Impact of perioperative antithrombotic strategies on clinical events in non-cardiac surgery.

Antithrombotic therapy including antiplatelet agents and anticoagulants are prescribed for secondary prevention in patients with established cardiovascular disease. Although antithrombotic therapy is often interrupted before non-cardiac surgery with or without perioperative bridging anticoagulation, the impact on thrombotic and bleeding events remains uncertain. A total of 360 patients chronically treated with antithrombotic therapy for secondary prevention underwent elective non-cardiac surgery under general anesthesia, with the complete interruption of antithrombotic agents. The study endpoints included all-cause death, thrombotic events, and major bleeding complications after surgical procedures. Of 360 patients, 190 (52.8%) and 200 (55.6%) received antiplatelet and anticoagulation perioperatively. Atrial fibrillation (32.8%) and coronary artery disease (22.5%) were the major indications for antithrombotic regimens. Antithrombotic therapy was interrupted from 5 [2, 7] days before the surgery to 4 [2, 7] days postoperatively. Perioperative bridging therapy with unfractionated heparin was employed in 113 (31.4%) patients. During the hospitalization, one (0.3%) patient died due to non-cardiovascular causes. Thrombotic events and major bleeding occurred in two (0.6%) and eight (2.2%) patients. Bridging therapy with heparin was significantly associated with an increased risk of bleeding events (5.3% vs. 0.8%, p = 0.02). Pre-operative bridging therapy with heparin and operative duration were significantly associated with bleeding complications. In the present study, complete interruption of antithrombotic therapy resulted in a few thrombotic events in patients undergoing elective non-cardiac surgery. Bridging therapy with heparin and longer operative duration were significantly associated with post-operative bleeding complications.

Influence of myocardial bridge on atherosclerotic plaque distribution and characteristics evaluated by near-infrared spectroscopy intravascular ultrasound.

BACKGROUND: This study aims to clarify whether myocardial bridge (MB) could influence atherosclerotic plaque characteristics assessed using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) imaging. METHODS: One hundred and sixteen patients who underwent percutaneous coronary intervention (PCI) using NIRS-IVUS imaging were included. MB was defined as an echo-lucent band surrounding left anterior descending artery (LAD). In MB patients, LAD was divided into three segments: proximal, MB, and distal segments. In non-MB patients, corresponding three segments were defined based on the average length of the above segments. Segmental maximum plaque burden and lipid content derived from NIRS-IVUS imaging in the section of maximum plaque burden were evaluated in each segment. Lipid content of atherosclerotic plaque was evaluated as lipid core burden index (LCBI) and maxLCBI4mm. LCBI is the fraction of pixels indicating lipid within a region multiplied by 1000, and the maximum LCBI in any 4-mm region was defined as maxLCBI4mm. RESULTS: MB was identified in 42 patients. MB was not associated with maximum plaque burden in proximal segment. LCBI and maxLCBI4mm were significantly lower in patients with MB than those without in proximal segment. Multivariable analysis demonstrated both MB and maximum plaque burden in proximal segment to be independent predictors of LCBI in proximal segment. CONCLUSIONS: Lipid content of atherosclerotic plaque assessed by NIRS-IVUS imaging was significantly smaller in patients with MB than those without. MB could be considered as a predictor of lipid content of atherosclerotic plaque when assessed by NIRS-IVUS imaging.

Utility of near-infrared spectroscopy to detect the extent of lipid core plaque leading to periprocedural myocardial infarction.

