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.

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.

Prasugrel switching from clopidogrel after percutaneous coronary intervention for acute coronary syndrome in Taiwanese patients: an analysis of safety and efficacy.

The recommended maintenance dose of prasugrel for East Asian populations (i.e., Japanese and Taiwanese) is 3.75 mg as part of dual antiplatelet therapy (DAPT) for the prevention of recurrent ischemia and stent thrombosis in acute coronary syndrome (ACS). This modified dosage regimen has been established in studies conducted in Japan; however, the efficacy and safety of switching from clopidogrel to prasugrel DAPT among Taiwanese patients remain to be explored. In this phase IV, multicenter, single-arm, open-label study, we evaluated the 4-week pharmacodynamic response, and the 48-week safety outcomes of prasugrel 3.75 mg after a switch from clopidogrel in Taiwanese ACS patients. A total of 203 prasugrel-naïve ACS patients (over 90% male) who had received post-PCI clopidogrel DAPT for at least 2 weeks were enrolled from ten medical centers in Taiwan and subsequently switched to prasugrel 3.75 mg DAPT. Four weeks after the switch, P2Y12 reaction unit (PRU) values were significantly decreased in the total cohort (mean - 18.2 ± 48.1; 95% confidence interval - 24.9 to - 11.5, p < 0.001), and there was an overall consistent antiplatelet response in the treated subjects. The proportion of patients with high on-treatment platelet reactivity (HPR; PRU > 208) dropped from 23.5 to 10% (p < 0.001). Female sex was associated with a greater PRU reduction with prasugrel, whereas HPR at baseline, age ≥ 65 years, and body mass index ≥ 25 best predicted HPR at Week 4. Throughout the 48-week treatment with prasugrel, the incidences of MACE (1.0%) and TIMI major bleeding (2.0%) were rather low, accompanying an acceptable safety profile of TIMI minor (6.4%) and non-major, non-minor clinically relevant bleeding (3.0%). Overall, switching to the maintenance dose of prasugrel (3.75 mg) was observed to be effective and well tolerated among post-PCI ACS patients in Taiwan. Clinical Trial Registration Number: NCT03672097.

Duration of Clopidogrel-Based Dual Antiplatelet Therapy and Clinical Outcomes in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention　- A Real-World Observation in Taiwan From 2012 to 2015.

BACKGROUND: Little information is available in Asia about the real-world practice of dual antiplatelet therapy (DAPT) duration for acute coronary syndrome (ACS) and its influence on clinical outcomes.Methods and Results:The Taiwan ACS STENT Registry was a prospective, multicenter study to observe ACS patients using clopidogrel-based DAPT after percutaneous coronary intervention (PCI). The primary outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Overall, 2,221 ACS patients (62 years, 83% men) were included. DAPT duration was ≤9 months in 935 (42.1%). The incidence of primary outcome was higher in patients receiving DAPT ≤9 months compared with those receiving DAPT >9 months at 1 year (3.5% vs. 1.6%, P=0.0026). The incidence of stent thrombosis (overall 0.5%) was similar between groups. Multivariable analysis showed that DAPT >9 months was associated with a significantly lower risk of primary outcome (odds ratio 0.725, 95% confidence interval 0.545-0.965). CONCLUSIONS: Our data showed that short duration of DAPT (≤9 months) was common (42.1%) in Taiwan for ACS patients undergoing PCI. DAPT ≤9 months increased the risk of the primary outcome.

Changing Practice Pattern of Acute Coronary Syndromes in Taiwan from 2008 to 2015.

BACKGROUND: Patients with acute coronary syndrome (ACS), including ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation (NSTE)-ACS have a significant risk of morbidity and mortality. This study evaluated the practice patterns of ACS care in Taiwan from 2005 to 2018. METHODS: Data from two nationwide ACS registries (2008-2010 and 2012-2015) were used. ACS patients who received percutaneous coronary interventions (PCIs) during admission were compared between the two registries. RESULTS: In STEMI, the door-to-balloon time for primary PCI decreased by 25 min from a median of 96 to 71 min (p < 0.0001) from the first to second registry. More complex PCI procedures and drug-eluting stents were used for ACS. However, the onset-to-door time was still long for both STEMI and NSTE-ACS. The D2B time for NSTE-ACS was long, especially in the elderly and female patients. Although the prescription rate of secondary preventive medications for ACS increased, it was still relatively low compared with Western data, especially in NSTE-ACS. CONCLUSIONS: The registry data showed that ACS care quality has improved in Taiwan. However, areas including onset-to-door time and use of secondary preventive medications still need further improvements.

Clinical Outcomes of Polytetrafluoroethylene-Covered Stents for Coronary Artery Perforation in Elderly Patients Undergoing Percutaneous Coronary Interventions.

