Intracoronary Injection Research Articles

Efficacy and Safety of High-Dose Intracoronary Adenosine Injection in Fractional Flow Reserve Assessment.

The recommended dosage of intracoronary adenosine in fractional flow reserve (FFR) assessment is controversial. High-dose adenosine may overcome the biological variability of adenosine response in hyperemia. We aimed to test the efficacy and safety of a high-dose escalation protocol at our institute. Using the adenosine dose escalation protocol, the percentages of FFR ≤ 0.75 and 0.80 after high-dose escalation were compared with those at conventional doses. The chi-squared test was used to evaluate the accuracy of FFR values with the tested doses by comparing them with the results of a non-invasive pretest. A total of 87 patients (130 vessels) were included, and protocol adherence was 93.1%. High-dose intracoronary adenosine was injected in 78.5% of the vessels. The dose escalation strategy was well-tolerated without serious complications. The positive rate increased significantly after conducting the protocol compared to that with a conventional dose (28.2% vs. 23.6% with an FFR threshold of 0.75, and 48.7% vs. 42.5% with a threshold of 0.80, both p < 0.05). In the validation cohort, only FFR ≤ 0.75 was associated with the binary result of the non-invasive pretest (p < 0.01 vs. p = 0.37). The high-dose adenosine escalation strategy did not increase the accuracy of FFR (77.8% vs. 75.6% in conventional dose and high-dose adenosine, respectively). The use of a high-dose escalation strategy increased the positive rate in FFR assessments.

First-in-human pilot trial of combined intracoronary and intravenous mesenchymal stem cell therapy in acute myocardial infarction.

BackgroundAcute ST-elevation myocardial infarction (STEMI) elicits a robust cardiomyocyte death and inflammatory responses despite timely revascularization.ObjectivesThis phase 1, open-label, single-arm, first-in-human study aimed to assess the safety and efficacy of combined intracoronary (IC) and intravenous (IV) transplantation of umbilical cord-derived mesenchymal stem cells (UMSC01) for heart repair in STEMI patients with impaired left ventricular ejection fraction (LVEF 30-49%) following successful reperfusion by percutaneous coronary intervention.MethodsConsenting patients received the first dose of UMSC01 through IC injection 4-5 days after STEMI followed by the second dose of UMSC01 via IV infusion 2 days later. The primary endpoint was occurrence of any treatment-related adverse events and the secondary endpoint was changes of serum biomarkers and heart function by cardiac magnetic resonance imaging during a 12-month follow-up period.ResultsEight patients gave informed consents, of whom six completed the study. None of the subjects experienced treatment-related serious adverse events or major adverse cardiovascular events during IC or IV infusion of UMSC01 and during the follow-up period. The NT-proBNP level decreased (1362 ± 1801 vs. 109 ± 115 pg/mL, p = 0.0313), the LVEF increased (52.67 ± 12.75% vs. 62.47 ± 17.35%, p = 0.0246), and the wall motion score decreased (26.33 ± 5.57 vs. 22.33 ± 5.85, p = 0.0180) at the 12-month follow-up compared to the baseline values. The serial changes of LVEF were 0.67 ± 3.98, 8.09 ± 6.18, 9.04 ± 10.91, and 9.80 ± 7.56 at 1, 3, 6, and 12 months, respectively as compared to the baseline.ConclusionThis pilot study shows that combined IC and IV transplantation of UMSC01 in STEMI patients with impaired LVEF appears to be safe, feasible, and potentially beneficial in improving heart function. Further phase 2 studies are required to explore the effectiveness of dual-route transplantation of UMSC01 in STEMI patients.

Efficacy and safety of intracoronary pro-urokinase injection during percutaneous coronary intervention in treating ST elevation myocardial infarction patients: a systematic review and meta-analysis of randomized controlled trials.