OBJECTIVES: The aim of this study was to investigate whether lipid core plaque (LCP) in the entire stented segment detected by near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) could predict procedural myocardial infarction (PMI) in patients undergoing percutaneous coronary artery intervention (PCI). BACKGROUND: NIRS-IVUS can identify LCP, described as high lipid core burden index (LCBI). Previously, the highest LCBI contained only in the 4-mm segment (maxLCBI4mm ) was reported to predict PMI. METHODS: Patients who underwent NIRS-IVUS examination during PCI for coronary artery disease at Chiba University Hospital were included. The extent of LCP in the stented segment derived from NIRS-IVUS analysis was presented as LCBI, maxLCBI4mm , and LCP area index (LAI), reflecting the total amount of LCP in the entire stented segment calculated as LCBI×lesion length. PMI was defined as an elevation of creatine kinase MB > 3 times upper reference level (URL), and periprocedural myocardial injury (PMInj) was defined as an elevation of troponin I>5 times URL within 12 to 24 h after PCI. RESULTS: Out of 141 enrolled patients, PMI occurred in 20 (14.2%) and PMInj occurred in 62 (44.0%) patients. Receiver-operating characteristic curve analysis revealed LAI was the strongest predictor for both PMI and PMInj (area under curve 0.771, p < 0.001, and 0.717, p < 0.001, respectively). Multiple logistic regression analysis determined high LAI value as the independent predictor of both PMI and PMInj. CONCLUSIONS: Greater extent of LCP in the entire stented segment detected by NIRS-IVUS was significantly associated with PMI as well as PMInj in patients undergoing PCI.

Vasospastic angina and overlapping cardiac disorders in patients resuscitated from cardiac arrest.

BACKGROUND: Vasospastic angina (VSA) reportedly accounts for one form of sudden cardiac arrest (SCA). Intracoronary acetylcholine (ACh) testing is useful for diagnosing VSA although invasive provocation testing after SCA is a clinical challenge. In addition, even if the ACh test is positive, any causal relationship between VSA and SCA is often unclear because patients with VSA may have other underlying cardiac disorders. METHODS: A total of 20 patients without overt structural heart disease who had been fully resuscitated from SCA were included. All patients underwent the ACh provocation test and scrutiny such as cardiac computed tomography or magnetic resonance imaging. Patients were followed up for all-cause death or recurrent SCA including appropriate implantable cardioverter defibrillator therapy. RESULTS: An ACh provocation test was performed 20 ± 17 days after cardiac arrest. Fifteen out of 20 (75.0%) patients had a positive ACh test and 2 (10.0%) had adverse events such as ventricular tachycardia and transient cardiogenic shock during the test. In patients with a positive ACh test, 6 of 15 (40.0%) patients had other overlapping cardiac disorders such as long QT syndrome, Brugada syndrome, cardiac sarcoidosis, myocarditis, or cardiomyopathy. Long-term prognosis was not different regardless of a positive ACh test or the presence of other cardiac disorders overlapping with VSA. CONCLUSIONS: Three-quarters of the patients who had been resuscitated from SCA had a positive ACh test. Further examinations revealed other overlapping cardiac disorders in addition to VSA in 40% of patients with a positive ACh test.

Greater coronary lipid core plaque assessed by near-infrared spectroscopy intravascular ultrasound in patients with elevated xanthine oxidoreductase: a mechanistic insight.

Elevated serum uric acid level was reportedly associated with greater coronary lipid plaque. Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine metabolism and believed to play an important role in coronary atherosclerosis. However, the relation of XOR to coronary lipid plaque and its mechanism are unclear. Patients with stable coronary artery disease undergoing elective percutaneous coronary intervention under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance were prospectively enrolled. They were divided into three groups according to serum XOR activities: low, normal, and high. Coronary lipid core plaques in non-target vessels were evaluated by NIRS-IVUS with lipid core burden index (LCBI) and a maximum LCBI in 4 mm (maxLCBI4mm). Systemic endothelial function and inflammation were assessed with reactive hyperemia index (RHI) and high-sensitivity C-reactive protein, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Of 68 patients, 26, 31, and 11 were classified as low, normal, and high XOR activity groups. LCBI (474.4 ± 171.6 vs. 347.4 ± 181.6 vs. 294.0 ± 155.9, p = 0.04) and maxLCBI4mm (102.1 ± 56.5 vs. 65.6 ± 48.5 vs. 55.6 ± 37.8, p = 0.04) were significantly higher in high XOR group than in normal and low XOR groups. Although RHI was significantly correlated with body mass index, diabetes, current smoking, and high-density lipoprotein cholesterol, no relation was found between XOR activity and RHI. There were also no relations between XOR activity and C-reactive protein, neutrophil-to-lymphocyte ratio, or platelet-to-lymphocyte ratio. In conclusion, elevated XOR activity was associated with greater coronary lipid core plaque in patients with stable coronary artery disease, without significant relations to systemic endothelial function and inflammation.

