Edoxaban Antithrombotic Therapy for Atrial Fibrillation and Stable Coronary Artery Disease.

BACKGROUND: Despite consistent recommendations from clinical guidelines, data from randomized trials on a long-term antithrombotic treatment strategy for patients with atrial fibrillation and stable coronary artery disease are still lacking. METHODS: We conducted a multicenter, open-label, adjudicator-masked, randomized trial comparing edoxaban monotherapy with dual antithrombotic therapy (edoxaban plus a single antiplatelet agent) in patients with atrial fibrillation and stable coronary artery disease (defined as coronary artery disease previously treated with revascularization or managed medically). The risk of stroke was assessed on the basis of the CHA2DS2-VASc score (scores range from 0 to 9, with higher scores indicating a greater risk of stroke). The primary outcome was a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and major bleeding or clinically relevant nonmajor bleeding at 12 months. Secondary outcomes included a composite of major ischemic events and the safety outcome of major bleeding or clinically relevant nonmajor bleeding. RESULTS: We assigned 524 patients to the edoxaban monotherapy group and 516 patients to the dual antithrombotic therapy group at 18 sites in South Korea. The mean age of the patients was 72.1 years, 22.9% were women, and the mean CHA2DS2-VASc score was 4.3. At 12 months, a primary-outcome event had occurred in 34 patients (Kaplan-Meier estimate, 6.8%) assigned to edoxaban monotherapy and in 79 patients (16.2%) assigned to dual antithrombotic therapy (hazard ratio, 0.44; 95% confidence interval [CI], 0.30 to 0.65; P<0.001). The cumulative incidence of major ischemic events at 12 months appeared to be similar in the trial groups. Major bleeding or clinically relevant nonmajor bleeding occurred in 23 patients (Kaplan-Meier estimate, 4.7%) in the edoxaban monotherapy group and in 70 patients (14.2%) in the dual antithrombotic therapy group (hazard ratio, 0.34; 95% CI, 0.22 to 0.53). CONCLUSIONS: In patients with atrial fibrillation and stable coronary artery disease, edoxaban monotherapy led to a lower risk of a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major bleeding or clinically relevant nonmajor bleeding at 12 months than dual antithrombotic therapy. (Funded by the CardioVascular Research Foundation and others; EPIC-CAD ClinicalTrials.gov number, NCT03718559.).

Upper turnaround point in a reentry circuit of the idiopathic left posterior fascicular ventricular tachycardia.

BACKGROUND: The anatomic extent of the reentry circuit in idiopathic left posterior fascicular ventricular tachycardia (LPF-VT) is yet to be fully elucidated. We hypothesized that entrainment mapping could be used to delineate the reentry circuit of an LPF-VT, especially including the upper turnaround point. METHODS: Twenty-three consecutive LPF-VT patients (mean age, 29 ± 9 years, 18 males) were included. We performed overdrive pacing with entrainment attempts at the left bundle branch (LBB) and the left His bundle (HB) region. RESULTS: Overdrive pacing from the LBB region showed concealed fusion in all 23 patients (post-pacing interval [PPI], 322.1 ± 64.3 ms; tachycardia cycle length [TCL], 319.0 ± 61.6 ms; PPI-TCL, 3.1 ± 4.6 ms) with a long stimulus-to-QRS interval (287.9 ± 58.0 ms, approximately 90% of the TCL). Pacing from the same LBB region at a slightly faster pacing rate showed manifest fusion with antidromic conduction to the LBB and minimal in-and-out time to the LBB potential (PPI-TCL, 21.3 ± 13.7 ms). Overdrive pacing from the left HB region showed manifest fusion with a long PPI-TCL (53.9 ± 22.5 ms). CONCLUSIONS: Our pacing study results suggest that the upper turnaround point in a reentry circuit of the LPF-VT may extend to the proximal His-Purkinje conduction system near the LBB region but below the left HB region. The LPF may constitute the retrograde limb of the reentry circuit.

Accuracy of Maxillary Positioning During Orthognathic Surgery: A Comparison of Web-based 3-Dimensional Virtual Surgical Planning and Actual Outcomes.

