Safety and Efficacy of Everolimus-Eluting Bioresorbable Vascular Scaffold Versus Second-Generation Drug-Eluting Stents in Real-World Practice.

BACKGROUND: The risk of device thrombosis and device-oriented clinical outcomes with bioresorbable vascular scaffold (BVS) was reported to be significantly higher than with contemporary drug-eluting stents (DESs). However, optimal device implantation may improve clinical outcomes in patients receiving BVS. The current study evaluated mid-term safety and efficacy of Absorb BVS with meticulous device optimization under intravascular imaging guidance. METHODS: The SMART-REWARD and PERSPECTIVE-PCI registries in Korea prospectively enrolled 390 patients with BVS and 675 patients with DES, respectively. The primary endpoint was target vessel failure (TVF) at 2 years and the secondary major endpoint was patient-oriented composite outcome (POCO) at 2 years. RESULTS: Patient-level pooled analysis evaluated 1,003 patients (377 patients with BVS and 626 patients with DES). Mean scaffold diameter per lesion was 3.24 ± 0.30 mm in BVS group. Most BVSs were implanted with pre-dilatation (90.9%), intravascular imaging guidance (74.9%), and post-dilatation (73.1%) at proximal to mid segment (81.9%) in target vessel. Patients treated with BVS showed comparable risks of 2-year TVF (2.9% vs. 3.7%, adjusted hazard ratio [HR], 1.283, 95% confidence interval [CI], 0.487-3.378, P = 0.615) and 2-year POCO (4.5% vs. 5.9%, adjusted HR, 1.413, 95% CI, 0.663-3.012, P = 0.370) than those with DES. The rate of 2-year definite or probable device thrombosis (0.3% vs. 0.5%, P = 0.424) was also similar. The sensitivity analyses consistently showed comparable risk of TVF and POCO between the 2 groups. CONCLUSION: With meticulous device optimization under imaging guidance and avoidance of implantation in small vessels, BVS showed comparable risks of 2-year TVF and device thrombosis with DES. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02601404, NCT04265443.

Exenatide Prevents Morphological and Structural Changes of Mitochondria Following Ischaemia-Reperfusion Injury.

BACKGROUND: Exenatide exerts cardioprotective effects by attenuating ischaemic reperfusion (IR) injury, possibly through activating the opening of mitochondrial ATP-sensitive potassium channels. We used atomic force microscopy (AFM) to investigate changes in mitochondrial morphology and properties in order to assess exenatide-mediated cardioprotection in IR injury. METHODS: We used an in vivo Sprague-Dawley rat IR model and ex vivo Langendorff injury model. In the left anterior descending artery (LAD) occlusion model, animals were randomly divided into three groups: sham-operated rats (Sham, n=5), IR-injured rats treated with placebo (IR, n=6), and IR-injured treated with exenatide (IR + EXE, n=6). For the Langendorff model, rats were randomly divided into two groups: IR injury with placebo (IR, n=4) and IR injury with exenatide (IR+EXE, n=4). Morphological and mechanical changes of mitochondria were analysed by AFM. RESULTS: Exenatide pre-treatment improved cardiac function as evidenced by improvement in echocardiographic results. The ratio of infarct area (IA) to risk area (RA) was significantly reduced in exenatide-treated rats. According to AFM, IR significantly increased the area of isolated mitochondria, indicative of mitochondrial swelling. Treatment with exenatide reduced the mitochondrial area and ameliorated the adhesion force of mitochondrial surfaces. CONCLUSIONS: Exenatide pre-treatment improves morphological and mechanical characteristics of mitochondria in response to IR injury in a rat model. These alterations in mitochondrial characteristics appear to play a cardioprotective role against IR injury.

Cardioprotective effects of exenatide in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of exenatide myocardial protection in revascularization study.

OBJECTIVE: Experimental evidence suggests that exenatide, a glucagon-like peptide 1 receptor analogue, has significant cardiovascular protective effects in various conditions. We examined whether routine use of exenatide at the time of primary percutaneous coronary intervention would reduce infarct size in patients with ST-segment-elevation myocardial infarction. APPROACH AND RESULTS: Fifty-eight patients with ST-segment-elevation myocardial infarction and thrombolysis in myocardial infarction flow 0 were enrolled in the study and randomly assigned to receive either exenatide or placebo (saline) subcutaneously. Infarct size was assessed by measuring the release of creatine kinase-MB and troponin I during 72 hours and by performing cardiac magnetic resonance imaging at 1 month after infarction. Routine and speckle tracking echocardiography was performed at initial presentation and at 3 days and 6 months after primary percutaneous coronary intervention. The exenatide and control groups had similar results with respect to ischemia time, demographic characteristics, and ejection fraction before primary percutaneous coronary intervention. The releases of creatine kinase-MB and troponin I were significantly reduced in the exenatide group. In 58 patients evaluated with cardiac magnetic resonance, the absolute mass of delayed hyperenhancement was significantly reduced in the exenatide group as compared with the control group (12.8±11.7 versus 26.4±11.6 g; P<0.01). At 6 months, the exenatide group showed a significantly lower value of E/E' with improved strain parameters. No significant adverse effects of exenatide administration were detected. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, adjunctive exenatide therapy with primary percutaneous coronary intervention was associated with reduction of infarct size and improvement of subclinical left ventricular function.

