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.

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.

Clinical outcomes of subcutaneous implantable cardiac defibrillator implantation - Iran SICD registry.

BACKGROUND: The subcutaneous implantable-defibrillator (S-ICD) is a relatively new alternative to the transvenous ICD system to minimize intravascular lead-related complications. This paper presents outcome of SICD implantation in patients enrolled in Iran S-ICD registry. METHODS: Between October 2015 and June 2022, this prospective multicenter national registry included 223 patients with a standard indication for an ICD, who neither required bradycardia pacing nor needed cardiac resynchronization to evaluate the early post-implant complications and long-term follow-up results of the S-ICD system. RESULTS: The mean age of the patients was 45 ± 17 years. The majority (79.4%) were male. Ischemic cardiomyopathy (39.5%) was the most common underlying disorder among patients selected for S-ICD implant. Most study patients (68.6%) had ICD for primary prevention of sudden cardiac death. Seven patients (3.1%) were found to have suboptimal lead positions. Six patients (2.7%) developed a pocket hematoma; all were managed medically. During a mean follow-up of 2 years, the appropriate therapy was recorded in 13% of the patients and inappropriate ICD intervention mainly due to supraventricular tachycardia in 8.9%. Pocket infection was observed in four patients (1.8%) and five patients (2.2%) died mainly due to heart failure. CONCLUSION: S-ICDs were effective at detecting and treating both induced and spontaneous ventricular arrhythmias. Major clinical complications were rare.

Compression stockings for treating vasovagal syncope (COMFORTS-II) trial: Rationale and design of a triple-blind, multi-center, randomized controlled trial.

BACKGROUND: Reduced venous return is an important trigger of vasovagal syncope (VVS). Elastic compression stockings (ECS) can modify venous return and be of therapeutic interest; however, evidence for ECS efficacy in VVS is scarce. This randomized controlled trial was designed to address the issue. METHODS: COMFORTS-II is a multicenter, triple-blind, parallel design, randomized controlled trial aimed to assess the efficacy of ECS in preventing VVS recurrences. Using central online randomization, 268 participants will be allocated to 2 arms (1:1 ratio), wearing intervention ECS (25-30 mm Hg pressure) or sham ECS (≤10 mm Hg pressure). All participants will receive standard VVS treatment in the form of education, and lifestyle modification recommendations (drinking 2-3 l/d of fluids and consuming 10 g/d-roughly half a tablespoon-of table salt). Adherence to ECS treatment will be evaluated through diary sheets, and compared between study arms. Follow-up continues for 1 year, and is conducted via a 24/7 phone line available to patients and trimonthly visits. The co-primary outcomes are proportion of participants with any syncopal recurrence and time to first syncopal episode. Secondary outcomes include frequency of VVS spells, time intervals between recurrences, and incidence of any patient-reported adverse effects. CONCLUSION: To the best of our knowledge, COMFORTS-II is the first clinical trial to assess ECS efficacy among patients with VVS, addressing an important gap in evidence for VVS treatments.

Prevalence of Return to Work in Cardiovascular Patients After Cardiac Rehabilitation: A Systematic Review and Meta-analysis.

The present systematic review and meta-analysis aimed to clarify the effects of cardiac rehabilitation (CR) on the prevalence of return to work (RTW) in cardiovascular diseases (CVDs) patients. CR plays a very important role in the management of CVDs and improves the patients' physical activity, quality of life, and a decrease in the cost of healthcare. RTW is the most important goal in the rehabilitation of CVD patients. PubMed, Web of Science, Scopus, and Google scholar were searched systematically from inception up to January 2021 for English published clinical trials and observational studies. In total, 16 studies were analyzed, of them, 8 were controlled studies. Pooled results showed that the mean age of patients was 52.30 (50.04, 54.57). The prevalence of RTW in the CR attending group was 66% (60%, 71%) and in the control group was 58% (47%, 68%). Subgroup analysis showed that the proportion of RTW was higher in white-collars 76% (73%-79%) compared to. blue-collars 63% (56%-70%). Out-patient CR with 72% (61%-81%) RTW was more effective compared to in-patient CR with 62% (44%- 78%) and usual care (control). It can be concluded that CR especially out-patient CR increases the prevalence of RTW but not much. Improved and appropriate CR programs related to each individual's disease and patient condition which follow the valid guidelines might help to increase the effectiveness of CR in terms of RTW.

