Low- or standard-dose edoxaban versus antiplatelet therapy for leaflet thrombus and cerebral thromboembolism after TAVR: A prespecified analysis of randomized ADAPT-TAVR trial.

BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.

A Modified Tip-to-Base LAMPOON to Prevent Left Ventricular Outflow Tract Obstruction in Valve-in-Ring or Valve-in-Valve Transcatheter Mitral Valve Replacement.

Background: The Laceration of the Anterior Mitral leaflet to Prevent Outflow ObtructioN (LAMPOON) procedure may be performed from the leaflet tip to base to prevent left ventricular outflow tract obstruction (LVOTO) in patients with high-risk anatomy undergoing valve-in-valve (VIV) or valve-in-(complete)-ring (VIR) transcatheter mitral valve replacement (TMVR). Methods and Results: Thirteen consecutive patients (6 females, average age 67.7 years) with a mean left ventricular ejection fraction of 60%, a median STS score of 3.2%, and degenerative surgical mitral bioprosthesis or ring were treated with a combined, single-stage procedure of preventive LAMPOON and trans-septal TMVR with SAPIEN 3 valves (Edwards Lifesciences, Irvine, CA). Under real-time 3-dimensional transesophageal echocardiography (RT 3D-TEE) guidance, we included the rendezvous technique in the LAMPOON procedure, and all 13 patients were successfully treated by tip-to-base LAMPOON and TMVR. The use of a modified LAMPOON procedure, aided by a rendezvous technique and guided by RT 3D-TEE imaging, offers precise guidance for positioning and aligning the guidewire. This approach not only reduces the need for fluoroscopy and shortens procedure times, but also significantly increases the likelihood of a successful outcome. Importantly, none of the patients in our study experienced unintentional aortic or aortic valve injuries, nor did they develop significant LVOTO following TMVR. In 11 of the 13 (85%) patients, we used a transcatheter SENTINELTM cerebral protection device (Boston Scientific, Marlborough, MA) for stroke prevention and capture of debris ≥ 2 mm were detected in 8/11 (73%) of the cases. Conclusions: Utilizing intra-operative RT 3D-TEE in conjunction with the rendezvous technique can make the tip-to-base LAMPOON procedure even safer and more effective for patients undergoing VIV or VIR TMVR. Our study also suggests that cerebral protection is indicated in patients undergoing TMVR.

Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial.

BACKGROUND: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. METHODS: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement. RESULTS: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; P=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. CONCLUSIONS: In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research. REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT03284827.

Inflammation and renal function decline in chronic coronary syndrome: a prospective multicenter cohort study.

BACKGROUND: Renal function decline is a frequently encountered complication in patients with chronic coronary syndrome. Aside from traditional cardiovascular risk factors, the inflammatory burden emerged as the novel phenotype that compromised renal prognosis in such population. METHODS: A cohort with chronic coronary syndrome was enrolled to investigate the association between inflammatory status and renal dysfunction. Levels of inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), tumour necrosis factor-α (TNF-α), adiponectin, matrix metalloproteinase-9, interleukin-6, lipoprotein-associated phospholipase A2, were assessed. Renal event was defined as > 25% decline in estimated glomerular filtration rate (eGFR). Inflammatory scores were calculated based on the aggregate of hs-CRP, TNF-α, and adiponectin levels. RESULTS: Among the 850 enrolled subjects, 145 patients sustained a renal event during an averaged 3.5 years follow-up. Multivariate analysis with Cox regression suggested elevations in hs-CRP, TNF-α, and adiponectin levels were independent risk factors for the occurrence of a renal event. Whereas, Kaplan-Meier curve illustrated significant correlation between high TNF-α (P = 0.005), adiponectin (P < 0.001), but not hs-CRP (P = 0.092), and eGFR decline. The aggregative effect of these biomarkers was also distinctly correlated with renal events (score 2: P = 0.042; score 3: P < 0.001). CONCLUSIONS: Inflammatory burden was associated with eGFR decline in patients with chronic coronary syndrome.

The clinical significance of osteopontin on the cardiovascular outcomes in patients with stable coronary artery disease.

