Impact of the use of plaque modification techniques on coronary microcirculation using an angiography-derived index of microcirculatory resistance.

Many lesions in patients undergoing percutaneous coronary intervention (PCI) exhibit significant calcification. Several techniques have been developed to improve outcomes in this setting. However, their impact on coronary microcirculation remains unknown. The aim of this study is to evaluate the influence of plaque modification techniques on coronary microcirculation across patients with severely calcified coronary artery disease. In this multicenter retrospective study, consecutive patients undergoing PCI with either Rotablation (RA) or Shockwave-intravascular-lithotripsy (IVL) were included. Primary endpoint was the impairment of coronary microvascular resistances assessed by Δ angiography-derived index of microvascular resistance (ΔIMRangio) which was defined as the difference in IMRangio value post- and pre-PCI. Secondary endpoints included the development of peri procedural PCI complications (flow-limiting coronary dissection, slow-flow/no reflow during PCI, coronary perforation, branch occlusion, failed PCI, stroke and shock developed during PCI) and 12-month follow-up adverse events. 162 patients were included in the analysis. Almost 80% of patients were male and the left descending anterior artery was the most common treated vessel. Both RA and IVL led to an increase in ΔIMRangio (22.3 and 10.3; p = 0.038, respectively). A significantly higher rate of PCI complications was observed in patients with ΔIMRangio above the median of the cohort (21.0% vs. 6.2%; p = 0.006). PCI with RA was independently associated with higher ΔIMRangio values (OR 2.01, 95% CI: 1.01-4.03; p = 0.048). Plaque modification with IVL and RA during PCI increases microvascular resistance. Evaluating the microcirculatory status in this setting might help to predict clinical and procedural outcomes and to optimize clinical results.

Standards for quantitative assessments by coronary computed tomography angiography (CCTA): An expert consensus document of the society of cardiovascular computed tomography (SCCT).

In current clinical practice, qualitative or semi-quantitative measures are primarily used to report coronary artery disease on cardiac CT. With advancements in cardiac CT technology and automated post-processing tools, quantitative measures of coronary disease severity have become more broadly available. Quantitative coronary CT angiography has great potential value for clinical management of patients, but also for research. This document aims to provide definitions and standards for the performance and reporting of quantitative measures of coronary artery disease by cardiac CT.

Impact of Significant Hemoglobin Drop Without Bleeding in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: Hemoglobin (Hgb) drop without bleeding is common among patients undergoing transcatheter aortic valve replacement; however, the clinical implications of significant Hgb drop have not been fully evaluated. METHODS AND RESULTS: Consecutive patients undergoing transcatheter aortic valve replacement at our institution from 2011 to 2021 were retrospectively reviewed. Three groups were assessed: no Hgb drop and no bleed (NoD-NoB [reference group]), Hgb drop with bleed, and Hgb drop and no bleed (D-NoB). Hgb drop was defined as ≥3 g/dL decrease from pre- to post-transcatheter aortic valve replacement. Outcomes of interest were in-hospital death and 1-year all-cause mortality. A total of 1851 cases with complete Hgb data were included: NoD-NoB: n=1579 (85.3%); D-NoB: n=49 (2.6%); Hgb drop with bleed: n=223 (12.6%). Compared with NoD-NoB, the D-NoB group was older (81.1 versus 78.9 years of age) with higher preprocedure Hgb (12.9 versus 11.7 g/dL). In-hospital death rate was higher among patients with D-NoB versus NoD-NoB (4.5% versus 0.8%, P<0.001) and similar to Hgb drop with bleed (4.5% versus 4.1%, P=0.999). Predictors of in-hospital death were D-NoB (odds ratio [OR], 3.45 [95% CI, 1.32-8.69]) and transfusion (OR, 10.6 [95% CI, 4.25-28.2]). Landmark survival analysis found that D-NoB experienced 1-year mortality rate comparable to NoD-NoB, whereas Hgb drop with bleed had higher midterm mortality (hazard ratio [HR], 3.2 [95% CI, 1.83-5.73]), and transfusion continued to impact mortality (HR, 2.5 [95% CI, 1.79-3.63]). CONCLUSIONS: Hgb drop without bleeding is common among patients undergoing transcatheter aortic valve replacement and may represent a higher risk of periprocedural death. Blood transfusion increases short- and midterm mortality risk in patients with and without bleeding, supporting a restrictive transfusion strategy.

