Metabolomics of repetitive myocardial stunning in chronic multivessel coronary artery stenosis: Effect of non-selective and selective ß1-receptor blockers.

Chronic coronary artery stenosis can lead to regional myocardial dysfunction in the absence of myocardial infarction by repetitive stunning, hibernation or both. The molecular mechanisms underlying repetitive stunning-associated myocardial dysfunction are not clear. We used non-targeted metabolomics to elucidate responses to chronically stunned myocardium in a canine model with and without ß-adrenergic blockade treatment. After development of left ventricular systolic dysfunction induced by ameroid constrictors on the coronary arteries, animals were randomized to 3 months of placebo, metoprolol or carvedilol. We compared these two ß-blockers with their different ß-adrenergic selectivities on myocardial function, perfusion and metabolic pathways involved in tissue undergoing chronic stunning. Control animals underwent sham surgery. Dysfunction in stunned myocardium was associated with reduced fatty acid oxidation and enhanced ketogenic amino acid metabolism, together with alterations in mitochondrial membrane phospholipid composition. These changes were consistent with impaired mitochondrial function and were linked to reduced nitric oxide and peroxisome proliferator-activated receptor signalling, resulting in a decline in adenosine monophosphate-activated protein kinase. Mitochondrial changes were ameliorated by carvedilol more than metoprolol, and improvement was linked to nitric oxide and possibly hydrogen sulphide signalling. In summary, repetitive myocardial stunning commonly seen in chronic multivessel coronary artery disease is associated with adverse metabolic remodelling linked to mitochondrial dysfunction and specific signalling pathways. These changes are reversed by ß-blockers, with the non-selective inhibitor having a more favourable impact. This is the first investigation to demonstrate that ß-blockade-associated improvement of ventricular function in chronic myocardial stunning is associated with restoration of mitochondrial function. KEY POINTS: The mechanisms responsible for the metabolic changes associated with repetitive myocardial stunning seen in chronic multivessel coronary artery disease have not been fully investigated. In a canine model of repetitive myocardial stunning, we showed that carvedilol, a non-selective ß-receptor blocker, ameliorated adverse metabolic remodelling compared to metoprolol, a selective ß1-receptor blocker, by improving nitric oxide synthase and adenosine monophosphate protein kinase function, enhancing calcium/calmodulin-dependent protein kinase, probably increasing hydrogen sulphide, and suppressing cyclic-adenosine monophosphate signalling. Mitochondrial fatty acid oxidation alterations were ameliorated by carvedilol to a larger extent than metoprolol; this improvement was linked to nitric oxide and possibly hydrogen sulphide signalling. Both ß-blockers improved the cardiac energy imbalance by reducing metabolites in ketogenic amino acid and nucleotide metabolism. These results elucidated why metabolic remodelling with carvedilol is preferable to metoprolol when treating chronic ischaemic left ventricular systolic dysfunction caused by repetitive myocardial stunning.

Potential Biomarkers and Therapeutic Targets: Inflammation and Oxidative Stress in Left Carotid Artery Stenosis with Coronary Artery Disease.

INTRODUCTION: Patients with left carotid artery atherosclerotic stenosis have an increased ischemic stroke risk. Left carotid stenosis, the most common cause of the transient ischemic attack, is related to a higher risk of acute stroke. Left carotid artery stenosis is also associated with cerebral artery infarction. The significant coronary stenosis promotes ST-segment elevation myocardial infarctions. The severe coronary stenosis plays an important role in development and progression of myocardial infarction. However, the dynamic changes of circulating oxidative stress and inflammatory markers in the carotid stenosis combined with coronary artery stenosis are not clear, and it also remains unknown whether mark of oxidative stress and inflammation are potential therapeutic targets for carotid stenosis combined with coronary artery stenosis. AIM: This study aims to explore the effects of oxidative stress combined with an inflammatory response on left carotid artery stenosis with coronary artery disease in patients. METHODS: We, therefore, tested the hypothesis that levels of markers of oxidative stress and inflammation are associated with coexistent severe carotid and coronary artery stenosis in patients. We measured the circulating levels of malondialdehyde (MDA), oxidized low-density lipoprotein (OX-LDL), homocysteine (Hcy), F2- isoprostanes (F2-IsoPs), tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), prostaglandin E2 (PG-E2) and interferon-gamma (IFN-γ) in patients with combined carotid and coronary artery severe stenosis. We also assessed the relationships among oxidative stress, inflammation, and severe stenosis of the carotid with a coronary artery in patients. RESULTS: Levels of MDA, OX-LDL, Hcy, F2-IsoPs, TNF-α, hs-CRP, PG-E2, and IFN-γ were remarkably increased (P < 0.001) in patients with combined carotid and coronary artery severe stenosis. High levels of oxidative stress and inflammation may be related to severe stenosis of the carotid with coronary arteries in patients. CONCLUSION: Our observations indicated that measurements of oxidative stress and inflammatory markers may be valuable for the assessment of the degree of carotid with coronary artery stenosis. The biomarkers of oxidative stress and inflammatory response may become therapeutic targets for carotid artery stenosis with coronary artery stenosis in patients.