Preventive effects of exenatide on endothelial dysfunction induced by ischemia-reperfusion injury via KATP channels.

OBJECTIVE: The purpose of this study was to evaluate whether exenatide administration can prevent impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) injury and whether this effect is mediated by K(ATP) channel opening. METHODS AND RESULTS: In a double-blind, placebo-controlled, crossover design, 20 volunteers were randomly assigned to 2 groups: subcutaneous exenatide (10 µg) or placebo administration. At 30 minutes after the study drug administration, endothelium-dependent flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion) injury. Seven days later, both groups were crossed over and received the other treatment (ie, placebo or exenatide) and underwent the same protocol. Pre-IR radial artery diameter, FMD, and baseline radial artery diameter after IR injury were similar between 2 groups (P=no significant difference). After placebo administration, IR significantly blunted FMD (before IR: 12.0±6.23%; after IR: 4.6±3.57%, P=0.02). Exenatide prevented this impairment (FMD before IR: 15.0±7.14%; FMD after IR: 15.0±5.96%, P=no significant difference; P<0.001 compared with placebo). In a separate protocol, this protective effect was completely abolished by pretreatment with glibenclamide (glyburide, 5 mg), a blocker of K(ATP) channels (n=7; FMD before IR: 12.0±2.2%; after IR: 3.2±2.1%, P<0.001). CONCLUSIONS: The present study demonstrates that subcutaneous exenatide protects IR-induced endothelial dysfunction through opening of K(ATP) channels in human IR injury model.

Clinical outcomes of patients with rheumatoid arthritis who underwent percutaneous coronary intervention: A Korean nationwide cohort study.

OBJECTIVE: Rheumatoid arthritis (RA) increases the risk of cardiovascular disease. This study aimed to investigate the short-and long-term prognosis of patients with and without RA who underwent percutaneous coronary intervention (PCI). METHODS: The Korean National Health Insurance Service claims database was used to extract data on 236,134 patients (34,493 with RA and 201,641 without RA) who underwent PCI between 2008 and 2019. The primary outcome was major adverse cardiovascular events (MACE), including all-cause mortality, myocardial infarction, stroke, transient ischemic attack, or coronary revascularization with short-term (30-day) and long-term outcomes. The secondary outcomes were the individual components of MACE. RESULTS: During a 10-year follow-up, patients with RA showed a shorter median survival time from MACE than their counterparts (with RA: 4.29 years vs. without RA: 6.10 years). RA was significantly associated with an increased risk of MACEs in long-term outcomes (hazard ratio (HR) 1.07, 95% confidence intervals (CI) 1.06-1.09, p<0.001), but not with short-term outcomes (HR 1.02, 95% CI 0.99-1.06, p = 0.222). RA was an independent predictor of an increased risk of all the MACE components. CONCLUSION: In patients who underwent PCI, RA did not increase the risk of short-term cardiovascular outcomes but increased the risk of long-term adverse outcomes.

Prognostic Impact of Coronary Microvascular Dysfunction According to Different Patterns by Invasive Physiologic Indexes in Symptomatic Patients With Intermediate Coronary Stenosis.

BACKGROUND: Coronary microvascular dysfunction is a clinically significant component of ischemic heart disease. There can be heterogenous patterns of coronary microvascular dysfunction defined by invasive physiologic indexes such as coronary flow reserve (CFR) and index of microcirculatory resistance (IMR). We sought to compare the prognosis of coronary microvascular dysfunction according to different patterns of CFR and IMR. METHODS: The current study included 375 consecutive patients undergoing invasive physiologic assessment for suspected stable ischemic heart disease and intermediate but functionally nonsignificant epicardial stenosis (fractional flow reserve, >0.80). According to cutoff values of invasive physiologic indexes reflecting microcirculatory function (CFR, <2.5; IMR, ≥25), patients were classified into 4 groups: (1) preserved CFR and low IMR (group 1), (2) preserved CFR and elevated IMR (group 2), (3) depressed CFR and low IMR (group 3), and (4) depressed CFR and elevated IMR (group 4). Primary outcome was a composite of cardiovascular death or admission for heart failure during the follow-up time. RESULTS: Cumulative incidence of the primary outcome was significantly different among the 4 groups (group 1, 20.1%; group 2, 18.8%; group 3, 33.9%; and group 4, 45.0%; overall P<0.001). Depressed CFR had significantly higher risk of primary outcome than preserved CFR in both low (hazard ratio [HR], 1.894 [95% CI, 1.112-3.225]; P=0.019) and elevated IMR subgroups (HR, 3.307 [95% CI, 1.519-7.202]; P=0.003). Conversely, the risk of primary outcome was not significantly different between elevated and low IMR in preserved CFR subgroups (HR, 0.926 [95% CI, 0.428-2.005]; P=0.846). Furthermore, as continuous variables, IMR-adjusted CFR (adjusted HR, 0.644 [95% CI, 0.537-0.772]; P<0.001) was significantly associated with the risk of primary outcome but CFR-adjusted IMR (adjusted HR, 1.004 [95% CI, 0.992-1.016]; P=0.515) was not. CONCLUSIONS: Among patients with suspected stable ischemic heart disease who were found to have an intermediate but functionally nonsignificant epicardial stenosis, depressed CFR was associated with an increased risk of cardiovascular death and admission for heart failure. However, elevated IMR alone with preserved CFR showed limited prognostic value in this population. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05058833.