In-Hospital Blood Pressure Variability: A Novel Prognostic Marker of Renal Function Decline and Cardiovascular Events in Patients with Coronary Artery Disease.

INTRODUCTION: Several measures of blood pressure (BP) variability have been associated with kidney disease and cardiovascular events. Although BP is routinely measured during hospitalization in daily practice, the prognostic impact of in-hospital BP and its variability are uncertain. METHODS: A total of 226 participants who underwent elective percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) were included. BP was measured by trained nurses during the 4-day hospitalization for PCI. BP variability was assessed by standard deviation (SD) and coefficient variation of systolic BP. Estimated glomerular filtration rate (eGFR) was calculated at baseline and follow-up (≥6 months). The cardiovascular end point was defined as a composite of cardiovascular death, acute coronary syndrome, stroke, heart failure hospitalization, and any coronary revascularization. RESULTS: In-hospital BP was measured 9.5 ± 0.8 times. During a median follow-up period of 1.7 years, mean eGFR change was -1.7 mL/min/1.73 m2 per year, and 35 (15.5%) participants met the cardiovascular end point. Mean systolic BP and SD were negatively correlated with eGFR change. In the receiver operating characteristic curve analysis, SD of systolic BP predicted the cardiovascular end point (AUC 0.63, best cutoff value 14.2 mm Hg, p = 0.003). Kaplan-Meier analysis demonstrated a significantly higher incidence of the cardiovascular end point in patients with SD of systolic BP ≥14.2 mm Hg compared to their counterpart (p = 0.003). A multivariable analysis showed SD of systolic BP as an independent predictor for the cardiovascular end point. When assessed with coefficient variation, BP variability was similarly related to eGFR change and clinical outcomes. CONCLUSION: Greater in-hospital BP variability was associated with renal function decline and cardiovascular events in patients with stable CAD.

Decreased Double Product at Rest in Patients With Severe Vasospasm.

BACKGROUND: Autonomic nerve system and endothelial function play important roles in vasospastic angina. Elevated heart rate (HR), blood pressure (BP), and double product (DP) can increase endothelial-dependent coronary artery dilation and blood flow. However, the impact of HR, BP, and DP on occurrence and severity of VSA in the clinical setting is unclear. METHOD: A total of 170 patients undergoing intracoronary acetylcholine (ACh) provocation test during hospitalisation was included. Resting HR, BP, and DP were measured at least four times, and their variabilities were evaluated by standard deviations (SD) and coefficient of variations (CVs). Angiographic coronary artery vasospasm was defined as total or subtotal occlusion induced by ACh provocation. RESULTS: Mean±SD HR (65.7±9.1 vs 69.6±7.9 beats per minute; p=0.003), systolic BP (122.3±13.4 vs 127.7±14.6 mmHg; p=0.01), and DP (8,001±1,229 vs 8,903±1,495; p<0.001) were significantly lower in patients with a positive ACh test than the counterpart, whereas SD and CV of both HR and systolic BP were not significantly different between the two groups. Mean HR, BP, and DP progressively decreased with increase in the number of vessels with angiographic vasospasm. Multivariate analysis showed current smoking and lower DP as independent predictors of the greater number of vessels with provoked angiographic vasospasm. CONCLUSIONS: Resting HR, BP, and DP were lower in patients with vasospastic angina, especially in those with severe vasospasm.

Novel predictor of target vessel revascularization after coronary stent implantation: Intraluminal intensity of blood speckle on intravascular ultrasound.

