Effect of Temperature Variation on the Incidence of Acute Myocardial Infarction.

BACKGROUND: Harsh temperature exposure has been associated with a high risk of cardiovascular events. We sought to investigate the influence of temperature change on long-term incidence of acute myocardial infarction (AMI) in Korean patients. METHODS: From the National Health Insurance Service (NHIS) customized health information database (from 2005 to 2014), data from a total of 192,567 AMI patients was assessed according to the International Classification of Disease 10th edition code and matched with temperature reports obtained from the Korea Meteorological Administration database. We analyzed data for a 10-year period on a monthly and seasonal basis. RESULTS: The incidence rate per 100,000 year of AMI exhibited a downward trend from 69.1 to 56.1 over the period 2005 to 2014 (P < 0.005), and the seasonal AMI incidence rate per 100,000 year was highest in spring (63.1), and winter (61.3) followed by autumn (59.5) and summer (57.1). On a monthly basis, the AMI incidence rate per 100,000 year was highest during March (64.4) and December (63.9). The highest incidence of AMI occurred during temperature differences of 8-10° in each season. Moreover, AMI incidence tended to increase as the mean temperature decreased (r = -0.233, P = 0.001), and when the mean daily temperature difference increased (r = 0.353, P < 0.001). CONCLUSION: The AMI incidence rate per 100,000 year has a decreasing trend over the 10-year period, derived from the Korean NHIS database. Modest daily temperature differences (8-10°) and the spring season are related to higher AMI incidence, indicating that daily temperature variation is more important than the mean daily temperature.

Role of Dual-Acquisition Noninvasive Cardiac CT Imaging for the Detection of Vasospastic Angina.

BACKGROUND: Vasospastic angina (VSA) is characterized by chest pain at rest with transient ischemic electrocardiographic changes in the ST segment, and a prompt response to nitrates. Vasospastic angina is among the most frequent of the coronary artery diseases in Asia, and coronary computed tomography angiography (CCTA) may become available as a non-invasive diagnosis method. METHODS: We prospectively enrolled 100 patients with suspected vasospastic angina at two centers from 2018 to 2020. All patients underwent baseline CCTA without a vasodilator in the early morning followed by catheterized coronary angiography and spasm testing. CCTA with intravenous infusion of nitrate (IV) was repeated within 2 weeks of baseline CCTA. Vasospastic angina as detected by CCTA was defined as significant stenosis (≥50%) with negative remodeling without definite plaques or diffuse small diameter (<2 mm) of a major coronary artery with a beaded appearance on baseline CT that completely dilated on IV nitrate CT. We analyzed diagnostic performance of dual-acquisition CCTA for the detection of vasospastic angina. RESULTS: The patients were categorized into three groups according to their provocation test result (negative, n = 36; probable positive, n = 18; positive, n = 31). The diagnostic accuracy in terms of CCTA per patient had a sensitivity of 55% (95% CI, 40-69), specificity of 89% (95% CI, 74-97), positive predictive value (PPV) of 87% (95% CI, 72-95), and negative predictive value (NPV) of 59% (95% CI, 51-67). CONCLUSIONS: Dual-acquisition CCTA can support the non-invasive detection of vasospastic angina with relatively good specificity and PPV. CCTA was helpful for non-invasive screening of variant angina.

Differences in Optimal Platelet Reactivity after Potent P2Y12 Inhibitor Treatment in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention.

