MIs/100 000 per year) resulting in IRR of 0.80, 95% CI (0.74 to 0.86), p<0.001. Results were consistent in all investigated patient subgroups, indicating no change in patient category seeking cardiac care. Kaplan-Meier event rates for 7-day case fatality were 439 (2.3%) compared with 37 (2.9%) (HR: 0.81, 95% CI (0.58 to 1.13), p=0.21). Time to percutaneous coronary intervention (PCI) was shorter during the pandemic and PCI was equally performed, indicating no change in quality of care during the pandemic. CONCLUSION: The COVID-19 pandemic has significantly reduced the incidence of MI referred for invasive treatment strategy. No differences in overall short-term case fatality or quality of care indicators were observed.

Index of Microcirculatory Resistance Measured during Intracoronary Adenosine-Induced Hyperemia.

BACKGROUND: The index of microcirculatory resistance is an invasive measure of coronary microvascular function that has to be calculated during maximal hyperemia, classically achieved with intravenous adenosine (IV). The aim of this study was to evaluate the use of intracoronary (IC) adenosine for the calculation of IMR. METHODS AND RESULTS: 31 patients with stable coronary artery disease were included in the study. Coronary pressure and thermodilution measurements were obtained at rest and during maximal hyperemia using a pressure-temperature sensor-tipped coronary guidewire. Duplicate measurements were performed using first IC and then IV adenosine. Dispersion of transit times was comparable for IC and IV adenosine. IMR values based on IC vs IV adenosine showed a high level of agreement and an intraclass correlation coefficient of 0.90. Applying an upper normal limit of 25, misclassification of IMR using IC adenosine was seen in just one patient in whom IC adenosine resulted in a lower value. A simplified procedure based on a single bolus dose of saline did not change the level of agreement or the rate of misclassification. CONCLUSIONS: We found an excellent agreement between IMR values measured during hyperemia induced by IC as compared to IV adenosine. The use of IC adenosine may facilitate invasive assessment of microvascular function and is potentially time- and cost-saving with less patient discomfort as compared to IV infusion. The trail is registered with NCT03369184.

Mapping interventional cardiology in Europe: the European Association of Percutaneous Cardiovascular Interventions (EAPCI) Atlas Project.

AIMS: The European Association of Percutaneous Cardiovascular Interventions (EAPCI) Atlas of Interventional Cardiology has been developed to map interventional practice across European Society of Cardiology (ESC) member countries. Here we present the main findings of a 16-country survey in which we examine the national availability of interventional infrastructure, human resource, and procedure volumes. METHODS AND RESULTS: Sixteen ESC member countries participated in the EAPCI Atlas survey. Interventional data were collected by the National Cardiac Society of each participating country. An annual median of 5131 [interquartile range (IQR) 4013-5801] diagnostic heart procedures per million people were reported, ranging from <2500 in Egypt and Romania to >7000 in Turkey and Germany. Procedure rates showed significant correlation (r = 0.67, P = 0.013) with gross national income (GNI) per capita. An annual median of 2478 (IQR 1690-2633) percutaneous coronary interventions (PCIs) per million people were reported, ranging from <1000 in Egypt and Romania to >3000 in Switzerland, Poland, and Germany. Procedure rates showed significant correlation with GNI per capita (r = 0.62, P = 0.014). An annual median of 48.2 (IQR 29.1-105.2) transcatheter aortic valve implantation procedures per million people were performed, varying from <25 per million people in Egypt, Romania, Turkey, and Poland to >100 per million people in Denmark, France, Switzerland, and Germany. Procedure rates showed significant correlation with national GNI per capita (r = 0.92, P < 0.001). CONCLUSION: The first report from the EAPCI Atlas has shown considerable international heterogeneity in interventional cardiology procedure volumes. The heterogeneity showed association with national economic resource, a reflection no doubt of the technological costs of developing an interventional cardiology service.

Survival of Patients With Angina Pectoris Undergoing Percutaneous Coronary Intervention With Intracoronary Pressure Wire Guidance.