PURPOSE: To determine the accuracy of planned maxillary positioning by virtual surgery by comparing planned and actual postoperative outcomes. MATERIALS AND METHODS: Twenty patients who underwent 2-jaw orthognathic surgery performed by a single surgeon from May 2017 to December 2020 were the subjects of this retrospective study. The coordinates of reference points in horizontal, sagittal, and coronal planes as determined by virtual surgery were compared with those of actual surgical outcomes. The reference points used were as follows: #16 mesiobuccal cusp tip (#16), #26 mesiobuccal cusp tip (#26), and #11 mesial tip (U1); anterior nasal spine; and posterior nasal spine. Three-dimensional linear distances between the reference point on which virtual surgery was performed and the reference point after the actual operation was calculated. RESULTS: Of the 20 patients, there were 11 males and 9 females of average age 20.65±2.41 years. Three-dimensional printed wafers had high accuracy with a maximum difference of 0.3 mm. No significant difference was observed in horizontal or coronal planes for any reference point, but a significant difference was observed in the sagittal plane. However, positional differences between planned and actual reference points were all <1 mm. CONCLUSIONS: Virtual surgical planning and 3-dimensional printed wafer achieved excellent maxillary positioning accuracies after orthognathic surgery.

Edoxaban-based long-term antithrombotic therapy in patients with atrial fibrillation and stable coronary disease: Rationale and design of the randomized EPIC-CAD trial.

BACKGROUND: Anticoagulants are the standard therapy for patients with atrial fibrillation (AF) and antiplatelet therapy for those with coronary artery disease (CAD). However, compelling clinical evidence is still lacking regarding the long-term maintenance strategy with the combination of anticoagulant and antiplatelet drugs in patients with AF and stable CAD. DESIGN: The EPIC-CAD trial is an investigator-initiated, multicenter, open-label randomized trial comparing the safety and efficacy of 2 antithrombotic strategies in patients with high-risk AF (CHA2DS2-VASc score ≥ 2 points) and stable CAD (≥6 months after revascularization for stable angina or ≥12 months for acute coronary syndrome; or medical therapy alone). Patients (approximately N = 1,038) will be randomly assigned at a 1:1 ratio to (1) monotherapy with edoxaban (a non-vitamin K antagonist oral anticoagulant) or (2) combination therapy with edoxaban plus a single antiplatelet agent. The primary endpoint is the net composite outcome of death from any cause, stroke, systemic embolism, myocardial infarction, unplanned revascularization, and major or clinically relevant nonmajor bleeding at 1 year after randomization. RESULTS: As of December 2021, approximately 901 patients had been randomly enrolled over 2 years at 18 major cardiac centers across South Korea. The completed enrollment is expected at the mid-term of 2022, and the primary results will be available by 2023. CONCLUSIONS: EPIC-CAD is a large-scale, multicenter, pragmatic design trial, which will provide valuable clinical insight into edoxaban-based long-term antithrombotic therapy in patients with high-risk AF and stable CAD.

Stimulated four-wave mixing in the cascade-type atomic system of a warm Cs atomic ensemble.

We investigate stimulated four-wave mixing (FWM) in the 6S1/2-6P3/2-8S1/2 open transition of a warm 133Cs atomic ensemble. Despite the absence of the two-photon cycling transition, we measure high-contrast FWM signals in the 6P3/2-8S1/2 transition between the upper excited states according to the frequency detuning and powers of the coupling and driving lasers. The FWM light generation in the upper excited states is interpreted as the FWM phenomena induced by the driving laser of the 6S1/2-6P3/2 transition from the cascade-type two-photon coherent atomic ensemble with the coupling and pump lasers. We believe that this work can contribute to the development of hybrid photonic quantum networks between photonic quantum states generated from different atomic systems.

Clinical Impact of Implantable Cardioverter-Defibrillator Therapy and Mortality Prediction Model for Effective Primary Prevention in Korean Patients.

