Antianginal effects of empagliflozin in patients with type 2 diabetes and refractory angina; a randomized, double-blind placebo-controlled trial (EMPT-ANGINA Trial).

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are emerging antidiabetic agents with various potential cardiovascular benefits. The EMPT-ANGINA trial examined the effect of empagliflozin on the angina burden in those with concurrent type 2 diabetes mellitus (T2DM) and refractory angina (RA). METHOD: In this 8-week, double-blind, randomized, placebo-controlled trial, 75 patients with T2DM and RA were randomly assigned to one of two groups: empagliflozin (n = 37) and placebo (n = 38). The primary outcome was an improvement in angina, which was assessed by the Seattle Angina Questionnaire (SAQ). The secondary outcomes of this study included alterations in the SAQ domains and exercise test components. RESULTS: The mean age of individuals in the empagliflozin and placebo groups was 67.46 ± 9.4 and 65.47 ± 7.0 years, respectively (p = .304). Patients who received empagliflozin showed a significant improvement in both the primary endpoint, which was the SAQ Summary Score (192.73 ± 20.70 vs. 224 ± 25.36, p < .001) and the secondary endpoints. Exercise test components, including treadmill exercise duration, time till angina, 1 mm ST-segment depression onset, and heart rate (HR) recovery, were all significantly improved in the empagliflozin group. This positive impact was reached with no clinically significant changes in resting and exertion HR or blood pressure. There were no significant side effects in the empagliflozin group (p = .125). CONCLUSION: Empagliflozin can be safely added as a metabolic modulator agent to existing antianginal medications in individuals with concurrent T2DM and RA to reduce angina symptoms and enhance exercise capacity with minimal side effects.

Blood group types and clinical, procedural, and adverse outcomes in ST-elevated myocardial infarction patients: A 3-year cohort in Iran.

Background: The objectives of this study were to assess the relation of blood groups and the rate of successful angioplasty in patients with ST-elevated myocardial infarction (STEMI) and also to investigate long-term adverse outcomes follow-up. Materials and Methods: In this study, 500 eligible patients with definitive diagnosis of STEMI who underwent primary percutaneous coronary intervention (PCI) were followed up for 3 years. The patient's angiography images were examined and thrombolysis in myocardial infarction (TIMI) flow rate and coronary artery patency rate were evaluated in different ABO blood groups. All patients were followed up after 3 years based on major adverse cardiovascular events. Results: There was no significant difference in coronary artery patency rate between the patients of the different blood types with respect to TIMI flow before (P = 0.19) and after revascularization (P = 0.69). The incidence of atrial fibrillation (AF) in blood Group A was the highest. Death in the blood Groups AB and O was significantly higher than the other groups. No significant differences were seen in different blood groups in the frequency of mortality (P = 0.13), myocardial infarction (P = 0.46), heart failure (P = 0.83), re-hospitalization, angiography (P = 0.90), PCI (P = 0.94), coronary artery bypass graft (P = 0.26), implantable cardioverter defibrillator (ICD) implantation (P = 0.26), and mitral regurgitation (P = 0.88). Conclusion: The incidence of AF in blood Group A and inhospital mortality in blood Groups AB and O were the highest. The blood group may be considered in assessment of clinical risk in STEMI patients.

Does Opioid Addiction Influence Clinical and Angiographic Outcomes in STEMI Patients Undergoing Emergency PCI?

