Association between defibrillation-to-adrenaline interval and short-term outcomes in patients with out-of-hospital cardiac arrest and an initial shockable rhythm.

Aim: The optimal timing of adrenaline administration after defibrillation in patients with out-of-hospital cardiac arrest (OHCA) and an initial shockable rhythm is unknown. We investigated the association between the defibrillation-to-adrenaline interval and clinical outcomes. Methods: Between 2011 and 2020, we enrolled 1,259,960 patients with OHCA into a nationwide prospective population-based registry in Japan. After applying exclusion criteria, 20,905 patients with an initial shockable rhythm documented at emergency medical services (EMS) arrival who received adrenaline after defibrillation were eligible for this study. Multivariable logistic regression analysis was used to predict favourable short-term outcomes: prehospital return of spontaneous circulation (ROSC), 30-day survival, or a favourable neurological outcome (Cerebral Performance Category 1 or 2) at 30 days. Patients were categorised into 2-minute defibrillation-to-adrenaline intervals up to 18 min, or more than 18 min. Results: At 30 days, 1,618 patients (8%) had a favourable neurological outcome. The defibrillation-to-adrenaline interval in these patients was significantly shorter than in patients with an unfavourable neurological outcome [8 (5-12) vs 11 (7-16) minutes; P < 0.001]. The proportion of patients with prehospital ROSC, 30-day survival, or a favourable neurological outcome at 30 days decreased as the defibrillation-to-adrenaline interval increased (P < 0.001 for trend). Multivariable analysis revealed that a defibrillation-to-adrenaline interval of > 6 min was an independent predictor of worse prehospital ROSC, 30-day survival, or neurological outcome at 30 days when compared with an interval of 4-6 min. Conclusion: A longer defibrillation-to-adrenaline interval was significantly associated with worse short-term outcomes in patients with OHCA and an initial shockable rhythm.

Relationship between Earlobe Crease and Anatomical Severity of Coronary Artery Disease in ST-segment Elevation Myocardial Infarction.

Objective Earlobe crease (ELC) is an easily detectable physical sign of cardiovascular risk and coronary artery disease (CAD). However, the relationship between ELC and CAD severity in patients with ST-segment elevation myocardial infarction (STEMI) requiring urgent clinical judgment is unknown. Using the residual synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score, we investigated the relationship between ELC and anatomical severity of CAD. Methods, patients or materials We studied 219 consecutive patients with STEMI (median age, 71 years old) and divided them into 2 groups according to the presence of ELC (ELC group, n=161; non-ELC group, n=58). Results The ELC group had a significantly higher number of diseased vessels than the non-ELC group (≥2 diseased vessels, 79% vs. 46%; ≥3 diseased vessels, 35% vs. 12%; P<0.001). In addition, a higher median residual SYNTAX score was observed after primary percutaneous coronary intervention than the non-ELC group [8 (4-12) vs. 3 (0-8), P<0.001]. Furthermore, a multivariable regression analysis showed that ELC was an independent predictor of the residual SYNTAX score (ß=3.620, P<0.001). Conclusions The presence of ELC was significantly associated with the anatomical severity of diseased coronary vessels in patients with STEMI who required emergency clinical judgment and treatment.

Effect of Eicosapentaenoic Acid/Docosahexaenoic Acid on Coronary High-Intensity Plaques Detected Using Noncontrast T1-weighted Imaging: The AQUAMARINE EPA/DHA Randomized Study.

AIM: Omega-3 fatty acids have emerged as a new option for controlling the residual risk for coronary artery disease (CAD) in the statin era. Eicosapentaenoic acid (EPA) is associated with reduced CAD risk in the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention trial, whereas the Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia trial that used the combination EPA/docosahexaenoic acid (DHA) has failed to derive any clinical benefit. These contradictory results raise important questions about whether investigating the antiatherosclerotic effect of omega-3 fatty acids could help to understand their significance for CAD-risk reduction. METHODS: The Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technic EPA/DHA study is a single-center, triple-arm, randomized, controlled, open-label trial used to investigate the effect of EPA/DHA on high-risk coronary plaques after 12 months of treatment, detected using cardiac magnetic resonance (CMR) in patients with CAD receiving statin therapy. Eligible patients were randomly assigned to no-treatment, 2-g/day, and 4-g/day EPA/DHA groups. The primary endpoint was the change in the plaque-to-myocardium signal intensity ratio (PMR) of coronary high-intensity plaques detected by CMR. Coronary plaque assessment using computed tomography angiography (CTA) was also investigated. RESULTS: Overall, 84 patients (mean age: 68.2 years, male: 85%) who achieved low-density lipoprotein cholesterol levels of ＜100 mg/dL were enrolled. The PMR was reduced in each group over 12 months. There were no significant differences in PMR changes among the three groups in the primary analysis or analysis including total lesions. The changes in CTA parameters, including indexes for detecting high-risk features, also did not differ. CONCLUSION: The EPA/DHA therapy of 2 or 4 g/day did not significantly improve the high-risk features of coronary atherosclerotic plaques evaluated using CMR under statin therapy.