BACKGROUND: Studies on the efficacy of implantable cardioverter-defibrillator (ICD) therapy for primary prevention in Asian patients are relatively lacking compared to those for secondary prevention. Also, it is important to stratify which patients will benefit from ICD therapy for primary prevention. METHODS: Of 483 consecutive patients who received new implantation of ICD in 9 centers in Korea, 305 patients with reduced left ventricular systolic function and/or documented ventricular fibrillation/tachycardia were enrolled and divided into primary (n = 167) and secondary prevention groups (n = 138). RESULTS: During mean follow-up duration of 2.6 ± 1.6 years, appropriate ICD therapy occurred in 78 patients (25.6%), and appropriate ICD shock and anti-tachycardia pacing occurred in 15.1% and 15.1% of patients, respectively. Appropriate ICD shock rate was not different between the two groups (primary 12% vs. secondary 18.8%, P = 0.118). However, appropriate ICD therapy rate including shock and anti-tachycardia pacing was significantly higher (primary 18% vs. secondary 34.8%, P = 0.001) in the secondary prevention group. Type of prevention and etiology, appropriate and inappropriate ICD shock did not affect all-cause death. High levels of N-terminal pro-B-type natriuretic peptide, New York Heart Association functional class, low levels of estimated glomerular filtration ratio, and body mass index were associated with death before appropriate ICD shock in the primary prevention group. When patients were categorized in 5 risk score groups according to the sum of values defined by each cut-off level, significant differences in death rate before appropriate ICD shock were observed among risk 0 (0%), 1 (3.6%), 2 (3%), 3 (26.5%), and 4 (40%) (P < 0.001). CONCLUSION: In this multicenter regional registry, the frequency of appropriate ICD therapy is not low in the primary prevention group. In addition, combination of poor prognostic factors of heart failure is useful in risk stratification of patients who are not benefiting from ICD therapy for primary prevention.

The Implication of Cardiac Injury Score on In-hospital Mortality of Coronavirus Disease 2019.

BACKGROUNDS: The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has spread worldwide. Cardiac injury after SARS-CoV-2 infection is a major concern. The present study investigated impact of the biomarkers indicating cardiac injury in coronavirus disease 2019 (COVID-19) on patients' outcomes. METHODS: This study enrolled patients who were confirmed to have COVID-19 and admitted at a tertiary university referral hospital between February 19, 2020 and March 15, 2020. Cardiac injury was defined as an abnormality in one of the following result markers: 1) myocardial damage marker (creatine kinase-MB or troponin-I), 2) heart failure marker (N-terminal-pro B-type natriuretic peptide), and 3) electrical abnormality marker (electrocardiography). The relationship between each cardiac injury marker and mortality was evaluated. Survival analysis of mortality according to the scoring by numbers of cardiac injury markers was also performed. RESULTS: A total of 38 patients with COVID-19 were enrolled. Twenty-two patients (57.9%) had at least one of cardiac injury markers. The patients with cardiac injuries were older (69.6 ± 14.9 vs. 58.6 ± 13.9 years old, P = 0.026), and were more male (59.1% vs. 18.8%, P = 0.013). They showed lower initial oxygen saturation (92.8 vs. 97.1%, P = 0.002) and a trend toward higher mortality (27.3 vs. 6.3%, P = 0.099). The increased number of cardiac injury markers was significantly related to a higher incidence of in-hospital mortality which was also evidenced by Kaplan-Meier survival analysis (P = 0.008). CONCLUSION: The increased number of cardiac injury markers is related to in-hospital mortality in patients with COVID-19.

Long Term Clinical Outcomes in Patients with Moderate Aortic Stenosis.

BACKGROUND: While the surgical correction of moderate aortic stenosis (AS) can be deferred with a watchful waiting according to the present guideline, the clinical outcomes for moderate AS with comorbidity have not extensively been studied. We aimed to explore the factors that would contribute to the outcomes of moderate AS with at least five years of follow-up duration. METHODS: Medical records review identified patients with moderate aortic valve (AV) stenosis from January 2008 and December 2012. Echocardiographic data were gathered, and the final 5-year clinical outcomes, defined as the composite of cardiovascular (CV) death, admission for heart failure (HF) aggravation, and AV replacement, were evaluated. RESULTS: Among 148 patients (mean age, 69.3 years; mean AV area, 1.24 cm2), 79 had adverse outcomes (16 CV deaths, 32 AV replacements, and 31 HF cases), during a mean follow-up of 5.6 years. The event group showed worse dyspnea of NYHA III-IV and a higher frequency of diabetes mellitus (DM). They had a higher frequency of moderate or moderate-to-severe functional mitral regurgitation (MR) and smaller AV area. In the multivariate analysis, DM (HR 2.29, 95% CI 1.03-5.10), moderate or moderate-to-severe MR (HR 4.84, 95% CI 1.66-10.07), and NYHA III-IV (HR 3.84, 95% CI 1.72-8.56) independently were associated with adverse outcomes. CONCLUSIONS: The symptomatic patients with moderate AS had higher events than expected, and early intervention should be considered in case of concomitant MR and DM.