Prognostic Impact of Coronary Flow Reserve in Patients With CKD.

Introduction: Both coronary flow reserve (CFR) and chronic kidney disease (CKD) are known to be associated with adverse cardiac events. However, it is unclear how these prognostic factors are interrelated. This study evaluated the association between intracoronary physiologic indexes and CKD and their prognostic implications. Methods: A total of 351 patients without left ventricular systolic dysfunction (ejection fraction ≥ 40%) and not on dialysis whose revascularization was deferred based on fractional flow reserve (FFR) > 0.80 were analyzed. Depressed CFR was defined as CFR ≤ 2.0. The primary outcome was a composite of cardiac death or hospitalization for heart failure at 3 years. Results: Patients with CKD showed lower CFR than the non-CKD population (3.28 ± 1.77 vs. 2.60 ± 1.09, P < 0.001), mainly driven by increased resting coronary flow. There was no significant difference in hyperemic coronary flow, FFR, and index of microvascular resistance between the 2 groups. CFR was significantly associated with estimated glomerular filtration rate (eGFR) (P = 0.045), and the proportion of depressed CFR was significantly increased with higher CKD stages (P = 0.011). The risk of cardiac death or hospitalization for heart failure was the lowest in the non-CKD and preserved CFR group (11.9%) and the highest in the CKD and depressed CFR group (60.0%, overall log rank P < 0.001). Both CKD (adjusted hazard ratio [HRadj] 2.614, 95% confidence interval [CI] 1.505-4.539, P < 0.001) and depressed CFR (HRadj 3.237, 95% CI 2.015-5.199, P < 0.001) were independently associated with the risk of the primary outcome. Conclusion: There was a significant association between severity of CKD and CFR. Both CKD and depressed CFR showed independent association with higher risk of cardiac death or hospitalization for heart failure.

Prognostic Impact of Indeterminate Diastolic Function in Patients With Functionally Insignificant Coronary Stenosis.

BACKGROUND: Cardiac diastolic dysfunction is an independent predictor of mortality, regardless of left ventricular (LV) systolic function. However, the current guidelines that define cardiac diastolic dysfunction may underrate the clinical implications of those with indeterminate diastolic function. OBJECTIVES: We sought to evaluate the prognostic implications of indeterminate diastolic function on echocardiography and its association with coronary microvascular dysfunction (CMD). METHODS: A total of 330 patients without LV systolic dysfunction and significant epicardial coronary stenosis (fractional flow reserve > 0.80) were analyzed from a prospective registry. Cardiac diastolic dysfunction was defined according to 2 algorithms depending on the presence of myocardial disease. First, the presence of myocardial disease and evidence of elevated LV filling pressure indicated diastolic dysfunction. Second, diastolic function in those without myocardial disease was defined using echocardiographic parameters (E/e', e' velocity, tricuspid regurgitation velocity, and left atrial volume index). Patients who did not meet half of the available criteria were classified as having indeterminate diastolic function. Coronary microvascular dysfunction was defined as coronary flow reserve < 2.0 and index of microcirculatory resistance ≥ 25 U. The primary outcome was cardiovascular death or admission for heart failure at 5 years. RESULTS: Coronary flow reserve was lower in patients with indeterminate diastolic function compared with those with no diastolic dysfunction (3.5 ± 1.6 vs 3.2 ± 1.6, P = .002). The prevalence of CMD was also higher in patients with indeterminate diastolic function than in those with no diastolic dysfunction (10.6% vs 4.9%, P < .034). Patients with indeterminate diastolic function showed significantly higher risk of cardiovascular death or admission for heart failure than those without indeterminate diastolic function but not greater than those with definite diastolic dysfunction (cumulative incidence: 12.6%, 27.2%, and 32.7%, respectively, log-rank P < .001). Presence of CMD and elevated LV filling pressure (E/e' > 14) were independent predictors for cardiovascular death or admission for heart failure in patients with indeterminate diastolic function. CONCLUSIONS: Patients with indeterminate diastolic function on echocardiogram showed higher risk of cardiovascular death or admission for heart failure than those with no diastolic dysfunction. Presence of CMD and elevated LV filling pressure were independent predictors for cardiovascular death or admission for heart failure among patients with indeterminate diastolic function.

Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function on Cardiovascular Death.