Utilidad de la tomografía de coherencia óptica como guía en el tratamiento del síndrome coronario agudo: reporte de un caso / Utility of optical coherence tomography to guide treatment in acute coronary syndromes: case report / Utilidade da tomografia de coerência óptica como guia no tratamento da síndrome coronariana aguda: relato de um caso

La tomografía de coherencia óptica (OCT) es una técnica de imagen endovascular con elevada resolución espacial que permite evaluar las diferentes estructuras que componen la pared de las arterias coronarias, caracterizar morfológicamente la placa aterosclerótica y establecer el mecanismo fisiopatológico subyacente en los síndromes coronarios agudos (SCA). Se presenta el caso clínico de un paciente con infarto agudo de miocardio, donde la OCT evidenció que la reducción de la luz arterial estaba determinada principalmente por la presencia de trombo, a la vez que demostró una disrupción endotelial (ruptura de placa) como mecanismo fisiopatológico subyacente. Se adoptó una estrategia invasivo-conservadora, donde finalmente no se implantó stent. La información surgida de la OCT en este caso particular fue fundamental en la toma de decisiones.

Optical coherence tomography (OCT) is an endovascular imaging technique with high spatial resolution. It allows to evaluate the different structures that compose coronary arteries' wall, morphologically characterize atherosclerotic plaques and establish the underlying pathophysiological mechanism in acute coronary syndromes (ACS). The case of a patient with acute myocardial infarction is presented, in which OCT showed that the reduction of arterial lumen was determined mainly by the presence of thrombus, while also demonstrated endothelial disruption (plaque rupture) as the underlying pathophysiological mechanism. An invasive-conservative strategy was adopted and finally stent was not implanted. The information that emerged from the OCT in this particular case was fundamental in decision-making.

A tomografia de coerência óptica (OCT) é uma técnica de imagem endovascular com alta resolução espacial que permite a avaliação das diferentes estruturas que compõem a parede das artérias coronárias, a caracterização morfológica da placa aterosclerótica e o estabelecimento do mecanismo fisiopatológico subjacente de síndrome coronariana aguda (SCA). Apresentamos o caso clínico de um paciente com enfarte agudo do miocárdio, onde a OCT mostrou que a redução do lúmen arterial foi determinada principalmente pela presença de trombo, ao mesmo tempo que demonstrou uma ruptura endotelial (ruptura da placa) como causa fisiopatológica subjacente. Adotou-se uma estratégia invasiva-conservadora, onde finalmente o stent não foi implantado. As informações obtidas da OCT neste caso específico foram fundamentais na tomada de decisão.

Comparison of efficacy and safety of intracoronary nicardipine and adenosine for fractional flow reserve assessment of coronary stenosis.