Background: Despite recognizing the traditional coronary artery disease (CAD) risk factors, some secondary factors, such as opioid substance abuse, have to be considered. We aimed to assess the relationship between opioid consumption and emergency percutaneous coronary intervention (PCI) revascularization results, according to Thrombolysis in Myocardial Infarction (TIMI) flow and in-hospital survival outcomes in ST-elevation myocardial infarction (STEMI) patients. Materials and Methods: This case-control study was conducted on 186 patients (93 patients in each group) with acute STEMI, who were referred to Chamran Heart Center, Isfahan, Iran. Opioid addiction was diagnosed by patients' records and confirmed by conducting an interview based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria. Patients in both groups were evaluated and compared for angioplasty results based on the TIMI flow grade and in-hospital cardiovascular events and complications. Results: Ninety-one patients (97.84%) of each group were male, and opioid-addicted patients were younger than the non-opioid users (52.95 9.91 vs. 57.90 12.17, P = 0.003). Among the CAD risk factors, prevalence of dyslipidemia was significantly higher in non-opioid users, whereas cigarette smoking was higher in opioid-addicted patients (P < 0.050). There was no significant difference between the two groups regarding pre- and post-procedural myocardial infarction complications as well as mortality rate (P > 0.050). Also, there were no significant differences between the opioid and non-opioid users regarding TIMI flow grading, and successful PCI rate based on achieving TIMI III was 60.21% versus 59.1% in opiate-dependent and non-opioid users, respectively (P = 0.621). Conclusion: Opioid addiction has no effects on post-PCI angiographic results and in-hospital survival outcomes in STEMI patients which undergoing emergency PCI.

Viewpoints on the Role of Transient Receptor Potential Melastatin Channels in Cardiovascular System and Disease: A Systematic Review.

Transient receptor potential (TRP) family play critical roles in cardiovascular system. TRPM family as largest TRP subfamily is non-voltage Ca2+-activated selective channels which has 8 members. This study aimed to discuss the role of TRPM family in cardiovascular system and diseases. Systematic search was performed covering PubMed, ISI Web of Science, and Google Scholar from inception until June 2021 using related keywords and Mesh terms for English studies with human, animal and in-vitro subjects. Finally 10 studies were selected for data extraction. Reviewing the articles showed that TRPM2, TRPM4, TRPM5, TRPM6 and TRPM7 play important roles in cardiovascular system and diseases. TRPM2 could be activated by reactive oxygen species (ROS) and effects on cardiac injury and cardiac fibrosis. TRPM7 and TRPM6 also have been reported to be associated with cardiac fibrosis and atrial fibrosis development respectively. TRPM4 channels contributed to resting membrane potential of cerebral artery smooth muscle cells and atrial contraction. TRPM5 channels are bitter taste sensors and prevent high salt intake and consequently high blood pressure due to the high salt intake. In conclusion based on the proof of the effectiveness of some members of TRPM family in the cardiovascular system, research on other members of this channel group seems to be useful and necessary to find their possible connection to the cardiovascular system.

Comparison of Pulmonary Emboli Management Between Pulmonary Emboli Response Team and the Conventional Method: The First Study From Iran.

BACKGROUND: We aimed to evaluate the effectiveness of the Pulmonary Embolism Response Team (PERT) for intermediate-high risk and high-risk pulmonary embolism (PE) patients. METHODS: This single-blind clinical trial was performed in 2019-2021, evaluating patients with intermediate-high risk and high risk of PE. Patients in the intervention group were managed by the PERT team, and treatment plans were implemented as soon as possible. Patients in the other group received conventional PE treatments based on the hospital protocols. We compared the primary outcome of short-term mortality between the 2 groups and secondary outcomes, including right ventricle indices, hospital length-of-stay, time to decision, 30-day and in-hospital bleeding. RESULTS: Data of 74 patients were analyzed. We found no significant differences between the 2 groups regarding short-term mortality (P = 0.642), bleeding, and other complications. However, the length-of-stay and time to decision were significantly lower in patients treated by the PERT team (P < 0.001 for both). Further evaluations revealed that patients in the intervention group had a more significant reduction in the right ventricle size and systolic pulmonary pressure compared with the control group (P = 0.015, P = 0.039, respectively). In addition, tricuspid annular plane systolic excursion and fractional area change increased more in the intervention group (P = 0.023, P = 0.016, respectively). CONCLUSIONS: The PERT team led to significantly less time to make decisions, and it was able to select patients for advanced treatments more appropriately. Due to these facts, patients treated by PERT had significantly lower hospitalization duration and better right ventricle indices compared to controls.

Anethum graveolens L. (Dill) Effect on Human Lipid Profile: An Updated Systematic Review.

