Transplantation of mesenchymal stem cells for prevention of acute myocardial infarction induced heart failure: study protocol of a phase III randomized clinical trial (Prevent-TAHA8).

BACKGROUND: Results from recent clinical trials on bone marrow mononuclear cell (BM-MNC) transplantation show that this intervention can help reduce the incidence of heart failure (HF) after acute myocardial infarction (AMI). However, no study has evaluated the effect of the transplantation of mesenchymal stem cells (MSCs) on a clinical endpoint such as HF. METHODS: This single-blinded, randomized, multicenter trial aims to establish whether the intracoronary infusion of umbilical cord-derived Wharton's jelly MSCs (WJ-MSCs) helps prevent HF development after AMI. The study will enroll 390 patients 3 to 7 days following AMI. Only patients aged below 65 years with impaired LV function (LVEF < 40%) will be included. They will be randomized (2:1 ratio) to either receive standard care or a single intracoronary infusion of 107 WJ-MSCs. The primary outcome of this study is the assessment of HF development during long-term follow-up (3 years). DISCUSSION: Data will be collected until Nov 2024. Thereafter, the analysis will be conducted. Results are expected to be ready by Dec 2024. We will prepare and submit the related manuscript following the CONSORT guidelines. This study will help determine whether or not the infusion of intracoronary WJ-MSCs in patients with AMI will reduce the incidence of AMI-induced HF. TRIAL REGISTRATION: ClinicalTrials.gov NCT05043610 , Registered on 14 September 2021 - retrospectively registered.

Single vs. double intracoronary injection of mesenchymal stromal cell after acute myocardial infarction: the study protocol from a randomized clinical trial: BOOSTER-TAHA7 trial.

BACKGROUND: Meta-analysis from previous studies have shown that treatment with mesenchymal stromal cell (MCSs) may increase the left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) by 3.84%, and the effect is greater in those who are not aged and have developed a reduced LVEF. However, it seems that MSC transplantation does its effect through an indirect paracrine effect, and direct differentiation to the cardiomyocytes does not occur. Therefore, it can be hypothesized that this paracrine effect would be augmented if repeated doses of MSC are transplanted. This study is conducted to compare single vs. double injection of MSCs. METHODS: This is a single-blind, randomized, multicenter trial aiming to determine whether intracoronary infusion of double doses of umbilical cord-derived Wharton's jelly MSCs (WJ-MSCs) improves LVEF more after AMI compared to single administration. Sixty patients 3 to 7 days after AMI will be enrolled. The patients should be under 65 years old and have a severe impairment in LV function (LVEF < 40%). They will be randomized to three arms receiving single or double doses of intracoronary infusion of WJ-MSCs or placebo. The primary endpoint of this study is assessment of improvement in LVEF at 6-month post intervention as compared to the baseline. DISCUSSION: This investigation will help to determine whether infusion of booster (second) dose of intracoronary WJ-MSCs in patients with AMI will contribute to increasing its effect on the improvement of myocardial function. TRIAL REGISTRATION: Iranian Registry of Clinical Trials ( www.IRCT.ir ) IRCT20201116049408N1. Registered on November 26 2020.

Pharmacological treatment of high-normal blood pressure (prehypertension) in high-risk patients for primary prevention of cardiovascular events.

Currently, the best treatment strategy for patients with a high-normal blood pressure (prehypertension) is not known. The authors aimed to determine whether pharmacological reduction of systolic blood pressure (SBP) to a normal level (<120 mm Hg) would prevent cardiac morbidity and mortality in prehypertensive patients. In this secondary analysis, the authors obtained the data from SPRINT from the National Heart, Lung, and Blood Institute data repository center. Among 9361 patients enrolled in SPRINT, 289 high-risk (ASCVD risk = 24.8% ± 13.0 [10-65]) prehypertensive patients without previous cardiovascular disease and not receiving any antihypertensive medications were enrolled. One hundred and forty-eight of them were assigned to standard treatment which consisted of clinical follow-up till SBP goes above 140 mm Hg and then staring medications to keep SBP <140 mm Hg. One hundred and forty-one were assigned to the intensive treatment receiving pharmacological SBP reduction to <120 mm Hg upon enrollment. The primary composite outcome was myocardial infarction, and other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. Throughout the 3.06 years of follow-up, a primary outcome event was confirmed in three participants (0.74% per year) in the intensive-treatment group and 8 (1.61% per year) in the standard-treatment group (hazard ratio [HR], 0.19; P = .045). Rates of serious adverse events were not increased by intensive-treatment (HR, 0.83; P = .506). Based on this secondary post hoc analysis, intensive SBP reduction may probably be beneficial for primary prevention of cardiovascular morbidity and mortality in high-risk prehypertensive patients. This finding needs to be evaluated in a larger trial designed specifically to answer this question.