Coronary Microvascular Disease Registry (CMDR): Study design and rationale.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a prevalent condition among patients with cardiovascular risk factors, leading to a reduced quality of life and an increased risk of major adverse cardiovascular events. Novel invasive techniques have emerged to more accurately diagnose CMD. However, CMD's natural history remains poorly understood due to limited data. To address this knowledge gap, the Coronary Microvascular Disease Registry (CMDR) was established with the primary aim of standardizing comprehensive coronary functional testing and understanding of CMD. DESIGN: CMDR is a prospective, multicenter registry enrolling an unlimited number of consecutive subjects who undergo comprehensive invasive hemodynamic assessment of the entire coronary arterial vasculature. Patients undergoing acetylcholine provocation test for coronary vasospasm will also be included. Follow-up assessments will be conducted at 30 days and annually for up to 5 years. The primary endpoint is Canadian Cardiovascular Society angina grade over time. Secondary endpoints, including all-cause mortality, cardiovascular death, acute myocardial infarction, stroke, hospitalizations, medication changes, and subsequent coronary interventions, will be analyzed to establish long-term safety and clinical outcomes in patients undergoing invasive CMD assessment. SUMMARY: CMDR aims to characterize the clinical and physiologic profile of patients undergoing comprehensive invasive coronary functional testing, simultaneously providing crucial longitudinal information on the natural history and outcomes of these patients. This will shed light on CMD's course and clinical implications, which, in turn, holds the potential to significantly improve diagnostic and treatment strategies for CMD patients, ultimately leading to the enhancement of their overall prognosis and quality of life. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, NCT05960474.

Correction: van Veelen et al. First-in-Human Drug-Eluting Balloon Treatment of Vulnerable Lipid-Rich Plaques: Rationale and Design of the DEBuT-LRP Study. J. Clin. Med. 2023, 12, 5807.

In the original publication [...].

Angiography-Derived Index of Microcirculatory Resistance to Define the Risk of Early Discharge in STEMI.

BACKGROUND: Patients with ST-segment-elevation myocardial infarction but no coronary microvascular injury are at low risk of early cardiovascular complications (ECC). We aim to assess whether nonhyperemic angiography-derived index of microcirculatory resistance (NH-IMRangio) could be a user-friendly tool to identify patients at low risk of ECC, potentially candidates for expedited care pathway and early hospital discharge. METHODS: Retrospective analysis of 2 independent, international, prospective, observational cohorts included 568 patients with ST-segment-elevation myocardial infarction. NH-IMRangio was calculated based on standard coronary angiographic views with 3-dimensional-modeling and computational analysis of the coronary flow. RESULTS: Overall, ECC (a composite of cardiovascular death, cardiogenic shock, acute heart failure, life-threatening arrhythmias, resuscitated cardiac arrest, left ventricular thrombus, post-ST-segment-elevation myocardial infarction mechanical complications, and rehospitalization for acute heart failure or acute myocardial infarction at 30 days follow-up), occurred in 54 (9.3%) patients. NH-IMRangio was significantly correlated with pressure/thermodilution-based index of microcirculatory resistance (r=0.607; P<0.0001) and demonstrated good accuracy in predicting ECC (area under the curve, 0.766 [95% CI, 0.706-0.827]; P<0.0001). Importantly, ECC occurred more frequently in patients with NH-IMRangio ≥40 units (18.1% versus 1.4%; P<0.0001). At multivariable analysis, NH-IMRangio provided incremental prognostic value to conventional clinical, angiographic, and echocardiographic features (adjusted-odds ratio, 14.861 [95% CI, 5.177-42.661]; P<0.0001). NH-IMRangio<40 units showed an excellent negative predictive value (98.6%) in ruling out ECC. Discharging patients with NH-IMRangio<40 units at 48 hours after admission would reduce the total in-hospital stay by 943 days (median 2 [1-4] days per patient). CONCLUSIONS: NH-IMRangio is a valuable risk-stratification tool in patients with ST-segment-elevation myocardial infarction. NH-IMRangio guided strategies to early discharge may contribute to safely shorten hospital stay, optimizing resources utilization.