The Association Between the Duration of Chest Compression and Thoracic Injuries in Patients With Non-Traumatic Out-of-Hospital Cardiac Arrest.

BACKGROUND: Current guidelines emphasize the indispensability of high-quality chest compression for improving survival in patients who experience out-of-hospital cardiac arrest (OHCA). However, chest compression can cause thoracic injuries that may contribute to poor prognosis; therefore, the purpose of this study is to identify the predictors of thoracic injuries and evaluate the association between thoracic injuries and prognosis.Methods and Results: Between June 2017 to July 2019, Utstein-style data on 384 consecutive adult patients who experienced non-traumatic OHCA and who were transferred to our hospital (Aso Iizuka Hospital) were collected. Each patient underwent a full-body computed tomography scan. Two-hundred and thirty-four patients (76%) had thoracic injuries (Group-T). The duration of chest compression was significantly longer in Group-T than in patients without thoracic injuries (Group-N; 43 vs. 32 min, respectively, P<0.001). Multivariate analysis revealed that older age and longer chest compression duration were predictors of thoracic injuries (odds ratios 1.03 and 1.07, respectively, P≤0.005). Among patients who achieved return of spontaneous circulation, Kaplan-Meier curves showed a significantly higher cumulative survival rate in Group-N than in Group-T at the 30-day follow up (log-rank test P=0.009). CONCLUSIONS: Older age and longer chest compression duration were independent predictors of thoracic injuries due to chest compression in patients who experienced non-traumatic OHCA. Moreover, the presence of thoracic injuries was associated with worse short-term prognosis.

The association between time to extracorporeal cardiopulmonary resuscitation and outcome in patients with out-of-hospital cardiac arrest.

AIMS: Extracorporeal cardiopulmonary resuscitation (ECPR) is considered for potentially reversible out-of-hospital cardiac arrest (OHCA). However, the association between time to ECPR and outcome has not been well established. METHODS AND RESULTS: Between June 2014 and December 2017, we enrolled 34 754 OHCA patients in a multicentre, prospective fashion [Japanese Association for Acute Medicine (JAAM)-OHCA registry]. After the application of exclusion criteria, 695 OHCA patients who underwent ECPR for cardiac causes were eligible for this study. We investigated the association between the call-to-ECPR interval and favourable neurological outcome (cerebral performance category 1 or 2) at 30 days. Seventy-seven patients (11%) had a favourable neurological outcome at 30 days. The call-to-ECPR intervals in these patients were significantly shorter than in those with an unfavourable neurological outcome [49 (41-58) vs. 58 (48-68) min, respectively, P < 0.001]. A longer call-to-ECPR interval was associated with a smaller proportion of patients undergoing percutaneous coronary intervention (PCI) (P = 0.034) or target temperature management (TTM) (P < 0.001). Stepwise multivariable logistic regression analysis revealed that the call-to-ECPR interval was an independent predictor of favourable neurological outcome [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.94-0.99, P = 0.001], as were age, male gender, initial shockable rhythm, transient return of spontaneous circulation in the prehospital setting, arterial pH at hospital arrival, PCI (OR 2.30, 95% CI 1.14-4.66, P = 0.019), and TTM (OR 2.28, 95% CI 1.13-4.62, P = 0.019). CONCLUSION: A shorter call-to-ECPR interval and implementation of PCI and TTM predicted a favourable neurological outcome at 30 days in OHCA patients who underwent ECPR for cardiac causes.