The Effect of Cardiopulmonary Resuscitation and Cardiac Chest Pain Management Training on Perceived Control, Depression, Stress and Anxiety in the Spouses of the Patients with Myocardial Infarction: A Randomized Controlled Trial.

BACKGROUND: Sudden cardiac death is the most common cause of mortality worldwide. Most cases occur at home and the individuals most likely witnessed are family members. Spouses play a significant role in the recovery of such patients. We aimed to investigate the effect of Cardiopulmonary Resuscitation (CPR) and cardiac chest pain management trainings on the perceived control, depression, stress and anxiety in the spouses of the patients with Myocardial Infarction (MI). METHODS: The present randomized controlled trial study was performed on 78 spouses of the patients admitted to Cardiac Care Unit of the hospitals affiliated to Shiraz University of Medical Sciences from August 2013 to April 2014. The subjects were randomly assigned into intervention (n=40) and control groups (n=38). The intervention group took part in educational workshop on CPR and cardiac chest pain management and followed-up for six weeks. Data were collected using Depression Anxiety Stress (DASS) Scale and Rotter's internal-external locus of Control Scale. Statistical methods of data analysis included descriptive statistics, Chi-squared test, paired sample t-test, independent sample t-test, one way analysis of covariance, and multivariate analysis of covariance. RESULTS: There were significant differences between intervention and control groups in perceived control and DASS subscales. After the intervention, perceived control scores reduced from 9.42±3.33 to 8.15±3.65 (P=0.001); depression from 28.85±11.99 to 21.65±8.64 (P=0.001); anxiety from 26.6±9.46 to 20.70±6.29 (P=0.02); and stress from 30.20±10.91 to 24.32±10.23 (P=0.01) in the intervention group. CONCLUSION: CPR and cardiac chest pain management trainings could effectively improve the perceived control, depression, anxiety, and stress in the spouses of the patients with MI. Trial Registration Number: IRCT201310128124N2.

Association of coronary artery dominance and mortality rate and complications in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) is the treatment of choice for patients with ST-segment elevation myocardial infarction (STEMI). Effect of coronary artery dominance on the patients' outcome following primary PCI (PPCI) is not fully investigated. We investigated the association of coronary artery dominance with complications and 1-year mortality rate of PPCI. MATERIALS AND METHODS: In this retrospective study, patients with STEMI treated with PPCI from March 2016 to February 2018 were divided into three groups based on their coronary dominancy: left dominance (LD), right dominance (RD), and codominant. Demographic characteristics, medical history, results of physical examination, electrocardiography, angiography, and echocardiography were compared between the groups. RESULTS: Of 491 patients included in this study, 34 patients (7%) were LD and 22 patients (4.5%) were codominant. Accordingly, 54 propensity-matched RD patients were included in the analysis. The demographics and comorbidities of the three groups were not different (P > 0.05); however, all patients in the RD group had thrombolysis in myocardial infarction (TIMI) 3, while five patients in the LD and five patients in the codominant group had a TIMI ≤2 (P = 0.006). At admission, the median left ventricular ejection fraction (LVEF) was highest in RD patients and lowest in LD and codominant patients (34%, P = 0.009). There was no difference in terms of success or complications of PCI, in-hospital, and 1-year mortality rate (P > 0.05). CONCLUSION: Patients with left coronary artery dominance had a higher value of indicators of worse outcomes, such as lower LVEF and TIMI ≤ 2, compared with RD patients, but not different rates of success or complications of PCI, in-hospital, and 1-year mortality. This finding may suggest that interventionists should prepare themselves with protective measures for no-reflow and slow-flow phenomenon and also mechanical circulatory support before performing PPCI in LD patients.

Correlation of Early and Late Ejection Fractions with CCL5 and CCL18 Levels in Acute Anterior Myocardial Infarction.