BACKGROUND: Osteopontin (OPN) is a noncollagenous matricellular protein which is mainly present in bone matrix. A high OPN level has been associated with heart failure and acute coronary syndrome, however data on patients with chronic coronary syndrome (CCS) are lacking. The present study aimed to evaluate the association between OPN and the prognosis of Taiwanese patients with CCS. METHODS: We enrolled participants from the Biosignature Registry, a nationwide prospective cohort study conducted at nine different medical centers throughout Taiwan. The inclusion criteria were participants who had received successful percutaneous coronary intervention at least once previously, and stable under medical therapy for at least 1 month before enrollment. They were followed for at least 72 months. Logistic regression and Cox proportional hazard model were used to investigate the association between OPN and clinical outcomes. The outcomes of this study were the first occurrence of hard cardiovascular events and composite cardiovascular outcomes including cardiovascular mortality, revascularization, hospitalization for acute myocardial infarction (AMI) or heart failure. RESULTS: A total of 666 patients with both hs-CRP and osteopontin measurements were enrolled and followed for 72 months. OPN was correlated positively with AMI-related hospitalization, where the highest tertile (Tertile 3) of baseline OPN had the highest risk of AMI-related hospitalization, which remained significant after multivariate adjustments (HR 3.20, p = 0.017). In contrast, combining OPN and hs-CRP did not improve the prediction of CV outcomes. CONCLUSION: OPN may be a potentially valuable biomarker in predicting CV outcomes. During 6 years of follow-up period, an OPN level >4810 pg/ml was associated with a significantly higher incidence of AMI-related hospitalization in CCS patients who received successful PCI before the enrollment.

2023 Consensus of Taiwan Society of Cardiology on the Pharmacological Treatment of Chronic Heart Failure.

The prevalence of heart failure is increasing, causing a tremendous burden on health care systems around the world. Although mortality rate of heart failure has been significantly reduced by several effective agents in the past 3 decades, yet it remains high in observational studies. More recently, several new classes of drugs emerged with significant efficacy in reducing mortality and hospitalization in chronic heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). To integrate these effective therapies and prioritize them in the management of Asian patients, Taiwan Society of Cardiology has recently appointed a working group to formulate a consensus of pharmacological treatment in patients with chronic heart failure. Based on most updated information, this consensus provides rationales for prioritization, rapid sequencing, and in-hospital initiation of both foundational and additional therapies for patients with chronic heart failure.

Factors Associated With the Utilization of Outpatient Virtual Clinics: Retrospective Observational Study Using Multilevel Analysis.

BACKGROUND: Although the COVID-19 pandemic has accelerated the adoption of telemedicine and virtual consultations worldwide, complex factors that may affect the use of virtual clinics are still unclear. OBJECTIVE: This study aims to identify factors associated with the utilization of virtual clinics in the experience of virtual clinic service implementation in Taiwan. METHODS: We retrospectively analyzed a total of 187,742 outpatient visits (176,815, 94.2%, in-person visits and 10,927, 5.8%, virtual visits) completed at a large general hospital in Taipei City from May 19 to July 31, 2021, after rapid implementation of virtual outpatient clinic visits due to the COVID-19 pandemic. Data of patients' demographic characteristics, disease type, physicians' features, and specialties/departments were collected, and physicians' opinions regarding virtual clinics were surveyed and evaluated using a 5-point Likert scale. Multilevel analysis was conducted to determine the factors associated with the utilization of virtual clinics. RESULTS: Patient-/visit-, physician-, and department-level factors accounted for 67.5%, 11.1%, and 21.4% of the total variance in the utilization of virtual clinics, respectively. Female sex (odds ratio [OR] 1.27, 95% CI 1.22-1.33, P<.001); residing at a greater distance away from the hospital (OR 2.36, 95% CI 2.15-2.58 if distance>50 km, P<.001; OR 3.95, 95% CI 3.11-5.02 if extensive travel required, P<.001); reimbursement by the National Health Insurance (NHI; OR 7.29, 95% CI 5.71-9.30, P<.001); seeking care for a major chronic disease (OR 1.33, 95% CI 1.24-1.42, P<.001); the physician's positive attitude toward virtual clinics (OR 1.50, 95% CI 1.16-1.93, P=.002); and visits within certain departments, including the heart center, psychiatry, and internal medicine (OR 2.55, 95% CI 1.46-4.46, P=.004), were positively associated with the utilization of virtual clinics. The patient's age, the physician's age, and the physician's sex were not associated with the utilization of virtual clinics in our study. CONCLUSIONS: Our results show that in addition to previously demonstrated patient-level factors that may influence telemedicine use, including the patient's sex and distance from the hospital, factors at the visit level (insurance type, disease type), physician level (physician's attitude toward virtual clinics), and department level also contribute to the utilization of virtual clinics. Although there was a more than 300-fold increase in the number of virtual visits during the pandemic compared with the prepandemic period, the majority (176,815/187,742, 94.2%) of the outpatient visits were still in-person visits during the study period. Therefore, it is of great importance to understand the factors impacting the utilization of virtual clinics to accelerate the implementation of telemedicine. The findings of our study may help direct policymaking for expanding the use of virtual clinics, especially in countries struggling with the development and promotion of telemedicine virtual clinic services.