Intracoronary injection of pro-urokinase (Pro-UK) during percutaneous coronary intervention (PCI) seems to be a promising treatment in improving myocardial perfusion. In this systematic review and meta-analysis, we aimed at investigating the efficacy and safety of intracoronary Pro-UK injection during PCI in ST elevation myocardial infarction (STEMI) patients. A comprehensive literature searched on PubMed, Embase, Cochrane, Ovid-MEDLINE, Ovid-Embase, Ovid-Cochrane Databases and ClinicalTrials.gov from inception until June 1, 2022, in English only. The primary outcome was myocardial perfusion, including thrombolysis in myocardial infarction (TIMI) grades, corrected TIMI frame count (CTFC), TIMI myocardial perfusion grades (TMPG). The secondary outcomes were ST-segment resolution (STR), major adverse cardiovascular events (MACE), myocardial marker, cardiac function and hemorrhagic complications. We identified 5 studies (all RCTs) involving 761 participants. Under PCI procedure, compared with placebo, intracoronary Pro-UK injection may improve myocardial perfusion, including increasing the TIMI grades [odd ratio (OR) 0.46; 95% confidence interval (CI) 0.28-0.75; p = 0.002; I2 = 0%] , CTFC (OR -3.47; 95% CI [-5.60, -1.33]; p = 0.001; I2 = 0%) and TMPG (OR 0.17; 95% CI [0.06-0.44]; p = 0.0003; I2 = 0%), increase the rate of STR (OR 2.25; 95% CI [1.56-3.26]; p < 0.0001; I2 = 0%), reduce the incidence of MACE (OR 0.51; 95% CI [0.33-0.81]; p = 0.004; I2 = 0%) and reduce myocardial infarct size (CK, standardized mean difference [SMD] -0.45; 95% [CI] [-0.62, -0.28]; p < 0.00001; I2 = 10%. CK-MB, [SMD] -0.43; 95% CI [-0.68, -0.18]; p = 0.0007; I2 = 60%. cTnI, [SMD] -0.31; 95% CI [-0.46, -0.17]; p < 0.0001; I2 = 0%). Moreover, the treatment may improve the cardiac functions (LVFE, pooled mean difference [MD] 1.23; 95% CI [0.66-1.79]; p < 0.0001; I2 = 24%. LVEDd, pooled MD -0.13; 95% CI [-0.17, -0.09]; p < 0.00001; I2 = 0%). But there is no statistically significant difference between the Pro-UK group and placebo in the occurrence of hemorrhagic complications (OR 1.19; 95% CI [0.75-1.87]; p = 0.46; I2 = 0%). Intracoronary Pro-UK injection during PCI in STEMI patients is an effective and safe treatment to perform. The treatment may improve myocardial perfusion and rate of STR, as well as decreasing the incidence of MACE and myocardial infarct size. Importantly, the treatment may improve the cardiac functions and life quality. In the future, more multi-centered and massive sample studies are required.

Preventive Effect of Bone Marrow Mononuclear Cell Transplantation on Acute Myocardial Infarction-Induced Heart Failure: A Meta-analysis of Randomized Controlled Trials.

Heart failure (HF) is a major complication of acute myocardial infarction (AMI). Transplantation of bone marrow mononuclear cells (BM-MNC) in the setting of AMI has been proposed as a means for myocardial tissue regeneration. Several trials have explored the outcomes of these cells on surrogate end points such as left ventricular ejection fraction (LVEF) in patients with AMI. However, the data regarding the clinical efficacy are infrequent. Here, we performed a meta-analysis investigating the effect of BM-MNCs injection on the rate of hospitalization for HF in the long-term follow-up period. PubMed, Scopus, and Cochrane databases were queried with various combinations of keywords through May 2, 2022. A random-effects meta-analysis was performed to calculate risk ratio (RR) and 95% confidence interval (CI) of hospitalization for HF, all-cause mortality, and stroke rate. Subgroup analyses for hospitalization based on time and cell dose were performed. A total of 2150 patients with AMI across 22 trials were included for quantitative synthesis. At long-term follow-up, AMI patients treated with an intracoronary injection of BM-MNCs were less likely to be hospitalized for heart failure compared to the control group receiving standard treatment (RR = 0.54, 95% CI = [0.37; 0.78], p = 0.002). There was no association between BM-MNC therapy and all-cause mortality (RR = 0.69, 95% CI = [0.47; 1.01], p = 0.05) and stroke (RR = 1.12, 95% CI= [0.24; 5.21], p = 0.85). Autologous injection of BM-MNC in the setting of AMI may be associated with decreased risk of hospitalization of heart failure in the long term. However, its effect on all-cause mortality and stroke rate is questionable.