Dill is an aromatic edible herb, belongs to the genus Anethum in the celery family (Apiaceae or Umbelliferae) with a long history of cultivation from ancient times and two closely related cultivated species, European dill (Anethum graveolens) and Indian dill (Anethum Sowa). We wanted to do this systematic review on the effect of Anethum graveolens intake on lipid profile because the outcomes of multiple research and meta-analyses in this regard were inconsistent. A systematic search for English published randomized controlled trials (RCTs) covering PubMed, EMBASE, Scopus, and Coherence library. The pooled weighted mean difference (MD) and its 95% confidence interval (CI) were calculated and pooled using a random-effects model. Pooled data of 6 RCTs involving 171 intervention cases indicated that dill supplementation was associated with a significant reduction in mean serum total cholesterol (MD 95% CI= -3.71(-5.71,-1.70); P < 0.001), low-density lipoprotein cholesterol (LDL-C) (MD 95% CI= -1.51(-2.65,-0.47); P = 0.005), TG (triglycerides) (MD 95% CI= -2.48(-3.98,-0.98); P = 0.001) and interestingly high-density lipoprotein cholesterol level (HDL-C) (MD 95% CI= -2.19(-3.58,-0.81); P = 0.002). Subgroup analysis showed that dill use was more effective in lowering triglyceride in both hyperlipidemic patients, MD 95% CI= -3.54(-6.49,-0.60); P = 0.02) and type 2 diabetes (MD 95% CI= -3.64(-5.69,-1.58); P = 0.001). Dill use reduced the LDL levels more effectively in patients with type 2 diabetes (MD 95% CI= -3.54(-6.49,-0.60); P = 0.03). Dill supplementation significantly improved LDL-C, TG, and Total cholesterol (TC) levels but not HDL-C. Further high quality controlled clinical trials on human is needed for more accurate and confirm conclusion.

The Pragmatic Role of COVID-19 on the Thrombus Grade of Patients with Contemporary ST-Segment-Elevation Myocardial Infarction.

Background: Limited data exist on the clinical outcomes of patients with coronavirus disease 2019 (COVID-19) presenting with ST-segment-elevation myocardial infarction (STEMI). Methods: This multicenter study, conducted in 6 centers in Iran, aimed to compare baseline clinical and procedural data between a case group, comprising STEMI patients with COVID-19, and a control group, comprising STEMI patients before the COVID-19 pandemic, and to determine in-hospital infarct-related artery thrombus grades and major adverse cardio-cerebrovascular events (MACCEs), defined as a composite of deaths from any cause (cardiovascular and noncardiovascular), nonfatal strokes, and stent thrombosis. Results: No significant differences were observed between the 2 groups regarding baseline characteristics. Primary percutaneous coronary intervention (PPCI) was performed in 72.9% of the cases and 98.5% of the controls (P=0.043), and primary coronary artery bypass grafting was performed in 6.2% of the cases and 1.4% of the controls (P=0.048). Successful PPCI procedures (final TIMI flow grade III) were significantly fewer in the case group (66.5% vs 93.5%; P=0.001). The baseline thrombus grade before wire crossing was not statistically significantly different between the 2 groups. The summation of thrombus grades IV and V was 75% in the case group and 82% in the control group (P=0.432). The rate of MACCEs was 14.5% and 2.1% in the case and control groups, respectively (P=0.002). Conclusion: In our study, the thrombus grade had no significant differences between the case and control groups; however, the in-hospital rates of the no-reflow phenomenon, periprocedural MI, mechanical complications, and MACCEs were statistically significantly higher in the case group.

The Effect of 3-Month Growth Hormone Administration and 12-Month Follow-Up Duration among Heart Failure Patients Four Weeks after Myocardial Infarction: A Randomized Double-Blinded Clinical Trial.