BACKGROUND: Administration of intracoronary (IC) adenosine allows an easily feasible, inexpensive, and more rapid alternative method for fractional flow reserve (FFR). It is common practice in many centers worldwide. Nicardipine is a strong coronary vasodilator but its efficacy and safety for assessing FFR is not established. The purpose of present study was to compare the efficacy and safety of IC nicardipine and adenosine for assessing FFR. METHODS: One hundred and fifty-nine patients with a total of 193 vessels undergoing clinically indicated FFR assessment of intermediate coronary stenoses were included. For the initial assessment of FFR, hyperemia was induced by an IC adenosine. After a washout period of 3 min, FFR was reassessed using 200 µg of IC nicardipine. RESULTS: Hyperemic efficacy among two different stimuli was compared. The mean FFR with IC adenosine was 0.83 ± 0.09 and that with an IC nicardipine was 0.84 ± 0.09. The median FFR with an IC adenosine was 0.83 (0.78-0.91) and that with an IC nicardipine was 0.85 (0.79-0.91) (p-value 0.246). Both FFR values showed an excellent correlation (R2 = 0.982, p < 0.001). Nicardipine produced fewer changes in heart rate, less chest pain and less flushing than adenosine. Transient atrioventricular block occurred in 29 patients with IC adenosine and none with IC nicardipine. CONCLUSIONS: IC bolus injection of nicardipine could be introduced as a safe and practical alternative method of inducing hyperemia during FFR measurements. Compared to IC adenosine, IC nicardipine has a similar hyperemic efficacy and excellent side-effect profile.

Type 2 Myocardial Infarction Resulted from the Left Thoracic Stomach.

The universal definition of myocardial infarction (MI) provides five subtypes of acute myocardial infarction (AMI). We present an interesting case of a type 2 myocardial infarction caused by the dilation of the left thoracic stomach.

Type 2 myocardial infarction resulted from the left thoracic stomach

Abstract The universal definition of myocardial infarction (MI) provides five subtypes of acute myocardial infarction (AMI). We present an interesting case of a type 2 myocardial infarction caused by the dilation of the left thoracic stomach.

Ranolazine may exert its beneficial effects by increasing myocardial adenosine levels.

We hypothesized that ranolazine-induced adenosine release is responsible for its beneficial effects in ischemic heart disease. Sixteen open-chest anesthetized dogs with noncritical coronary stenosis were studied at rest, during dobutamine stress, and during dobutamine stress with ranolazine. Six additional dogs without stenosis were studied only at rest. Regional myocardial function and perfusion were assessed. Coronary venous blood was drawn. Murine endothelial cells and cardiomyocytes were incubated with ranolazine and adenosine metabolic enzyme inhibitors, and adenosine levels were measured. Cardiomyocytes were also exposed to dobutamine and dobutamine with ranolazine. Modeling was employed to determine whether ranolazine can bind to an enzyme that alters adenosine stores. Ranolazine was associated with increased adenosine levels in the absence (21.7 ± 3.0 vs. 9.4 ± 2.1 ng/mL, P < 0.05) and presence of ischemia (43.1 ± 13.2 vs. 23.4 ± 5.3 ng/mL, P < 0.05). Left ventricular end-systolic wall stress decreased (49.85 ± 4.68 vs. 57.42 ± 3.73 dyn/cm2, P < 0.05) and endocardial-to-epicardial myocardial blood flow ratio tended to normalize (0.89 ± 0.08 vs. 0.76 ± 0.10, P = nonsignificant). Adenosine levels increased in cardiac endothelial cells and cardiomyocytes when incubated with ranolazine that was reversed when cytosolic-5'-nucleotidase (cN-II) was inhibited. Point mutation of cN-II aborted an increase in its specific activity by ranolazine. Similarly, adenosine levels did not increase when cardiomyocytes were incubated with dobutamine. Modeling demonstrated plausible binding of ranolazine to cN-II with a docking energy of -11.7 kcal/mol. We conclude that the anti-adrenergic and cardioprotective effects of ranolazine-induced increase in tissue adenosine levels, likely mediated by increasing cN-II activity, may contribute to its beneficial effects in ischemic heart disease.NEW & NOTEWORTHY Ranolazine is a drug used for treatment of angina pectoris in patients with ischemic heart disease. We discovered a novel mechanism by which this drug may exhibit its beneficial effects. It increases coronary venous levels of adenosine both at rest and during dobutamine-induced myocardial ischemia. Ranolazine also increases adenosine levels in endothelial cells and cardiomyocytes in vitro, by principally increasing activity of the enzyme cytosolic-5'-nucleotidase. Adenosine has well-known myocardial protective and anti-adrenergic properties that may explain, in part, ranolazine's beneficial effect in ischemic heart disease.