Effect of CYP2C19 status on platelet reactivity in Taiwanese acute coronary syndrome patients switching to prasugrel from clopidogrel: Switch Study.

BACKGROUND/PURPOSE: Pharmacogenetics is a potential driver of the "East Asian paradox," in which East Asian acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy (DAPT) with clopidogrel following percutaneous coronary intervention (PCI) demonstrate higher levels of platelet reactivity on treatment than Western patients, yet have lower ischemic risk and higher bleeding risk at comparable doses. However, the impact of pharmacogenetics, particularly regarding CYP2C19 genotype, on the pharmacodynamics of P2Y12 inhibitors has not been extensively studied in Taiwanese ACS patients as yet. METHODS: CYP2C19 genotyping and pharmacogenetic analysis was conducted on 102 subjects from the Switch Study, a multicenter, single-arm, open-label intervention study that examined the effects on platelet activity and clinical outcomes of switching from clopidogrel (75 mg daily) to low-dose prasugrel (3.75 mg daily) for maintenance DAPT after PCI in 203 Taiwanese ACS patients. RESULTS: Genotyping results revealed that 43.1% were CYP2C19 extensive metabolizers (EM), while 56.9% were reduced metabolizers (RM). After switching to prasugrel, mean P2Y12 reaction units (PRU) values were significantly reduced in both EM and RM populations, while the proportion of high on-treatment platelet reactivity (HPR) patients significantly declined in RM patients. No increase in bleeding risk after switching was observed during follow-up. Multivariate analysis indicated that for RM patients, low estimated glomerular filtration rate (eGFR) and low hemoglobin were associated with greater HPR risk on clopidogrel, but not after switching to prasugrel. CONCLUSION: Switching to low-dose prasugrel from clopidogrel reduced mean PRU levels and proportion of HPR patients, with more significant reduction in RM patients.

Right Ventricular Pump Efficiency in Secundum-Type Atrial Septal Defect.

BACKGROUND: A well-functioning cardiopulmonary system, which works as a pump, should generate adequate stroke volume with as little stroke work as possible. We propose a new composite parameter, right ventricular (RV) pump efficiency (η) = left ventricular stroke volume / right ventricular stroke work, to describe this idea in a volume overload population with secundum-type atrial septal defect (ASD). METHODS: We consecutively enrolled 50 patients with secundum-type ASD to investigate the relationship between right-sided volume overload and RV pump efficiency. Sixteen patients with a pulmonary to systemic flow ratio (Qp/Qs) > 1.5 underwent implantation of an occluder. The paired t test was used to compare RV pump efficiency before and after ASD closure. RESULTS: RV pump efficiency was inversely correlated with Qp/Qs and was 60 ± 20‰ · mmHg-1 at Qp/Qs = 1. After ASD closure, RV volume, ejection fraction and free wall strain all significantly decreased, while RV pump efficiency significantly increased from 27.4 ± 13.6 to 63.9 ± 20.4‰ · mmHg-1. CONCLUSIONS: RV pump efficiency can superiorly reflect the chronicity and severity of secundum-type ASD.

A HANC Risk Stratification Score for Antiplatelet Therapy Optimization with Low-Dose Prasugrel in Taiwanese Acute Coronary Syndrome Patients from the Switch Study.