BACKGROUND: The probable impact of growth hormone (GH) as a heart failure (HF) treatment strategy is still less investigated. Therefore, we aimed to evaluate the relation of 3-month GH prescription on left ventricular ejection fraction (LVEF), interventricular septum (IVS), posterior left ventricle (LV) thickness, end systolic and end diastolic diameters (ESD and EDD), and pulmonary arterial pressure (PAP) among Iranian individuals suffering from HF due to MI attack. METHODS: A total of 16 clinically stable participants with HF diagnosis and LVEF < 40% were selected for enrollment in this pilot randomized double-blinded study. They were randomly assigned equally to groups received 5 IU subcutaneous GH or placebo. Injections were done every other day for a total of 3-month duration. After termination of intervention and nine months afterwards, cardiac outcomes were assessed. RESULTS: Baseline and 12-month posttrial participants' characteristics were similar. LVEF was increased significantly by three months started from baseline in individuals receiving GH (32 ± 3.80% to 43.80 ± 4.60%, P = 0.002). During the next 9 months of follow-up concurrent with cessation of injections, LVEF was declined (43.80 ± 4.60% to 32.20 ± 6.97%, P = 0.008). LVEF and ESD were remarkably higher and lower in GH group compared with controls by the end date of injections (43.80 ± 4.60% vs. 33.14 ± 4.84%, P = 0.02 and 39.43 ± 3.45 mm vs. 33 ± 3.16 mm, P = 0.03, respectively). No other considerable association was found in terms of other predefined variables in neither GH nor placebo groups. CONCLUSIONS: GH administration in HF patients was associated with increased LVEF function. Several randomized clinical trials are necessary proving this relation. This trial is registered with IRCT201704083035N1.

Resistin and prooxidant-antioxidant balance: Markers to discriminate acute coronary syndrome from stable angina.

BACKGROUND: Resistin and oxidative stress may play a role in the pathogenesis of coronary heart disease (CHD) including acute coronary syndrome (ACS). The aim of this study was to investigate the role of serum resistin and prooxidant-antioxidant balance (PAB) in ACS occurrence in order to differentiate it from stable angina. Moreover, we aimed to determine the correlation between resistin and PAB in patients with ACS and its difference from patients with stable CHD. METHODS: This cross-sectional, descriptive study was conducted on 50 patients with ACS and 50 patients with stable CHD who underwent coronary angiography (CAG). Serum resistin level was measured using enzyme-linked immunosorbent assay (ELISA). PAB and other variables were analyzed using standard methods. RESULTS: A significant increase in serum resistin and PAB was observed in patients with ACS (2.55 ± 0.13 ng/ml and 123.5 ± 5.58 HK unit, respectively) compared to patients with stable CHD (1.53 ± 0.12 ng/ml and 95.9 ± 2.7 HK unit, respectively) (P < 0.001). In addition, a significant positive correlation was seen between serum resistin and PAB in patients with ACS (r = 0.39; P = 0.005), but this correlation was not found in patients with stable CHD (r = 0.21; P = 0.140). Resistin (r = 0.52; P < 0.001) and PAB (r = 0.55; P < 0.001) were significantly associated with high-sensitivity C-reactive protein (hs-CRP) in patients with ACS, but this association was not found in patients with stable CHD (resistin: r = 0.24; P = 0.090; PAB: r = -0.02: P = 0.910). CONCLUSION: High serum resistin or PAB levels, and their association with the occurrence of ACS, can be used as a robust discriminating factor to differentiate ACS from stable CHD.

Endothelial dysfunction in patients with lone atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common tachyarrhythmia in patients with cardiovascular diseases (CVDs) and may have significant complications such as stroke. The present study aims to evaluate endothelial dysfunction in patients with lone atrial fibrillation (LAF) through flow-mediated dilation (FMD) in the brachial artery, as a non-invasive method for evaluating functional and structural markers of endothelial dysfunction. METHODS: In this case-control study, 43 patients with LAF were selected. 51 age and sex-matched healthy individuals were selected as the control group. The brachial artery diameter of the subjects in both groups was measured through FMD. The obtained data were analyzed by SPSS software. RESULTS: Patients with LAF and healthy subjects did not have any difference in terms of gender, heart rate (HR), and systolic blood pressure (SBP) (P > 0.05 for all). FMD of the patients with AF was significantly lower (P = 0.04) than FMD of the healthy controls. CONCLUSION: Our findings showed that LAF was associated with systemic endothelial dysfunction. AF plays an important and independent role in reducing FMD.