BACKGROUND: The difference in intraluminal intensity of blood speckle (IBS) on integrated backscatter-intravascular ultrasound (IB-IVUS) across the coronary artery stenosis (i.e., ΔIBS) has been reported to negatively correlate with fractional flow reserve. Fractional flow reserve after coronary stenting is known as a predictor of target vessel revascularization (TVR). However, the relation between ΔIBS and TVR is unclear. METHODS: Seven hundred and three vessels which underwent percutaneous coronary intervention with stents were screened. Vessels without IVUS-guidance and follow-up information were excluded. Intraluminal IBS values were measured using IB-IVUS in cross-sections at the ostium of the target vessel and at the distal reference of implanted stent. ΔIBS was calculated as (distal IBS) - (ostium IBS). RESULTS: A total of 393 vessels were included. Mean ΔIBS at postprocedure was 6.22 ± 5.65. During the follow-up period (11.2 ± 3.1 months), 24 cases (6.1%) had TVR. ΔIBS was significantly greater in the vessels with TVR than in those without (11.10 ± 5.93 vs. 5.90 ± 5.49, P <0.001). In receiver operating characteristic curve analysis, ΔIBS significantly predicted TVR (AUC 0.74, best cut-off value 8.24, P < 0.001). Multiple logistic regression analysis showed use of drug eluting stent and ΔIBS ≥ 8.24 as independent predictors of TVR. CONCLUSIONS: ΔIBS at postprocedure was significantly associated with TVR. IVUS may be able to predict TVR by physiological assessment with measurement of ΔIBS.

Prevalence of Achilles tendon xanthoma and familial hypercholesterolemia in patients with coronary artery disease undergoing percutaneous coronary intervention.

Familial hypercholesterolemia (FH) is reportedly associated with the development of coronary artery disease (CAD), especially acute coronary syndrome (ACS). However, the prevalence of FH in patients with stable CAD is still unclear. The aim of this study was to investigate the prevalence of Achilles tendon xanthoma (ATX) and heterozygous FH in patients with stable CAD and ACS undergoing percutaneous coronary intervention (PCI). A total of 423 patients with CAD (273 stable CAD and 150 ACS) undergoing PCI at Chiba University Hospital between June 2016 and February 2018 were enrolled in this study. Soft X-ray radiography of the Achilles tendon was performed in all patients, and a maximum thickness of 9 mm or more is regarded as ATX. Heterozygous FH was diagnosed according to the Japan Atherosclerosis Society Guidelines. In comparisons between stable CAD and ACS patients, ATX was observed in 9.2% vs. 15.3% (p = 0.055), and heterozygous FH was diagnosed in 3.7% vs. 5.3% (p = 0.416), respectively. Among ACS patients, those with ST elevation myocardial infarction (STEMI) showed the highest prevalence of ATX (19.5%) and FH (7.3%). Whereas ATX and heterozygous FH were considerably observed in patients with ACS, a certain number of ATX and heterozygous FH were also detected in stable CAD patients.

Regional layer-specific longitudinal peak systolic strain using exercise stress two-dimensional speckle-tracking echocardiography for the detection of functionally significant coronary artery disease.

The present study aimed to investigate whether layer-specific regional peak-systolic longitudinal strain (LS) measurement on transthoracic echocardiogram (TTE) with exercise stress can be useful for the detection of functionally significant coronary artery disease as confirmed by invasive fractional flow reserve (FFR) in stable patients. This is a prospective analysis of 88 coronary arteries in 30 stable patients undergoing invasive FFR measurement and ergometer exercise stress TTE. Regional LS in the mid, endocardial and epicardial layers was calculated at rest, peak stress and early and late recovery phases after the exercise stress test. The endocardial-to-epicardial LS ratio was calculated as an indicator of endocardial-layer dependency of the left ventricular myocardium. Ischemic FFR defined as FFR ≤ 0.80 was observed in 33 of 88 coronary arteries. The mid-, endocardial- and epicardial-layer LS at early recovery (- 15.4 ± 5.2 vs. - 13.0 ± 4.4%, P = 0.040; - 15.7 ± 5.1 vs. - 13.2 ± 4.5%, P = 0.029; - 14.6 ± 5.1 vs. - 12.4 ± 4.0%, P = 0.038, respectively) and the percent change in the endocardial-to-epicardial LS ratio from baseline to peak stress, early recovery, and late recovery phases (1.5 ± 11.2% vs. 6.6 ± 10.5%, P = 0.009; 2.8 ± 8.9% vs. 7.1 ± 12.6%, P = 0.002; 5.2 ± 8.8% vs. 8.5 ± 13.7%, P = 0.026; respectively) were significantly more impaired in the ischemic territories (FFR ≤ 0.80) compared with the non-ischemic territories (FFR > 0.80). According to the receiver operating characteristic curve analysis, a combination of endocardial LS and percent change in the endocardial-to-epicardial LS ratio at early recovery phase plus visual evaluation of LV wall motion had incremental diagnostic value for the detection of the ischemic territory compared with visual evaluation alone (area under the curve = 0.752 and 0.618, P = 0.006). The results of this study suggested that assessing layer-specific LS and the endocardial-to-epicardial LS ratio after exercise stress on speckle-tracking TTE may have potential for objective and quantitative evaluation in the assessment of myocardial ischemia. Further studies in a larger population are needed to confirm these findings.