Comparison of Clinical Characteristics of Intravenous Infusion Versus Intracoronary Injections of Adenosine for Evaluation of Intermediate Coronary Artery Lesions in Patients Diagnosed With Severe Aortic Stenosis

Comparison of Clinical Characteristics of Intravenous Infusion Versus Intracoronary Injections of Adenosine for Evaluation of Intermediate Coronary Artery Lesions in Patients Diagnosed With Severe Aortic Stenosis

ALDH2 mutation results in excessive basal nitric oxide production and a delayed response to nitroglycerin

Abstract Background and purpose: Nitroglycerin tolerance is a common phenomenon in patients with coronary artery disease (CAD). Aldehyde dehydrogenase 2 (ALDH2) is the enzyme that metabolizes nitroglycerin to its active form nitric oxide (NO). Previous studies showed altered nitroglycerin in subjects with ALDH2 mutation, but the functional impact on endothelial cells is not fully understood. Methods: In the first step of in vitro experiments, we examined functional properties of induced pluripotent stem cell-derived CD144+ endothelial cells (iPSC-ECs) that expressed wildtype (WT) vs ALDH2+/− variant. In the second step of human studies, diameter of the left anterior descending (LAD) coronary artery was determined using angiography in 151 adult volunteers (111 with WT ALDH2, 32 with ALDH2+/− and 8 with ALDH2−/− genotype) prior to as well as after intracoronary injection of 200-μg nitroglycerin. Results: Briefly, the ALDH2+/− iPSC-ECs demonstrated impaired low-density lipoprotein (LDL) uptake, proliferation, migration, tube formation, oxidative stress resistance, and viability. In comparison to the WT control, the ALDH2+/− iPSC-ECs had elevated NO production under baseline conditions, but exhibited a delayed NO release after nitroglycerin treatment. Exposure to 10-μg/mL nitroglycerin for 2 h increased NO production in WT iPSC-ECs but 4-h exposure was required to stimulate NO production in the ALDH2+/− iPSC-ECs. In comparison to the WT control, the subjects carrying the ALDH2+/− variants had seemingly larger LAD coronary artery diameter (3.5 and 3.8 mm vs 3.4 mm in the WT control), but attenuated vasodilatory response to nitroglycerin (ALDH2MUT group vs the WT control, 7.1 ± 0.6% vs 10.1 ± 0.8%, P = 0.024). Conclusion: These findings indicated elevated NO production by endothelia cells under basal conditions but attenuated response to nitroglycerin upon ALDH2 mutation.

Resistive reserve ratio and microvascular resistance reserve in patients with coronary vasospastic angina.

Patients with epicardial coronary vasospastic angina (VSA) may be likely to have coronary microvascular dysfunction, although mixed results have been reported. The aim of this study was to evaluate coronary microvascular function in detail using novel invasive physiologic indices, such as resistive reserve ratio (RRR) and microvascular resistance reserve (MRR). A total of 45 patients undergoing intracoronary acetylcholine (ACh) provocation test and invasive coronary circulatory evaluation using a thermodilution method were prospectively included. VSA was diagnosed as angiographic vasospasm accompanied by chest pain and/or ischemic electrocardiographic changes by intracoronary injection of ACh. Coronary circulation was assessed with physiologic indices including fractional flow reserve, resting and hyperemic mean transit time (Tmn), coronary flow reserve (CFR), basal resistance index, index of microcirculatory resistance (IMR), RRR, and MRR. Of 45 patients, 23 (51.1%) were diagnosed as having VSA. Patients with positive ACh test had longer resting Tmn (slower coronary flow velocity), higher basal resistance index, and greater RRR and MRR than those without, while fractional flow reserve, CFR, and IMR did not differ significantly between the two groups. In conclusion, although conventional measures such as CFR and IMR failed to show significant differences, RRR and MRR, novel invasive coronary physiologic indices, provided counterintuitive insights that coronary microvascular dilation function was better preserved in patients with VSA than those without.

Evaluation of Melatonin Therapy in Patients with Myocardial Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis.