BACKGROUND: Intracoronary pressure wire measurement of fractional flow reserve (FFR) provides decision-making guidance during percutaneous coronary intervention (PCI). However, limited data exist on the effect of FFR on long-term clinical outcomes in patients with stable angina pectoris. OBJECTIVES: The purpose of this study was to determine the association between the usage of FFR and all-cause mortality in patients with stable angina undergoing PCI. METHODS: Data was used from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) on all patients undergoing PCI (with or without FFR guidance) for stable angina pectoris in Sweden between January 2005 and March 2016. The primary endpoint was all-cause mortality, and the secondary endpoints were stent thrombosis (ST) or restenosis and peri-procedural complications. The primary model was multilevel Cox proportional hazards regression adjusted with Kernel-based propensity score matching. RESULTS: In total, 23,860 patients underwent PCI for stable angina pectoris; of these, FFR guidance was used in 3,367. After a median follow-up of 4.7 years (range 0 to 11.2 years), the FFR group had lower adjusted risk estimates for all-cause mortality (hazard ratio: 0.81; 95% confidence interval [CI]: 0.73 to 0.89; p < 0.001), and ST and restenosis (hazard ratio: 0.74; 95% CI: 0.57 to 0.96; p = 0.022). The number of peri-procedural complications did not differ between the groups (adjusted odds ratio: 0.96; 95% CI: 0.77 to 1.19; p = 0.697). CONCLUSIONS: In this observational study, the use of FFR was associated with a lower risk of long-term mortality, ST, and restenosis in patients undergoing PCI for stable angina pectoris. This study supports the current European and American guidelines for the use of FFR during PCI and shows that intracoronary pressure wire guidance confers prognostic benefit in patients with stable angina pectoris.

Blood haemoglobin, renal insufficiency, fractional flow reserve and plasma NT-proBNP is associated with index of microcirculatory resistance in chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMVD) is associated with adverse cardiovascular outcome. We aimed to determine the prevalence of CMVD and factors related to index of microcirculatory resistance (IMR) in consecutive patients with chronic coronary syndrome (CCS) undergoing elective coronary angiography. METHODS AND RESULTS: Non-interventional physicians enrolled 274 patients with CCS before angiography, to minimize selection bias by PCI-operators. Fractional flow reserve (FFR) and IMR were measured in the LAD. Subjects with extensively diseased LAD, no measures due to technical reasons or violation of protocol were excluded from the analysis (n = 54). The proportion of patients with IMR corrected for collateral flow (IMRcorr) >25 units was 25% (95% confidence interval [CI] 19%-31%) in all 220 patients. In subjects with FFR ≤0.80 in the LAD the proportion of IMRcorr > 25 units was 21% (95% CI 13%-30%) as compared to subjects with FFR >0.80, 29% (95% CI 21%-36%), p = .268. Haemoglobin (p < .005; r2 = 0.084), FFR in the LAD (p = .001; r2 = 0.049), creatinine clearance (p = .001; r2 = 0.049; inversely), and NT-proBNP (p = .038; r2 = 0.021) were independently associated with IMRcorr in multivariate linear regression analysis. CONCLUSIONS: We report that IMRcorr is associated with renal dysfunction, NT-proBNP, FFR in the LAD and, for the first time, blood haemoglobin. One in four of patients referred for coronary angiography due to CCS have CMVD defined as IMRcorr > 25 in the LAD.

Percutaneous Treatment and Outcomes of Small Coronary Vessels: A SCAAR Report.

OBJECTIVES: The aim of this study was to investigate the outcomes of patients with de novo lesions in small coronary vessels undergoing percutaneous coronary intervention (PCI) with drug-coated balloons (DCBs) or newer-generation drug-eluting stents (n-DES). BACKGROUND: Notwithstanding the available evidence from a few randomized clinical trials and meta-analyses, the best device for PCI in patients with small-vessel coronary artery disease is not yet established. METHODS: The study included all consecutive patients with de novo lesions in small coronary vessels undergoing PCI in Sweden from April 2009 to July 2017. A small coronary vessel was defined by a device diameter ≤2.5 mm. The primary outcomes were restenosis and definite target lesion thrombosis at 3-year follow-up. The secondary outcomes were the occurrence of all-cause death and myocardial infarction. RESULTS: The study population included 14,788 patients: 1,154 treated with DCBs and 13,634 with n-DES. Overall, 35,541 PCIs were performed using 2,503 DCBs and 33,038 n-DES. The propensity score-adjusted regression analysis showed a significantly higher risk for restenosis in the DCB group compared with the n-DES group (adjusted hazard ratio [HR]: 2.027; 95% confidence interval [CI]: 1.537 to 2.674). Conversely, no difference in the risk for target lesion thrombosis (adjusted HR: 0.741; 95% CI: 0.412 to 1.331) was detected. The risk for all-cause death (adjusted HR: 1.178; 95% CI: 0.992 to 1.399) and myocardial infarction (adjusted HR: 1.251; 95% CI: 0.960 to 1.629) was comparable between groups. CONCLUSIONS: Because of the significantly higher risk for restenosis up to 3 years, this research suggests that DCBs are not an equally effective alternative to n-DES for percutaneous treatment of small coronary vessels.

Changes in Index of Microcirculatory Resistance during PCI in the Left Anterior Descending Coronary Artery in Relation to Total Length of Implanted Stents.