Background Coronary microvascular dysfunction (CMD) has been considered as a possible cause of cardiac diastolic dysfunction. The current study evaluated the association between cardiac diastolic dysfunction and CMD, and their prognostic implications in patients without significant left ventricular systolic dysfunction and epicardial coronary stenosis. Methods and Results A total of 330 patients without left ventricular systolic dysfunction (ejection fraction ≥50%) and significant epicardial coronary stenosis (fractional flow reserve >0.80) were analyzed. Cardiac diastolic dysfunction was defined by echocardiographic parameters (early diastolic transmitral flow velocity/early diastolic mitral annular velocity, e' velocity, tricuspid regurgitation velocity, and left atrial volume index). Overt CMD was defined as coronary flow reserve <2.0 and index of microcirculatory resistance ≥25 U. The primary end point was cardiovascular death or admission for heart failure during 5 years of follow-up. In patients without left ventricular systolic dysfunction and significant epicardial coronary stenosis, prevalence of cardiac diastolic dysfunction and overt CMD was 25.5% and 11.2%, respectively. Overt CMD was independently associated with cardiac diastolic dysfunction (adjusted odds ratio, 3.440 [95% CI, 1.599-7.401]; P=0.002). Patients with cardiac diastolic dysfunction showed significantly higher risk of the primary outcome than those without (adjusted hazard ratio [HR], 2.996 [95% CI, 1.888-4.755]; P<0.001). Patients with overt CMD also showed significantly higher risk of the primary outcome than those without (adjusted HR, 2.939 [95% CI, 1.642-5.261]; P<0.001). Presence of overt CMD was associated with significantly increased risk of cardiovascular death among the patients with cardiac diastolic dysfunction (43.8% versus 14.5%; P=0.006) but not in patients without cardiac diastolic dysfunction (interaction P<0.001). Inclusion of overt CMD into the model with cardiac diastolic dysfunction significantly improved predictive ability for cardiovascular death or heart failure admission (conconrdance index, 0.719 versus 0.737; P for comparison=0.034). Conclusions There was significant association between the presence of cardiac diastolic dysfunction and overt CMD. Both cardiac diastolic dysfunction and overt CMD were associated with increased risk of cardiovascular death or admission for heart failure. Integration of overt CMD into cardiac diastolic dysfunction showed improvement of the risk stratification in patients without significant left ventricular systolic dysfunction and epicardial coronary stenosis. Registration DIAST-CMD (Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function) registry; Unique identifier: NCT05058833.

Atherosclerosis Imaging Quantitative Computed Tomography (AI-QCT) to guide referral to invasive coronary angiography in the randomized controlled CONSERVE trial.

AIMS: We compared diagnostic performance, costs, and association with major adverse cardiovascular events (MACE) of clinical coronary computed tomography angiography (CCTA) interpretation versus semiautomated approach that use artificial intelligence and machine learning for atherosclerosis imaging-quantitative computed tomography (AI-QCT) for patients being referred for nonemergent invasive coronary angiography (ICA). METHODS: CCTA data from individuals enrolled into the randomized controlled Computed Tomographic Angiography for Selective Cardiac Catheterization trial for an American College of Cardiology (ACC)/American Heart Association (AHA) guideline indication for ICA were analyzed. Site interpretation of CCTAs were compared to those analyzed by a cloud-based software (Cleerly, Inc.) that performs AI-QCT for stenosis determination, coronary vascular measurements and quantification and characterization of atherosclerotic plaque. CCTA interpretation and AI-QCT guided findings were related to MACE at 1-year follow-up. RESULTS: Seven hundred forty-seven stable patients (60 ± 12.2 years, 49% women) were included. Using AI-QCT, 9% of patients had no CAD compared with 34% for clinical CCTA interpretation. Application of AI-QCT to identify obstructive coronary stenosis at the ≥50% and ≥70% threshold would have reduced ICA by 87% and 95%, respectively. Clinical outcomes for patients without AI-QCT-identified obstructive stenosis was excellent; for 78% of patients with maximum stenosis < 50%, no cardiovascular death or acute myocardial infarction occurred. When applying an AI-QCT referral management approach to avoid ICA in patients with <50% or <70% stenosis, overall costs were reduced by 26% and 34%, respectively. CONCLUSIONS: In stable patients referred for ACC/AHA guideline-indicated nonemergent ICA, application of artificial intelligence and machine learning for AI-QCT can significantly reduce ICA rates and costs with no change in 1-year MACE.

The presence of hypertension during pregnancy determines the future risk of metabolic syndrome: An observational study.