Uninterrupted direct-acting oral anticoagulation in patients undergoing transradial percutaneous coronary procedures: The DOAC-NOSTOP study rationale and design.

BACKGROUND: patients with atrial fibrillation (AF) under treatment with chronic oral anticoagulation (OAC) often require coronary angiography with or without percutaneous coronary intervention (PCI). Deciding the management of OAC during this periprocedural period requires balancing the risks of hemorrhage and thrombotic complications. Guidelines recommend an uninterrupted strategy in patients receiving Vitamin-K Antagonists (VKA). However, for patients undergoing coronary angiography or PCI while on direct oral anticoagulants (DOACs), withdrawal 12-24 h prior to the procedure is still recommended. This is based on expert opinions given the lack of evidence. Therefore, whether DOAC discontinuation prior to trans-radial coronary procedures should be the strategy of choice is a matter of debate and solid evidence is needed to guide clinical decision making. METHODS: The DOAC-NOSTOP study is a prospective, single-arm, open-label study evaluating the safety of DOACs continuation in 200 patients undergoing transradial percutaneous coronary procedures. DOAC treatment will not be interrupted throughout the periprocedural period. Primary outcome will be Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 events, assessed at a 30-day follow-up. CONCLUSIONS: The DOAC-NOSTOP is the first study prospectively assessing the risk of bleeding with uninterrupted DOAC in patients undergoing trans-radial percutaneous coronary procedures.

Invasive coronary imaging of inflammation to further characterize high-risk lesions: what options do we have?

Coronary atherosclerosis remains a leading cause of morbidity and mortality worldwide. The underlying pathophysiology includes a complex interplay of endothelial dysfunction, lipid accumulation and inflammatory pathways. Multiple structural and inflammatory features of the atherosclerotic lesions have become targets to identify high-risk lesions. Various intracoronary imaging devices have been developed to assess the morphological, biocompositional and molecular profile of the intracoronary atheromata. These techniques guide interventional and therapeutical management and allow the identification and stratification of atherosclerotic lesions. We sought to provide an overview of the inflammatory pathobiology of atherosclerosis, distinct high-risk plaque features and the ability to visualize this process with contemporary intracoronary imaging techniques.

Data-driven models for the prediction of coronary atherosclerotic plaque progression/regression.

Coronary artery disease is defined by the existence of atherosclerotic plaque on the arterial wall, which can cause blood flow impairment, or plaque rupture, and ultimately lead to myocardial ischemia. Intravascular ultrasound (IVUS) imaging can provide a detailed characterization of lumen and vessel features, and so plaque burden, in coronary vessels. Prediction of the regions in a vascular segment where plaque burden can either increase (progression) or decrease (regression) following a certain therapy, has remained an elusive major milestone in cardiology. Studies like IBIS-4 showed an association between plaque burden regression and high-intensity rosuvastatin therapy over 13 months. Nevertheless, it has not been possible to predict if a patient would respond in a favorable/adverse fashion to such a treatment. This work aims to (i) Develop a framework that processes lumen and vessel cross-sectional contours and extracts geometric descriptors from baseline and follow-up IVUS pullbacks; and to (ii) Develop, train, and validate a machine learning model based on baseline/follow-up IVUS datasets that predicts future percent of atheroma volume changes in coronary vascular segments using only baseline information, i.e. geometric features and clinical data. This is a post hoc analysis, revisiting the IBIS-4 study. We employed 140 arteries, from 81 patients, for which expert delineation of lumen and vessel contours were available at baseline and 13-month follow-up. Contour data from baseline and follow-up pullbacks were co-registered and then processed to extract several frame-wise features, e.g. areas, plaque burden, eccentricity, etc. Each pullback was divided into regions of interest (ROIs), following different criteria. Frame-wise features were condensed into region-wise markers using tools from statistics, signal processing, and information theory. Finally, a stratified 5-fold cross-validation strategy (20 repetitions) was used to train/validate an XGBoost regression models. A feature selection method before the model training was also applied. When the models were trained/validated on ROI defined by the difference between follow-up and baseline plaque burden, the average accuracy and Mathews correlation coefficient were 0.70 and 0.41 respectively. Using a ROI partition criterion based only on the baseline's plaque burden resulted in averages of 0.60 accuracy and 0.23 Mathews correlation coefficient. An XGBoost model was capable of predicting plaque progression/regression changes in coronary vascular segments of patients treated with rosuvastatin therapy in 13 months. The proposed method, first of its kind, successfully managed to address the problem of stratification of patients at risk of coronary plaque progression, using IVUS images and standard patient clinical data.