Background: East Asian patients receiving treatment with the potent P2Y12 inhibitors prasugrel or ticagrelor experience more potent platelet inhibition than with clopidogrel. Methods: This study investigated differences in OPR rates with reduced doses of prasugrel (n = 38) or ticagrelor (n = 40) for maintenance therapy in 118 Korean ACS patients who had undergone PCI, in comparison to conventional-dose clopidogrel (n = 40). We assessed drug responses at one- and three-months post-PCI with VerifyNow and multiple electrode aggregometry assays. Results: At the one-month period, patients receiving standard-dose prasugrel or ticagrelor had lower platelet reactivity as determined by the three assays than those receiving the conventional dose of clopidogrel (VN: p = 0.000; MEA: p = 0.000; LTA: p = 0.000). At the 3-month point, platelet reactivity was lower in those receiving reduced-dose prasugrel or ticagrelor than the clopidogrel-treated patients (VN: p = 0.000; MEA: p = 0.012; LTA: p = 0.002). Prasugrel resulted in significantly lower platelet inhibition than ticagrelor as determined by VN and LTA (VN: p = 0.000; LTA: p = 0.003). At three months, there was a significant overall difference in OPR among the three groups when measured by VN (p < 0.001), but not when measured by MEA (p = 0.596). OPR in the reduced-dose prasugrel group was not significantly different to the clopidogrel group at three months (VN: p = 0.180; MEA: p = 0.711). OPR in the reduced-dose ticagrelor group was similar to clopidogrel as determined by MEA at three months, but was different when assessed by VN (VN: p = 0.000; MEA: p = 0.540). Compared to standard-dose, the reduced-dose prasugrel OPR rate was significantly increased (VN: p = 0.008; MEA: p = 0.020). Conclusions: OPR values for reduced-dose prasugrel and conventional-dose clopidogrel at three months were similar but higher than for reduced-dose ticagrelor as determined by VN, but no differences were noted by MEA. The MEA assay might have less sensitivity and consistency than the VN assay. Further studies are needed to explore this discrepancy.

Pharmacodynamics and Outcomes of a De-Escalation Strategy with Half-Dose Prasugrel or Ticagrelor in East Asians Patients with Acute Coronary Syndrome: Results from HOPE-TAILOR Trial.

East Asians treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) generally experience more intense platelet inhibitory responses resulting in an increased risk of major bleeding. Whether a half-dose de-escalation strategy improves the net clinical benefit in Korean patients with acute coronary syndrome (ACS) remains uncertain. A total of 120 patients were pragmatically randomized to either prasugrel (n = 39, 60 mg loading dose (LD)/10 mg maintenance dose (MD)), ticagrelor (n = 40, 180 mg LD/90 mg MD), or clopidogrel (n = 41, 600 mg LD/75 mg MD) followed by a half-dose reduction at 1 month, or conventional dose 75 mg clopidogrel. The primary endpoint was the incidence of optimal platelet reactivity (OPR), defined as a P2Y12 reaction unit (PRU) value between 85 and 208 (by VerifyNow) at 3 months. Ticagrelor treatment achieved a significantly lower PRU compared with prasugrel and clopidogrel (31.0 ± 34.5 vs. 93.2 ± 57.1 vs. 153.1 ± 69.4), resulting in the lowest rate of OPR (12.5% vs. 48.7% vs. 63.4%). At 9 months, the minor bleeding was significantly higher with potent P2Y12 inhibitors than with clopidogrel (31.6% vs. 12.2%; HR, 2.93; 95% CI, 1.12-7.75). Only a few patients experienced ischemic complications. In Korean ACS patients, a de-escalation strategy with half-dose ticagrelor and prasugrel from standard dose increased the OPR rate significantly. Half-dose ticagrelor had a lower OPR rate and greater platelet inhibition compared with half-dose prasugrel as well as conventional-dose clopidogrel. Optimal dose reduction strategies for potent P2Y12 inhibitors require further investigation to balance safety and efficacy.

Hybrid cardiac imaging-guided optimal management of right anomalous coronary artery origin from the opposite sinus with interarterial course (R-ACAOS): a case report.

BACKGROUND: Determining the optimal management of right anomalous coronary artery from the opposite sinus (R-ACAOS) with an interarterial course (IAC) in middle-aged adults remains elusive. Hybrid cardiac imaging combining non-invasive and invasive approaches to identify high-risk anatomic features, as well as functional testing to assess potential ischaemic status by dynamic compression, can guide therapeutic decisions. CASE SUMMARY: A 65-year-old female was newly diagnosed with R-ACAOS with IAC, accompanied by suspected angina and two syncope episodes. She was initially considered as non-specific chest pain based on negative treadmill test (TMT) taken 10 years earlier. An anomaly of R-ACAOS with IAC travelling between the aorta and pulmonary artery was detected by coronary computed tomography angiography with a severe stenosis at the ostium, but with little evidence of atherosclerotic plaque. Exercise test (TMT) and single-photon emission computed tomography (SPECT) results were negative. Invasive imaging revealed a luminal area stenosis of 45% at the ostial right coronary artery, and a slit-like orifice anatomical feature, with a minimal lumen area of 5.81 mm2 at diastole determined by intravascular ultrasound. Based on hybrid cardiac imaging results and previous data from a case series, conservative management was recommended with strenuous exercise restrictions. The patient fared well during 12 months of follow-up after discharge. DISCUSSION: Hybrid cardiac imaging-guided conservative management including exercise restriction appears justifiable in such middle-aged adults with R-ACAOS accompanied by suspected angina in absence of ischaemia in stress-induced tests (TMT or SPECT), despite high-risk anatomical features of an IAC and slit-like orifice being present.

