Transcatheter Aortic Valve Replacement in Patients With a Small Annulus　- From the Japanese Nationwide Registry (J-TVT).

BACKGROUND: The details and consequences of a small aortic annulus among transcatheter aortic valve replacement (TAVR) patients remain uncertain. This study investigated the short-term outcomes in patients with small annular size and compared the 30-day outcome between intra- and supra-annular devices, with similar outer casing diameter in this subgroup.Methods and Results:Cases registered in the Japanese national TAVR registry between August 2013 and December 2017 were analyzed. Among a total of 5,870 registered patients, 647 (11.0%) had small annulus (area ≤314 mm2) measured by multi-detector computed tomography. Patients with a small annulus had a significantly smaller indexed effective orifice area (iEOA, 1.10 cm2/m2[0.92-1.35] vs. 1.16 cm2/m2[0.96-1.39], P<0.001) and higher mean pressure gradient (mPG, 10.0 mmHg [6.9-14.2] vs. 8.5 mmHg [6.0-11.5], P<0.001) compared with a normal-sized annulus. Among patients with a small annulus, those receiving a 20 mm intra-annular device had a smaller iEOA (0.94 cm2/m2[0.78-1.06] vs. 1.07 cm2/m2[0.8-1.24], P=0.001) and higher mPG (14.0 mmHg [10.0-18.5] vs. 11.0 [7.0-14.0], P<0.001) compared with those receiving a 23-mm supra-annular device, although the incidence of paravalvular leakage (≥moderate) was similar (14.4% vs. 16.5%, P=0.69). CONCLUSIONS: Patients with a small annulus were associated with less hemodynamic improvement. A supra-annular device is associated with better echocardiographic improvement in patients with a small annulus, without increasing paravalvular leakage.

Characteristics of carotid atherosclerosis in patients with plaque erosion.

Plaque erosion (PE) is a major underlying mechanism of acute coronary syndrome (ACS). Patients with PE may have less systemic atherosclerosis. We aimed to clarify the status of carotid atherosclerosis in patients with PE. A total of 115 consecutive patients with ACS who underwent optical coherence tomography (OCT) imaging of the culprit lesion were enrolled. Patients were classified into PE (n = 26), plaque rupture (n = 56) or calcified plaque (CP, n = 33) based on OCT findings of the culprit lesions. The status of carotid atherosclerosis was assessed by the findings of carotid echography. The mean IMT was the lowest in the PE group (1.5 ± 0.6 mm) among the three groups (p = 0.004) with a significant difference between the PE group and the CP group (2.1 ± 0.6 mm, p < 0.001). The plaque score was the lowest in the PE group (6.6 ± 2.5) among the three groups (p = 0.004) with a significant difference between the PE group and the CP group (9.0 ± 2.7, p < 0.001). Multivariate analyses demonstrated that the PE was independently associated with the presence of lower mean IMT (below median; 1.85 mm) (odds ratio 3.34; 95 % confidence interval 1.07-10.4; p = 0.035) and the lack of heterogenous plaque (odds ratio 2.92; 95 % confidence interval 1.02-8.32; p = 0.037). Patients with PE were associated with less atherosclerosis in the carotid artery than other patients with ACS. These findings may help further clarify the distinct pathophysiology of PE. Carotid atherosclerosis and plaque erosion.

Achilles tendon thickening is associated with higher incidence of adverse cardiovascular event in patients with coronary artery disease.