The efficacy and safety of Shenzhu Guanxin Recipe Granules for the treatment of patients with coronary artery disease: protocol for a double-blind, randomized controlled trial.

BACKGROUND: Coronary artery disease (CAD) is one of the most common types of the cardiovascular disease. Previous pilot trials have suggested that Traditional Chinese Medicine (TCM) has brought clinical benefits for patients with CAD. We will conduct this trial to determine the efficacy and safety of Shenzhu Guanxin Recipe Granules (SGR) for the treatment of patients with CAD. METHODS: This randomized controlled trial recruited 190 patients who were diagnosed with CAD by clinical manifestation and examination and in which coronary computed tomography angiography (CCTA) showed 50-70% stenosis, with soft or mixed plaque types. The included participants were randomly assigned to the case group and control group using a 1:1 allocation ratio; patients in the case group received SGR and usual care, and those in the control group received placebo (6 g/day for 6 months) and usual care. The endpoint of the study included Calcium Coverage Score (CCS), C-reactive protein (CRP) level, and the levels of blood lipids, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and ATP-binding membrane cassette transporter A1 (ABCA1) were calculated before recruiting and at the sixth month. The indicators were Seattle Angina Questionnaire (SAQ) and TCM Syndrome Questionnaire scores at 0, 3, and 6 months. DISCUSSION: This clinical trial may provide reliable evidence regarding the clinical effectiveness and safety of SGR therapy for patients with CAD diagnosed by clinical manifestation and examination, in which CCTA showed 50-70% stenosis, with soft or mixed plaque types. TRIAL REGISTRATION: ClinicalTrials.gov, ID: ChiCTR1900020501 . The trial was registered on 25 December 2018.

Regressed coronary ostial stenosis in a young female with Takayasu arteritis: a case report.

BACKGROUND: Takayasu arteritis is a rare systemic vasculitis, which affects the aorta and its major branches, especially in young females. Diagnosis and treatment for Takayasu arteritis with coronary stenosis are important to prevent fatal complications. Immunosuppressive treatment such as corticosteroid is a common treatment for this condition. However, the effects of immunosuppressive treatment on inflammatory coronary stenosis caused by Takayasu arteritis remains unknown. CASE PRESENTATION: An 18-year-old female had chest oppression on effort and was referred to our hospital due to ST-segment depression in I, aVL, and V2-4 on electrocardiogram. Coronary angiography showed severe stenosis in the ostium of both the left main trunk and the right coronary artery. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography showed isolated inflammation of the aortic root. She was diagnosed with Takayasu arteritis and treated with combined immunosuppressive treatment with corticosteroid and tocilizumab, which decreased the FDG uptake in the aortic root. Four months after initiation of the immunosuppressive treatment, coronary angiography showed regression of the coronary ostial stenosis. Coronary artery bypass surgery was considered, but the patient rejected invasive revascularization for coronary artery disease. She did not have chest oppression or ST-segment depression after the immunosuppressive treatment. She had no cardiac events for 6 months after discharge. CONCLUSIONS: We described regressed coronary ostial stenosis in a young female patient with Takayasu arteritis. Immunosuppressive treatment might have a favorable effect on coronary ostial stenosis in Takayasu arteritis.

Impact of long-term therapy with acetylsalicylic acid on immature platelet count: a single-centre cohort study.