Pharmacodynamic study of prasugrel or clopidogrel in non-ST-elevation acute coronary syndrome with CYP2C19 genetic variants undergoing percutaneous coronary intervention (PRAISE-GENE trial).

BACKGROUND: The CYP2C19*2 or *3 loss-of-function (LOF) allele is associated with high platelet reactivity (HPR) on clopidogrel treatment. East Asians may benefit from a lower dose of prasugrel due to their more potent platelet inhibitory response. The impact of LOF alleles on the pharmacodynamic response to half-dose prasugrel in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) is unknown. METHODS: Seventy patients with the LOF alleles were assigned to half-dose prasugrel (n = 35, 30-mg load followed by 5 mg daily) or clopidogrel (n = 35, 600-mg load followed by 75 mg daily). The primary endpoint was the rate of HPR, defined as VerifyNow-P2Y12 reaction unit (PRU) >235, at 24 h post loading. RESULTS: Prasugrel achieved a lower PRU compared to clopidogrel after loading (119 [56-175] vs. 245 [189-299]), at 24 h (34 [8-58] vs. 196 [122-244]), and at 30 days (134 [98-189] vs. 203 [144-248]). Prasugrel had a lower rate of HPR after loading (5.7% vs. 57.1%, p <0.001), at 24 h (2.9% vs. 28.6%, p=0.006), and at 30 days (11.4% vs. 34.3%, p=0.004). Prasugrel had a similar rate of optimal platelet reactivity at 30 days (71.4% vs. 60.0%, p=0.450). There was no significant difference in the occurrence of periprocedural myonecrosis within 48 h after PCI with clopidogrel and prasugrel (22.9% vs. 17.1%, p>0.960). CONCLUSIONS: Half-dose prasugrel provided potent platelet inhibition in NSTE-ACS patients that were carriers of the CYP2C19*2 or *3 allele, with a lower rate of HPR. Periprocedural myonecrosis was not significantly different in the 2 groups.

Severe multivessel coronary artery spasm detected by computed tomography: a case report.

BACKGROUND: Ventricular arrhythmia and sudden cardiac arrest caused by multivessel coronary artery spasm (CAS) is rare. Although coronary angiography (CAG) with provocation testing is the diagnostic gold standard in current vasospastic angina guidelines, it can cause severe procedure-related complications. Here, we report a novel technique involving dual-acquisition coronary computed tomography angiography (CCTA) to detect multivessel CAS in a patient who survived out-of-hospital cardiac arrest (OHCA). CASE SUMMARY: A 58-year-old healthy Korean male survived OHCA caused by ventricular fibrillation (VF), experiencing seven episodes of defibrillation and cardiopulmonary resuscitation, and was referred to the Emergency Room. Vital signs were stable and physical examination, electrocardiogram, chest, and brain CT did not show any abnormal findings, except elevated hs-Troponin I levels (0.1146 ng/mL). Echocardiogram revealed a regional wall motion abnormality in the inferior wall, with a low normal left ventricular ejection fraction (50%). A multivessel CAS (both left and right) was detected using a dual-acquisition CCTA technique (presence and absence of intravenous nitrate). During CAG with the 2nd injection of ergonovine, a prolonged and refractory total occlusion in the proximal-ostial right coronary artery was completely relieved after a seven-cycle intracoronary injection regimen of nitroglycerine. The patient was discharged with the recommendation of smoking and alcohol cessation. Nitrate and calcium channel blockers were also prescribed. The patient had no further events at 3 months of follow-up after discharge. DISCUSSION: Dual-acquisition CCTA is a promising tool to detect multivessel CAS.