Background: A significant proportion of acute coronary syndrome (ACS) patients experience high on-treatment platelet reactivity (HPR) on clopidogrel-based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). Objectives: This study assessed key independent risk factors associated with significant HPR risk on clopidogrel, but not prasugrel, in the Switch Study cohort of 200 Taiwanese ACS patients who switched from clopidogrel to low-dose prasugrel for maintenance DAPT after PCI. Methods: Univariate analysis and stepwise multivariate logistic regression analysis were conducted to identify key independent risk factors for HPR on clopidogrel, but not prasugrel. Results: A HANC [H: low hemoglobin (< 13 g/dL for men and < 12 g/dL for women); A: age ≥ 65 years; N: non-ST elevation myocardial infarction; C: chronic kidney disease as defined by estimated glomerular filtration rate < 60 mL/min] risk stratification score was developed, and demonstrated optimal sensitivity and specificity at a cutoff score of ≥ 2. The HANC score compared favorably against the recently validated ABCD score in the full Switch Study cohort (n = 200), and the ABCD-GENE score in a genotyped cohort (n = 102). Conclusions: The HANC score may serve to alert clinicians to patients at potentially higher HPR risk on clopidogrel, but not prasugrel. Further research to validate this score and assess its correlation with clinical outcomes is warranted.

The Efficacy and Safety of Short-Term Tolvaptan Usage in Patients with Acute Decompensated Heart Failure.

Background: Patients admitted with acute decompensated heart failure (ADHF) have a poor prognosis and poor quality of life due to dyspnea and edema. Tolvaptan, a vasopressin V2 receptor antagonist, is an effective water diuretic. This study aimed to evaluate the efficacy and safety of a short course of tolvaptan to treat volume overload in patients with ADHF. Methods: We conducted a phase III, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a short course of tolvaptan (15 mg/day for 4 days) in hospitalized ADHF patients with volume overload despite the use of conventional diuretics. The primary end-point was the change in body weight after 4 days of treatment. The secondary end-points were the change in intake/output balance, change in serum sodium/potassium concentrations, physician/patient assessed signs and symptoms of heart failure after 4 days of treatment, and all-cause mortality in 1 month. Results: A total of 110 patients were screened, and 91 were randomized to receive 15 mg/day of tolvaptan for 4 days (n = 46) or matching placebo (n = 45). Compared to the placebo-treated patients, tolvaptan significantly reduced body weight (-1.36 ± 2.13 kg in the tolvaptan group vs. -0.59 ± 1.27 kg in the placebo group, p = 0.0394). The tolvaptan group also had a negative intake/urine volume balance compared to the placebo group (-509.3 ± 2788.2 ml vs. 975.5 ± 1903.1 ml, p = 0.0059). The safety profile of tolvaptan was acceptable. Conclusions: Tolvaptan significantly reduced volume overload in hospitalized ADHF patients with volume overload despite the use of conventional diuretics.

Multicentre, randomized comparison of two-stent and provisional stenting techniques in patients with complex coronary bifurcation lesions: the DEFINITION II trial.

AIM: The present study aimed to assess the benefits of two-stent techniques for patients with DEFINITION criteria-defined complex coronary bifurcation lesions. METHODS AND RESULTS: In total, 653 patients with complex bifurcation lesions at 49 international centres were randomly assigned to undergo the systematic two-stent technique (two-stent group) or provisional stenting (provisional group). The primary endpoint was the composite of target lesion failure (TLF) at the 1-year follow-up, including cardiac death, target vessel myocardial infarction (TVMI), and clinically driven target lesion revascularization (TLR). The safety endpoint was definite or probable stent thrombosis. At the 1-year follow-up, TLF occurred in 37 (11.4%) and 20 (6.1%) patients in the provisional and two-stent groups, respectively [77.8%: double-kissing crush; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.30-0.90; P = 0.019], largely driven by increased TVMI (7.1%, HR 0.43, 95% CI 0.20-0.90; P = 0.025) and clinically driven TLR (5.5%, HR 0.43, 95% CI 0.19-1.00; P = 0.049) in the provisional group. At the 1 year after indexed procedures, the incidence of cardiac death was 2.5% in the provisional group, non-significant to 2.1% in the two-stent group (HR 0.86, 95% CI 0.31-2.37; P = 0.772). CONCLUSION: For DEFINITION criteria-defined complex coronary bifurcation lesions, the systematic two-stent approach was associated with a significant improvement in clinical outcomes compared with the provisional stenting approach. Further study is urgently warranted to identify the mechanisms contributing to the increased rate of TVMI after provisional stenting. STUDY REGISTRATION: http://www.clinicaltrials.com; Identifier: NCT02284750.