Hyperfine-state dependence of highly efficient amplification from diode-pumped cesium vapor.

We report optical amplification with an optical-to-optical conversion efficiency of 70 ± 1% from a diode-pumped Cs vapor cell. When pump (852 nm; D2-line) and signal (895 nm; D1-line) lasers with a narrow spectral width of ∼2 MHz are resonant on the hyperfine states (F = 3 or 4) of the 6S1/2 state, we observe that the amplification factors are significantly changed according to the hyperfine-state combination of the pump and signal lasers. We find that the optical frequencies of the pumping and signal lasers need to be controlled near the hyperfine state of 6S1/2 (F = 4) to obtain an efficient diode-pumped alkali amplifier (DPAA). To realize highly efficient optical gain conditions, both the spatial modes of the pump and signal lasers are made to overlap in the Cs vapor cell with the use of a single-mode optical fiber. An amplification factor of 430 ± 15 is achieved under the following conditions: cell temperature of 90 °C, signal power of 0.1 mW, and pump power of 200 mW. We believe that our results can aid in the development of highly efficient diode-pumped alkali-vapor lasers and amplifiers.

Supraventricular tachyarrhythmias in patients with a persistent left superior vena cava.

Aims: A persistent left superior vena cava (PLSVC) is the most common thoracic venous anomaly. This venous anomaly can impact the evaluation and treatment of supraventricular tachyarrhythmia (SVA). The aim of this study was to assess the proportion and characteristics of PLSVC in adult SVA patients. Methods and results: From July 2002 to July 2012, clinical and procedural data from databases of 10 cardiac electrophysiology laboratories in the Yeungnam region of the Republic of Korea were reviewed. Of 6662 adult SVA patients who underwent an EP study or catheter ablation of SVA during the 10-year study period, 18 patients had PLSVC (mean age 47.6 ± 14.8 years, 10 men). The proportion of PLSVC in adult SVA patients was 0.27% (18/6662). SVA type and procedural outcomes of radiofrequency (RF) catheter ablation in these patients were investigated and the results were as follows: successful slow pathway modification in six of seven patients with atrioventricular nodal reentrant tachycardia (AVNRT), successful ablation of accessory pathway in three of four patients with atrioventricular reentrant tachycardia, and successful ablation of atrial tachycardia (cavotricuspid isthmus-dependent in two, septal macroreentry in one, focal from the PLSVC in one) in three of four patients. In one patient with junctional tachycardia, catheter ablation failed. In two patients with atrial fibrillation, catheter ablation was successful. Conclusion: Among adult SVA patients who underwent an EP study or RF catheter ablation during the 10-year study period, 0.27% had PLSVC. The most common type of SVA was AVNRT. The success rate of catheter ablation was 82% in SVA patients with PLSVC. There were no procedure-related complications.

Implication of ultrasound contrast-enhancement of carotid plaques in prevalence of acute coronary syndrome and occurrence of cardiovascular outcomes.