Effect of Endothelial Adhesion Molecules on Atrial Fibrillation: A Systematic Review and Meta-analysis.

Background: Endothelial adhesion molecules (EAMs), and more specifically vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), belong to a family of immunoglobulin-like molecules and are found to have increased expression in inflamed microvessels. Due to the growing evidence regarding EAM effects on cardiovascular diseases, we aimed to investigate the link between EAMs and atrial fibrillation (AF) to discover the efficacy of EAMs assessment as predictive markers in high-risk patients. Methods: We searched for articles published from January 1990 to April 2022. Two independent researchers selected studies that examined the relationship between VCAM-1 and ICAM-1 levels and AF. Study design, patient characteristics, VCAM-1 and ICAM-1 levels, and measurement methods were extracted from the selected articles. Results: Of 181 records, 22 studies were finally included in the systematic review. Meta-analyses showed a significant difference in serum levels of EAMs in patients with AF compared with patients with sinus rhythms (VCAM-1: mean difference [MD] 86.782, 95% CI 22.805-150.758, p=0.008; ICAM-1: MD 28.439 ng/mL, 95% CI 12.540-44.338, p<0.001). In subgroup analysis of persistent AF, the differences were still significant (VCAM-1: MD 98.046, 95% CI 26.582-169.510, p=0.007; ICAM-1: MD 25.091, 95% CI 12.952-37.230, p<0.001). We also found the mean ranges of VCAM-1 (95% CI 661.394-927.984 ng/mL) and ICAM-1 (95% CI 190.101-318.169 ng/mL) in patients with AF. Conclusion: This study suggests a positive association between serum levels of VCAM-1 and ICAM-1 with AF, but there is a need for further large-scale studies.

The survey of electrophysiology lab activity during the COVID-19 pandemic.

BACKGROUND: With the onset and spread of the COVID-19 pandemic, the hospitalization and treatment of noncovid patients were dramatically affected. The aim of this study is to evaluate the electrophysiology (EP) lab activity in a referral center in Iran during the COVID-19 era. METHODS: A cross-sectional descriptive survey was conducted on EP lab activity in Shahid Chamran Heart Center, Isfahan, Iran. Two periods of COVID-19 occurrence peaks in Iran were compared with same date in 2019. Information was collected on number of diagnostic and therapeutic electrophysiology studies (EPSs) and implantation of intracardiac devices such as permanent pacemaker (PPM), implantable cardioverter defibrillator (ICD), and cardiac resynchronization therapy (CRT). RESULTS: In the first peak of COVID-19 pandemic, both of EPSs and intracardiac device implantations decreased by 80% compared to the same period in 2019. The most common type of device implanted during this period was PPM (70%); however, at the time of control, the ICD (73%) was the most common. Paroxysmal supraventricular tachyarrhythmia (PSVT) was the best indication for diagnostic and therapeutic EPSs in covid and control periods. In the second peak of prevalence of COVID-19 virus infection in Iran, 6% and 36% decreases in device implantations and EPSs were seen, respectively. During this period, the number of procedures increased, although it was still lower than in 2019. CONCLUSION: A significant reduction in the EP lab activity has been observed during both the COVID-19 pandemic peaks.

Effect of COVID-19 medications on corrected QT interval and induction of torsade de pointes: Results of a multicenter national survey.