This study aimed to examine the prevalence and time interval of metabolic syndrome (MS) development among women with hypertensive disorders of pregnancy (HDP) compared to women with a normal delivery. Data (4,723,541 deliveries) from 2002 to 2012 from the National Health Insurance System Database in Korea were used to compare women diagnosed with HDP with those with a normal singleton pregnancy. Using the customized database, we conducted a longitudinal analysis of MS development. MS was observed in 20.3% of the patients in the normal delivery group and 37.1% in the HDP group (P < .0001). The time to MS development in the HDP group was significantly shorter than that in the normal delivery group (6.6 ±â€…3.4 vs 8.2 ±â€…3.4 years, P < .0001). The HDP group had a significantly increased risk [odd ratio (OR) 1.23; 95% confidence interval (CI), 1.12-1.35] of developing MS, and elevated systolic blood pressure strongly contributed to the increased risk of developing MS (OR 1.644; 95% CI, 1.610-1.678). HDP increased the risk of MS development later in life, and MS development exhibited a shorter time period in women with HDP. Women with HDP should undergo intensive assessment for MS components.

Effect of vitamin D on endothelial and ventricular function in chronic heart failure patients: A prospective, randomized, placebo-controlled trial.

BACKGROUND: Low 25-hydroxyvitamin D (25OHD) levels are common in patients with chronic heart failure (HF) and are associated with increased mortality risk. This study aimed to establish the safety and efficacy of oral vitamin D3 (cholecalciferol) supplementation and its effect on endothelial and ventricular function in patients with stable HF. METHODS: This study was an investigator-initiated, multicenter, prospective, randomized, placebo-controlled trial. Seventy-three HF patients with 25OHD levels < 75 nmol/L (30 ng/mL) were randomized to receive 4000 IU vitamin D daily or a placebo for 6 months. The primary endpoint was a change in endothelial function between the baseline and after 6 months as assessed using EndoPAT. Secondary endpoints included changes in echocardiographic parameters and differences in quality of life (6-min walking test and New York Heart Association functional status) at 6 months. RESULTS: There were no adverse events in either group during the study period. Vitamin D supplementation did not improve endothelial dysfunction (EndoPAT: baseline, 1.19 ± 0.4 vs 6 months later, 1.22 ± 0.3, P = .65). However, patients' blood pressure, 6-min walking distance, and EQ-5D questionnaire scores improved after vitamin D treatment. In addition, a significant reduction in the left atrial diameter was observed. CONCLUSION: A daily vitamin D dose of 4000 IU for chronic HF appears to be safe. This dosage did not improve endothelial function but did improve the 6-min walk distance, symptoms, and left atrial diameter at 6 months.

The long-term prognostic value of E/e' in patients with ST segment elevation myocardial infarction.

OBJECTIVES: This study aimed to evaluate the long-term prognostic value of E/e' ratio in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We retrospectively assessed 314 patients who underwent primary coronary interventions between January 2010 and December 2015. The included patients were classified into two groups according to the E/e' ratios: E/e'<15 (n = 245) and E/e'≥15 (n = 69). We investigated the incidence of major adverse cardiac events (MACEs) from the event to the final follow-up period of at least three years. RESULTS: A total of 55 cases of MACEs occurred during the follow-up. The E/e'≥15 group showed a significantly higher rate of MACEs than the E/e'<15 group (34.8% vs. 12.7%, p < 0.001). Among the MACE, the percentage of cardiac deaths (17.4% vs. 0.4%, p < 0.001) was higher in the E/e'≥15 group than in the E/e'<15 group. In the multivariable model, E/e'≥15 was demonstrated as the strongest prognostic factor for MACEs (hazard ratio [HR], 2.597; 95% confidence interval [CI], 1.294-5.211; p = 0.007) and cardiac death (HR, 27.537; 95% CI, 3.287-230.689; p = 0.002), while left ventricular ejection fraction (LVEF) was not. Neither the discrepancy of systolic nor diastolic function between initial and follow-up echocardiography affected the overall prevalence of MACEs. A disparity was observed between the two groups, with a significant increase in the rate of MACEs in the E/e'≥15 group (log-rank test, p < 0.001). CONCLUSION: The baseline E/e'≥15 in patients with STEMI after successful reperfusion is the strongest predictor of poor long-term clinical outcomes among those analyzed.

Anatomic and Hemodynamic Plaque Characteristics for Subsequent Coronary Events.