Achilles tendon thickening (ATT) is a marker of high risk for coronary artery disease (CAD). However, the association between the presence of ATT and the incidence of cardiovascular events in patients with CAD is unclear. A total of 406 consecutive patients who underwent percutaneous coronary intervention (PCI) and ATT assessment were analyzed. ATT was defined as the Achilles tendon thickness of 9 mm or more on radiography. The incidence of major adverse cardiovascular events (MACE) at 1-year was compared between patients with ATT and those without ATT. MACE included cardiac death, non-fatal myocardial infarction, stroke, target vessel revascularization (TVR), and non-TVR. ATT was found in 67 patients (16.5%). The incidence of cardiac death (3.2 vs. 0.0%, p = 0.001), TVR (12.7 vs. 4.0%, p = 0.005) and MACE (20.6 vs. 9.6%, p = 0.011) was significantly higher in the ATT group than the no ATT group. Patients with ATT had significantly higher incidence of cardiac death (5.6 vs. 0%, p < 0.001) than those without ATT even if they did not meet the diagnostic criteria of familial hypercholesterolemia. A multivariate model demonstrated that ATT was independently associated with the MACE at 1-year (Hazard ratio, 2.09; 95% Confidence Interval, 1.09-4.00, p = 0.026). The presence of ATT was independently associated with 1-year recurrence of cardiovascular events in patients with CAD undergoing PCI. Assessment of ATT might be useful for risk stratification of secondary cardiovascular events.

Clinical outcome of biodegradable polymer sirolimus-eluting stent and durable polymer everolimus-eluting stent in patients with diabetes.

BACKGROUND: Diabetes mellitus is a risk for increased incidence of adverse clinical events after percutaneous coronary intervention. However, the difference in the incidence of adverse clinical events according to stent type in patients with diabetes remains to be elucidated. In the present study, we aimed to compare the clinical outcomes between patients treated with the biodegradable polymer sirolimus-eluting stents (BP-SES) and the durable polymer everolimus-eluting stents (DP-EES) among patients with diabetes. METHODS: Among 631 lesions in 510 consecutive patients treated with either BP-SES or DP-EES, 165 lesions in 141 patients with diabetes mellitus and stable angina pectoris were identified and classified into the BP-SES group (48 lesions in 44 patients) and the DP-EES group (117 lesions in 100 patients). The incidence of adverse clinical events after stent implantation was compared between the 2 groups. RESULTS: There was no significant difference in the prevalence of conventional risk factors, lesion characteristics, and procedural characteristics between the 2 groups. During median 386 [334-472] days follow-up, the incidence of target lesion revascularization (11.4 vs. 2.0%, p = 0.003) and device-oriented clinical endpoint (13.6 vs. 6.0%, p = 0.035) in the BP-SES group was significantly greater than that in the DP-EES group. A univariate model demonstrated that the BP-SES usage was significantly associated with the higher incidence of target lesion revascularization (odds ratio, 6.686; 95% confidence interval, 1.234-36.217; p = 0.028). CONCLUSION: BP-SES was associated with the greater incidence of TLR than the DP-EES in patients with diabetes mellitus. Further studies with larger cohorts and longer follow-up are required to confirm the present results.

Age- and Gender-Related Differences in Coronary Lesion Plaque Composition on Optical Coherence Tomography.

BACKGROUND: The pathophysiology and chronological course of atherosclerosis seems to be different between men and women due to biological differences, and age and gender differences in plaque composition of coronary lesions remain to be elucidated.Methods and Results:A total of 860 consecutive patients with a median age of 69 years (IQR, 60-78 years) who underwent optical coherence tomography (OCT) of culprit lesions was included. The composition of culprit plaque on OCT was compared between female (n=171) and male (n=689) subjects in younger (<70 years old) and elderly (≥70 years old) patients. In elderly patients, the prevalence of thin-cap fibroatheroma (TCFA) was significantly higher in women than in men (30.6 vs. 15.2%, P<0.001). In younger patients, the prevalence of large calcification was significantly higher in women than in men (60.0 vs. 32.8%, P<0.001). The prevalence of other vulnerable plaque characteristics (i.e., macrophages, microchannels, and spotty calcification), was similar between women and men. Elderly women had a significantly higher prevalence of TCFA (OR, 2.13; 95% CI: 1.33-3.44, P=0.002) than other patients. CONCLUSIONS: Women had a higher prevalence of TCFA and of large calcification than men in patients ≥70 and <70 years old, respectively. This may facilitate the understanding of gender differences in the pathogenesis of coronary atherosclerosis, and the tailoring of therapy and of prevention according to age and gender.

Physical exertion as a trigger of acute coronary syndrome caused by plaque erosion.