Microbubble contrast enhancement of neointima after drug-eluting stent implantation: an optical coherence tomography study.

Microvessels within neoatherosclerosis are associated with vulnerability and increase from the early to the very late phase after drug-eluting stent implantation. Microbubble contrast agents have been suggested to enhance tissue microvasculature for optical coherence tomography (OCT) imaging. The present study investigated whether OCT signal intensity of neointima within stented segments was enhanced after intracoronary administration of microbubble contrast agents. A total of 40 patients who underwent follow-up coronary angiography after drug-eluting stent implantation were enrolled. At the time of follow-up coronary angiography, OCT images of the stented segments were recorded before and after intracoronary administration of microbubble contrast agents. Mean OCT signal intensity of neointima after microbubble administration significantly increased [95.5 (85.7, 106.2) vs. 96.5 (88.7, 109.9), p = 0.001]. Multivariate analysis demonstrated the relationship between diabetes and greater neointima enhancement. The change in the OCT signal intensity of neointima following microbubble administration tended to be higher in diabetic patients than in non-diabetic patients [4.6 (0.6, 8.5) vs. 1.4 (- 1.1, 3.0), p = 0.05]. These findings suggest that this methodology may allow identification of neovascularization in neointima and evaluation of vulnerability of neoatherosclerosis. Microvessels in neointima may be a future target of pharmacological and interventional innovations for preventing stent failure.

Assessment of strut coverage of everolimus-eluting platinum chromium stent 2 weeks after implantation by optical coherence tomography.

The SYNERGY coronary stent is new-generation drug-eluting stents, which has a thin-strut platinum-chromium platform with everolimus in a biodegradable polymer applied to the abluminal surface. It would be speculated that favorable arterial healing with early strut coverage could be achieved. The present study investigated the degree of strut coverage using optical coherence tomography (OCT) 2 weeks after SYNERGY implantation and clinical factors contributing to strut coverage. A total of 29 patients who underwent staged percutaneous coronary intervention (PCI) to residual lesions 2 weeks after the index PCI with SYNERGY stent implantation were enrolled. At the time of staged PCI, OCT examinations of the SYNERGY stent were performed for conventional OCT analysis on both cross-sectional and strut level. SYNERGY stent showed a high level of strut coverage and apposition, and the percentage was 82.4 ± 12.4% and 96.2 ± 5.0%, respectively. The lesion complexity was significantly related to greater strut coverage on univariate analysis; however, it was found to be insignificant in multivariate analysis. Our findings suggest early arterial healing after SYNERGY stent implantation.

Multicenter research of bleeding risk between prasugrel and clopidogrel in Japanese patients with coronary artery disease undergoing percutaneous coronary intervention.