Paradoxical Cerebellar Embolism Associated with Platypnea-orthodeoxia Syndrome.

Platypnea-orthodeoxia syndrome is a rare clinical entity characterized by dyspnea and arterial blood deoxygenation in a sitting position. An 89-year-old woman was diagnosed with subacute cerebellar infarction. Her blood oxygen saturation decreased to 88% in a sitting position, resulting in dyspnea. Cardiological thoracic computed tomography revealed an unruptured aortic aneurysm, an enlarged ascending aorta, right atrial compression, and counterclockwise rotation of the heart. An anatomical distortion of the atrial septum induced by these abnormalities directed the atrial venous inflow such that the right-left shunt flow was exacerbated in a sitting position.

Predicting Parameters for Successful Weaning from Veno-Arterial Extracorporeal Membrane Oxygenation in Cardiogenic Shock.

AIMS: Percutaneous veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is utilized for patients with cardiogenic shock or cardiac arrest. However, the procedure protocol for weaning from VA-ECMO has not been well established. The present study aimed to determine the usefulness of echocardiographic and pulmonary artery catheter parameters for predicting successful weaning from VA-ECMO in patients with refractory cardiogenic shock. METHODS AND RESULTS: We retrospectively studied 50 patients who were hospitalized and supported by VA-ECMO for >48 h between January 2013 and March 2017. Patients successfully weaned from VA-ECMO without reintroduction of VA-ECMO or left ventricular assist device implantation were defined as 30 day survivors. Echocardiographic and pulmonary artery catheter parameters were evaluated when ECMO flow was limited to a maximum of 1.5-2.0 L/min. Twenty-four patients were successfully weaned from VA-ECMO, whereas 26 were not. Fractional shortening, corrected left ventricular ejection time (LVETc, defined as LVET divided by the square root of heart rate), left ventricular outflow tract velocity time integral, and LVETc divided by pulmonary artery wedge pressure (PAWP) were significantly larger in the 30 day survivor groups. Multivariable analysis revealed LVETc∕PAWP as a significant independent predictor of successful weaning (LVETc∕PAWP, odds ratio 0.82, 95% confidence interval 0.71-0.94, P = 0.005). Receiver operating characteristic curve analysis revealed 15.9 as the optimal LVETc∕PAWP for predicting successful weaning (area under the curve 0.82). CONCLUSIONS: The present findings indicate that LVETc∕PAWP is a potential predictor of successful weaning from VA-ECMO.

Novel Non-Invasive Index for Prediction of Responders in Cardiac Resynchronization Therapy Using High-Resolution Magnetocardiography.

BACKGROUND: Approximately one-third of patients with advanced heart failure (HF) do not respond to cardiac resynchronization therapy (CRT). We investigated whether the left ventricular (LV) conduction pattern on magnetocardiography (MCG) can predict CRT responders.Methods and Results:This retrospective study enrolled 56 patients with advanced HF (mean [±SD] LV ejection fraction [LVEF] 23±8%; QRS duration 145±19 ms) and MCG recorded before CRT. MCG-QRS current arrow maps were classified as multidirectional (MDC; n=28) or unidirectional (UDC; n=28) conduction based on a change of either ≥35° or <35°, respectively, in the direction of the maximal current arrow after the QRS peak. Baseline New York Heart Association functional class and LVEF were comparable between the 2 groups, but QRS duration was longer and the presence of complete left bundle branch block and LV dyssynchrony was higher in the UDC than MDC group. Six months after CRT, 30 patients were defined as responders, with significantly more in the UDC than MDC group (89% vs. 14%, respectively; P<0.001). Over a 5-year follow-up, Kaplan-Meyer analysis showed that adverse cardiac events (death or implantation of an LV assist device) were less frequently observed in the UDC than MDC group (6/28 vs. 15/28, respectively; P=0.027). Multivariate analysis revealed that UDC on MCG was the most significant predictor of CRT response (odds ratio 69.8; 95% confidence interval 13.14-669.32; P<0.001). CONCLUSIONS: Preoperative non-invasive MCG may predict the CRT response and long-term outcome after CRT.

Diminished response to statins predicts the occurrence of heart failure after acute myocardial infarction.

BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) levels using a statin is a cornerstone of preventive therapeutic management following acute myocardial infarction (AMI). In addition to its anti-atherosclerotic effects, recent studies reported a lower occurrence of heart failure (HF) under statin therapy. However, there is a wide variability in statin response. The association between the response to statin and the occurrence of HF in AMI subjects remains unclear. The purpose of present study is to examine whether the variability in statin response affects HF risk after AMI. METHODS: We analyzed 505 statin-naïve AMI subjects undergoing primary percutaneous coronary intervention (PCI) who commenced atorvastatin, rosuvastatin, or pitavastatin. Statin hyporesponse was defined as a reduction in LDL-C levels <15% from baseline to 1 month after statin therapy. HF outcomes were compared between patients with and without statin hyporesponse. RESULTS: Statin hyporesponse was identified in 15.2% (77/505) of study subjects. During a median 4.4-year observational period, statin hyporesponse was associated with a greater likelihood of HF [hazard ratio (HR) =3.01, 95% confidence interval (CI): 1.27-6.79, P=0.01]. This increased HF risk in statin hyporesponders was consistently observed in a multivariate Cox proportional hazards model (HR =2.74, 95% CI: 1.01-6.75, P=0.04), a propensity score-matched cohort (HR =12.30, 95% CI: 1.50-100.3, P=0.01) and in an inverse probability of treatment weights analysis with average treatment effects (coefficient =7.02, 95% CI: 2.29-21.58, P=0.0006). CONCLUSIONS: Hyporesponse to statins increases HF risk after AMI. Our findings highlight statin hyporesponse as a high-risk feature associated with HF events.

Antithrombotic therapy in atrial fibrillation patients with coronary artery disease: shifting paradigm to a "less is more" concept regimen.

Dual antiplatelet therapy (DAPT) reduces the risk of ischemic events, including stent thrombosis, in patients undergoing percutaneous coronary intervention (PCI), while oral anticoagulants are superior to antiplatelet therapy for preventing thromboembolic events, including ischemic stroke, in patients with atrial fibrillation (AF). Reportedly, the AF population accounts for approximately 5 to 10% of patients undergoing PCI. From a theoretical viewpoint, combination therapy of DAPT and oral anticoagulation was previously recommended in patients with AF undergoing PCI. However, long-term triple therapy carries the risk of major bleeding. Recent clinical trials (WOEST, PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, and ENTRUST AF-PCI trials) demonstrated the advantage of dual therapy with an oral anticoagulant (warfarin or direct oral anticoagulant) plus an antiplatelet agent, which decreased the rate of major bleeding in the acute phase in AF patients who underwent PCI. These results affected guidelines, which now recommend that the duration of triple therapy should be limited, and dual therapy should be considered an alternative regimen when considering the bleeding risk. The current guidelines recommend monotherapy with an oral anticoagulant after 12 months of combination therapy, or in patients with AF and stable coronary artery diseases not requiring intervention. However, this approach has yet to be validated by randomized, controlled trials. Recently, the AFIRE trial demonstrated that rivaroxaban monotherapy was noninferior to dual therapy in terms of efficacy and superior in terms of safety in this population. Accumulating evidence demonstrates that there has been a paradigm shift in antithrombotic therapy to a "less is more" regimen. This article reviews current evidence and focuses on the optimal approach to antithrombotic treatment in patients with AF undergoing PCI in acute and chronic/stable phases.

Peripartum Serial Echocardiographic Findings in a Patient with Life-threatening Peripartum Cardiomyopathy.

A 35-year-old woman was referred to our hospital for the management of acutely decompensated heart failure due to peripartum cardiomyopathy (PPCM). Generally, cardiac examinations are performed after the manifestation of heart failure in patients with PPCM. Thus, reports of serial cardiac examinations before the onset of PPCM are scarce. In this case, we were able to document the serial echocardiographic findings before the onset of life-threatening PPCM. We found that the left ventricular systolic function was preserved at 35 weeks of gestation but declined acutely after delivery at 38 weeks. Although speculative, these findings suggest that left ventricular dilation might precede the onset of PPCM.

Clinical determinants of successful weaning from extracorporeal membrane oxygenation in patients with fulminant myocarditis.