Circulating fatty-acid binding-protein 4 levels predict CV events in patients after coronary interventions.

BACKGROUND: Fatty-acid binding protein-4 (FABP4) has been associated with the metabolic syndrome, diabetes mellitus, atherosclerosis, incident heart failure, and the prognosis of coronary heart disease (CHD). However, recent studies have not reported a significant correlation between FABP4 and cardiovascular (CV) mortality in high-risk patients or those with documented CHD. The present study aimed to evaluate the association between FABP4 and the prognosis in a cohort of patients with CHD who received coronary interventions. METHODS: Serum FABP4 levels were measured in 973 patients after a successful intervention for CHD, who were then prospectively followed for 30 months. RESULT: During this period, 223 patients experienced composite CV outcomes (22.92%), defined as cardiovascular/cerebrovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for refractory or unstable angina, hospitalization for heart failure, and peripheral artery occlusive disease. Kaplan-Meier curves showed a significant association between FABP4 levels at baseline (categorized in tertiles) and composite CV outcomes during follow-up (log-rank test, p < 0.003). The patients with the highest tertile of baseline FABP4 had an increased risk of composite CV outcomes (hazard ratio (HR) 1.662; 95% confidence interval (CI), 1.2-2.302; p = 0.0022), which remained significant after multivariate adjustments for traditional risk factors and hs-CRP (HR 1.596; 95% CI, 1.088-2.342; p = 0.0168). In contrast, FABP4 failed to show a significant association with cardiovascular/cerebrovascular death, nonfatal MI, or nonfatal stroke after multivariate adjustments (HR, 1.594; 95% CI, 0.651-3.904, p = 0.3073). CONCLUSION: In conclusion, circulating FABP4 is an independent prognostic predictor for the composite cardiovascular events in the patients with stable CHD after coronary interventions.

The Characteristics and Outcomes of Patients with Heart Failure and Reduced Ejection Fraction: The Eligibility of Novel Heart Failure Medications.

BACKGROUND: Renin-angiotensin system inhibitors and beta-blockers are the initial treatment of choice for heart failure with reduced ejection fraction (HFrEF), whereas sacubitril/valsartan (SAC/VAL) and ivabradine are considered to second-line therapies. The eligibility of SAC/VAL and ivabradine according to the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) labels, Taiwan National Health Insurance (TNHI) reimbursement regulations, and European Society of Cardiology (ESC) heart failure (HF) guidelines are diverse, and they may not fulfill the needs of real-world HFrEF patients. METHODS: Patients hospitalized for HF with left ventricular ejection fraction (LVEF) ≤ 40% were recruited from 21 hospitals in Taiwan between 2013 and 2014. The criteria for SAC/VAL and ivabradine according to the different regulations were applied. RESULTS: Of 1,474 patients, 86.8%, 29.4%, and 9.5% met the EMA/FDA label criteria, TNHI-regulation, and ESC guidelines for SAC/VAL, compared to 47.1%, 37.2%, and 45.6% for ivabradine, respectively. Ineligible reasons for the TNHI regulations included LVEF > 35% (19.9%, for SAC/VAL and ivabradine) and sinus rate < 75 beats per minute (bpm) (29.9%, for ivabradine). Although not meeting the TNHI regulations, patients with LVEF 35-40% had a similar 1-year mortality rate (15.6% vs. 15.8%, p = 0.876) to those with LVEF ≤ 35%, whereas patients with a sinus rate 70-74 bpm had a similar 1-year mortality rate (15.3% vs. 16.1%, p = 0.805) to those with a sinus rate ≥ 75 bpm. CONCLUSIONS: Approximately 70% and 63% of TSOC-HFrEF registry patients were ineligible for SAC/VAL and ivabradine, respectively, according to current TNHI regulations. Regardless of the eligibility for novel HFrEF medications, the high incidence of adverse events suggests that all patients should be treated cautiously.

Circulating TNFSF14 (Tumor Necrosis Factor Superfamily 14) Predicts Clinical Outcome in Patients With Stable Coronary Artery Disease.