Objectives We conducted a meta-analysis to quantitatively evaluate the effect of melatonin therapy on patients with myocardial ischemia-reperfusion injury (MIRI) and explore the influencing factors. Background Although preclinical studies have shown that melatonin can alleviate MIRI, its protective effect on MIRI in patients remains controversial. Methods We searched PubMed, the Cochrane Library, and Embase. The primary outcome was cardiac function (left ventricular ejection fraction [LVEF], left ventricular end-diastolic volume [LVEDV], and left ventricular end-systolic volume [LVESV]) and myocardial infarct parameters (total left ventricular mass and infarct size). Results We included nine randomized controlled clinical trials with 631 subjects. Our results showed that melatonin had no significant effects on the primary outcome, but subgroup analyses indicated that when melatonin was administered by intravenous and intracoronary injection at the early stage of myocardial ischemia, LVEF was improved (<3.5 h; standardized mean difference [SMD]:0.50; 95% CI: 0.06 to 0.94; P = 0.03) and the infarct size was reduced (<2.5 h, SMD: −0.86; 95% CI: −1.51 to −0.22; P = 0.01), whereas when melatonin was injected at the late stage of myocardial ischemia (≥3.5 h or 2.5 h), the results were the opposite. Furthermore, melatonin intervention reduced the level of cardiac injury markers, inflammatory cytokines, oxidation factors, and increased the level of antioxidant factors (P < 0.001). Conclusions The results indicated that the cardioprotective function of melatonin for MIRI was influenced by the route and timing regimen of melatonin administration; the mechanism of which may be associated with the production of inflammatory cytokines, the balance of oxidation, and antioxidant factors.

Human Growth Factor/Immunoglobulin Complexes for Treatment of Myocardial Ischemia-Reperfusion Injury.

Hepatocyte Growth Factor (HGF) and Fibroblast Growth Factor 2 (FGF2) are receptor tyrosine kinase agonists that promote cell survival after tissue injury and angiogenesis, cell proliferation and migration during tissue repair and regeneration. Both ligands have potential as systemic treatments for ischemia-reperfusion injury, however clinical use of HGF and FGF2 has been limited by poor pharmacokinetic profiles, i.e., their susceptibility to serum proteases, rapid clearance and short half-lives. Previously, we reported vaso- and cardioprotective protein complexes formed between HGF and polyclonal, non-specific immunoglobulin (IgG) with therapeutic efficacy in a rat model of myocardial ischemia with reperfusion (MI/R). Here, using a pre-clinical porcine MI/R model, we demonstrate human HGF/IgG complexes provide significant myocardial salvage, reduce infarct size, and are detectable in myocardial tissue 24 h after intracoronary injection. Furthermore, we show that multiple daily infusions of HGF/IgG complexes after MI do not lead to production of HGF-specific auto-antibodies, an important concern for administered biologic drugs. In experiments to identify other growth factors that non-covalently interact with IgG, we found that human FGF2 associates with IgG. Similar to human HGF/IgG complexes, FGF2/IgG complexes protected primary human cardiac endothelial cells under simulated ischemia (1% oxygen and nutrient deprivation) for 48–72 h. Molecular modeling studies suggested that FGF2 and HGF both interact with the Fc domain of IgG. Also, we tested whether an Fc-fusion protein would bind FGF2 to form complexes. By native gel electrophoretic assays and biochemical pulldowns, we found that Jagged1, a Notch1 ligand that controls stem cell self-renewal and tissue regeneration, bound FGF2 when presented as a Jagged1- Fc fusion protein. Our results suggest that human growth factor/IgG and FGF2/Fc- fusion complexes have potential to provide a biologics platform to treat myocardial ischemia-reperfusion and other forms of tissue injury.

Eptifibatida y vasodilatadores intracoronarios para prevenir la ausencia de reperfusión en el IAMCEST con diabetes y alta carga de trombos. Un ensayo aleatorizado