PURPOSE: Ultrasonographic contrast enhancement of carotid plaque (CECP) has been used to detect neovascularization of vasa vasorum and plaque. However, it is uncertain whether CECP can provide risk stratification of coronary artery disease (CAD). This study aimed to evaluate the relationship between CECP and manifestations of acute coronary syndrome (ACS) in established CAD patients and to explore the prognostic implication of CECP for cardiovascular (CV) clinical outcomes. METHODS: A medical record review revealed that contrast-enhanced ultrasonography was performed to evaluate carotid atherosclerosis in 209 coronary artery-stented and 105 non-stented patients. The rate of ACS manifestations was compared depending on contrast uptake patterns: grade 0, absent; grade 1, dot; and grade 2, diffuse pattern. CV primary outcomes were assessed during a mean 7.6 months of follow-up. RESULTS: Male sex, smoking, history of old myocardial infarction, intensive medications, and a favorable lipid profile were common in the stented versus non-stented group. Patients with grade 2 CECP had a higher rate of ACS, greater plaque thickness, and class I-II of Gray-Weale plaque echogenicity. During follow-up, 10 coronary revascularizations (nine ACSs), six strokes, and four heart failures occurred. Grade 2 CECP was more closely related with CV primary outcomes and showed a tendency toward more acute CV outcomes. CONCLUSION: ACS manifestations were proportionate to CECP grade. Diffuse CECP uptake could be a risk factor for acute CV outcomes.

Radiofrequency Catheter Ablation Targeting the Vein of Marshall in Difficult Mitral Isthmus Ablation or Pulmonary Vein Isolation.

INTRODUCTION: The ligament of Marshall may hinder the creation of mitral isthmus (MI) block or pulmonary vein (PV) isolation (PVI) in radiofrequency (RF) catheter ablation of atrial fibrillation (AF). We aimed to assess the benefit of RF ablation targeting the vein of Marshall (VOM) in failed cases of MI block or PVI. METHODS AND RESULTS: We reviewed the medical records of patients who underwent RF ablation targeting the VOM after failed MI ablation or left PVI using the conventional method, which included circumferential point-by-point ablation around the PV antrum and carina for PVI, and endocardial MI and epicardial distal coronary sinus (CS) ablation for MI block. The VOM was identified by using selective VOM venography with an external irrigation RF ablation catheter. RF ablation targeting the VOM was performed with RF application at the ostium of the VOM inside the CS or at the endocardial region facing the VOM course. During the set period, CS venography was performed in 42 patients after failure of left PVI (n = 5) or MI block (n = 37). Under CS venography, the VOM was visualized in 22 of 42 patients (MI = 19 and PVI = 3). During selective venography of the VOM, no procedure-related complication was observed. RF application targeting the VOM successfully achieved MI block in 13 patients (68.4%) and PVI in 2 patients (66.7%). CONCLUSION: Selective VOM venography using an irrigated ablation catheter is feasible and safe. RF ablation targeting the VOM may provide additional benefit in failed cases of MI block or PVI.

Evaluation of ventricular pacing suppression algorithms in dual chamber pacemaker: Results of "LEADER" study.

Background: There is limited research on the intra-individual efficacy of ventricular pacing minimization algorithms developed by Biotronik-the Ventricular Pace Suppression algorithm (VpS) and the Intrinsic Rhythm Support plus algorithm (IRSplus) (BIOTRONIK SE & Co. KG, Berlin, Germany). We performed a randomized pilot trial that evaluated the efficacy of two algorithms in patients with symptomatic sinus node dysfunction (SND) who received a dual-chamber pacemaker. Methods: The trial was conducted in 11 tertiary hospitals in South Korea. The patients were randomized to either the VpS or IRSplus algorithm group after a 3-month period of fixed atrioventricular (AV) delay. The primary outcome was the ventricular pacing percentage (Vp%) at each follow-up visit. The secondary outcomes were the occurrence of heart failure (HF) and atrial fibrillation (AF) during the study period. Results: Data from 131 patients were analyzed. Initially, their average Vp% over 3 months with a fixed AV interval was 14.1 ± 19.4%. Patients were randomly assigned to VpS and IRSplus groups, with 66 and 65 in each. Algorithms reduced average Vp% to 4.0 ± 11.3% at 9 months and 6.7 ± 14.9% at 15 months. These algorithms were more effective for patients with paced AV delay (PAVD) ≤300 ms compared to those with PAVD >300 ms. Both algorithms were equally effective in reducing Vp%. Clinical AF or HF hospitalization was not observed during the study period. Conclusion: The VpS and IRSplus algorithms are effective and safe in minimizing unnecessary ventricular pacing in patients with SND.

Comparing the Efficacy of Carvedilol and Flecainide on the Treatment of Idiopathic Premature Ventricular Complexes from Ventricular Outflow Tract: A Multicenter, Randomized, Open-Label Pilot Study.