Objective- Basic research indicates that TNFSF14 (tumor necrosis factor superfamily 14) may be involved in the pathogenesis of atherosclerosis. Given the requirements of new biomarkers for risk classification in coronary artery disease (CAD), we conducted a longitudinal analysis to investigate if TNFSF14 levels are associated with the risk of cardiovascular events among patients with stable CAD. Approach and Results- In total, 894 patients with CAD were enrolled in a multicenter prospective study. The primary outcome was the occurrence of cardiovascular death, nonfatal myocardial infarction, and stroke. The secondary outcome was the occurrence of all-cause death, nonfatal myocardial infarction, stroke, revascularization, and hospitalization because of angina or heart failure. During the mean follow-up period of 22±9 months, 32 patients reached the primary outcome and 166 patients reached the secondary outcome. Kaplan-Meier analysis showed that the event-free survival was significantly different in the first and fourth quartile groups in subjects categorized by TNFSF14 levels. In multivariate Cox proportional hazard regression analysis, TNFSF14 was independently associated with the risk of cardiovascular events after adjustment for various relevant factors (adjusted hazard ratio, 1.14; 95% CI, 1.04-1.25). In the validation cohort of 126 multivessel patients with CAD, TNFSF14 was confirmed to provide good prognostic predictive value for composite cardiovascular events (adjusted hazard ratio, 1.11; 95% CI, 1.04-1.19). Conclusions- This is the first study to demonstrate that increased TNFSF14 levels were independently associated with the occurrence of cardiovascular events in patients with stable CAD. Future studies are worthy to validate if TNFSF14 could be a novel prognostic biomarker for CAD outcomes over different populations.

Stepwise manipulation of cardiac computed tomography multi-planar reconstruction to mimic transesophageal echocardiography.

Cardiac computed tomography (CT) is increasingly used to plan transcatheter structural heart interventions. However, intraoperative guidance relies on transesophageal echocardiography (TEE) and fluoroscopy. This study sought to develop a stepwise CT multi-planar reconstruction manipulation method to mimic TEE, bridging the gap between preoperative planning and intraoperative guidance tools. This CT manipulation reproduced similar configurations as TEE views in the mid-esophageal left ventricle (LV) views, transgastric LV 2-chamber views for mitral apparatus, and other miscellaneous views. Stepwise cardiac CT manipulation to mimic TEE is the final piece of the puzzle in the mental co-registration of these three crucial imaging modalities. Now, we can predict the TEE images and fluoroscopy projections in a preoperative rehearsal, thus improving the intraoperative accuracy of interventions.

Delayed Coronary Obstruction after Transcatheter Aortic Valve Replacement - An Uncommon But Serious Complication.

As transcatheter aortic valve replacement (TAVR) becomes the mainstream treatment for valvular aortic stenosis, it is vitally important to recognize its associated procedural complications. Among the clinically relevant but uncommonly seen complications, the development of delayed coronary obstruction (DCO) occurring during the early post-procedural phase or even later following the index TAVR procedure, has been reported. These reports have raised concerns as TAVR comes more common in lower-risk patients. In this review article, we explored the implications of DCO for pre-procedural computed tomography evaluation, valve selection and sizing, intra-procedural manipulation, and approaches to post-procedural management.

Incremental value of right parasternal transthoracic echocardiographic examination over the left parasternal approach in assessing ascending aorta size: Additional benefit of three-dimensional echocardiography.

BACKGROUND: The ascending aorta (AA) has not been well studied using two-dimensional right parasternal transthoracic echocardiographic examination (2DRPE). AIM: The aim of the present study was to assess the incremental value of 2DRPE over two-dimensional left parasternal transthoracic echocardiographic examination (2DLPE) in evaluating the size of AA in adult patients (pts) and, secondly, to determine whether live/real time three-dimensional (3D) RPE provided any additional benefit over 2DRPE. MATERIALS AND METHODS: The AA was successfully imaged by 2DLPE, 2DRPE, and 3D RPE in 87 of 141 (61.7%) pts which comprised of two groups of consecutive pts separated by an interval of 2 weeks. RESULTS: The maximum length of AA visualized by 2DRPE (4.98 ± 0.89) was larger than 2DLPE in 76/87(87%) pts (P < 0.001). Both the maximum systolic AA inner luminal width and leading edge-to-leading edge width by 2DRPE were greater than 2DLPE (P < 0.001). Similar to other noninvasive imaging modalities where mid-AA width is taken at level of right pulmonary artery, mid-AA width could also be taken at this level by 2DRPE in 79/87(91%) pts since this landmark was visualized during 2DRPE. However, this vessel could be visualized in only 2/87 (2%) pts with 2DLPE. 3DRPE conferred additional benefit over 2DRPE. The maximal AA length by 3DRPE was larger than 2DRPE in 60/87(69%) pts, and the maximal inner lumen and leading edge to leading edge widths were larger in 54/87(62%) and 66/87(76%) pts, respectively. CONCLUSION: Our preliminary study demonstrates significant incremental value of 2DRPE over 2DLPE in the assessment of AA. 3DRPE confers an additional advantage over 2DRPE.