Although it has been reported that prasugrel achieves stronger antiplatelet effect and fewer cardiovascular events compared to clopidogrel in Japanese patients, there are limited data comparing the safety between the 2 dose regimens. Data from 1031 consecutive patients with coronary artery disease undergoing PCI at 5 institutions from May 2014 to April 2016, who received aspirin plus either clopidogrel (619 patients) or prasugrel (412 patients), were retrospectively analyzed. The choice of clopidogrel or prasugrel was left to the operator's discretion. Adverse events were defined as a composite of bleeding, hepatopathy, leukopenia, thrombopenia, exanthema, and major adverse cardiovascular events (MACE). MACE was defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke. The average follow-up period was 143 days in the prasugrel group and 263 days in the clopidogrel group. Adverse events occurred in 34.5% of patients in the prasugrel group and in 28.6% in the clopidogrel group. Although the Kaplan-Meier curves showed lower survival rates from MACE, all-bleeding, major bleeding, minor bleeding, and adverse events, in the prasugrel group compared to the clopidogrel group (log rank test p = 0.009, p = 0.001, p = 0.012, p = 0.018, and p < 0.001, respectively), multivariate Cox-regression analyses determined prasugrel as a significant risk factor for all-bleeding, minor bleeding, and adverse events, but not for MACE and major bleeding events. Dual antiplatelet therapy with prasugrel was independently associated with minor bleeding events, but not with MACE and major bleeding events, compared to clopidogrel, after PCI in common clinical settings.

Efficacy of 2.5-mg Prasugrel in Elderly or Low-Body-Weight Patients.

BACKGROUND: Due to concern about bleeding complications, a maintenance dose of prasugrel 2.5 mg may be used in elderly or low-body-weight patients in Japan. There is little information, however, on the efficacy and safety of a 2.5-mg maintenance dose of prasugrel. Methods and Results: In this single-center, prospective, open-label, cross-over study, a total of 44 elderly (≥75 years old) or low body-weight (<50 kg) Japanese patients >1 month after percutaneous coronary intervention who were treated with aspirin 81-100 mg and clopidogrel 75 mg were randomized to either prasugrel 2.5 mg or 3.75 mg instead of clopidogrel for 14 days, with a cross-over directly to the alternate treatment for another 14 days. Platelet inhibition was assessed with the VerifyNow assay (Accumetrics, San Diego, CA, USA) at 3 time points: baseline; day 14; and day 28. P2Y12 reaction units (PRU) ≤95 was defined as low on-treatment platelet reactivity (LPR), and PRU ≥262 as high on-treatment platelet reactivity (HPR). The prevalence of LPR was 2.2% in patients treated with clopidogrel, 2.2% in those with prasugrel 2.5 mg, and 22.7% in those with prasugrel 3.75 mg (P<0.001). Clopidogrel resulted in the higher prevalence of HPR compared with 2.5-mg and 3.75-mg prasugrel (40.9% vs. 18.2% vs. 6.8%, P<0.001). CONCLUSIONS: Prasugrel 2.5 mg may be more appropriate in elderly or lower-body-weight Japanese patients.

Predictors of in-hospital cardiac complications in patients with Takotsubo syndrome.

Takotsubo syndrome (TTS) has been recognized as a benign condition mainly due to its reversibility. However, recent researches have demonstrated that serious cardiac complications could occur during hospitalization. Thus, the aim of this study is to detect factors associated with in-hospital cardiac complications in patients with TTS. A total of 154 consecutive patients with TTS were enrolled retrospectively. In-hospital cardiac complications were observed in 61 patients (40%), including 44 patients with pulmonary edema (29%) and 25 patients with cardiogenic shock (16%). Multivariate logistic regression analysis identified lower systolic blood pressure on admission (OR 0.97, 95% CI 0.96-0.99, p = 0.001), history of diabetes mellitus (OR 2.92, 95% CI 1.01-8.41, p = 0.04), and ß-blocker use before admission (OR 16.9, 95% CI 1.57-181.7, p = 0.006) as independent predictors of in-hospital cardiac complications, while chest pain at onset was identified as a negative predictor of cardiac complications during hospitalization (OR 0.20, 95% CI 0.07-0.55, p = 0.001). Patients with cardiac complications more often needed hemodynamic support and longer hospital stay than those without (21.2 ± 19.4 vs. 11.8 ± 16.8 days, p = 0.002). TTS should be no longer recognized as a benign disease, but requiring careful management. We should obtain vital signs and patient's medical history carefully as soon as possible after admission to predict in-hospital cardiac complications.