Objectives: While coronary computed tomography angiography (CCTA) enables the evaluation of anatomic and hemodynamic plaque characteristics of coronary artery disease (CAD), the clinical roles of these characteristics are not clear. We sought to evaluate the prognostic implications of CCTA-derived anatomic and hemodynamic plaque characteristics in the prediction of subsequent coronary events. Methods: The study cohort consisted of 158 patients who underwent CCTA with suspected CAD within 6-36 months before percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) or unstable angina and age-/sex-matched 62 patients without PCI as the control group. Preexisting high-risk plaque characteristics (HRPCs: low attenuation plaque, positive remodeling, napkin-ring sign, spotty calcification, minimal luminal area <4 mm2, or plaque burden ≥70%) and hemodynamic parameters (per-vessel fractional flow reserve [FFRCT], per-lesion ΔFFRCT, and percent ischemic myocardial mass) were analyzed from prior CCTA. The primary outcome was a subsequent coronary event, which was defined as a composite of vessel-specific MI or revascularization for unstable angina. The prognostic impact of clinical risk factors, HRPCs, and hemodynamic parameters were compared between vessels with (160 vessels) and without subsequent coronary events (329 vessels). Results: Vessels with a subsequent coronary event had higher number of HRPCs (2.6 ± 1.4 vs. 2.3 ± 1.4, P = 0.012), lower FFRCT (0.76 ± 0.13 vs. 0.82 ± 0.11, P < 0.001), higher ΔFFRCT (0.14 ± 0.12 vs. 0.09 ± 0.08, P < 0.001), and higher percent ischemic myocardial mass (29.0 ± 18.5 vs. 26.0 ± 18.4, P = 0.022) than those without a subsequent coronary event. Compared with clinical risk factors, HRPCs and hemodynamic parameters showed higher discriminant abilities for subsequent coronary events with ΔFFRCT being the most powerful predictor. HRPCs showed additive discriminant ability to clinical risk factors (c-index 0.620 vs. 0.558, P = 0.027), and hemodynamic parameters further increased discriminant ability (c-index 0.698 vs. 0.620, P = 0.001) and reclassification abilities (NRI 0.460, IDI 0.061, P < 0.001 for all) for subsequent coronary events. Among vessels with negative FFRCT (>0.80), adding HRPCs into clinical risk factors significantly increased discriminant and reclassification abilities for subsequent coronary events (c-index 0.687 vs. 0.576, P = 0.005; NRI 0.412, P = 0.002; IDI 0.064, P = 0.001) but not for vessels with positive FFRCT (≤0.80). Conclusion: In predicting subsequent coronary events, both HRPCs and hemodynamic parameters by CCTA allow better prediction of subsequent coronary events than clinical risk factors. HRPCs provide more incremental predictability than clinical risk factors alone among vessels with negative FFRCT but not among vessels with positive FFRCT. Clinical Trial Registration: PreDiction and Validation of Clinical CoursE of Coronary Artery DiSease With CT-Derived Non-INvasive HemodYnamic Phenotyping and Plaque Characterization (DESTINY Study), NCT04794868.

Functional angiography-derived index of microcirculatory resistance validated with microvascular obstruction in cardiac magnetic resonance after STEMI.

INTRODUCTION AND OBJECTIVES: The index of microcirculatory resistance (IMR) measured after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is associated with microvascular obstruction (MVO) and adverse clinical events. To evaluate MVO after successful primary PCI for STEMI without pressure wires or hyperemic agents, we investigated the feasibility and usefulness of functional angiography-derived IMR (angio-IMR). METHODS: The current study included a total of 285 STEMI patients who underwent primary PCI and cardiac magnetic resonance (CMR). Angio-IMR of the culprit vessel after successful primary PCI was calculated using commercial software. MVO, infarct size, and myocardial salvage index were assessed using CMR, which was obtained a median of 3.0 days [interquartile range, 3.0-5.0] after primary PCI. RESULTS: Among the total population, 154 patients (54.0%) showed elevated angio-IMR (> 40 U) in the culprit vessel. MVO was significantly more prevalent in patients with angio-IMR> 40 U than in those with angio-IMR ≤ 40 U (88.3% vs 32.1%, P <.001). Infarct size, extent of MVO, and area at risk were significantly larger in patients with angio-IMR> 40 U than in those with angio-IMR ≤ 40 U (P <.001 for all). Angio-IMR showed a significantly higher discriminatory ability for the presence of MVO than thrombolysis in myocardial infarction flow grade or myocardial blush grade (area under the curve: 0.821, 0.504, and 0.496, respectively, P <.001). CONCLUSIONS: Angio-IMR was significantly associated with CMR-derived infarct size, extent of MVO, and area at risk. An elevated angio-IMR (> 40 U) after primary PCI for STEMI was highly predictive of the presence of MVO in CMR. This trial was registered at ClnicalTrialsgov (Identifier: NCT04828681).

Erythropoietin therapy improves endothelial function in patients with non-dialysis chronic kidney disease and anemia (EARNEST-CKD): A clinical study.

BACKGROUND: This study investigated whether administering erythropoiesis-stimulating agents (ESAs) improves endothelial function in patients with non-dialysis chronic kidney disease (CKD) and anemia. METHODS: This single-center, prospective, single-arm comparison study enrolled patients with non-dialysis CKD (stages 4-5) and hemoglobin levels <10 g/dL. ESA administration followed the Kidney Disease: Improving Global Outcomes guideline. The primary endpoint was the change in flow-mediated dilatation after ESA administration in individual patients. The secondary endpoints were changes in 6-minute walk test results, blood pressure, New York Heart Association class, and echocardiographic parameters. The echocardiographic parameters examined included chamber quantification, Doppler parameters, and systolic and diastolic function parameters. RESULTS: Initially, 13 patients were screened, but 2 discontinued due to either heart failure or voluntary withdrawal. The mean flow-mediated dilatation values significantly increased by 10.59% (from 1.36% ±â€Š1.91% to 11.95% ±â€Š8.11%, P = .001). Echocardiographic findings showed that the left ventricular mass index decreased by 11.9 g/m2 (from 105.8 ±â€Š16.3 to 93.9 ±â€Š19.5 g/m2, P  =  .006), and the left atrial volume index decreased by 10.8 mL/m2 (from 50.1 ±â€Š11.3 to 39.3 ±â€Š11.3 mL/m2, P = .004) after 12 weeks of ESA administration. There were no significant differences between pre- and post-ESA treatment 6-minute walk test results. No significant side effects were observed during the study period. CONCLUSIONS: This is the first clinical study to demonstrate that an ESA improves endothelial dysfunction, left ventricular hypertrophy, and left atrial volume in patients with non-dialysis CKD. Thus, ESAs may be considered as adjunctive therapy for reducing cardiovascular risk in these patients.