Distinct clinical characteristics have been demonstrated in patients with plaque erosion as compared with those with plaque rupture. We reasoned that greater physical activity might influence the onset of plaque erosion. In total, 97 consecutive patients with non ST-segment elevation acute coronary syndrome (ACS) who underwent optical coherence tomography (OCT) imaging of the culprit lesion were enrolled. OCT-determined culprit plaque characteristics were plaque erosion (18.6%), calcified plaque (26.8%), plaque rupture (32.0%) and other (22.7%). The physical activity evaluated by estimated metabolic equivalents (METs) at ACS onset was significantly greater in the plaque erosion group than in the plaque rupture group (3.3 ± 1.7 vs. 2.1 ± 1.0, p = 0.011). The rate of ACS onset outdoors was the highest (61.1%) in the plaque erosion group. The combination of greater physical activity (> 3 METs), outdoor onset and higher body mass index (> 25.1 kg/m2) had a significant odds ratio for the incidence of plaque erosion (odds ratio 15.0, 95% confidence interval 3.81 to 59.0, p < 0.001). Plaque erosion was associated with greater physical activity at the onset. This finding may help to further clarify the pathogenesis of ACS Impact of physical exertion on the incidence of plaque erosion. NSTE-ACS, non ST-segment elevation acute coronary syndrome.

Transaortic Access Using Vascular Graft for Transcatheter Aortic Valve Implantation.

A 92-year-old man with acute heart failure due to severe aortic stenosis underwent transcatheter aortic valve implantation (TAVI). Computed tomography demonstrated severe stenosis of the right common iliac artery, occlusion of the left external iliac artery, and stenosis of the left subclavian artery. Severe calcification was observed in the sinotubular junction, which was considered a risk factor for aortic dissection with transapical TAVI using a balloon-expanding bioprosthetic valve. Therefore, transaortic (TAo) access was the only option for this high-risk surgical patient. As the maximum distance from the aortic valve annulus to the sheath insertion point was less than 60 mm, TAVI was performed transaortically using a vascular graft that extended this distance, in order to avoid sheath dislocation. Our experience demonstrates that vascular graft application is a viable option in patients with an inadequate distance between the aortic valve annulus and the puncture site in TAo-TAVI.

Impaired Flow-Mediated Dilation and Severity and Vulnerability of Culprit Plaque in Patients with Coronary Artery Disease.

The association between endothelial function, evaluated using flow-mediated dilatation (FMD), and the severity of coronary artery disease remains to be elucidated.A total of 245 consecutive patients with stable angina were prospectively enrolled. FMD was evaluated in the brachial artery before percutaneous coronary intervention. Patients were divided into 2 groups according to the FMD value (lower FMD group [FMD < 2.0], n = 82; higher FMD group [FMD ≥ 2.0], n = 163). The severity of coronary artery disease was evaluated using findings of angiography and optical coherence tomography, and compared between the 2 groups.The prevalence of left main (LM) disease was significantly higher in the lower FMD group than in the higher FMD group (8.5% versus 2.5%, P = 0.046), although the prevalence of multivessel disease was comparable between the groups. Lower FMD was independently associated with a higher prevalence of LM disease (odds ratio, 3.89; 95% confidence interval, 1.12-15.5; P = 0.033). A general linear model with multiple variables revealed that the minimal lumen area (MLA) in the culprit lesion was significantly smaller in patients with lower FMD than in those with higher FMD (regression coefficient b, -0.249 mm2; 95% confidence interval, -0.479--0.018 mm2; P = 0.035). The prevalence ofvulnerable plaque characteristics was comparable between the 2 groups.Patients with lower FMD had a higher incidence of LM disease and a smaller MLA in the culprit lesion. FMD may be a useful, noninvasive indicator for identifying patients with severe coronary artery disease.

Contrast Volume and Decline in Kidney Function in Optical Coherence Tomography-Guided Percutaneous Coronary Intervention.

Optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) may increase contrast volume. However, the impact of OCT-guided PCI on the decline in kidney function (DKF) in actual clinical practice remains unclear.Among 1,003 consecutive patients who underwent either OCT-guided or intravascular ultrasound (IVUS)-guided PCI in our institute, we identified 202 propensity score-matched pairs adjusted by baseline factors. The incidence of DKF was compared between the OCT-guided PCI group and the IVUS-guided PCI group. DKF was defined as an increase in serum creatinine level of ≥ 0.5 mg/dL or a relative increase of ≥ 25% over baseline within 48 hours (acute DKF) or 1 month (sustained DKF) after PCI.Baseline characteristics, including the prevalence of chronic kidney disease (54% versus 46%, P = 0.09), were comparable between the OCT- and IVUS-guided PCI groups except for the age. The contrast volume was comparable between the two groups (153 ± 56 versus 144 ± 60 mL, P = 0.09), although it was significantly greater in the OCT-guided PCI group in patients with acute coronary syndrome (ACS; 175 ± 55 versus 159 ± 43 mL, P = 0.04). The incidence of acute DKF (0.5% versus 2.5%, P = 0.22) and sustained DKF (5.0% versus 10.4%, P = 0.31) was comparable between the two groups. Multivariate analysis demonstrated that ACS (odds ratio 4.74, 95% confidence interval 2.72-8.25, P < 0.001) was a predictor of sustained DKF.Compared with IVUS-guided PCI, OCT-guided PCI did not increase the incidence of DKF in actual clinical practice, although the increased contrast volume was observed in ACS cases.

Early Safety and Efficacy of Sapien 3 20 mm Transcatheter Heart Valve Implantation in Small Japanese Body Size.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is effective in treating severe aortic stenosis in inoperable or high-risk surgical patients, however, the little is known about outcomes after Sapien 3 20 mm transcatheter heart valve (THV) implantation. The purpose of this study was to investigate the short term outcomes of Sapien 3 20 mm THV implantation in Japanese people with a small body size. METHODS: We retrospectively collected the hospital records of consecutive patients who underwent TAVI using the Sapien 3 20 mm THV between October 2016 and March 2017. Clinical and echocardiographic data from before and one week after TAVI were collected. RESULTS: Six Japanese patients (all female, mean age 89 ± 5 years, body surface area [BSA] 1.29 ± 0.16m2) received a Sapien 3 20 mm THV. All the procedures were feasible and successful, and the 30-day mortality rate was 0%. The functional class and the echocardiographic findings significantly improved (aortic valve area, 0.5 ± 0.1 cm2 to 0.8 ± 0.1cm2; mean pressure gradient, 55 ± 15 mmHg to 19 ± 7 mmHg; P = .043, respectively). However, the values of the indexed effective orifice area in all patients after Sapien 3 20 mm THV implantation were less than 0.85 cm2/m2, suggesting prosthesis-patient mismatch (PPM). CONCLUSIONS: The implantation of a Sapien 3 20 mm THV was safe and effective in high surgical risk elderly Japanese patients with a small body size. PPM after Sapien 3 20mm THV may be prevalent among Asians with small body sizes. Careful clinical follow-up will be necessary after Sapien 3 20 mm THV implantation.

Endothelial Dysfunction Is Associated with Cognitive Impairment of Elderly Cardiovascular Disease Patients.

Cognitive impairment is frequently represented in elderly patients with cardiovascular disease (CVD); yet, the mechanism is uncertain. Recent studies have suggested the association between the vascular endothelial dysfunction and cognitive impairment. The aim of this study was to clarify the association between endothelial dysfunction and cognitive impairment in elderly patients with CVD.A total of 80 elderly patients (> 70 years old) with CVD were included. Patients who had already pharmacologically intervened for cognitive impairment were excluded. The endothelial dysfunction was assessed by the reactive hyperemia-peripheral arterial tonometry (RH-PAT). Cognitive impairment was diagnosed by the Mini-mental state examination.The RH-PAT index was significantly lower in cognitive impairment (median 1.60 [interquartile range (IQR) 1.34 to 1.89], n = 51) as compared with non-cognitive impairment (median 1.75 [IQR 1.55 to 2.30], n = 29, P = 0.005). By a multivariate analysis, the RH-PAT index was independently associated with cognitive impairment (odds ratio: 0.89; 95% confidence interval: 0.81 to 0.97; per 0.1, P = 0.044). In the receiver-operating characteristic analysis, the best cut-off of the RH-PAT index to identify cognitive impairment was 1.65 (area under the curve 0.67; P = 0.011) with limited the sensitivity (63%) and specificity (66%).A lower RH-PAT index was significantly associated with the presence of cognitive impairment in elderly CVD patients. Further studies are required to clarify the mechanism and the causal relationship between the endothelial dysfunction and cognitive impairment in patients with CVD.