Assessing Vessel Tone during Coronary Artery Spasm by Dual-Acquisition Multidetector Computed Tomography Angiography.

BACKGROUND: Diminished vascular tone is an established biomarker of heart damage. Little is known about the extent of coronary vessel tone (CVT) with spasm as assessed by dual-acquisition multidetector computed tomography angiography (MCTA) in patients with vasospastic angina (VSA). OBJECTIVE: We evaluated the CVT modulated by intravenous nitrate injection (INI) using MCTA imaging in VSA patients. METHODS: Twenty-one VSA patients (60 ± 9 years; 76% males) who underwent initial MCTA (without morning vasodilation), followed by an intracoronary ergonovine provocation test were included. Within 3 days after the initial MCTA patients received INI followed by 28-vessel segment spasm analyzed by MCTA 3D software, applying the following formula as the definition of CVT index (CVTI): (CSAIV nitrate - CSAinitial/CSAIV nitrate) ×100 %, where CSA is the cross-sectional area. RESULTS: Compared to the initial MCTA measures, the INI provocation resulted in the significant increase of average diameter and CSA at the spasm site (2.60 mm [2.11-3.16] vs. 1.42 mm [1.13-2.13]; 5.37 mm2 [3.67-7.54] vs. 1.62 mm2 [1.02-3.02]; p < 0.001). The CVTI at the spastic segments was higher than at the proximal reference segments (41.0% [21.8-52.3] vs. 18.8% [5.9-26.6] for CVTI diameter; 65.1% [38.6-77.0] vs. 33.9% [5.2-48.1] for CVTI CSA, respectively). To predict VSA, the cut-off value for CVTI diameter was 38.6% (AUC 0.777; 95% CI 0.653-0.901) and 62.5% (AUC 0.779; 95% CI 0.657-0.902) for CVTI CSA in a receiver-operating characteristic curve analysis, with 57.1% sensitivity and 92.9% specificity. CONCLUSIONS: This novel imaging technique for assessing CVT by dual-acquisition MCTA after applying INI provocation is suitable for the detection of coronary artery spasm in patients with VSA.

A Prospective, Randomized, Open-Label, Blinded, Endpoint Study Exploring Platelet Response to Half-Dose Prasugrel and Ticagrelor in Patients with the Acute Coronary Syndrome: HOPE-TAILOR Study.

BACKGROUND: The optimal dosing of novel oral P2Y12 receptor platelet inhibitors such as prasugrel or ticagrelor is unclear and especially challenging in East Asians. We hypothesize that half-dose prasugrel and ticagrelor may be sufficient for long-term maintenance management in Korean patients with the acute coronary syndrome (ACS) compared with conventional dosages. DESIGN: HOPE-TAILOR (Half Dose of Prasugrel and Ticagrelor in Platelet Response after Acute Coronary Syndromes) is a prospective, randomized, open-label, blinded, endpoint (PROBE) single-center, clinical trial. A total of 100 patients with ACS undergoing drug-eluting stent implantation will be randomly assigned to prasugrel, ticagrelor, or clopidogrel, and the patients in each treatment group will receive 1-month therapy with 100 mg q.d. aspirin plus prasugrel 10 mg q.d., ticagrelor 90 mg b.i.d., or clopidogrel 75 mg q.d., followed by half-dose prasugrel 5 mg q.d. or ticagrelor 45 mg b.i.d. for maintenance treatment but without clopidogrel dose reduction. The primary endpoint will be optimal platelet reactivity 3 months after coronary intervention, defined by VerifyNow Analyzer (PRU: 85-208) and vasodilator-stimulated phosphoprotein P2Y12 flow cytometry assay (platelet reactivity indices: 16-50%). Clinical outcomes will also be assessed, including major efficacy (composite of cardiac death, nonfatal myocardial infarction, repeat revascularization, or stroke) and safety (bleeding ≥2 according to the Bleeding Academic Research Consortium). CONCLUSION: HOPE-TAILOR is a prospective, randomized, open-label, blinded, endpoint study to explore the efficacy and safety of novel P2Y12 receptor inhibitors administered orally at half the dose in Korean patients with ACS. The results will be available late in 2017.