Functional Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients With ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy and prognostic implications of angiography-derived index of microcirculatory resistance (angio-IMR) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The index of microcirculatory resistance (IMR) is a reliable invasive measure of coronary microvascular dysfunction in patients with STEMI. A functional coronary angiography-derived method to estimate IMR is a wire- and hyperemic agent-free alternative to IMR. METHODS: The study population consisted of 2 independent cohorts. The diagnostic cohort comprised patients with IMR from the culprit vessel immediately after successful primary percutaneous coronary intervention (n = 31). The prognostic cohort was patients with STEMI who were successfully treated with primary percutaneous coronary intervention and followed for 10 years from the index procedure (n = 309). Angio-IMR was calculated using computational flow and pressure simulation. The primary outcome was a composite of cardiac death and readmission for heart failure over 10 years of follow-up. RESULTS: In the diagnostic cohort, angio-IMR correlated well with IMR (R = 0.778; P < 0.001). Sensitivity, specificity, accuracy, and area under the curve of angio-IMR to predict IMR >40 U were 75.0%, 84.2%, 80.6%, and 0.899 (95% confidence interval: 0.786-0.949), respectively. In the prognostic cohort, patients with angio-IMR >40 U showed significantly higher risk for cardiac death or readmission for heart failure than did those with angio-IMR ≤40 U (46.7% vs 16.6%; adjusted hazard ratio: 2.909; 95% CI: 1.670-5.067; P < 0.001). Angio-IMR >40 U was an independent predictor of cardiac death or readmission for heart failure (hazard ratio: 2.173; 95% CI: 1.157-4.079; P = 0.016) and showed incremental prognostic value compared with a model with clinical risk factors only (C index = 0.726 vs 0.666 [P < 0.001], net reclassification index = 0.704 [P < 0.001]). CONCLUSIONS: Angio-IMR showed high correlation and diagnostic accuracy to predict IMR. Patients with STEMI with angio-IMR >40 U showed a significantly higher risk for cardiac death or readmission for heart failure than those with preserved angio-IMR values. (Prognostic Implication of Angiography-Derived IMR in STEMI Patients; NCT04628377).

Physiological Distribution and Local Severity of Coronary Artery Disease and Outcomes After Percutaneous Coronary Intervention.

OBJECTIVES: The aim of this study was to evaluate prognostic implications of physiological 2-dimensional disease patterns on the basis of distribution and local severity of coronary atherosclerosis determined by quantitative flow ratio (QFR) virtual pull back. BACKGROUND: The beneficial effect of percutaneous coronary intervention (PCI) is determined by physiological distribution and local severity of coronary atherosclerosis. METHODS: The study population included 341 patients who underwent angiographically successful PCI and post-PCI fractional flow reserve (FFR) measurement. Using pre-PCI virtual pull backs of QFR, physiological distribution was determined by pull back pressure gradient index, with a cutoff value of 0.78 to define predominant focal versus diffuse disease. Physiological local severity was assessed by instantaneous QFR gradient per unit length, with a cutoff value of ≥0.025/mm to define a major gradient. Suboptimal post-PCI physiological results were defined as both post-PCI FFR ≤0.85 and percentage FFR increase ≤15%. Clinical outcome was assessed by target vessel failure (TVF) at 2 years. RESULTS: QFR pull back pressure gradient index was correlated with post-PCI FFR (R = 0.423; P < 0.001), and instantaneous QFR gradient per unit length was correlated with percentage FFR increase (R = 0.370; P < 0.001). Using the 2 QFR-derived indexes, disease patterns were classified into 4 categories: predominant focal disease with and without major gradient (group 1 [n = 150] and group 2 [n = 21], respectively) and predominant diffuse disease with and without major gradient (group 3 [n = 115] and group 4 [n = 55], respectively). Proportions of suboptimal post-PCI physiological results were significantly different according to the 4 disease patterns (18.7%, 23.8%, 22.6%, and 56.4% from group 1 to group 4, respectively; P < 0.001). Cumulative incidence of TVF after PCI was significantly higher in patients with predominant diffuse disease (8.1% in group 3 and 9.9% in group 4 vs 1.4% in group 1 and 0.0% in group 2; overall P = 0.024). CONCLUSIONS: Both physiological distribution and local severity of coronary atherosclerosis could be characterized without pressure-wire pull backs, which determined post-PCI physiological results. After successful PCI, TVF risk was determined mainly by the physiological distribution of coronary atherosclerosis. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship With Post-PCI Clinical Outcomes [Algorithm-PCI], NCT04304677; Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [PERSPECTIVE], NCT01873560).