Ezetimibe enhances and stabilizes anticoagulant effect of warfarin.

Ezetimibe reduces plasma levels of low-density lipoprotein cholesterol by inhibiting Niemann-Pick C1-like protein 1 (NPC1L1). A recent study demonstrated that NPC1L1 plays an important role in absorption of fat-soluble vitamins including vitamin K. We evaluated whether the add-on treatment of ezetimibe affects anticoagulation in patients taking warfarin. Between October 2007 and March 2015, the administration of ezetimibe was started to a total of 101 outpatients who were already on oral anticoagulation with warfarin. We retrospectively analyzed blood lipid levels, prothrombin time international normalized ratio (PT-INR) and time in therapeutic INR range (TTR). Seventy-one patients (70 %) showed increase in PT-INR after ezetimibe treatment (1.96 ± 0.45 to 2.20 ± 0.61, p < 0.001). It was necessary to reduce the warfarin dose in 9 of 101 patients for clinical indication. There was a significant positive correlation between change in PT-INR and statin usage at baseline (p = 0.03). The mean value of changes in PT-INR of patients with taking statin was significantly larger than that of patients without taking statin (0.34 ± 0.54 vs. 0.06 ± 0.36, p = 0.03). There was an increase in the TTR (52 ± 26 to 61 ± 23 %, p < 0.0001) and a decrease in the frequency to change the dose of warfarin after the ezetimibe treatment [45 times of 735 examination days (6 %) to 20 times of 695 examination days (3 %), p = 0.02]. Our data suggest possible drug interaction between warfarin and ezetimibe. Ezetimibe may increase and stabilize the anticoagulant effect of warfarin, especially in patients taking statins.

Effects on bone metabolism markers and arterial stiffness by switching to rivaroxaban from warfarin in patients with atrial fibrillation.

In recent years, direct oral anticoagulants (DOACs) of dabigatran, rivaroxaban, apixaban, edoxaban, which are all alternatives to warfarin, have been released. The use of DOACs is becoming more widespread in the clinical management of thrombotic stroke risk in patients with atrial fibrillation (AF). In large-scale clinical trials of each drug, DOACs were reported to inhibit intracranial hemorrhage, stroke, and death compared to warfarin. Warfarin is an endogenous vitamin K antagonist; therefore, patients who are taking warfarin must be prohibited from taking vitamin K. Vitamin K is an essential cofactor required for the ɤ-carboxylation of vitamin K-dependent proteins including coagulation factors, osteocalcin (OC), matrix Gla protein (MGP), and the growth arrest-specific 6 (GAS6). OC is a key factor for bone matrix formation. MGP is a local inhibitor of soft tissue calcification in the vessel wall. GAS6 prevents the apoptosis of vascular smooth muscle cells. Therefore, decrease of blood vitamin K levels may cause osteoporosis, vascular calcification, and the inhibition of vessels angiogenesis. This study aimed to evaluate the effects of changing from warfarin to rivaroxaban on bone mineral metabolism, vascular calcification, and vascular endothelial dysfunction. We studied 21 consecutive patients with persistent or chronic AF, who were treated with warfarin at least for 12 months. Warfarin administration was changed to rivaroxaban (10 or 15 mg/day) in all patients. Osteopontin (OPN), bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were measured. Pulse wave velocity (PWV) and augmentation index (AI) were also measured as atherosclerosis assessments. All measurements were done before and six months after the rivaroxaban treatment. There was a significant increase in serum level of BAP compared to baseline (12.5 ± 4.6 to 13.4 ± 4.1 U/L, P < 0.01). In contrast, there was a significant decrease in the serum level of ucOC (9.5 ± 5.0 to 2.7 ± 1.3 ng/ml, P < 0.01). Also, in the ucOC levels, there was a significant negative correlation between baseline values and baseline to 6-months changes in high ucOC group (r = -0.97, P < 0.01). The atherosclerosis- and osteoporosis-related biomarker, serum level of OPN were significantly decreased compared to baseline (268.3 ± 46.8 to 253.4 ± 47.1 ng/ml, P < 0.01). AI and PWV were significantly decreased after 6 months of treatment with rivaroxaban (33.9 ± 18.4 to 24.7 ± 18.4%, P = 0.04; 1638.8 ± 223.0 to 1613.0 ± 250.1 m/s, P = 0.03, respectively). Switching to rivaroxaban from warfarin in patients with atrial fibrillation was associated with an increase of bone formation markers and a decrease of bone resorption markers, and also improvements of PWV and AI.