Computed tomography fractional flow reserve discrepancies with invasive angiography and physiology - Case series.

BACKGROUND: Computed tomography with fractional flow reserve (CT-FFR) is increasingly common in assessing coronary artery disease. CASE PRESENTATION: We report five cases of discrepancies that led to changes in treatment. CONCLUSIONS: This report highlights discordant findings between modalities, which should be considered during the diagnostic assessment of chest pain.

Diagnostic performances of Nonhyperemic Pressure Ratios and Coronary Angiography-Based Fractional Flow Reserve against conventional Wire-Based Fractional Flow Reserve.

BACKGROUND: Nonhyperemic pressure ratios (NHPRs) have been proposed as alternatives to fractional flow reserve (FFR) without induction of hyperemia. More recently, imaging based-FFR estimation, especially coronary angiography-derived FFR (Angio-FFR) measurement, is proposed to estimate wire-based FFR. However, little is known about the diagnostic performance of these indices against conventional FFR. AIMS: We aimed to assess and compare the diagnostic performance of both NHPRs and coronary Angio-FFR against wire-based conventional FFR. METHODS: PubMed and Embase databases were systematically searched for peer-reviewed original articles up to 08/2022. The primary outcomes were the pooled sensitivity and specificity as well as the area under the curve (AUC) of the summary receiver-operating characteristic curve of those indices. RESULTS: A total of 6693 records were identified after a literature search, including 37 reports for NHPRs and 34 for Angio-FFR. Overall, NHPRs have a lower diagnostic performance in estimating wire-based FFR with an AUC of 0.85 (0.81, 0.88) when compared with Angio-FFR of 0.95 (0.93, 0.97). When all four modalities of NHPRs (iFR, Pd/Pa, DPR, RFR) were compared, those had overlapping AUCs without major differences among each other. Similarly, when the two most commonly used Angio-FFR (QFR, FFR angio ) were compared, those had overlapping AUCs without major differences among each other. CONCLUSION: Angio-FFR may offer a better estimation of wire-based FFR than NHPRs. Our results support a wider use of Angio-FFR in the cardiac catheterization laboratory to streamline our workflow for coronary physiologic assessment. CLASSIFICATIONS: FFR,, stable ischemic disease and non-ST elevation acute coronary syndrome.

Comparison of endothelial shear stress between ultrathin strut bioresorbable polymer drug-eluting stent vs durable-polymer drug-eluting stent post-stent implantation: An optical coherence tomography substudy from BIOFLOW II.