Introduction and objectivesTo study the impact of injecting intracoronary eptifibatide plus vasodilators via thrombus aspiration catheter vs thrombus aspiration alone in reducing the risk of no-reflow in acute ST-elevation myocardial infarction (STEMI) with diabetes and high thrombus burden. MethodsThe study involved 413 diabetic STEMI patients with high thrombus burden, randomized to intracoronary injection (distal to the occlusion) of eptifibatide, nitroglycerin and verapamil after thrombus aspiration and prior to balloon inflation (n=206) vs thrombus aspiration alone (n=207). The primary endpoint was post procedural myocardial blush grade and corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (cTFC). Major adverse cardiovascular events were reported at 6 months. ResultsThe intracoronary eptifibatide and vasodilators arm was superior to thrombus aspiration alone regarding myocardial blush grade-3 (82.1% vs 31.4%; P=.001). The local intracoronary eptifibatide and vasodilators arm had shorter cTFC (18.16±6.54 vs 29.64±5.53, P=.001), and better TIMI 3 flow (91.3% vs 61.65%; P=.001). Intracoronary eptifibatide and vasodilators improved ejection fraction at 6 months (55.2±8.13 vs 43±6.67; P=.005). There was no difference in the rates of major adverse cardiovascular events at 6 months. ConclusionsAmong diabetic patients with STEMI and high thrombus burden, intracoronary eptifibatide plus vasodilators injection was beneficial in preventing no-reflow compared with thrombus aspiration alone. Larger studies are encouraged to investigate the benefit of this strategy in reducing the risk of adverse clinical events.

Severe coronary artery spasm during left atrial appendage closure plus catheter ablation for atrial fibrillation: case presentation

BackgroundLeft atrial appendage closure (LAAC) combined with radiofrequency catheter ablation (RFCA) as a hybrid procedure is commonly performed to treat atrial fibrillation (AF). Although this treatment carries a low risk of coronary artery spasm (CAS), and has never been observed in LAAC procedure, caution still needed to be taken. We presented a case of CAS that occurred in an AF patient during the hybrid procedure.Case presentationThe patient was a 65-year-old man with paroxysmal AF who developed CAS during RFCA and LAAC. In this case, LAAC was performed ahead of RFCA. After atrial septal puncture, the occluder was advanced into left atrium through delivery sheath, and successfully deployed in the LAA. After verifying the assessment of “PASS” criteria, we decided to release the device. However, before releasing the occluder in LAAC, the patient’s blood pressure (BP) fell to 70/45 mmHg with heart rate (HR) drop and ST-segment elevation in II, III, and aVF and reciprocal ST-segment depression in I and aVL. Isotonic sodium chloride load was administered. After 3 min, the BP and HR raised, and ST-segment returned to normal. The occluder was successfully released after the stable condition of the patient. Then, RFCA was sequentially performed. When isolating the right pulmonary veins, the patient’s BP and HR fell again with ST-segment elevation in inferior leads. Spontaneous ventricular tachycardia and fibrillation developed rapidly and defibrillation was performed immediately with success. Coronary angiography revealed the obstruction of the right coronary artery which disappeared completely after intracoronary nitroglycerin injection (1 mg). Under systemic diltiazem infusion, the RFCA procedure was accomplished. After the procedure, the patient recovered without any neurologic deficit, and CAS has never recurred with isosorbide mononitrate treatment during follow-up.ConclusionsCAS is a rare complication associated with AF hybrid procedure. Attention should be paid to this rare but potentially life-threatening complication.

Evaluate the Correlation between the TIMI Frame Count, IMR, and CFR in Coronary Microvascular Disease.

Objective To evaluate the correlation between the TIMI frame count, IMR, and CFR in coronary microvascular disease (slow flow phenomenon). Methods TFC and IMR were recorded in the nitroglycerin and ATP administration states, and the relationship between TFC, IMR, and CFR in specific states was analyzed. Results A total of 41 patients with baseline TFC >25 frames on coronary angiography were enrolled, and nitroglycerin reduced TFC by 50% from baseline in 24 (58.54%) patients; 16 of the remaining 17 patients were able to achieve a 50% reduction in TFC by further intracoronary ATP injection. 10 patients were further tested for IMR, and the results showed significant correlations between baseline TFC and IMR (r = 0.775, P=0.008), TFC and IMR after nitroglycerin (r = 0.875, P=0.001), and the minimal TFC and IMR that could be obtained with nitroglycerin or ATP administration (r = 0.890, P=0.001). There was also a significant correlation between the proportional improvement in TFC and CFR before and after nitroglycerin injection (r = 0.685, P=0.029). In addition, we observed a lower IMR measured after nitroglycerin than after ATP in three patients, suggesting that CMD may be dominated by NO-sensitive vascular such as prearterioles and that an extensive analysis of the target site of CMD may be achieved by stepwise drug administration. Conclusion Induction of TFC in different states by a stepwise drug approach may serve as a potential primary screening method for coronary microcirculatory dysfunction, thereby reducing the need for further IMR or CFR testing.