: Acetylsalicylic acid (ASA) represents one of the most widely used pharmacological treatments for the prevention of atherothrombotic events. However, its use in low-risk patients is still debated, due to the complex balance between benefits and bleeding complications, therefore requiring new tools for the assessment of cardiovascular risk. Immature platelet count (IPC) has been suggested as a marker of platelet reactivity and turnover, thus potentially reflecting the progression of the chronic atherothrombotic vascular damage, which could be prevented by ASA. However, no study has evaluated, so far, the impact of long-term therapy with ASA on the IPC among patients undergoing coronary angiography, which was the aim of the present study. We included patients from a single centre. Significant coronary artery disease (CAD) was defined as at least one-vessel stenosis more than 50%. Immature platelet fraction (IPF) levels were measured by routine blood cells count (a Sysmex XE-2100) in patients naive or chronically treated with ASA at admission. Among 1475 patients, 464 (31.5%) were ASA-naive. Patients on long-term antiplatelet therapy were more often men (P < 0.001), with a higher prevalence of cardiovascular risk factors and CAD. The mean levels of IPC did not differ between ASA-naive and treated patents (8 ±â€Š5.3 vs. 7.8 ±â€Š4.9, P = 0.48). Similar results were obtained when considering IPC distribution across tertiles, as ASA therapy did not result as an independent predictor of IPC levels above the third tertile (≥8.6 × 10/ml) [adjusted odds ratio (95% confidence interval) = 0.96 (0.63-1.48), P = 0.87]. Results were confirmed in major higher risk subgroups of patients. The present study shows that among high-risk patients undergoing coronary angiography, the long-term therapy with ASA does not affect the levels of IPC.

Reduced efficacy of transcatheter and surgical revascularization in Takayasu arteritis.

A 55-year-old woman with newly diagnosed Takayasu arteritis was followed for 7 years, during which time she underwent bare metal stenting, drug eluting stenting and coronary bypass grafting for critical coronary and renal artery stenoses. Interventions were initially successful but restenosis occurred within 24 months for all modalities. In contrast, native vessel disease was largely stable after the introduction of immunosuppressive therapy. We advocate a conservative revascularization approach in Takayasu arteritis in the absence of critical end organ ischemia and early optimization of medical therapy.

Comparison of sodium nitroprusside and adenosine for fractional flow reserve assessment: a systematic review and meta-analysis.

BACKGROUND: Fractional flow reserve (FFR) has become a useful tool in the assessment of physiological significance of coronary artery stenosis (CAS), and Adenosine (ADE) is associated with a high incidence of transient side effects. Sodium nitroprusside (NPS) has been proposed as an alternative vasodilator agent. A meta-analysis of studies comparing ADE and NPS for FFR assessment in the same coronary lesions was performed. METHODS: Authors searched for articles comparing NPS and ADE for FFR assessment in intermediate coronary lesions published through January 2018. The following keywords were used: 'fractional flow reserve' AND 'nitroprusside'. Data were summarized using weighted mean differences for paired data. RESULTS: Seven studies were identified comprising 342 patients and 401 lesions. Four studies evaluated intravenous ADE and 3 studies intracoronary ADE administration. Weighted means FFR values obtained with ADE and NPS were 0.8411 and 0.8445, respectively (weighted mean difference: 0.00, 95% confidence interval (CI) -0.01 to 0.01, p = 0,548). Adverse events were significantly reduced with IC NPS (RR = 0.08, 95%CI 0.02-0.30, P < 0.0001). CONCLUSIONS: NPS produces similar FFR measurements compared to ADE with a significant reduction in adverse effects. These results may support its use as a suitable alternative to ADE for FFR assessment.

Role of TLR4/MyD88/NF-κB signaling pathway in coronary microembolization-induced myocardial injury prevented and treated with nicorandil.

Coronary microembolization (CME) is a common complication during the treatment of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). Nicorandil can be used to prevent myocardial injury after PCI to reduce the incidence of coronary no-reflow and slow flow, and play a role in myocardial protection, suggesting that its mechanism may be related to the inhibition of CME-induced inflammation of cardiomyocytes. However, the specific mechanism remains unclear. This study investigated the myocardial protective effects of nicorandil pretreatment on CME-induced myocardial injury and the specific mechanism of its inhibition of myocardial inflammation. An CME rat model exhibited CME-induced myocardial inflammation and the elevation of serum tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1ß based on echocardiography, myocardial enzyme detection, hematoxylin and eosin (HE) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, ELISA, quantitative real-time PCR, and western blotting. Nicorandil treatment seven days before CME induction effectively inhibited myocardial inflammation, ameliorated myocardial injury, and improved cardiac function, mainly by inhibiting Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response protein 88 (MyD88)-dependent nuclear factor-kappa B (NF-κB) signaling. Rat neonatal cardiomyocyte experiments further confirmed that nicorandil ameliorated lipopolysaccharide (LPS)-induced myocardial inflammation and improved cardiomyocyte survival. The specific mechanisms mainly involved the inhibition of TLR4/MyD88/NF-κB signaling and the reduction of the inflammatory cytokines TNF-α and IL-1ß released from cardiomyocytes. In summary, nicorandil significantly protected cardiomyocytes from CME-induced myocardial injury mainly by inhibiting TLR4/MyD88/NF-κB signaling, thereby reducing the onset of CME-induced myocardial inflammation. This could be one of the important mechanisms for reducing postoperative myocardial injury via PCI-preoperative prophylactic treatment with nicorandil.