BACKGROUND: There are some data showing that repurposed drugs used for the Coronavirus disease-19 (COVID-19) have potential to increase the risk of QTc prolongation and torsade de pointes (TdP), and these arrhythmic side effects have not been adequately addressed in COVID-19 patients treated with these repurposed medications. METHODS: This is the prospective study of 2403 patients hospitalised at 13 hospitals within the COVID-19 epicentres of the Iran. These patients were treated with chloroquine, hydroxychloroquine, lopinavir/ritonavir, atazanavir/ritonavir, oseltamivir, favipiravir and remdesivir alone or in combination with azithromycin. The primary outcome of the study was incidence of critical QTc prolongation, and secondary outcomes were incidences of TdP and death. RESULTS: Of the 2403 patients, 2365 met inclusion criteria. The primary outcome of QTc ≥ 500 ms and ∆QTc ≥ 60 ms was observed in 11.2% and 17.6% of the patients, respectively. The secondary outcomes of TdP and death were reported in 0.38% and 9.8% of the patients, respectively. The risk of critical QT prolongation increased in the presence of female gender, history of heart failure, treatment with hydroxychloroquine, azithromycin combination therapy, simultaneous furosemide or beta-blocker therapy and acute renal or hepatic dysfunction. However, the risk of TdP was predicted by treatment with lopinavir-ritonavir, simultaneous amiodarone or furosemide administration and hypokalaemia during treatment. CONCLUSION: This cohort showed significant QTc prolongation with all COVID-19 medications studied, however, life-threatening arrhythmia of TdP occurred rarely. Among the repurposed drugs studied, hydroxychloroquine or lopinavir-ritonavir alone or in combination with azithromycin clearly demonstrated to increase the risk of critical QT prolongation and/or TdP.

Comparison of Outcomes with Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS trial): Rationale and design for a multi-center randomized controlled trial.

BACKGROUND: The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions. METHODS: In this open-label multi-center randomized controlled trial, we are going to randomize 1375 patients with VVS who had ≥2 syncopal episodes in the last year into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or no medication. All patients will be recommended to drink 2 to 3 liters of fluids per day, consume 10 grams of NaCl per day, and practice counter-pressure maneuvers. In medication arms, patients will start on 5 mg of midodrine TDS or 0.05 mg of fludrocortisone BD. After one week the dosage will be up-titrated to midodrine 30 mg/day and fludrocortisone 0.2 mg/day. Patient tolerance will be the principal guide to dosage adjustments. We will follow-up the patients on 3, 6, 9, and 12 months after randomization. The primary outcome is the time to first syncopal episode. Secondary outcomes include the recurrence rate of VVS, time interval between first and second episodes, changes in quality of life (QoL), and major and minor adverse drug reactions. QoL will be examined by the 36-Item Short Form Survey questionnaire at enrollment and 12 months after randomization. CONCLUSION: The COMFORTS trial is the first study that aims to make a head-to-head comparison between midodrine and fludrocortisone, against a background of lifestyle modifications for preventing recurrences of VVS and improving QoL in patients with VVS.

Proximal coronary sinus pacing induced prolonged asystole.

BACKGROUND: Atrioventricular node (AVN) is an interatrial septum structure located at the apex of triangle of Koch that modulates the transmission of impulses from atria to the ventricles. Vagally mediated AVN block with high frequency stimulation (HFS) was investigated in a few animal and human studies, but prolonged ventricular asystole that was induced by a low frequency proximal coronary sinus (CS) overdrive pacing has rarely been reported. CASE REPORT: A 40-year-old man was admitted in our hospital for evaluation of syncope and palpitation. He presented with prolonged ventricular asystole by proximal CS pacing during electrophysiological study (EPS). CONCLUSION: There is no comprehensive clinical study to investigate the association of vasovagal syncope with vagally mediated atrioventricular block (AVB) which is induced by posteroseptal area stimulation. Radiofrequency catheter ablation of ganglionated plexi (GP) located close to sinus node and AVN was reported to eliminate the vagal efferent output during vasovagal syncope as a new treatment strategy.

A Systematic Review and Meta-analysis on the Prevalence of Smoking Cessation in Cardiovascular Patients After Participating in Cardiac Rehabilitation.