CRT-700.06 Comparison of Clinical Characteristics of Intravenous Infusion Versus Intracoronary Injections of Adenosine for Evaluation of Intermediate Coronary Artery Lesions in Patients Diagnosed With Severe Aortic Stenosis

CRT-700.06 Comparison of Clinical Characteristics of Intravenous Infusion Versus Intracoronary Injections of Adenosine for Evaluation of Intermediate Coronary Artery Lesions in Patients Diagnosed With Severe Aortic Stenosis

Intracoronary eptifibatide with vasodilators to prevent no-reflow in diabetic STEMI with high thrombus burden. A randomized trial

Introduction and objectivesTo study the impact of injecting intracoronary eptifibatide plus vasodilators via thrombus aspiration catheter vs thrombus aspiration alone in reducing the risk of no-reflow in acute ST-elevation myocardial infarction (STEMI) with diabetes and high thrombus burden. MethodsThe study involved 413 diabetic STEMI patients with high thrombus burden, randomized to intracoronary injection (distal to the occlusion) of eptifibatide, nitroglycerin and verapamil after thrombus aspiration and prior to balloon inflation (n=206) vs thrombus aspiration alone (n=207). The primary endpoint was post procedural myocardial blush grade and corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (cTFC). Major adverse cardiovascular events were reported at 6 months. ResultsThe intracoronary eptifibatide and vasodilators arm was superior to thrombus aspiration alone regarding myocardial blush grade-3 (82.1% vs 31.4%; P=.001). The local intracoronary eptifibatide and vasodilators arm had shorter cTFC (18.16±6.54 vs 29.64±5.53, P=.001), and better TIMI 3 flow (91.3% vs 61.65%; P=.001). Intracoronary eptifibatide and vasodilators improved ejection fraction at 6 months (55.2±8.13 vs 43±6.67; P=.005). There was no difference in the rates of major adverse cardiovascular events at 6 months. ConclusionsAmong diabetic patients with STEMI and high thrombus burden, intracoronary eptifibatide plus vasodilators injection was beneficial in preventing no-reflow compared with thrombus aspiration alone. Larger studies are encouraged to investigate the benefit of this strategy in reducing the risk of adverse clinical events.

Effectiveness of Intra-Coronary Injection of Sodium Nitroprusside for the Treatment of Coronary No-Reflow through Punctured Coronary Balloon

Rapid restoration of thrombolysis in myocardial infarction III in case of no-reflow during percutaneous coronary intervention is imperative. Application of punctured coronary balloon intracoronary injection of sodium nitroprusside is a prompt, safe and effective method. To investigate the effectiveness of intracoronary injection of sodium nitroprusside via punctured coronary balloon in the treatment of no-reflow in coronary artery is the main objective of the study. We retrospectively analyzed 76 patients treated with intracoronary injection of sodium nitroprusside via punctured coronary balloon for coronary no-reflow. All 76 patients successfully completed intracoronary injection of sodium nitroprusside with the improvement of no-reflow in coronary artery for thrombolysis in myocardial infarction grade III in 74 patients. There were two complications which occurred in the early application of this technique. One was a punctured coronary balloon fracture left in the distal coronary artery and the other was a difficult pullback of the punctured coronary balloon catheter. After improving the application method, later no more complications occurred in 67 patients and no complications such as coronary guide wire pulling out of the coronary artery, coronary artery dissection, coronary artery perforation and coronary artery air embolism occurred. Coronary no-reflow treatment with intracoronary injection of sodium nitroprusside via punctured coronary balloon is safe and effective when properly applied.