The mechanism of premature ventricular complexes (PVC) occurring in the ventricular outflow tract (OT) is related to an intracellular calcium overload and delayed afterdepolarizations that lead to triggered activity. The guidelines recommend using beta-blockers and flecainide for idiopathic PVCs, but they also acknowledge the limited evidence supporting this recommendation. We conducted a multicenter, randomized, open-label pilot study comparing the effect of carvedilol and flecainide on OT PVC, which are widely used to treat this arrhythmia. Patients with a 24 h Holter recording a PVC burden ≥ 5%, which showed positive R waves in leads II, III, and aVF, and without structural heart disease were enrolled. They were randomly assigned to the carvedilol or flecainide group, and the maximum tolerated dose was administered for 12 weeks. A total of 103 participants completed the protocol: 51 with carvedilol and 52 with flecainide. After 12 weeks of treatment, the mean PVC burden significantly decreased in both groups: 20.3 ± 11.5 to 14.6 ± 10.8% with carvedilol (p < 0.0001) and 17.1 ± 9.9 to 6.6 ± 9.9% with flecainide (p < 0.0001). Both carvedilol and flecainide effectively suppressed OT PVCs in patients without structural heart disease, with flecainide showing a superior efficacy compared to carvedilol.

Effect of number and geometry of resorbable screws on biomechanical stability of in vitro model with sagittal split ramus osteotomy.

The purpose of this study was to investigate the effect of the number and the geometry of resorbable screws (RSs; Inion CPS System; Inion Ltd, Tampere, Finland) on the biomechanical stability of the in vitro model with sagittal split ramus osteotomy. The sagittal split ramus osteotomy polyurethane hemimandible (Synbone, Malans, Switzerland) was fixed by 7 osteosynthesis methods after 5 mm advancement of the distal segment (n = 5 for each method): 1TP (1 titanium miniplate and 4 screws), 3RL (3 RSs with linear configuration at the retromolar area [RMA]), 2R1B (2 RSs at RMA and 1 RS at the mandibular body [MB]), 2R1A (2 RSs at the RMA and 1 RS at the mandibular angle [MA]), 3R1B (3 RSs at RMA and 1 RS at the MB), 3R1A (3 RSs at RMA and 1 RS at the MA), and 3R1A1B (3 RSs at the RMA, 1 RS at the MA, and 1 RS at the MB). Values of linear compressive load were measured at 1- to 5-mm displacement of the lower first molar with a 1-mm interval and were statistically analyzed. From 1- to 5-mm displacement, there were significant differences in load values among groups (P < 0.05, P < 0.01, P < 0.01, P < 0.001, and P < 0.001, respectively). When the amount of displacement was increased, the difference in load values between 1TP, 3RL, and 2R1B became significantly prominent. There was a significant difference in total load values according to number and geometry of RSs (P < 0.001). All kinds of geometry with more than 3 RSs were more rigid than 1TP. The 3R1A1B method showed better biomechanical stability than 1TP, 3RL, and 2R1B. In 3 RS and 4 RS groups, fixation in MA (2R1A, 3R1A) exhibited a tendency of better stability than fixation in MB (2R1B, 3R1B). Fixation with 2R1A could provide better biomechanical stability than 1TP and similar rigidity with 3R1A1B.

A risk scoring system to predict progression to severe pneumonia in patients with Covid-19.

Rapid outbreak of coronavirus disease 2019 (Covid-19) raised major concern regarding medical resource constraints. We constructed and validated a scoring system for early prediction of progression to severe pneumonia in patients with Covid-19. A total of 561 patients from a Covid-19 designated hospital in Daegu, South Korea were randomly divided into two cohorts: development cohort (N = 421) and validation cohort (N = 140). We used multivariate logistic regression to identify four independent risk predictors for progression to severe pneumonia and constructed a risk scoring system by giving each factor a number of scores corresponding to its regression coefficient. We calculated risk scores for each patient and defined two groups: low risk (0 to 8 points) and high risk (9 to 20 points). In the development cohort, the sensitivity and specificity were 83.8% and 78.9%. In the validation cohort, the sensitivity and specificity were 70.8% and 79.3%, respectively. The C-statistics was 0.884 (95% CI 0.833-0.934) in the development cohort and 0.828 (95% CI 0.733-0.923) in the validation cohort. This risk scoring system is useful to identify high-risk group for progression to severe pneumonia in Covid-19 patients and can prevent unnecessary overuse of medical care in limited-resource settings.