BACKGROUND: Recent clinical data indicate a different performance of biodegradable polymer (BP)-drug eluting stent (DES) compared to durable polymer (DP)-DES. Whether this can be explained by a beneficial impact of BP-DES stent design on the local hemodynamic forces distribution remains unclear. OBJECTIVES: To compare endothelial shear stress (ESS) distribution after implantation of ultrathin (us) BP-DES and DP-DES and examine the association between ESS and neointimal thickness (NIT) distribution in the two devices at 9 months follow up. METHODS AND RESULTS: We retrospectively identified patients from the BIOFLOW II trial that had undergone OCT imaging. OCT data were utilized to reconstruct the surface of the stented segment at baseline and 9 months follow-up, simulate blood flow, and measure ESS and NIT in the stented segment. The patients were divided into 3 groups depending on whether DP-DES (N = 8, n = 56,160 sectors), BP-DES with a stent diameter of >3 mm (strut thickness of 80 µm, N = 6, n = 36,504 sectors), or BP-DES with a stent diameter of ≤3 mm (strut thickness of 60 µm, N = 8, n = 50,040 sectors) were used for treatment. The ESS, and NIT distribution and the association of these two variables were estimated and compared among the 3 groups. RESULTS: In the DP-DES group mean NIT was 0.18 ± 0.17 mm and ESS 1.68 ± 1.66 Pa; for the BP-DES ≤3 mm group the NIT was 0.17 ± 0.11 mm and ESS 1.49 ± 1.24 Pa and for the BP-DES >3 mm group 0.20 ± 0.23 mm and 1.42 ± 1.24 Pa respectively (p < 0.001 for both NIT and ESS comparisons across groups). A negative correlation between NIT and baseline ESS was found, the correlation coefficient for all the stented segments was -0.33, p < 0.001. CONCLUSION: In this OCT sub-study of the BIOFLOW II trial, the NIT was statistically different between groups of patients treated with BP-DES and DP-DES. In addition, regions of low ESS were associated with increased NIT in all studied devices.

Drug-Eluting Resorbable Scaffold versus Angioplasty for Infrapopliteal Artery Disease.

BACKGROUND: Among patients with chronic limb-threatening ischemia (CLTI) and infrapopliteal artery disease, angioplasty has been associated with frequent reintervention and adverse limb outcomes from restenosis. The effect of the use of drug-eluting resorbable scaffolds on these outcomes remains unknown. METHODS: In this multicenter, randomized, controlled trial, 261 patients with CLTI and infrapopliteal artery disease were randomly assigned in a 2:1 ratio to receive treatment with an everolimus-eluting resorbable scaffold or angioplasty. The primary efficacy end point was freedom from the following events at 1 year: amputation above the ankle of the target limb, occlusion of the target vessel, clinically driven revascularization of the target lesion, and binary restenosis of the target lesion. The primary safety end point was freedom from major adverse limb events at 6 months and from perioperative death. RESULTS: The primary efficacy end point was observed (i.e., no events occurred) in 135 of 173 patients in the scaffold group and 48 of 88 patients in the angioplasty group (Kaplan-Meier estimate, 74% vs. 44%; absolute difference, 30 percentage points; 95% confidence interval [CI], 15 to 46; one-sided P<0.001 for superiority). The primary safety end point was observed in 165 of 170 patients in the scaffold group and 90 of 90 patients in the angioplasty group (absolute difference, -3 percentage points; 95% CI, -6 to 0; one-sided P<0.001 for noninferiority). Serious adverse events related to the index procedure occurred in 2% of the patients in the scaffold group and 3% of those in the angioplasty group. CONCLUSIONS: Among patients with CLTI due to infrapopliteal artery disease, the use of an everolimus-eluting resorbable scaffold was superior to angioplasty with respect to the primary efficacy end point. (Funded by Abbott; LIFE-BTK ClinicalTrials.gov number, NCT04227899.).

Clinical comparison of a handheld cardiac ultrasound device for the assessment of left ventricular function.