Teneligliptin improves left ventricular diastolic function and endothelial function in patients with diabetes.

Incretin hormones have been reported to have cytoprotective actions in addition to their glucose-lowering effects. We evaluated whether teneligliptin, a novel dipeptidyl peptidase-4 (DPP-4) inhibitor, affects left ventricular (LV) function in patients with type 2 diabetes mellitus (T2DM). Twenty-nine T2DM patients not receiving any incretin-based drugs were enrolled and prescribed with teneligliptin for 3 months. Compared to baseline levels, hemoglobin A1c levels decreased (7.6 ± 1.0 % to 6.9 ± 0.7 %, p < 0.01) and 1,5-anhydro-D-glucitol levels increased (9.6 ± 7.2 µg/mL to 13.5 ± 8.7 µg/mL, p < 0.01) after treatment. Clinical parameters, including body mass index and blood pressure, did not show any difference before and after treatment. Three months after treatment, there were improvements in LV systolic and diastolic function [LV ejection fraction, 62.0 ± 6.5 % to 64.5 ± 5.0 %, p = 0.01; peak early diastolic velocity/basal septal diastolic velocity (E/e') ratio, 13.3 ± 4.1 to 11.9 ± 3.3, p = 0.01]. Moreover, there was an improvement in endothelial function (reactive hyperemia peripheral arterial tonometry [RH-PAT] index; 1.58 ± 0.47 to 2.01 ± 0.72, p < 0.01). There was a significant negative correlation between changes in the E/e' ratio and RH-PAT values. Furthermore, circulating adiponectin levels increased (27.0 ± 38.5 pg/mL to 42.7 ± 33.2 pg/mL, p < 0.01) without changes in patient body weight. Teneligliptin treatment was associated with improvements in LV function and endothelial functions, and an increase in serum adiponectin levels. These results support the cardio-protective effects of teneligliptin in T2DM patients and increase in serum adiponectin levels.

Automatic assessment of atherosclerotic plaque features by intracoronary imaging: a scoping review.

Background: The diagnostic performance and clinical validity of automatic intracoronary imaging (ICI) tools for atherosclerotic plaque assessment have not been systematically investigated so far. Methods: We performed a scoping review including studies on automatic tools for automatic plaque components assessment by means of optical coherence tomography (OCT) or intravascular imaging (IVUS). We summarized study characteristics and reported the specifics and diagnostic performance of developed tools. Results: Overall, 42 OCT and 26 IVUS studies fulfilling the eligibility criteria were found, with the majority published in the last 5 years (86% of the OCT and 73% of the IVUS studies). A convolutional neural network deep-learning method was applied in 71% of OCT- and 34% of IVUS-studies. Calcium was the most frequent plaque feature analyzed (26/42 of OCT and 12/26 of IVUS studies), and both modalities showed high discriminatory performance in testing sets [range of area under the curve (AUC): 0.91-0.99 for OCT and 0.89-0.98 for IVUS]. Lipid component was investigated only in OCT studies (n = 26, AUC: 0.82-0.86). Fibrous cap thickness or thin-cap fibroatheroma were mainly investigated in OCT studies (n = 8, AUC: 0.82-0.94). Plaque burden was mainly assessed in IVUS studies (n = 15, testing set AUC reported in one study: 0.70). Conclusion: A limited number of automatic machine learning-derived tools for ICI analysis is currently available. The majority have been developed for calcium detection for either OCT or IVUS images. The reporting of the development and validation process of automated intracoronary imaging analyses is heterogeneous and lacks critical information. Systematic Review Registration: Open Science Framework (OSF), https://osf.io/nps2b/.Graphical AbstractCentral Illustration.