Predicting Successful Recanalization in Patients with Native Coronary Chronic Total Occlusion: The Busan CTO Score.

BACKGROUND: The optimal strategy to manage chronic total occlusion (CTO) remains unclear. The Japanese CTO multicenter registry (J-CTO) score is an established tool for predicting successful recanalization. However, it does not take into account nonangiographic predictors for final technique success. In the present study, we designed and tested a scoring model called the Busan single-center CTO registry (B-CTO) score combining clinical and angiographic characteristics to predict successful CTO recanalization in Korean patients. METHODS: Prospectively enrolled CTO patients (n = 438) undergoing coronary intervention (1999-2015) were assessed. The B-CTO score comprises 6 independent predictors: age 60-74 years and lesion length ≥20 mm were assigned 1 point each, while age ≥75 years, female gender, lesion location in the right coronary artery, blunt stump, and bending >45° were assigned 2 points each. For each predictor, the points assigned were based on the associated odds ratio by multivariate analysis. The lesions were classified into 4 groups according to the summation of points scored to assess the probability of successful CTO recanalization: easy (score 0-1), intermediate (score 2-3), difficult (score 4-5), and very difficult (score ≥6). CTO opening was designated as the primary endpoint regardless of the interventional era or the skill of the operator. RESULTS: The final success rate for B-CTO was 81.1%. The probability of successful recanalization for patient groups classified as easy (n = 64), intermediate (n = 148), difficult (n = 134), and very difficult (n = 92) was 95.3, 86.5, 79.1 and 65.2%, respectively (p for trend <0.001). When compared to the J-CTO, the B-CTO score demonstrated a significant improvement in discrimination as indicated by the area under the receiver-operator characteristic curve (AUC 0.083; 95% CI 0.025-0.141), with a positive integrated discrimination improvement of 0.042 and a net reclassification improvement of 56.0%. CONCLUSIONS: The B-CTO score has been designed and validated in Korean patients with native coronary CTO and is an improved tool for predicting successful recanalization. Wider application of the B-CTO score remains to be explored.

Long-term clinical outcomes after successful and failed recanalization to native chronic Total occlusion: Insights from the Busan chronic Total occlusion (B-CTO) Registry.

OBJECTIVE: To assess hard major adverse clinical events (HMACE) after successful versus failed percutaneous coronary intervention for chronic total occlusion (PCI-CTO). BACKGROUND: There are limited data regarding long-term HMACE risks based on PCI-CTO success. METHODS: First-time PCI was performed in 438 consecutive patients with 473 target CTO lesions. Patients after procedural success (n=355; 378 CTO lesions) and failure (n=83; 95 CTO lesions) were followed for an average 40months (7-77months range). We compared HMACE (composite of cardiac death, non-fatal myocardial infarction (MI), and stroke) dependent on the success of PCI. RESULTS: The incidence of HMACE was low, with a total of 16 events, and did not differ {6% vs.3.1%, HR=0.47; CI [0.16-1.35; p=0.162} dependent on the success of PCI-CTO. There were less cardiac deaths {0.3% vs. 1.2%, RR=0.22; CI [0.01-3.50];p=0.283}, non fatal MI {1.1% vs.3.6%, RR=0.27; CI [0.06-1.22], p=0.089}, but more strokes {1.7% vs.1.2%, RR=1.32; CI [0.16-10.99], p=0.795} after successful PCI-CTO. CONCLUSIONS: The risks of HMACE after PCI-CTO over long-term follow-up were minimal, and do not depend on the procedure success. This unexpected finding somewhat challenge the aggressive interventional approach, and should be confirmed in the adequately powered randomized trial.