Anti-platelet effects of epigallocatechin-3-gallate in addition to the concomitant aspirin, clopidogrel or ticagrelor treatment.

BACKGROUND/AIMS: Although epigallocatechin-3-gallate (EGCG), which is found in high contents in the dried leaves of green tea, has been reported to have an anti-platelet effect, synergistic effects of EGCG in addition to current anti-platelet medications remains to be elucidated. METHODS: Blood samples were obtained from 40 participants who took aspirin (ASA, n = 10), clopidogrel (CPD, n = 10), ticagrelor (TCG, n = 10) and no anti-platelet medication (Control, n = 10). Ex vivo platelet aggregation and adhesion under various stimulators were analyzed by multiple electrode aggregometry (MEA) and Impact-R systems. PAC-1 and P-selectin expressions in human platelets were analyzed by flow cytometry. RESULTS: In MEA analysis, adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP)-induced platelet aggregations were lower in the CPD and the TCG groups; arachidonic acid (AA)-induced platelet aggregation was lower in the ASA group, whereas collagen (COL)-induced platelet aggregations were comparable among four groups. EGCG significantly reduced ADP- and COL-induced platelet aggregation in dose-dependent manner (ADP, p = 0.04; COL, p < 0.01). There were no additional suppressions of platelet aggregation stimulated by AA in the ASA group, and by ADP in the CPD and TCG groups. Moreover, EGCG suppressed shear stress-induced platelet adhesion on Impact-R, and had no effect on P-selectin and PAC-1 expressions. CONCLUSIONS: Ex vivo treatment of EGCG inhibited platelet adhesion and aggregation without changes in P-selectin and PAC-1 expression. There was no additional suppressions in platelet aggregation stimulated by AA in the ASA group and ADP in the CPD and TCG groups.

VEGF attenuates 2-VO induced cognitive impairment and neuronal injury associated with the activation of PI3K/Akt and Notch1 pathway.

Vascular endothelial growth factor (VEGF) has been identified as a potential treatment for effectively improving cognitive function in several neuropathological conditions. However, the underlying mechanism and the relevant downstream protective pathways that are activated in neurons by VEGF remain elusive, especially in chronic global cerebral ischemia. In this study, we intended to investigate the signaling mechanisms of VEGF in cognitive protection and anti-apoptosis in a rat model of chronic global cerebral ischemia induced by permanent bilateral common carotid artery occlusion (2-VO). The results showed that intranasal administration of VEGF (72h post-ischemia for 6 successive days) caused a significant improvement in the cognitive deficits induced by 2-VO, accompanied by a reversal of oxidative stress and VEGF depletion in the hippocampus. In addition, VEGF-treatment decreased the expression of Bax and Caspase-3, increased the expression of anti-apoptotic Bcl-xl and the main protein involved in energy homeostasis AMP-activated protein kinase (AMPK), which may account for the anti-apoptotic effects of VEGF. Importantly, VEGF administration upregulated the phosphorylation levels of Akt (pAkt) and PI3K, activated Notch1 pathway in 2-VO hippocampus. These findings suggested that intranasal administration of VEGF alleviated cognitive impairment induced by 2-VO injury, and attenuated oxidative damage and neuronal injury in hippocampus associated with the regulation of PI3K/Akt and Notch1 signaling pathway, which might be the underlying mechanisms of VEGF on global chronic cerebral ischemia.