Intravenous nicorandil versus adenosine for fractional flow reserve measurement: a crossover, randomized study.

Nicorandil has vasodilatory effects on both the epicardial coronary arteries and the coronary microvasculature, thereby increasing coronary blood flow. The objective of the present study was to investigate the effectiveness of intravenous (IV) nicorandil infusion for fractional flow reserve (FFR) measurement. In this crossover randomized study, 49 patients underwent FFR measurement with a consecutive randomized order of patient-blind infusions of continuous IV adenosine administration and a single bolus IV administration of nicorandil. The primary endpoint was the difference between the FFR by nicorandil and the FFR by adenosine, as assessed by the Bland-Altman method. The mean FFR value measured by nicorandil was not significantly different from that measured by adenosine [0.8125 ± 0.1349 vs. 0.7978 ± 0.124; mean difference, 0.0147 (95% confidence interval - 0.0373, 0.0667); P = 0.58]. There was no clinically significant diagnostic discordance, with the FFR by nicorandil > 0.80 and that by adenosine < 0.75. Hyperemia was achieved earlier using nicorandil than adenosine (34 ± 13 vs. 58 ± 15, P < 0.001). The duration of hyperemia after IV nicorandil was variable (6-570 s, mean 89 ± 98 s). IV nicorandil decreased systolic blood pressure by 32 ± 16 mm Hg (24 ± 10%) from baseline. Linear regression analysis showed that the average FFR value and the difference in systolic blood pressure were significantly associated with the bias in the FFR value between the two drugs. In conclusions, the results of the present study suggest that IV nicorandil can achieve maximal hyperemia easily and rapidly, providing an acceptable diagnostic performance for FFR assessment. However, a wide range of variation in hyperemic plateau and a decrease in blood pressure are the major limitations of this method.

Feasibility and safety of outpatient cardiac catheterization with intracoronary acetylcholine provocation test.

Intracoronary acetylcholine (ACh) provocation test is useful to diagnose vasospastic angina. Although outpatient coronary angiography has been widely performed in current clinical settings, the feasibility and safety of ACh provocation test in outpatient services are unclear. A total of 323 patients, who electively underwent ACh provocation test in hospitalization and outpatient services, were included. Coronary angiography was performed after insertion of a temporary pacing electrode in the right ventricle. The positive diagnosis of intracoronary ACh provocation test was defined as total or subtotal coronary artery narrowing accompanied by chest pain and/or ischemic electrocardiographic changes. Cardiac complications defined as composite of death, ventricular fibrillation or sustained ventricular tachycardia, myocardial infarction, cardiogenic shock, and cardiac tamponade, were evaluated. There were 201 patients (62%) in the hospitalization group and 122 patients (38%) in the outpatient group. The incidence of positive ACh provocation test was similar between the 2 groups (47 vs. 54%, p = 0.21). Coronary angiography in the outpatient group was performed through the radial artery, mostly (98%) with a 4 F sheath. Venous access site was not significantly different between the 2 groups, and the sheath size was 5 F in all cases. There were 2 cases (1.0%) of cardiac complications in the hospitalization group, whereas 1 case (0.8%), which led to unexpected hospitalization, occurred in the outpatient group. In conclusion, intracoronary ACh provocation test for the diagnosis of vasospastic angina in outpatient services was feasible and safe in selected patients.

Feasibility of omitting provocation test with 50 µg of acetylcholine in left coronary artery.