AIM: To investigate the relationship between stent length and changes in microvascular resistance during PCI in stable coronary artery disease (CAD). METHODS AND RESULTS: We measured fractional flow reserve (FFR), index of microcirculatory resistance (IMR), and coronary flow reserve (CFR) before and after stenting in 42 consecutive subjects with stable coronary artery undergoing PCI with stent in the LAD. Patients that had very long stent length (38-78 mm) had lower FFR before stenting than patients that had long (23-37 mm) and moderate (12-22 mm) stent length (0.59 (±0.16), 0.70 (±0.12), and 0.75 (±0.07); p=0.002). FFR improved after stenting and more so in subjects with very long stent length compared to long and moderate stent length (0.27 (s.d ± 16), 0.15 (s.d ± 0.12), and 0.12 (s.d ± 0.07); p for interaction = 0.013). Corrected IMR (IMRcorr) increased after stenting in subjects who had very long stent length, whereas IMRcorr was lower after stenting in subjects who had long or moderate stent length (4.6 (s.d. ± 10.7), -1.4 (s.d. ± 9,9), and -4.2 (s.d. ± 7.8); p for interaction = 0.009). CONCLUSIONS: Changes in IMR during PCI in the LAD in stable CAD seem to be related to total length of stents implanted, possibly influencing post-PCI FFR. Larger studies are needed to confirm the relationship.

The cholinergic anti-inflammatory pathway in resistant hypertension treated with renal denervation.

BACKGROUND: Renal denervation (RDN) reduces sympathetic tone and may alter the sympathetic-parasympathetic balance. The autonomic nervous system is partly a regulator of innate immunity via the cholinergic anti-inflammatory pathway (CAP) which inhibits inflammation via the vagus nerve. Placental Growth Factor (PlGF) influences a neuro-immunological pathway in the spleen which may contribute to hypertension. The aim of this study was to investigate if modulation of renal sympathetic nerve activity affects CAP in terms of cytokine release as well as levels of PlGF. METHODS: Ten patients treated with RDN (Medtronic Inc), were analyzed for TNF, IL-1b and IL-10 and Lipopolysaccharide (LPS)-stimulated cytokine release before RDN, 1 day after and at 3- and 6-months follow-up. Four patients who underwent elective coronary angiography served as disease controls (DC). RESULTS: Baseline TNF was significantly lower 1 day after RDN (p = 0.03). LPS-stimulated (0, 10 and 100 ng/mL) TNF and IL-1b were significantly lower 1 day after RDN (TNF p = 0.0009, p = 0.0009 and p = 0.001, IL-1b; p = 0.0001, p = 0.002 and p = 0.005). IL-10 was significantly higher one day after RDN (p = ns, p = 0.02 and p = 0.01). These differences however declined during follow up. A more marked TNF reduction was achieved with a cholinergic analogue, GTS-21, in LPS-stimulated whole blood as compared with samples without GTS-21. Cytokine levels in controls did not differ before and 1 day after coronary angiography. PlGF was significantly higher in RDN patients and DC compared with healthy controls but did not change during follow-up. CONCLUSION: RDN has an immediate effect on TNF in vivo and cytokine release ex vivo but seems to wane over time suggesting that current RDN techniques may not have long-lasting immunomodulatory effect. Repeated and extended stimulation of CAP in resistant hypertension by targeting neural circuits may be a potential therapeutic strategy for treatment of both hypertension and inflammation.

Clinical and angiographic outcomes of bioabsorbable vs. permanent polymer drug-eluting stents in Sweden: a report from the Swedish Coronary and Angioplasty Registry (SCAAR).

AIMS: Randomized clinical trials have consistently demonstrated the non-inferiority of bioabsorbable polymer drug-eluting stents (BP-DES) with respect to DES having permanent polymers (PP-DES). To date, the comparative performance of BP- and PP-DES in the real world has not been extensively investigated. METHODS AND RESULTS: From October 2011 to June 2016, we analysed the outcomes associated with newer generation DES use in Sweden. After stratification according to the type of DES received at the index procedure, a total of 16 504 and 79 106 stents were included in the BP- and PP-DES groups, respectively. The Kaplan-Meier estimates for restenosis at 2 years were 1.2% and 1.4% in BP- and PP-DES groups, respectively. Definite stent thrombosis (ST) was low in both groups (0.5% and 0.7% in BP- and PP-DES groups, respectively). The adjusted hazard ratio (HR) for either restenosis or definite ST did not differ between BP- and PP-DES [adjusted HR 0.95, 95% confidence interval (CI) 0.74-1.21; P = 0.670 and adjusted HR 0.79, 95% CI 0.57-1.09; P = 0.151, respectively]. Similarly, there were no differences in the adjusted risk of all-cause death and myocardial infarction (MI) between the two groups (adjusted HR for all-cause death 1.01, 95% CI 0.82-1.25; P = 0.918 and adjusted HR for MI 1.05, 95% CI 0.93-1.19; P = 0.404). CONCLUSION: In a large, nationwide, and unselected cohort of patients, percutaneous coronary intervention with BP-DES implantation was not associated with an incremental clinical benefit over PP-DES use at 2 years follow-up.