Computed Tomography Angiography Images of Coronary Artery Stenosis Provide a Better Prediction of Risk Than Traditional Risk Factors in Asymptomatic Individuals With Type 2 Diabetes: A Long-term Study of Clinical Outcomes.

OBJECTIVE: We investigated the efficacy of coronary computed tomography angiography (CCTA) in predicting the long-term risks in asymptomatic patients with type 2 diabetes and compared it with traditional risk factors. RESEARCH DESIGN AND METHODS: We analyzed 933 patients with asymptomatic type 2 diabetes who underwent CCTA. Stenosis was considered obstructive (≥50%) in each coronary artery segment using CCTA. The extent and severity scores for coronary artery disease (CAD) were evaluated. The primary end point was major adverse cardiovascular events (MACE), including all-cause mortality, nonfatal myocardial infarction, and late coronary revascularization during a mean follow-up period of 5.5 ± 2.1 years. RESULTS: Ninety-four patients with MACE exhibited obstructive CAD with a greater extent and higher severity scores (P < 0.001 for all). After adjusting for confounding risk factors, obstructive CAD remained an independent predictor of MACE (hazard ratio 3.11 [95% CI 2.00-4.86]; P < 0.001]). The performance of a risk prediction model based on C-statistics was significantly improved (C-index 0.788 [95% CI 0.747-0.829]; P = 0.0349) upon the addition of a finding of obstructive CAD using CCTA to traditional risk factors, including age, male, hypertension, hyperlipidemia, smoking, estimated glomerular filtration rate, and HbA1c. Both integrated discrimination improvement (IDI) and net reclassification improvement (NRI) analyses further supported this finding (IDI 0.046 [95% CI 0.020-0.072], P < 0.001, and NRI 0.55 [95% CI 0.343-0.757], P < 0.001). In contrast, the risk prediction power of the coronary artery calcium score remained unimproved (C-index 0.740, P = 0.547). CONCLUSIONS: Based on our data, the addition of CCTA-detected obstructive CAD to models that include traditional risk factors improves the predictions of MACE in asymptomatic patients with type 2 diabetes.

Unrecognized coronary vasospasm in patients referred for percutaneous coronary intervention: Intracoronary nitroglycerin, the forgotten stepchild of cardiovascular guidelines.

OBJECTIVE: The goal of this study was to demonstrate the importance of intracoronary nitroglycerin (IC NTG) administration during diagnostic coronary angiography and prior to percutaneous coronary intervention (PCI). BACKGROUND: PCI has been a mainstay treatment for patients with symptomatic coronary artery disease. While current guidelines emphasize the importance of periprocedural antithrombotic medications, they fail to mention the use of nitroglycerin prior to PCI. METHODS: Retrospective chart and angiographic review was performed to identify patients referred for PCI who had significant angiographic stenoses that resolved after administration of IC NTG. RESULTS: The study group consisted of 6 patients (3 men, 3 women) with mean age 52 ± 4years (range 46-57 years). All had anginal symptoms and significant (>70%) stenosis on diagnostic coronary angiography. None had documented ST segment elevation. The median interval between diagnostic and staged PCI procedures was 3 days. IC NTG was not administered to any of the patients at the time of diagnostic coronary angiography. In each case, repeat coronary angiography following administration of IC NTG (155 ± 46 mcg) before planned PCI demonstrated resolution of the target stenosis. PCI was deferred and all patients were successfully managed medically. CONCLUSION: Coronary artery spasm is an under-recognized cause of chest pain in patients with significant angiographic lesions. Coronary spasm should be suspected especially in younger patients (less than 60 years old) with apparent single vessel disease. IC NTG should be routinely administered during diagnostic angiography and before PCI to avert unnecessary coronary interventions. © 2017 Wiley Periodicals, Inc.

Successful coronary stenting in a patient with factor V deficiency in the absence of fresh frozen plasma transfusion: Case report.