AIMS: Patients with fulminant myocarditis (FM) often present with cardiogenic shock and require mechanical circulatory support, including extracorporeal membrane oxygenation (ECMO) and ventricular assist device (VAD) implantation. This study sought to clarify the determinants of successful weaning from ECMO in FM patients. METHODS AND RESULTS: We studied 37 consecutive FM patients supported by ECMO as the initial form of mechanical circulatory support between January 1995 and December 2014 in our hospital. Twenty-two (59%) patients were successfully weaned from ECMO, while 15 (41%) were not. There were significant differences in levels of peak creatine kinase and those of its MB isoform (CK-MB), left ventricular posterior wall thickness (LVPWT), and prevalence of cardiac rhythm disturbances. Receiver operating characteristic curve analysis revealed that a peak CK-MB level of 185 IU/L and LVPWT of 11 mm were the optimal cut-off values for predicting successful weaning from ECMO (areas under the curve, 0.89 and 0.85, respectively). During the follow-up [median 48 (interquartile range 8-147) months], 83% of FM patients who were weaned from ECMO survived, with preserved fractional shortening based on echocardiography. Of the 15 FM patients who were not weaned from ECMO, nine bridged to VAD, and only two were successfully weaned from VAD and survived. CONCLUSIONS: These results indicate that myocardial injury, as evidenced by CK-MB and LVPWT, and prolonged presence of cardiac rhythm disturbances are important clinical determinants of successful weaning from ECMO.

Effect of eicosapentaenoic acid/docosahexaenoic acid on coronary high-intensity plaques detected with non-contrast T1-weighted imaging (the AQUAMARINE EPA/DHA study): study protocol for a randomized controlled trial.

BACKGROUND: Despite the success of HMG-CoA reductase inhibitor (statin) therapy in reducing atherosclerotic cardiovascular events, a residual risk for cardiovascular events in patients with coronary artery disease (CAD) remains. Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are promising anti-atherosclerosis agents that might reduce the residual CAD risk. Non-contrast T1-weighted imaging (T1WI) with cardiac magnetic resonance (CMR) less invasively identifies high-risk coronary plaques as high-intensity signals. These high-intensity plaques (HIPs) are quantitatively assessed using the plaque-to-myocardium signal intensity ratio (PMR). Our goal is to assess the effect of EPA/DHA on coronary HIPs detected with T1WI in patients with CAD on statin treatment. METHODS/DESIGN: This prospective, controlled, randomized, open-label study examines the effect of 12 months of EPA/DHA therapy and statin treatment on PMR of HIPs detected with CMR and computed tomography angiography (CTA) in patients with CAD. The primary endpoint is the change in PMR after EPA/DHA treatment. Secondary endpoints include changes in Hounsfield units, plaque volume, vessel area, and plaque area measured using CTA. Subjects are randomly assigned to either of three groups: the 2 g/day EPA/DHA group, the 4 g/day EPA/DHA group, or the no-treatment group. DISCUSSION: This trial will help assess whether EPA/DHA has an anti-atherosclerotic effect using PMR of HIPs detected by CMR. The trial outcomes will provide novel insights into the effect of EPA/DHA on high-risk coronary plaques and may provide new strategies for lowering the residual risk in patients with CAD on statin therapy. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000015316 . Registered on 2 October 2014.

Coronary Artery Ectasia Predicts Future Cardiac Events in Patients With Acute Myocardial Infarction.

OBJECTIVE: Coronary artery ectasia (CAE) is an infrequently observed vascular phenotype characterized by abnormal vessel dilatation and disturbed coronary flow, which potentially promote thrombogenicity and inflammatory reactions. However, whether or not CAE influences cardiovascular outcomes remains unknown. APPROACH AND RESULTS: We investigated major adverse cardiac events (MACE; defined as cardiac death and nonfatal myocardial infarction [MI]) in 1698 patients with acute MI. The occurrence of MACE was compared in patients with and without CAE. CAE was identified in 3.0% of study subjects. During the 49-month observation period, CAE was associated with 3.25-, 2.71-, and 4.92-fold greater likelihoods of experiencing MACE (95% confidence interval [CI], 1.88-5.66; P<0.001), cardiac death (95% CI, 1.37-5.37; P=0.004), and nonfatal MI (95% CI, 2.20-11.0; P<0.001), respectively. These cardiac risks of CAE were consistently observed in a multivariate Cox proportional hazards model (MACE: hazard ratio, 4.94; 95% CI, 2.36-10.4; P<0.001) and in a propensity score-matched cohort (MACE: hazard ratio, 8.98; 95% CI, 1.14-71.0; P=0.03). Despite having a higher risk of CAE-related cardiac events, patients with CAE receiving anticoagulation therapy who achieved an optimal percent time in target therapeutic range, defined as ≥60%, did not experience the occurrence of MACE (P=0.03 versus patients with percent time in target therapeutic range <60% or without anticoagulation therapy). CONCLUSIONS: The presence of CAE predicted future cardiac events in patients with acute MI. Our findings suggest that acute MI patients with CAE are a high-risk subset who might benefit from a pharmacological approach to controlling the coagulation cascade.