Surveillance of adenosine stress myocardial contrast echocardiography following percutaneous coronary intervention.

BACKGROUND: The ability of adenosine stress myocardial contrast echocardiography (AS-MCE) to reveal decreased coronary blood flow or perfusion defects (PDs) has not been explored for clinical implications after coronary revascularization. This study sought to identify the prognostic value of PDs in asymptomatic patients following percutaneous coronary intervention (PCI). METHODS: We retrospectively analyzed 342 asymptomatic patients (67 years of mean age, 72% male) who underwent PCI with stents at least 9 months before AS-MCE between May 2019 and December 2020. Resting regional wall motion abnormality (rRWMA) and the patterns of PDs were assessed, and further PDs were classified as ischemic or fixed type. The primary endpoint was the composite of hospitalization for worsening heart failure, coronary revascularization, and cardiac death. RESULTS: In AS-MCE (median time interval following PCI: 17.4 months), PDs were present in 93 (27.2%) out of 342 patients; 70 of ischemic PD (75.3%), 58 of fixed PD (62.4%). Those with PD showed a higher frequency of rRWMA than those without PD (53.8 vs. 15.7%, p < 0.001). During the median follow-up of 22.6 months, 26 (7.6%) patients experienced more associated clinical outcomes with PD than rRWMA. Cox analysis revealed that the combined findings of rRWMA and PD, and specifically, ischemic PD of ≥ 2 segments were associated with a high increase in adverse outcomes. CONCLUSIONS: AS-MCE provided prognostic value in asymptomatic patients with prior PCI. PD might be complementary to rRWMA in risk stratification.

The benefits of the earlier use of sacubitril/valsartan in de novo heart failure with reduced ejection fraction patients.

AIMS: We evaluated the clinical outcomes and trajectory of cardiac reverse remodelling according to the timing of sacubitril/valsartan (Sac/Val) use in patients with heart failure (HF) with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Patients with de novo HFrEF who used Sac/Val between June 2017 and October 2019 were retrospectively enrolled. Patients were grouped into the earlier use group (initiation of Sac/Val < 3 months after the first HFrEF diagnosis) and the later use group (initiation of Sac/Val ≥ 3 months after the first HFrEF diagnosis). Primary outcome was a composite of HF hospitalization and cardiac death. Secondary outcomes were HF hospitalization, cardiac death, all-cause death, significant ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation), and echocardiographic evidence of cardiac reverse remodelling including left ventricular ejection fraction (LVEF) change during follow-up. Among 115 enrolled patients, 67 were classified in the earlier use group, and 48 were classified in the later use group. Mean period of HFrEF diagnosis to Sac/Val use was 52.1 ± 14.3 days in the earlier use group, and 201.8 ± 127.3 days in the later use group. During the median follow-up of 721 days, primary outcome occurred in 21 patients (18.3%). The earlier use group experienced significantly fewer primary outcome than the later use group (10.4% vs. 29.2%, P = 0.010). The Kaplan-Meier survival curve showed better event-free survival in the earlier use group than in the later use group (log rank = 0.017). There were no significant differences in cardiac death, all-cause death, and ventricular arrhythmia between two groups (1.5% vs. 2.1%, P = 0.811; 1.5% vs. 4.2%, P = 0.375; 3.0% vs. 0%, P = 0.227, respectively). Despite a significantly lower baseline LVEF in the earlier use group (21.3 ± 6.4% vs. 24.8 ± 7.9%, P = 0.012), an early prominent increase of LVEF was noted before 6 months (35.2 ± 11.9% vs. 27.8 ± 8.8%, P = 0.007). A delayed improvement of LVEF in the later use group resulted in similar LVEF at last follow-up in both groups (40.7 ± 13.4% vs. 39.4 ± 10.9%, P = 0.686). Although the trajectory of left ventricular remodelling showed similar pattern in two groups, left atrial (LA) reverse remodelling was less prominent in the later use group during the follow-up period (final LA volume index: 43.6 ± 14.3 mL/m2 vs. 55.2 ± 17.1 mL/m2 , P = 0.011). CONCLUSIONS: Earlier use of Sac/Val was related with better clinical outcome and earlier left ventricular reverse remodelling. Remodelling of LA was less prominent in the later use group implying delayed response in diastolic function.