Smoking is the most important modifiable cardiovascular risk factor causes around approximately one of every 4 cardiovascular-related deaths worldwide. Cardiac rehabilitation (CR) is the standard way of management of heart diseases after myocardial infraction. This study aimed to determine the prevalence of cardiovascular patients' quit smoking after participation in CR. PubMed, EMBASE, Web of Science, Scopus, and google scholar were searched systematically. In total, 18 studies were analyzed. Results showed that the mean age of smokers' were 54.80 (52.06, 57.55), and of them 53 % (22%, 83%) quit smoking after participating in CR. Subgroup analysis showed that among type of CR the most effective one was the educational along with physical exercise (comprehensive CR) cause 99% (98%, 100%) smoking cessation (SC). Group-based methods with76% (57%, 94%) of quitters showed to be more effective than individual-based. It can be concluded that CR has been effective in terms of smoking cessation.

The association of anthropometric indices and cardiac function in healthy adults.

BACKGROUND: Obesity is a major risk factor for many diseases including cardiovascular diseases (CVDs). Recently, it has been shown that upper body obesity can predict CVDs per se. In this study, we aimed to determine the association between indicators of upper body obesity and echocardiographic indices. METHODS: In this cross-sectional study conducted in Hajar Hospital in Shahrekord, Iran, from March to August 2014, 80 healthy adults were included. Participants' neck circumference (NC), waist circumference (WC), body mass index (BMI), and blood pressure were measured. Echocardiography was performed for all participants, and echocardiographic indices such as early (E') and late (A') diastolic tissue velocity, early (E) and late (A) transmitral flow velocity, E/E' ratio, pulmonary arterial pressure (PAP), and left atrial volume (LAV) were recorded. The association between these indices were investigated using bivariate Pearson correlation coefficient. RESULTS: For men, NC had a significant correlation with LAV, systolic blood pressure (SBP), diastolic blood pressure (DBP), PAP, and A', and a negative correlation with E'. WC had a significant correlation with LAV, SBP, and PAP, and a negative correlation with E', while BMI had a significant correlation with LAV, PAP, SBP, A, and A'. For women, NC had a significant positive correlation with LAV, A, ejection fraction (EF), SBP, PAP, and A', and a negative correlation with E' and E/E'. WC had a significant positive correlation with LAV, DBP, PAP, A, A', and a negative correlation with E', while BMI had a significant correlation with LAV, EF, SBP, PAP, E', A, and A'. CONCLUSION: The positive correlation of NC with SBP, A, and A', as well as NC, WC, and BMI with LAV and PAP in both sexes, and the negative correlation of NC with E' show the importance of these measures in estimation of metabolic and cardiovascular risk factors.

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.

The Effect of Acupressure on Physiological Parameters of Myocardial Infarction Patients: A Randomized Clinical Trial.

BACKGROUND: Myocardial infarction is a major complication of coronary heart disease, and due to high mortality, is a part of important medical emergencies. Today, complementary and alternative medicine, as nonpharmacological and health promotion methods is considered. Therefore, this study was designed to evaluate the effectiveness of acupressure on physiological parameters of patients with myocardial infarction. MATERIALS AND METHODS: This clinical trial was carried out among two groups and three stages in 2015. Study participants included 64 patients hospitalized in Iran, Isfahan Shahid Chamran hospital. Acupressure in five points and at any point for 2 minutes, twice per day for 3 days was done in the experimental group and as the same at a false point for the control group. Physiological parameters were recorded before, immediately, and 30 minutes after intervention. Data were analyzed using SPSS 20 and independent t-tests, Chi-square, Mann-Whitney test, repeated-measurements analysis of variance. RESULTS: Independent t-test immediately and 30 minutes after the intervention showed that mean systolic blood pressure and arterial oxygen saturation in the intervention group were significantly lower and higher than the control group, respectively; however, mean diastolic blood pressure and heart rate were not significantly different. However, 30 minutes after intervention, diastolic blood pressure and heart rate were significantly lower in the intervention group. CONCLUSIONS: Acupressure in five points of body had a positive effect on physiological parameters, and showed that after a short time of interventions these parameters lead to promotion over time.