Prinzmetal’s variant angina during laparoscopy: a case report of vasospasm in the context of cardiac arrest

We report the case of a 43-year-old male patient who experienced cardiac arrest during two elective laparoscopies for cholecystectomy. The first procedure was prematurely interrupted after the return of spontaneous circulation (ROSC) while the other was continued under intravenous (IV) perfusion of nitrates (isosorbide dinitrate). At each time, after a cycle of cardiopulmonary resuscitation (CPR) and injection of atropine 0.5 mg, sinus rhythm was restored. Only 3-lead electrocardiogram (ECG) outlines were recorded, showing ST-elevation in lead II. During the first incident, a coronary angiography was performed showing a vasospasm of the left anterior descending (LAD) coronary artery, reversible upon intracoronary injection of nitrates. ECG during catheterization showed ST-elevation in the anterior coronary territory. Calcium-channel blockers (CCB) were prescribed, and oral nitrates were added after the second episode. Cardiovascular prevention consisted in smoking cessation, aspirin and statins. Reporting this case seems to be relevant due to its unusual presentation: Prinzmetal’s angina is usually described as morning chest pains, and it rarely concerns Caucasian men. Moreover, the vasospasm was associated with cardiac arrest and ECG changes suggestive of ST-elevation myocardial infarction (STEMI). The final diagnosis was myocardial infarction with non-obstructive coronary arteries (MINOCA) due to coronary vasospasm, a few minutes after insufflation of pneumoperitoneum. So far, few cases have been described during non-cardiac surgery, and even fewer during laparoscopy. Sharing our experience seems important to attract attention to cardiovascular events that can occur under general anesthesia, especially when clinical presentation is rare.

Effects of nicorandil on systemic inflammation and oxidative stress induced by percutaneous coronary intervention in patients with coronary heart disease.

ObjectiveThe present study investigated the effects of a bolus intracoronary injection of nicorandil on systemic inflammation and oxidative stress induced by percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD).MethodsPatients undergoing coronary angiography (CAG) were enrolled into the CAG group (n = 30). Patients undergoing PCI were randomly divided into the PCI (n = 30) and PCI + nicorandil groups (n = 30).ResultsBlood taken from patients in the placebo group 24 hours after PCI exhibited significant increases in the expression of inflammatory indicators and mild increases in the expression of anti-inflammatory indicators. The intracoronary injection of nicorandil reversed the elevation of inflammatory indicators and significantly increased the levels of anti-inflammatory indicators in the blood of patients with PCI. Blood taken from patients in the placebo group 24 hours after PCI also displayed significant decreased superoxide dismutase levels and increased malondialdehyde levels. Nicorandil treatment reversed these changes of oxidative stress marker levels.ConclusionsThese results indicated the possible medical application of intracoronary injections of nicorandil for reducing systemic inflammation and oxidative stress in the peripheral blood of patients undergoing PCI.

Abstract 14441: Anemia is Associated With Coronary Microvascular Dysfunction and Future Adverse Outcomes in Patients With Non-Obstructive Coronary Artery Disease

Introduction: Coronary microvascular dysfunction (CMD) is associated with increased morbidity and mortality. Anemia is an important predictor of outcomes in several cardiovascular diseases, such as heart failure and coronary artery disease (CAD), however its significance in patients with non-obstructive CAD is not fully elucidated. Hypothesis: We hypothesized that anemia would be associated with CMD and future adverse outcomes. Methods: We enrolled 1334 patients with signs and/or symptoms of ischemia and with non-obstructive CAD (&lt;50% angiographic stenosis) who underwent invasive CMD evaluation and had follow-up data. CMD was defined as coronary flow reserve (CFR) (hyperemic flow/baseline flow as measured by the doppler wire) of ≤2 in response to intracoronary adenosine injection. Anemia was defined as a Hgb &lt; 13.0 g/L in males and &lt;12.0 g/L in females. MACE was defined as any incidence of myocardial infarction, cardiac revascularization (PCI, CABG) and all-cause mortality. Results: Overall mean age was 51.3±12.4 years, 66% were female. Patients with anemia were more likely to be female and have diabetes mellitus. Anemics were more likely to be diagnosed with CMD (Odds Ratio 2.01, 95% Confidence Interval [1.14-3.54]; P = 0.02). This relationship remained significant even after adjusting for cardiovascular risk factors like age, sex, hypertension, diabetes mellitus and dyslipidemia (OR 1.84, 95% CI [1.03-3.29], P = 0.04). Furthermore, patients with anemia were more likely to experience MACE (OR 1.86, 95% CI [1.30-2.66], P = 0.001), independent of possible confounders (OR 1.84, 95% CI [1.27-2.69], P = 0.002). Conclusions: Anemia is an independent predictor of CMD and future adverse cardiovascular events in patients with NOCAD. Moreover, it was associated with an increased risk of future adverse events. Further studies are needed to elucidate whether treatment of anemia in this population translates into outcomes.