Effect of Atorvastatin on Serial Changes in Coronary Physiology and Plaque Parameters.

Background: The effects of statin on coronary physiology have not been well evaluated. Objectives: The authors performed this prospective study to investigate changes in coronary flow indexes and plaque parameters, and their associations with atorvastatin therapy in patients with coronary artery disease (CAD). Methods: Ninety-five patients with intermediate CAD who received atorvastatin therapy underwent comprehensive physiological assessments with fractional flow reserve (FFR), coronary flow reserve, index of microcirculatory resistance, and intravascular ultrasound at the index procedure, and underwent the same evaluations at 12-month follow-up. Optimal low-density lipoprotein cholesterol (LDL-C) was defined as LDL-C <70 mg/dL or ≥50% reduction from the baseline. The primary endpoint was a change in the FFR. Results: Baseline FFR, minimal lumen area, and percent atheroma volume (PAV) were 0.88 ± 0.05, 3.87 ± 1.28, 55.92 ± 7.30, respectively. During 12 months, the percent change in LDL-C was -33.2%, whereas FFR was unchanged (0.87 ± 0.06 at 12 months; P = 0.694). Vessel area, lumen area, and PAV were significantly decreased (all P values <0.05). The achieved LDL-C level and the change of PAV showed significant inverse correlations with the change in FFR. In patients with optimally modified LDL-C, the FFR had increased (0.87 ± 0.06 vs 0.89 ± 0.07; P = 0.014) and the PAV decreased (56.81 ± 6.44% vs 55.18 ± 8.19%; P = 0.031), whereas in all other patients, the FFR had decreased (0.88 ± 0.05 vs 0.86 ± 0.06; P = 0.025) and the PAV remained unchanged. Conclusions: In patients with CAD, atorvastatin did not change FFR despite a decrease in the PAV. However, in patients who achieved the optimal LDL-C target level with atorvastatin, the FFR had significantly increased with decrease of the PAV. (Effect of Atorvastatin on Fractional Flow Reserve in Coronary Artery Disease [FORTE]; NCT01946815).

Features and implications of higher systolic central than peripheral blood pressure in patients at very high risk of atherosclerotic cardiovascular disease.

Peripheral blood pressure (PBP) is usually higher than central blood pressure (CBP) due to pulse amplification; however, it is not well understood why cuff-measured PBP can be lower than CBP estimated by the late systolic pressure of radial pulse waves. We explored the implications of systolic PBP-CBP (P-CBP) differences for cardiovascular (CV) prognosis. In total, 335 patients at very high risk of atherosclerotic cardiovascular disease (ASCVD) underwent automated applanation tonometry and brachial-ankle pulse wave velocity (baPWV), and they were classified into groups according to positive or negative systolic P-CBP differences. Between-group characteristics and clinical outcomes (the composite of coronary revascularization, stroke, heart failure hospitalization, and CV death) were evaluated. Patients with negative differences had significantly higher frequency of hypertension, coronary artery disease, higher ASCVD risk burden, and elevated N-terminal pro b-type natriuretic peptide. They had higher left atrial volume index (LAVI) and lower systolic mitral septal tissue velocity (TVI-s') than those with a positive difference. These patients showed higher systolic PBP and CBP, and a higher baPWV. Multivariable analysis indicated that TVI-s', LAVI, and ASCVD risk burden were independent determinants of such systolic P-CBP differences. During a median follow-up of 12.6 months, clinical outcomes were significantly related to a negative difference (11.5% vs. 3.4%, p = 0.014), and a systolic P-CBP difference ≤ -8 mmHg was associated with a threefold higher likelihood of poor prognosis. In patients at very high risk of ASCVD, systolic P-CBP difference was associated with cardiac dysfunction and ASCVD risk burden, allowing further risk stratification.