BACKGROUND: Coronary artery perforation (CAP) during percutaneous coronary intervention (PCI) is associated with increased mortality. Polytetrafluoroethylene covered stents (CS) are an effective approach to treat CAP, but data regarding elderly patients requiring CS implantation for CAP are limited. The aim of this study is to report clinical data for elderly CAP patients undergoing CS implantation during PCI. METHODS: Nineteen consecutive elderly patients (≥ 65 years) undergoing CS implantation due to PCI-induced CAP in a tertiary referral center from July 2003 to April 2016 were retrospectively examined. RESULTS: There were 13 men and six women, with a mean age of 75.3 ± 5.6 years (range: 65-86 years). Perforation grade was Ellis type II in five patients (26.3%), and Ellis type III in 14 patients (73.7%). Cardiac tamponade developed in six patients (31.6%), and intra-aortic balloon pumping was needed in four patients (21.1%). The overall success rate for CS implantation rate was 94.7%. The overall in-hospital mortality rate was 15.8%; the in-hospital myocardial infarction rate was 63.2%. Among 16 survival-to-discharge cases, dual antiplatelet therapy (DAPT) was prescribed in 14 cases (87.5%) for a mean duration of 14 months. Overall, there were five angiogram- proven CS failures among 18 patients receiving successful CS implantation. The 1, 2 and 4 years of actuarial freedom from the CS failure were 78%, 65%, and 43% in the angiogram follow-up patients. CONCLUSIONS: CS implantation for CAP is feasible and effective in elderly patients, while CS failure remains a major concern that encourages regular angiographic follow-up in these case.

Atrial Septostomy for Left Atrial Decompression During Extracorporeal Membrane Oxygenation by Inoue Balloon Catheter.

BACKGROUND: Refractory pulmonary edema is an infrequent but serious complication in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) for myocardial failure. Left atrial (LA) decompression in this setting is important. Although a few methods have been reported, the experience is mostly limited to children. We aimed to evaluate the feasibility of Inoue balloon catheter in percutaneous trans-septal LA decompression in adult cardiogenic patients.Methods and Results:We retrospectively analyzed 16 procedures of trans-septal LA decompression by Inoue balloon catheter in 15 VA-ECMO patients (aged 22-65 years, 6 men) with refractory pulmonary edema from May 2012 to December 2014. Mean left ventricular ejection fraction was 15%. The cause of cardiogenic shock included 7 cases of ischemic heart disease, 1 of dilated cardiomyopathy, 5 of myocarditis, and 2 of fatal ventricular arrhythmia.The procedures were performed 4.3 days after ECMO. Inoue balloon size was 24-27 mm. LA septostomy were successfully created in 14 patients. Procedure time on average was 36.8 min (range, 15-85 min). There were no procedure-related complications.Radiography on the next day showed rapid resolution of pulmonary edema. CONCLUSIONS: Trans-septal LA decompression by Inoue balloon catheter is a feasible alternative method for adult patients with refractory pulmonary edema under ECMO.

Inoue-Balloon Percutaneous Transvenous Mitral Valvuloplasty through the Left Femoral Vein in Anomalous Inferior Vena Cava.

UNLABELLED: Inoue-balloon percutaneous transvenous mitral valvuloplasty is conventionally performed via the right femoral vein. However, atrial transseptal access can be technically challenging. Herein, we describe a 54-year-old male who had balloon mitral valvuloplasty performed via the left femoral vein because of an anomalous inferior vena cava course, including the technical issues encountered using this approach. KEY WORDS: Anomalous inferior vena cava; Left femoral vein approach; Mitral valvuloplasty.

Precordial ST-Segment Elevation Caused by Proximal Occlusion of a Non-Dominant Right Coronary Artery.

UNLABELLED: For patients with ST-segment elevation myocardial infarction, primary percutaneous coronary intervention to the culprit lesion via electrocardiographic guidance is essential. We herein report the rare case of a 49-year-old man who presented with ST-segment elevation in the precordial leads, while coronary angiography results indicated total occlusion of the proximal non-dominant right coronary artery. We evaluated its possible pathophysiologic mechanisms and thoroughly discussed isolated right ventricular infarction and its electrocardiography findings. KEY WORDS: Coronary angiography; Myocardial infarction; Total occlusions.

Prognostic significance of reciprocal ST-segment depression in patients with acute STEMI undergoing immediate invasive intervention.

PURPOSES: Reciprocal changes are frequent in patients with acute ST-segment elevation myocardial infarction (STEMI). However, their prognostic significance is not clear in patients undergoing immediate invasive intervention. BASIC PROCEDURE: We retrospectively examined 165 consecutive patients with STEMI receiving immediate invasive intervention. The first electrocardiography taken in the emergency department was analyzed. Patients were assigned to 2 groups: with a reciprocal change (group I, n = 100) and without a reciprocal change (group II, n = 65). MAIN FINDINGS: Electrocardiographs revealed that more anterolateral and inferior STEMI occurred in group I and more anterior STEMI occurred in group II. In the emergency department, group I had lower systolic and diastolic blood pressures, higher ventricular tachycardia and fibrillation rates, and higher cardiopulmonary resuscitation rates than did group II. Upon admission, peak troponin I levels were significantly higher in group I, and more group I patients required intra-aortic balloon pumping support. This unstable hemodynamic condition in group I patients was reflected by their higher in-hospital mortality rate. Multivariate analysis showed that age (odds ratio [OR], 1.103; 95% confidence interval [CI], 1.022-1.190; P = .012), Killip class (OR, 2.785; 95% CI, 1.049-7.400; P = .040), and reciprocal change (OR, 9.553; 95% CI, 1.146-79.608; P = .037) remained as independent predictors of in-hospital mortality. Actuarial freedom from all-cause mortality was worse in group I (P = .046). PRINCIPAL CONCLUSIONS: The data suggest that patients with STEMI with reciprocal electrocardiographic changes have unstable hemodynamic status and poorer outcomes. Further prospective studies using a larger patient population are needed.