Abstract 12340: Early Restoration of Coronary Vasomotor Function Following Drug-Coated Balloon Only Angioplasty of de novo Lesions

Introduction: We evaluated whether drug-coated balloon (DCB)-treated de novo lesions are prone to vasospasm and how these segments respond to ergonovine and nitrate in comparison with angiographically normal segments and other untreated segments showing prominent vasoreactivity. Hypothesis: DCB angioplasty is an emerging treatment approach for coronary artery disease. Evidences in balloon angioplasty era, however, repeatedly reported the presence of abnormal vasomotor function at balloon-injured segment, leading to fatal spasm. Methods: 68 DCB angioplasty recipients underwent 6-months follow-up coronary angiography. Vasomotor function was assessed using intracoronary injection of incremental dose of ergonovine, followed by nitrate. Percent change of mean lumen diameter was assessed by quantitative coronary angiography at three different sites: DCB-treated segment vs. angiographically normal segment ( control ) vs. normal or mildly diseased segment (diameter stenosis &lt; 30%) showing prominent vasomotor response ( other diseased segment ). Results: All patients were event-free during 6-month follow-up. A total of 87 DCB-treated lesions were analyzed. Significant ergonovine-induced vasospasm developed in 8 patients; however, none of them showed focal spasm involving DCB-treated lesion only. There was no significant difference in mean lumen diameter after ergonovine provocation between DCB-treated lesions vs. angiographically normal segments. However, vasoconstrictor response was greater in other diseased segments than in DCB-treated lesions. After nitrate injection, all segments dilated significantly. Vasoreactivity, defined as combined constrictor and dilator response, was comparable between DCB-treated lesions and controls (p&gt;0.05); while significant difference was found against other diseased segment (p&lt;0.005), implicating the restoration of vasomotor function after DCB angioplasty. Conclusions: Lesion treated by DCB did not harbor increased risk for clinically or angiographically significant vasospasm and showed vasomotor function similar to angiographically normal segments. These findings support feasibility and safety of DCB-only strategy for the treatment of de novo coronary artery disease.

Abstract 9172: Feasibility and Efficacy of Targeted Cardiac NF-kB Inhibition in Experimental Diastolic Dysfunction Using Drug-Delivery Technology: A Proof-of-Concept Study

Introduction: Elastin-like polypeptides (ELP) are novel drug delivery vectors that can be fused to therapeutic agents and cell penetrating peptides (CPPs), slowing their plasma clearance and increasing uptake by target tissues. We developed a CPP-ELP fusion to a specific inhibitor of the p50 subunit of NF-kB (SynB1-ELP-p50i). We developed a swine model of chronic kidney disease (CKD) that also fosters hypertension, cardiac remodeling, and diastolic dysfunction, and observed that cardiac abnormalities associate with increased cardiac expression of NF-kB, a ubiquitous transcription factor that modulates cardiac inflammation, fibrosis, and vascular remodeling. Hypothesis: We aimed to define the feasibility and efficacy of intra-coronary (IC) SynB1-ELP-p50i administration to test whether a targeted inhibition of NF-kB can improve cardiac abnormalities in CKD. Methods: We first performed a biodistribution study (BDS) in 3 pigs, 4 hours after IC injection of fluorescently labeled SynB1-ELP-p50i (10 mg/kg). Then, CKD was induced in 6 pigs (bilateral renovascular disease and dyslipidemia), treated with a single IC SynB1-ELP-p50i or placebo at 6 weeks and observed for 8 more weeks. Cardiac morphology and function were quantified before/after treatment by echocardiography. After completion of the studies, pigs were euthanized and hearts excised for ex vivo studies. Results: Using IVIS technology, the BDS showed significant retention of SynB1-ELP-p50i in the heart. In the efficacy study, a single IC administration of IC SynB1-ELP-p50i reduced cardiac NF-kB expression, improved cardiac relaxation, and remodeling compared to untreated CKD (Figure). Conclusions: We show for the first time the feasibility of a targeted inhibition of cardiac NF-kB using ELP technology in a translational model of CKD and diastolic dysfunction. Our study may set the stage for a new therapeutic strategy using unique drug-delivery technology never tested before to protect the heart.