BACKGROUND: Acute Myocardial Infarction (AMI) is the leading cause of disability and death in Iran and many other countries. OBJECTIVE: To investigate the prognostic value of CCL5 and CCL18 in patients with acute myocardial ischemia. METHODS: In this cohort study we recruited and followed 50 patients with acute anterior myocardial infarction (AAMI) for developing cardiovascular accidents in a 6-month period. CCL5 and CCL18 levels were measured on admission, at day 5 and at day 180 post-hospitalization. RESULTS: CCL18 and CCL5 levels at day 180 were higher in patients with late (day 180) and early (day 5) LVEF less than 35% compared to those with higher LVEF (p=0.05 and p=0.042, respectively). There was a negative correlation between early and late LVEF and regional wall motion abnormalities (p=0.001 and p=0.002, respectively). There was also a trend of negative correlation between CCL18 levels at day 5 and LVEF levels at day 180 post-hospitalization (p=0.06). CONCLUSION: CCL18 has a correlation with cardiac function in patients with AAMI and it might be considered as an indicator of poor LVEF in patients with AAMI.

Pulmonary artery stenosis caused by a large aortic arch pseudoaneurysm detected 10 years after a minor trauma.

Pseudoaneurysm of aorta is a rare condition usually seen after aortic surgeries or serious accidents. Here we report a 60 years old man without any previous medical condition who presented with non-specific symptoms and underwent different investigations for more than 1 year, until the presence of a continuous murmur raised suspicion toward his cardiovascular system. In echocardiographic and computed tomography (CT) angiographic studies a large pseudoaneurysm of aortic arch with compression effect on pulmonary artery was detected. At this stage he remembered having suffered a minor trauma 10 years ago. He finally underwent operation and his aortic wall was repaired successfully with a patch. This case highlights the importance of thorough history taking and physical examination in patients irrespective of symptoms and high index of suspicion to detect this life-threatening condition.

The Comparison Between Two Surgical Methods for Left Internal Mammary Artery (LIMA) Anastomosis on Left Anterior Descending (LAD) Artery in Patients with Severe Diffuse Lesions: Short to Mid-Term Results.

Coronary artery disease is the leading cause of death worldwide. In this study, we compared two surgical methods of left internal mammary artery (LIMA) anastomosis on left anterior descending (LAD) artery in patients with severe diffuse lesions. A total of 40 patients were included in our study and randomly assigned into two groups. In group A, after a long arteriotomy on LAD, the posterior surface of left internal mammary artery (LIMA) was opened by the same length and was anastomosed along the LAD course through normal and diseased parts. In group B instead of complete opening of LAD, a small arteriotomy was done only in areas where the wall of the vessel was nearly normal (especially the anterolateral wall), and LIMA was anastomosed to these areas in a sequential (Jump) method. The patients were then followed for post-operation results. The two groups showed equal results regarding early mortality, post-operation bleeding, and infection, pleural and pericardial effusion. There were two cases of myocardial infarction (MI) in group A with one mortality after 18 months, while no MI was reported in group B. Group B demonstrated significantly superior results regarding the rise in ejection fraction and the improvement in functional class. In this study it was demonstrated that diffuse coronary artery lesions of LAD should be preferably operated using LIMA with the sequential-jump anastomoses method and the surgeon should avoid long arteriotomy with single long anastomosis because of lower chance of long-term patency.

Adjunctive use of verapamil in patients with refractory temporal lobe epilepsy: a pilot study.

OBJECTIVE: The present study aimed to determine if adjunctive use of verapamil, as a P-glycoprotein (P-gp) inhibitor, is efficacious in decreasing seizure frequency in patients with refractory temporal lobe epilepsy. MATERIALS AND METHODS: This was an open-label pilot study. Adult patients with refractory temporal lobe epilepsy were studied. Baseline seizure type and seizure count were determined. Patients were divided randomly into two groups. Group A received verapamil 120 mg/day (n=13), and group B received 240 mg/day (n=6). All patients were followed for eight weeks. The proportion of responders, which consist of patients with more than 50% reduction in seizure frequency from baseline, was tabulated. RESULTS: Nineteen patients were studied. Seven patients (36.84%) reached the responder rate. Three patients (50%) in group B were among the responders; two of these patients achieved seizure freedom. Four patients (30.7%) in group A responded favorably to verapamil. CONCLUSION: Developing new means of improving the effectiveness of existing antiepileptic drugs is a desirable way of tackling the dilemma of medically refractory epilepsy. Hypothetically, P-gp inhibitors (e.g., verapamil) might be used to counteract the removal of AEDs from the epileptogenic tissue. Such a strategy was adopted in this non-placebo-controlled, open-label, pilot study. We observed a significant achievement in seizure control associated with adjunctive use of verapamil in patients with refractory temporal lobe epilepsy.