Clinical and Prognostic Impact From Objective Analysis of Post-Angioplasty Fractional Flow Reserve Pullback.

OBJECTIVES: This study sought to evaluate clinical implications of the residual fractional flow reserve (FFR) gradient after angiographically successful percutaneous coronary intervention (PCI). BACKGROUND: Recent studies have demonstrated FFR measured after PCI is associated with clinical outcome after PCI. Although post-PCI FFR pull back tracings provide clinically relevant information on the residual FFR gradient, there are no objective criteria for assessing post-PCI FFR pull back tracings. METHODS: A total of 492 patients who underwent angiographically successful PCI and post-PCI FFR measurement with pull back tracings were analyzed. The presence of the major residual FFR gradient after PCI was assessed by both conventional visual interpretation of the pull back tracings and objective analysis using the instantaneous FFR gradient per unit time (dFFR(t)/dt) with a cutoff value of dFFR(t)/dt ≥0.035. Classification agreement between 2 independent operators for the presence of the major residual FFR gradient was compared before and after providing dFFR(t)/dt results. Target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 2 years, was compared according to the presence of the major residual FFR gradient. RESULTS: Among the study population, 33.9% had the major residual FFR gradient defined by dFFR(t)/dt. The classification agreement between operators' assessments for the major residual FFR gradient increased with dFFR(t)/dt results compared with conventional visual assessment (Cohen's kappa = 0.633 to 0.819; P < 0.001; intraclass correlation coefficient: 0.776 to 0.901; P < 0.001). Patients with major residual FFR gradient were associated with a higher risk of TVF at 2 years than those without major residual FFR gradient (9.0% vs 2.2%; P < 0.001). Inclusion of the major residual FFR gradient to a clinical prediction model significantly increased discrimination and reclassification ability (C-index = 0.539 vs 0.771; P = 0.006; net reclassification improvement = 0.668; P = 0.007; integrated discrimination improvement = 0.033; P = 0.017) for TVF at 2 years. The presence of the major residual FFR gradient was independently associated with TVF at 2 years, regardless of post-PCI FFR or percent FFR increase (adjusted hazard ratio: 3.930; 95% confidence interval: 1.353-11.420; P = 0.012). CONCLUSIONS: Objective analysis of post-PCI FFR pull back tracings using dFFR(t)/dt improved classification agreement on the presence of the major residual FFR gradient among operators. Presence of the major residual FFR gradient defined by dFFR(t)/dt after angiographically successful PCI was independently associated with an increased risk of TVF at 2 years. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship with Post-PCI Clinical Outcomes [Algorithm-PCI]; NCT04304677; Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [COE-PERSPECTIVE]; NCT01873560).

Immediate and Evolutionary Recovery of Left Ventricular Diastolic Function after Transcatheter Aortic Valve Replacement: Comparison with Surgery.

PURPOSE: We aimed to compare the effect of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (sAVR) on recovery of left ventricular (LV) diastolic function and afterload through serial echocardiographic examinations in patients with symptomatic high-risk severe aortic stenosis during early follow-up. MATERIALS AND METHODS: We included 38 patients undergoing TAVR (mean age, 80±6 years; male:female=18:20) and 27 patients undergoing sAVR (mean age, 78±3 years; male:female=12:15). We compared changes in the LV diastolic function and afterload before, immediately after, and 3 months after the procedure using serial transthoracic echocardiography. RESULTS: Immediately after the procedure, 16 (42%) and 3 (11%) patients in the TAVR and sAVR groups, respectively, showed rapid improvement in diastolic filling patterns. E wave to e' ratio (E/e') and right ventricular systolic pressure (RVSP) decreased significantly in the TAVR group (E/e': TAVR, from 24.6±12.9 to 20±9.5, p=0.048 vs. sAVR, from 21.5±9.4 to 20.64±6.4, p=0.361; RVSP: TAVR, 38.4±17.2 vs. 34±12.4, p=0.032 vs. sAVR, 32.2±11.7 vs. 30±6.8, p=0.27). After 3 months, diastolic grade distribution, E/e', and RVSP were similar. Valvuloarterial impedance significantly decreased immediately after the procedure in both groups (TAVR, from 5.1±1.4 to 3.1±1.0 vs. sAVR, from 4.5±1.5 to 3.1±0.8 mm Hg · mL⁻¹ · m⁻², p=0.001), but after 3 months, decreases were greater in the sAVR group (from 3.1±0.8 to 2.2±1.5 mm Hg · mL⁻¹ · m⁻², p=0.093). CONCLUSION: LV diastolic function improved more rapidly and earlier in patients treatment with TAVR than in patients treated with sAVR. These results might explicate the remarkable clinical improvement in improvements in advanced diastolic dysfunction immediately after the TAVR procedure than sAVR.