Comparing efficacy of receiving different dosages of eptifibatide in bleeding after percutaneous coronary intervention in patients with myocardial infarction.

BACKGROUND: Acute coronary syndrome (ACS) is a common condition that needs appropriate treatment like percutaneous coronary intervention (PCI). Glycoprotein IIb/IIIa inhibitors (GPI) like eptifibatide prevent procedural ischemic complications after PCI. Eptifibatide has increased the risk of bleeding complications, although it is effective in reducing mortality and morbidity. Eptifibatide is routinely used in bolus and infusion forms and the aim of this study is to evaluate the efficacy of bolus-only dose and bolus + infusion strategy for administrating eptifibatide in bleeding complications and consequences after PCI. METHODS: This randomized clinical trial was conducted on subjects who experienced PCI after incidence of myocardial infarction (MI). Patients were randomly divided into two groups who received bolus-only dose (n = 51) or bolus + infusion form of eptifibatide (n = 50). Then, PCI blood pressure, mean time duration of hemostasis after arterial sheath removal, laboratory data, need for blood transfusion, and presence of bleeding complications were evaluated. After 6 months, patients were followed for needs for additional coronary interventions. RESULTS: The mean age of participants was 61.68 ± 1.50 years. The prevalence of men was 70.29%. There was no significant difference in mean of systolic blood pressure (SBP) and diastolic blood pressure (DBP) during hospitalization (P > 0.050). The mean time duration of hemostasis was 8.13 ± 0.45 minutes in the bolus-only group and 16.46 ± 0.71 minutes in the bolus + infusion group (P < 0.001). There was no significant difference in the hemoglobin (Hb) level, platelet count, white blood cell (WBC), blood urea nitrogen (BUN), and creatinine level (P > 0.050). CONCLUSION: The results of this study suggested that bolus-only dose of eptifibatide before PCI could be able to decrease significantly bleeding complication and other clinical and cardiovascular outcomes.

The effect of intracoronary versus intralesional injection of eptifibatide on myocardial perfusion outcomes during primary percutaneous coronary intervention in acute ST-segment elevation myocardial infarction; A randomized clinical trial study.

BACKGROUND: Previous studies have proved that intracoronary injection of eptifibatide is safe and more effective in infarct size reduction and clinical outcomes than intravenously injection in the patients with acute myocardial infarction (AMI). This study aimed to compare the effect of localized and intracoronary injection of eptifibatide on myocardial perfusion improvement and its outcomes. METHODS: We conducted a randomized clinical trial study of 60 patients presented with thrombotic AMI. The patients underwent percutaneous coronary intervention (PCI), and were randomly divided into two equal number groups. The first group received two bolus doses of 180 µg/kg eptifibatide through guiding catheter. The second group received the same bolus doses through export aspiration catheter into the coronary lesion directly. Thrombolysis in myocardial infarction (TIMI) flow, myocardial blush grade (MBG), and no-reflow phenomenon were primary end points. Secondary end points were pre- and postprocedure cardiac arrhythmia, in-hospital mortality, adverse effects, reinfection, pre-discharge ventricular systolic function, and re-hospitalization and mortality after 6 month of follow up. RESULTS: The mean ages of group I and group II were 58.3 ± 1.8 and 57.0 ±2.0 years, respectively, and most of patient were men (90% in group I and 80% in group II). Postprocedural TIMI flow grade 3 was achieved in 60.0% and 76.7% of the intracoronary and intralesional groups, respectively (P = 0.307). Postprocedural MBG grade 3 was achieved in 53.3% and 70.0% in intracoronary and intralesional groups, respectively (P = 0.479). There was no significant difference between the groups in no-reflow assessment. Moreover, no significant difference was seen between the two groups in secondary end-point analysis. CONCLUSION: Both methods of intracoronary and intralesional eptifibatide administration during primary PCI in patients with acute ST-elevation myocardial infarction (STEMI) were safe and similar in myocardial perfusion outcomes.