PURPOSE: Recently developed handheld ultrasound devices (HHUD) represent a promising method to evaluate the cardiovascular abnormalities at the point of care. However, this technology has not been rigorously evaluated. The aim of this study was to explore the correlation and the agreement between the LVEF (Left Ventricular Ejection Fraction) visually assessed by a moderately experienced sonographer using an HHUD compared to the routine LVEF assessment performed at the Echocardiography Laboratory. METHODS: This was a prospective single center study which enrolled 120 adult inpatients and outpatients referred for a comprehensive Echocardiography (EC). RESULTS: The mean age of the patients was 69.9 ± 12.5 years. There were 47 females (39.2%). The R-squared was r 0.94 (p < 0.0001) and the ICC was 0.93 (IC 95% 0.91-0.95, p ≤ 0.0001). The Bland-Altman plot showed limits of agreement (LOA): Upper LOA 10.61 and Lower LOA - 8.95. The overall agreement on the LVEF assessment when it was stratified as "normal" or "reduced" was 89.1%, with a kappa of 0.77 (p < 0.0001). When the LVEF was classified as "normal", "mildly reduced", "moderately reduced", or "severely reduced," the kappa was 0.77 (p < 0.0001). The kappa between the HHUD EC and the comprehensive EC for the detection of RWMAs in the territories supplied by the LAD, LCX and RCA was 0.85, 0.73 and 0.85, respectively. CONCLUSION: With current HHUD, an averagely experienced operator can accurately bedside visual estimate the LVEF. This may facilitate the incorporation of this technology in daily clinical practice improving the management of patients.

Temporal changes in coronary plaque as assessed by an artificial intelligence-based optical coherence tomography: from the first-in-human trial on DREAMS 3G scaffold.

AIMS: The aim of the study is to assess the impact of the baseline plaque composition on the DREAMS 3G luminal late loss and to compare the serial plaque changes between baseline and 6 and 12 months (M) follow-up. METHODS AND RESULTS: A total of 116 patients were enrolled in the BIOMAG-I trial. Patients were imaged with optical coherence tomography (OCT) pre- and post-DREAMS 3G implantation and at 6 and 12 M. OCTPlus software uses artificial intelligence to assess composition (i.e. lipid, calcium, and fibrous tissue) of the plaque. The differences between the OCT-derived minimum lumen area (MLA) post-percutaneous coronary intervention and 12 M were grouped into three terciles. Patients with larger MLA differences at 12 M (P = 0.0003) had significantly larger content of fibrous tissue at baseline. There was a reduction of 24.8% and 20.9% in lipid area, both P < 0.001, between the pre-DREAMS 3G OCT and the 6 and 12 M follow-up. Conversely, the fibrous tissue increased by 48.4% and 36.0% at 6 and 12 M follow-up, both P < 0.001. CONCLUSION: The larger the fibrous tissue in the lesion at baseline, the larger the luminal loss seen at 6 and 12 M. Following the implantation of DREAMS 3G, favourable healing of the vessel coronary wall occurs as shown by a decrease in the lipid area and an increase in fibrous tissue.

Impact of age on the outcomes of Takotsubo syndrome.

BACKGROUND: The impact on age on the short-term and long-term prognosis in patients with Takotsubo syndrome (TTS) is unclear. We aimed to evaluate whether age has prognostic implications during hospital stay and long-term follow-up of TTS patients. METHODS: 688 consecutive patients were admitted for TTS in 7 tertiary centers from January-2008 to June-2021. We divided our cohort into two groups (patients <75 years and ≥75 years). Clinical, analytical, and hemodynamic variables as well as in-hospital management were registered and compared between groups. Mortality rates during hospital stay and follow-up were assessed. Adverse cardiovascular events (ACE) were defined as the composite of cardiovascular death, heart failure event, acute myocardial infarction, stroke and symptomatic arrhythmia. RESULTS: Median age was 74.7 years and 49.4 % were ≥75 years. 86.9 % were women and 22.3 % were secondary forms of TTS. In-hospital mortality was 3.6 % (1.5 % cardiovascular). Median clinical follow-up was 4.3 years. Mortality during the follow-up period was 23 % (5.0 % cardiovascular) while ACE were 22.5 %, mainly due to heart failure events. Kaplan-Meier curves showed both higher rates of mortality and ACE in ≥75 years group (30.2 % vs 15.8 %; p < 0.001 and 28.3 % vs 16.7 %; p < 0.001). Age was independently associated with higher rates of overall mortality and ACE in patients with TTS. Hypertension, absence of sinus rhythm, Killip class > I and a more impaired coronary microvascular resistance were also associated to ACE in TTS patients. CONCLUSIONS: Advanced age was associated with higher rate of overall mortality and ACE during long-term follow-up in TTS patients.