According to the Japanese Circulation Society guideline of vasospastic angina, incremental doses of acetylcholine (ACh) are prescribed for coronary spasm provocation: 20 and 50 µg for the right coronary artery (RCA), and 20, 50 and 100 µg for the left coronary artery (LCA). However, provocation by low doses of ACh in patients with low vasoreactivity may be less needed, and the requirement of 50 µg of ACh for the LCA in these patients has not been evaluated. In the present study, patients who underwent ACh provocation test for both the RCA and LCA were included. The positive diagnosis of intracoronary ACh provocation test was defined as total or subtotal coronary artery narrowing (i.e., angiographic coronary artery spasm) accompanied by chest pain and/or ischemic electrocardiographic changes. Coronary artery constriction was visually evaluated and defined as coronary artery diameter reduction <25 or 25-90% in patients without angiographic coronary artery spasm by 20 µg of ACh in the LCA. There were 33 out of 249 patients (13%) with LCA spasm by 20 µg of ACh. In subjects without LCA spasm by 20 µg of ACh, patients with coronary constriction <25% (n = 101) by 20 µg of ACh in the LCA rarely showed coronary artery spasm induced by 50 µg of ACh in the LCA, in comparison to those with coronary constriction 25-90% (n = 115) (2.6 vs. 32.7%, p < 0.001). None of the patients with coronary constriction <25% by 20 µg of ACh in the LCA had cardiac complications associated with administration of ACh. In conclusion, omission of 50 µg of ACh in the LCA may be possible when there is little coronary artery constriction by 20 µg of ACh in the LCA during provocation test, leading to less contrast and shortens overall procedure time.

Paroxysmal atrial fibrillation during intracoronary acetylcholine provocation test.

Intracoronary acetylcholine (ACh) provocation test is useful to diagnose vasospastic angina. However, paroxysmal atrial fibrillation (AF) often occurs during intracoronary ACh provocation test, leading to disabling symptoms. The aim of this study was to investigate the incidence and predictors of paroxysmal AF during the test. A total of 377 patients without persistent AF who underwent intracoronary ACh provocation test were included. Paroxysmal AF during ACh provocation test was defined as documented AF on electrocardiogram during the procedure. There were 31 patients (8%) with paroxysmal AF during the test. Of these, 11 (35%) required antiarrhythmic drugs, but none received electrical cardioversion. All of them recovered sinus rhythm within 48 h. At procedure, paroxysmal AF occurred mostly during provocation for the right coronary artery (RCA) rather than for the left coronary artery (LCA) (90 vs. 10%). Multivariate logistic regression analysis demonstrated that a history of paroxysmal AF (OR 4.38 CI 1.42-13.51, p = 0.01) and body mass index (OR 0.88 CI 0.78-0.99, p = 0.03) were independent predictors for occurrence of paroxysmal AF during intracoronary ACh provocation test. In conclusions, paroxysmal AF mostly occurs during ACh provocation test for the RCA, especially in patients with a history of paroxysmal AF and lower body mass index. It may be better to initially administer intracoronary ACh in the LCA when the provocation test is performed.

Prevalence and Clinical Features of Focal Takotsubo Cardiomyopathy.

BACKGROUND: Because it is difficult to distinguish between focal takotsubo cardiomyopathy and aborted myocardial infarction, there is little information about the prevalence and clinical features of focal takotsubo cardiomyopathy. METHODS AND RESULTS: Our cardiac catheterization databases were queried to identify patients with focal takotsubo cardiomyopathy and other types of takotsubo cardiomyopathy. We defined focal takotsubo cardiomyopathy as hypo-, a- or dyskinesis in both anterolateral and septal segments without obstructive coronary artery disease explaining the wall motion abnormality. A total of 10 patients were diagnosed with focal takotsubo cardiomyopathy. The control group comprised patients with takotsubo cardiomyopathy with apical, mid-ventricular, or basal ballooning. Clinical features and in-hospital outcomes were compared between patients with focal takotsubo cardiomyopathy and those with other types of takotsubo cardiomyopathy. Among the 144 patients with takotsubo cardiomyopathy, the apical, mid-ventricular, basal, and focal types occurred in 85 (59.0%), 49 (34.0%), 0 (0%), and 10 patients (6.9%), respectively. The left ventricular ejection fraction was significantly higher in the focal group compared with the apical and mid-ventricular group (56±13 vs. 45±13 vs. 46±12%, P=0.03). In-hospital outcome was not significantly different among the 3 groups. CONCLUSIONS: Focal takotsubo cardiomyopathy is not rare. Biplane left ventriculography is useful for its diagnosis. (Circ J 2016; 80: 1824-1829).