Impact of type D personality on clinical outcomes in Asian patients with stable coronary artery disease.

BACKGROUND: Some personality types are associated with cardiovascular (CV) diseases and may be related to clinical outcomes in coronary artery disease (CAD). This study investigates the association between type D personality and clinical outcomes in stable CAD patients in an Asian cohort. METHODS: Stable CAD patients were enrolled and prospectively followed up for at least 1 year in Taiwan. The inclusion criteria were at least one successful percutaneous coronary intervention (PCI) and stable medical treatment for at least 1 month before enrollment. Vulnerability to psychological distress was measured by the Type D Personality Scale (DS14) after enrollment. The end point was the occurrence of total CV events. Cox regression models of CV events were used to investigate the role of type D personality in clinical outcomes. RESULTS: The study included 777 patients, among which 122 (15.77%) had type D personality. Forty-two CV events were identified: 3 cardiac deaths, 5 nonfatal myocardial infarctions, 1 stroke, 4 congestive heart failures (CHF), 6 peripheral arterial occlusive disorder cases, and 23 readmissions for angina/revascularization treatment. Patients with type D personality had significantly higher incidence of future CV events (9.84% vs. 4.58%, p = 0.018%) and admission for angina/revascularization (5.74% vs. 2.44%, p = 0.049). Patients with subsequent CV events were more likely to have type D personality (28.57% vs. 14.97%, p=0.018). After proportional Cox regression analysis, type D personality remained an independent predictor of future CV events (HR: 3.21, 95% CI: 1.06-9.69). In subgroup analyses, type D personality was especially associated with higher risk of total CV events among females, the elderly, hypertension patients, diabetes patients, and non-smokers. CONCLUSION: Type D personality was an independent predictor of CV outcomes in an Asian cohort of stable CAD patients. This personality type may be identified in risk stratification for secondary prevention after PCI.

Quantification of Stent Creep by Three-Dimensional Transesophageal Echocardiography in Patients Undergoing Transcatheter Aortic Valve-in-Valve Implantation for Failed Bioprostheses.

BACKGROUND: Transcatheter aortic valve-in-valve implantation (aVIV) has been used to treat bioprosthetic failure due to "stent creep", defined as inward flexion or bending of stent posts. The aim of this study was to develop quantitative three-dimensional transesophageal echocardiography (3D-TEE) geometric analysis of failed bioprostheses to determine the incidence of stent creep in patients undergoing aVIV and its contribution to the hemodynamics of those valves. METHODS: We retrospectively examined the 3D-TEE of 22 consecutive patients (age 74.4 ± 11.3 years; M/F = 12/10) who underwent aVIV for failed bioprostheses. The modes of bioprosthesis failure included stenosis (n = 8), regurgitation (n = 9), and combined (n = 5). The degree of stent creep was assessed by calculating the triangular area obtained by projecting the apex of stent posts on a reconstructed plane. This measured area was divided by that of the regular triangle defined by the base of stent posts to calculate a ratio, which we termed the "stent creep ratio" (SCR). RESULTS: The mean SCR was lower in the patients with failed prostheses than that in the controls (0.82 ± 0.16 vs. 0.96 ± 0.05, p = 0.02). The SCR was negatively correlated with the peak trans-aortic pressure gradient (r = -0.62, p < 0.01). An SCR cut-off point of 0.79 was associated with aortic peak velocity > 4 m/s (AUC = 0.81, sensitivity = 0.79, specificity = 0.83). Fourteen of the 22 patients had pre- and post-aVIV 3D-TEE, and the SCR was corrected satisfactorily from 0.81 ± 0.13 to 1.04 ± 0.19 (p < 0.01). CONCLUSIONS: SCR measured by 3D-TEE is feasible to quantitatively evaluate stent creep. Stent creep is an important mode of structural deterioration in surgical bioprostheses, which can be treated by aVIV.