Radial arterial approach with adjunctive urokinase for treating occluded autogenous radial-cephalic fistulas.

There are no data regarding the feasibility and safety of a radial arterial approach with adjunctive urokinase for treating occluded autogenous radial-cephalic fistulas. We retrospectively examined 54 transradial interventions performed to treat occluded autogenous radial-cephalic fistulas within 72 h of occurrence. Urokinase was used in patients with a large thrombus burden. A total of 92 lesions in 54 consecutive patients (27 males, 27 females; mean age, 61.8+/-12.3 years) were treated via radial access. All radial punctures were successful except in one patient. Most thrombotic lesions were located within 1 cm of the radiocephalic anastomosis (79.6%). The mean length of treated thrombotic lesions was 10.3+/-5.4 cm (range, 4-32 cm). Twenty-five patients (46.3%) received urokinase (mean dose, 96,000+/-30,000 U). After transradial intervention, systolic, diastolic, and mean pressures in the radial artery decreased from 179+/-41, 77+/-17, and 111+/-22 mm Hg to 71+/-29, 36+/-15, and 48+/-19 mm Hg (all p's\0.001), respectively. Four radial interventions were unsuccessful. The anatomic and clinical success rates of the radial approach were both 92.6%; postinterventional primary patency rates were 65% at 6 months and 40% at 12 months. Two minor vascular complications were noted, one caused by guidewire-induced contrast extravasation and the other by balloon-induced contrast extravasation. No patient developed clinical signs of pulmonary embolism. In conclusion, the radial approach with adjunctive urokinase is an effective and safe approach to treat occluded autogenous radial-cephalic fistulas.

Inoue-balloon mitral valvuloplasty in double-orifice mitral stenosis.

We report 7 symptomatic patients with stenotic double-orifice mitral valve of incomplete bridge type. In each patient, the fibrous bridge tissue between the valve leaflets was successfully split using an Inoue balloon valvuloplasty technique with stepwise dilations applied only to the posteromedial orifice.

Transcatheter closure of patent ductus arteriosus using Gianturco coils in adolescents and adults.

We present the short- and intermediate-term results of transcatheter closure of patent ductus arteriosus with Gianturco coils in adolescents and adults. During a 5-year period, 55 patients (44 females, 11 males) with ages ranging from 14 to 72 years (median, 23) underwent attempted transcatheter closure of patent ductus with the Gianturco coils. The diameter of the narrowest segment of the ductus ranged from 0.8 to 7.6 mm (3.9 +/- 1.3 mm). The 55 patients were divided into three groups. Group I consisted of nine patients with a ductal diameter < or = 3 mm, group II consisted of 27 patients with a ductal diameter > 3 mm but < or = 4 mm, and group III consisted of 19 patients with a ductal diameter > 4 mm. Four- to five-loop Gianturco coils were used, which were deployed via retrograde aortic route. Multiple-coil technique was generally applied in group II patients. Balloon occlusion technique in combination with multiple-coil technique was generally used in group III patients. Deployment of coil was successful in 51 patients (93%) but failed in 4. The success rate of coil deployment in group I, II, and III were 100% (9/9), 96% (26/27), and 84% (16/19), respectively. A mean of 1.9 +/- 0.7 coils was deployed per patient. Of the four patients with unsuccessful coil deployment, three underwent surgery and one received implantation with Amplatzer duct occluder. Distal embolization of 21 coils occurred in 10 patients (3 in group II and 7 in group III), from whom 20 coils were retrieved with a gooseneck snare and 1 coil was removed during surgery. The mean diameter of ductus in the 10 patients with distal embolization was significantly larger than that in those without (5.2 +/- 1.4 vs. 3.7 +/- 1.1 mm; P < 0.01). Among the 51 patients with successful coil deployment, immediate complete closure was achieved in 20 (39%), while trivial to mild leak was present in 31 (61%). No significant complications were encountered. After a follow-up period ranging from 5 to 42 months, four patients had a small residual shunt and three underwent a second intervention with complete occlusion. None had left pulmonary artery stenosis documented with Doppler echocardiography. Transcatheter closure of ductus with the Gianturco coils is safe and feasible in the majority of adolescents and adults. Taking high embolization rate in patients with a ductus diameter > 4 mm into consideration, controlled-release coils, Buttoned device, or Amplatzer duct occluder can be a better choice.