Serum interleukin-18 and extent of coronary artery disease in unstable angina.

BACKGROUND: Interleukin-18 (IL-18) is an inflammatory marker with challenging role in atherosclerosis. The present study was carried out aiming to evaluate the association between IL-18 serum level and extent and severity of atherosclerosis among young patients with unstable angina (UA) who underwent coronary angiography. METHODS: This cross sectional study was performed from July to October 2015 in Chamran heart center, Isfahan, Iran. 180 patients with UA in the age range of below 50 years entered the study. All demographic, past history, physical examination, electrocardiogram (EKG or ECG), and transthoracic echocardiogram (TTE) data were collected. Serum level of IL-18 was measured using enzyme-linked immunosorbent assay (ELISA) method. A coronary angiography was performed on all patients to evaluate the presence and the incidence rate of coronary artery disease (CAD). RESULTS: Mean age of the patients was 46.0 ± 4.6 years [47.4 ± 4.3 and 45.9 ± 4.9 among patients with CAD and normal coronary, respectively (P = 0.040)]. Rate of severe CAD was greater among men compared to women with values 67.8% and 51.8%, respectively (P = 0.032). The median [interquartile range (IQR)] value of serum IL-18 among patients with CAD [192.86 (128.03,325.75)] was higher than normal coronary subjects [172.81 (139.77,243.21)], however it was not significant (198.4 ± 93.5, P = 0.287). A significant difference between serum IL-18 level and number of stenosis vessels was detected only among women (P = 0.032). CONCLUSION: Serum IL-18 level can predict the number of coronary arteries with significant stenosis among women with unstable angina.

Right ventricular (RV) echocardiographic parameters in patients with pulmonary thromboembolism (PTE).

BACKGROUND: Acute pulmonary thromboembolism (PTE) is a common disease with a high mortality rate, and a variable and nonspecific clinical presentation. To detect the nonspecific signs and symptoms associated with this condition, several right ventricular (RV) echocardiographic parameters have been proposed as practical marker. METHODS: This cross-sectional study was performed on 93 patients with PTE diagnosed by computed tomography (CT) angiography, and 57 patients with negative PTE based on CT angiography. During the experiment, all patients underwent both transthoracic echocardiography (TTE) and multi-slice CT pulmonary angiography. Transthoracic echocardiography measurements were obtained as patients went through both experimental procedures. These measurements were later compared between the patients with and without PTE. RESULTS: Tricuspid annulus plain systolic excursion (TAPSE) (1.65 ± 0.09 vs. 2.00 ± 0.08 cm, P < 0.001) and left ventricular (LV) end-diastolic diameter (4.54 ± 0.26 vs. 5.40 ± 0.24 cm, P < 0.001) were significantly lower in patients with PTE as compared to patients without it. Whereas, RV end-diastolic and end-systolic diameters at the papillary muscle levels (3.41 ± 0.09 vs. 3.02 ± 0.12 cm, and 2.48 ± 0.08 vs. 2.16 ± 0.06 cm, respectively, P < 0.001 for both), and tricuspid valve (TV) annulus tissue Doppler imaging (TDI) measurements (6.02 ± 0.10 vs. 5.78 ± 0.14, P < 0.001) were significantly greater in patients with PTE. On the other hand, no significant difference was found between the two groups of patients regarding pulmonary artery pressure (PAP) (P = 0.416), and RV fractional shortening (P = 0.157). Moreover, our results indicated that RV/LV (cut-off point: 0.6898) had high sensitivity (93.5%), specificity (100%), positive predicting value (PPV) (100%), and negative predicting value (NPV) (90.4%) in diagnosing PTE. CONCLUSION: TTE may be valuable as a substitute diagnostic method for patients with PTE. This technique may also assist in detecting the severity of the illness, by evaluating RV/LV in cut-off point of 0.6898.