Isolated Late Activation Detected by Magnetocardiography Predicts Future Lethal Ventricular Arrhythmic Events in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Risk stratification of ventricular arrhythmias is vital to the optimal management in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We hypothesized that 64-channel magnetocardiography (MCG) would be useful to detect isolated late activation (ILA) by overcoming the limitations of conventional noninvasive predictors of ventricular tachyarrhythmias, including epsilon waves, late potential (LP), and right ventricular ejection fraction (RVEF), in ARVC patients.Methods and Results:We evaluated ILA on MCG, defined as discrete activations re-emerging after the decay of main RV activation (%magnitude >5%), and conventional noninvasive predictors of ventricular tachyarrhythmias (epsilon waves, LP, and RVEF) in 40 patients with ARVC. ILA was noted in 24 (60%) patients. Most ILAs were found in RV lateral or inferior areas (17/24, 71%). We defined "delayed ILA" as ILA in which the conduction delay exceeded its median (50 ms). During a median follow-up of 42.5 months, major arrhythmic events (MAEs: 1 sudden cardiac death, 3 sustained ventricular tachycardias, and 4 appropriate implantable cardioverter defibrillator discharges) occurred more frequently in patients with delayed ILA (6/12) than in those without (2/28; log-rank: P=0.004). Cox regression analysis identified delayed ILA as the only independent predictor of MAEs (hazard ratio 7.63, 95% confidence interval 1.72-52.6, P=0.007), and other noninvasive parameters were not significant predictors. CONCLUSIONS: MCG is useful to identify ARVC patients at high risk of future lethal ventricular arrhythmias.

Mature proprotein convertase subtilisin/kexin type 9, coronary atheroma burden, and vessel remodeling in heterozygous familial hypercholesterolemia.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), an important contributor to low-density lipoprotein metabolism in heterozygous familial hypercholesterolemia (HeFH), exhibits direct proatherogenic effects. PCSK9 circulates as mature and furin-cleaved forms, which differ in its biological activity. However, it remains to be elucidated whether each PCSK9 subtype has different atherogenic properties. OBJECTIVE: To investigate the association of each PCSK9 subtype with coronary atherosclerosis in HeFH. METHODS: About 204 nonculprit segments in 138 HeFH subjects with coronary artery disease were evaluated by using intravascular ultrasound. Mature, furin-cleaved PCSK9 and total concentration of PCSK9 subtypes were measured by using enzyme-linked immunosorbent assay (BML Inc., Tokyo, Japan). The relationship of these PCSK9 values with intravascular ultrasound measures was investigated. RESULTS: Mature PCSK9 level was positively associated with percent atheroma volume (PAV: r = 0.78, P = .003). Despite extensive atheroma under a higher mature PCSK9 level, vessel volume did not change across any mature PCSK9 levels (r = 0.05, P = .78). These responses resulted in smaller lumen volume, which was negatively correlated to mature PCSK9 level (r = 0.65, P = .009). By contrast, there were no significant relationships of PAV with furin-cleaved (r = 0.12, P = .45) and total PCSK9 (r = 0.37, P = .25) levels. On multivariate analysis, mature PCSK9 level independently contributed to PAV (odds ratio: 1.45, 95% confidence interval: 1.11-1.67, P = .01). Even in subjects with low-density lipoprotein cholesterol level <2.6 mmol/L, greater PAV was still observed in association with an elevated mature PCSK9 level (P = .003). CONCLUSIONS: Mature PCSK9 associated with atheroma volume and impaired vessel remodeling in HeFH patients with coronary artery disease. These findings suggest the potential role of mature PCSK9 in propagation of coronary atherosclerosis in HeFH.