RATIONALE: Drug-eluting stent (DES) implantation in a patient with factor V deficiency (F5D) is very complex. No antithrombotic therapy study has been reported for F5D patients who undergo a coronary stenting procedure. PATIENT CONCERNS: A 73-year-old woman presented with chest discomfort and exertional dyspnea. Coronary stenting was performed successfully using DES stents. DIAGNOSES: The D-dimer, prothrombin time, and partial thromboplastin time prolongation persisted from admission until 24 hours after coronary stenting. Epistaxis and blood-tinged sputum occurred on day 3. The antiplatelet therapy measured using a Multiplate Analyzer was adequate, and other laboratory findings except factor V activity (14%) were within normal ranges; she was diagnosed with F5D based on low factor V activity. INTERVENTIONS: While taking 90 mg of ticagrelor and 100 mg of aspirin daily, the patient revisited due to recurrent epistaxis, hemoptysis, and coughing on day 26. Epistaxis and hemoptysis stopped after the aspirin was discontinued. Finally, the daily maintenance dose was reduced to 90 mg of ticagrelor once. OUTCOMES: She led healthy life for 9 months without any recurrent symptoms and the test results also were stabilized. LESSONS: We report a case of an F5D patient who underwent coronary stenting in the absence of frozen fresh plasma transfusion who received successful maintenance therapy using a single antiplatelet agent (90 mg of ticagrelor/day) with recurrent multiple mucosal bleeding events after coronary stenting.

Intracoronary adenosine-induced ventricular arrhythmias during fractional flow reserve (FFR) measurement: case series and literature review.

Fractional flow reserve (FFR) is a standardized and well-established method frequently used in clinical practice to evaluate the hemodynamic significance of epicardial coronary stenosis identified by coronary angiography. It is based on the change in the pressure gradient across the stenosis after the achievement of maximal hyperemia of the coronary circulation which is commonly induced by intravenous (IV) or intracoronary (IC) administration of adenosine. Here, we have described three cases of IC adenosine-induced ventricular arrhythmias during FFR measurement from our institution, and after literature review we found that all the cases of ventricular arrhythmias induced by adenosine during FFR measurement were observed where it was administered via IC route. Although a causal relationship between the use of IC adenosine during FFR measurement and the induction of ventricular arrhythmias is not yet established, we suggest using IV adenosine as the preferred route of administration until we better understand the incidence and mechanism underlying this phenomenon.

Effect of High (200 µg/kg per Minute) Adenosine Dose Infusion on Fractional Flow Reserve Variability.

BACKGROUND: Variations in distal coronary pressure (Pd)/aortic pressure (Pa) ratio during steady-state hyperemia with standard (140 µg/kg per minute) adenosine dose may hamper accurate fractional flow reserve assessment. This study investigated to what extent an increased adenosine dose can overcome Pd/Pa variation. METHODS AND RESULTS: In a prospective, single-arm study, out of 95 prospectively screened patients, 38 (40.0%) exhibited significant (≥0.05 difference of max Pd/Pa minus min Pd/Pa) variations in Pd/Pa from 15 s post Pd/Pa dip and until the end of a 3-minute adenosine (140 µg/kg per minute) infusion. Thirty patients agreed to participate in a post 5-minute repeat fractional flow reserve assessment using 200 µg/kg per minute 3-minute adenosine infusion. The study's co-primary end point of Pd/Pa coefficient of dispersion was lower for the high versus standard adenosine dose: 1.31 (1.13-2.72) versus 2.76 (2.38-5.60), P=0.002. The study's co-primary end point of ΔPd/Pa was also lower for the high versus standard adenosine dose: 0.065 (0.038-0.10) versus 0.08 (0.06-0.11), P=0.002. This difference was mainly driven by the lowering effect of the high adenosine dose on the maximum Pd/Pa compared to the standard dose: 0.84 (0.81-0.93) versus 0.90 (0.83-0.95), P=0.007, while minimum Pd/Pa remained unaffected. High adenosine dose was adequately tolerated by all patients, without requiring infusion discontinuation in any case. CONCLUSIONS: Pd/Pa variability is frequently observed during standard adenosine infusion and is significantly decreased following a high (200 µg/kg per minute) adenosine dose. This is achieved without a significant difference in the minimum Pd/Pa. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02350439.