Comparison of Prasugrel and Ticagrelor Antiplatelet Effects in Korean Patients Presenting With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: There is insufficient data on the efficacy of prasugrel and ticagrelor in Korean patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: I n the current double-blind, prospective pilot study, 39 patients with STEMI undergoing primary percutaneous coronary intervention were randomized to receive prasugrel 60 mg loading dose (LD) followed by 10 mg daily maintenance dose (n=19), or ticagrelor 180 mg LD followed by 90 mg twice daily maintenance dose (n=20). We assessed platelet reactivity with the VerifyNow and Vasodilator-Stimulated Phosphoprotein (VASP) P2Y12 assays. Compared to baseline platelet reactivity, both prasugrel and ticagrelor groups achieved similar and significantly lower P2Y12 reaction units (PRU) (259 [IQR: 230 to 281] vs. 28 [12 to 55] for prasugrel; 261 [196 to 286] vs. 43 [11 to 61] for ticagrelor), and platelet reactivity indexes (PRI) (51.2% [39.3 to 61.3] vs. 8.1% [6.1 to 14.7] for prasugrel; 47.5% [38.4 to 50.4] vs. 11.2% [7.1 to 15.5] for ticagrelor, all P values <0.001) at 48 h post-LD. Most patients had low platelet reactivity with 95% PRU values <85 and 82% with PRI <16%. CONCLUSIONS: Both prasugrel and ticagrelor were effective for platelet inhibition in Korean STEMI patients with almost no patients exhibiting high platelet reactivity at 48 h after the LD. Our finding of a high number of patients with very low platelet reactivity deserves further studies to assess the safety of the drugs (Prasugrel and Ticagrelor in ST-segment Elevation Myocardial Infarction Study, NCT02075125).

Comparison of pharmacodynamics between low dose ticagrelor and clopidogrel after loading and maintenance doses in healthy Korean subjects.

The novel antiplatelet agent ticagrelor has been demonstrated to exert a faster and more powerful inhibition of platelet aggregation in comparison to clopidogrel in coronary artery disease patients. However, a ticagrelor dose of 90 mg twice daily might not be suitable for patients of East Asian ethnicity, and has not been fully investigated. The aim of this study was to assess the effects of low loading doses (LD, 90 mg) and maintenance doses (MD, 90 mg daily) of ticagrelor in comparison to clopidogrel (600 mg LD, 75 mg daily MD) in healthy Korean volunteers. Twelve subjects were randomized into two groups, receiving either clopidogrel (600 mg LD, followed by 75 mg MD daily for 5 days) or ticagrelor (90 mg LD, followed by 90 mg MD daily for 5 days). Following a 2-week washout period, the treatments were switched between the groups. Three platelet function assessment methods which included light transmission aggregometry (LTA), the VerifyNow assay and multiple electrode platelet aggregometry (MEA) were then used to serially measure platelet function at various time points (baseline, 0.5, 2, 6, 24, 26, 120 and 122 h). The mean IPA to 10 µM ADP in the ticagrelor group was significantly higher than that for the clopidogrel group at the 0.5, 2, 6, 26 and 122 h time points (p ≤ 0.001). However, there was no significant difference between the two groups at the 24- and 120-hour time points (p > 0.05). The assay results produced by the other two platelet function tests (VerifyNow and MEA) were similar to those obtained by LTA. The low loading and maintenance doses of ticagrelor (90 mg LD, 90 mg daily MD) cause a more rapid and potent inhibition of platelet function when compared to clopidogrel (600 mg LD and 75 mg MD). Additionally, at the lowest value of platelet inhibition strength, oral once-daily administration of ticagrelor was no less efficacious than clopidogrel at the 24- and 120-hour time points. Due to a large diurnal variation occurring with a single daily dose, a lower dose twice-daily could be a better option for patients of East Asian ethnicity.

Falsely high B-type natriuretic peptide concentration in patients without heart failure attributed to AxSYM assay: case series of eight subjects.

We report a case series of eight subjects complaining of non-specific chest pain without heart failure, but with apparent high concentrations of plasma B-type natriuretic peptide (BNP). No positive clinical characteristics were identified in physical examinations, cardiac imaging, laboratory findings, or pulmonary function tests. However, we observed unusually high BNP values when analysing blood samples of the patients using the AxSYM assay, and this was not supported by readings from Triage® or ADVIA Centaur® assays on the same samples, which showed BNP within the normal range. We believe that the possibility for false readings for high BNP levels in healthy individuals measured by AxSYM assay should be taken into account by physicians in clinical practice to avoid medical errors.