Association of Preoperative Copeptin Levels with Risk of All-Cause Mortality in a Prospective Cohort of Adult Cardiac Surgery Patients.

We aimed to investigate the association of preoperative copeptin, a new cardiovascular biomarker, with short- and long-term mortality in a cohort of adult patients undergoing cardiac surgery, including its potential as a prognostic marker for clinical outcome. Preoperative blood samples of the Bern Perioperative Biobank, a prospective cohort of adults undergoing cardiac surgery during 2019, were analyzed. The primary and secondary outcome measures were 30-day and 1-year all-cause mortality. Optimal copeptin thresholds were calculated with the Youden Index. Associations of copeptin levels with the two outcomes were examined with multivariable logistic regression models; their discriminatory capacity was assessed with the area under the receiver operating characteristic (AUROC). A total of 519 patients (78.4% male, median age 67 y (IQR: 60-73 y)) were included, with a median preoperative copeptin level of 7.6 pmol/L (IQR: 4.7-13.2 pmol/L). We identified an optimal threshold of 15.9 pmol/l (95%-CI: 7.7 to 46.5 pmol/L) for 30-day mortality and 15.9 pmol/L (95%-CI: 9.0 to 21.3 pmol/L) for 1-year all-cause mortality. Regression models featured an AUROC of 0.79 (95%-CI: 0.56 to 0.95) for adjusted log-transformed preoperative copeptin for 30-day mortality and an AUROC of 0.76 (95%-CI: 0.64 to 0.88) for 1-year mortality. In patients undergoing cardiac surgery, the baseline levels of copeptin emerged as a strong marker for 1-year all-cause death. Preoperative copeptin levels might possibly identify patients at risk for a complicated, long-term postoperative course, and therefore requiring a more rigorous postoperative observation and follow-up.

Concomitant Coronary Atheroma Regression and Stabilization in Response to Lipid-Lowering Therapy.

BACKGROUND: The frequency, characteristics, and outcomes of patients treated with high-intensity lipid-lowering therapy and showing concomitant atheroma volume reduction, lipid content reduction, and increase in fibrous cap thickness (ie, triple regression) are unknown. OBJECTIVES: This study was designed to investigate rates, determinants, and prognostic implications of triple regression in patients presenting with acute myocardial infarction and treated with high-intensity lipid-lowering therapy. METHODS: The PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients with Acute Myocardial Infarction) trial used serial intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography to compare the effects of alirocumab vs placebo in patients receiving high-intensity statin therapy. Triple regression was defined by the combined presence of percentage of atheroma volume reduction, maximum lipid core burden index within 4 mm reduction, and minimal fibrous cap thickness increase. Clinical outcomes at 1-year follow-up were assessed. RESULTS: Overall, 84 patients (31.7%) showed triple regression (40.8% in the alirocumab group vs 23.0% in the placebo group; P = 0.002). On-treatment low-density lipoprotein cholesterol levels were lower in patients with vs without triple regression (between-group difference: -27.1 mg/dL; 95% CI: -37.7 to -16.6 mg/dL; P < 0.001). Triple regression was independently predicted by alirocumab treatment (OR: 2.83; 95% CI: 1.57-5.16; P = 0.001) and a higher baseline maximum lipid core burden index within 4 mm (OR: 1.03; 95% CI: 1.01-1.06; P = 0.013). The composite clinical endpoint of death, myocardial infarction, and ischemia-driven revascularization occurred less frequently in patients with vs without triple regression (8.3% vs 18.2%; P = 0.04). CONCLUSIONS: Triple regression occurred in one-third of patients with acute myocardial infarction who were receiving high-intensity lipid-lowering therapy and was associated with alirocumab treatment, higher baseline lipid content, and reduced cardiovascular events. (Vascular Effects of Alirocumab in Acute MI-Patients [PACMAN-AMI]; NCT03067844).