Medical Journal of The Islamic Republic of Iran (MJIRI)

---

During a period of four years between June, IS, 1988 to June, IS, 1992 one hundred and fourteen patients with congestive heart failure (CHF) were admitted to the pediatric department of Taleghani General Hospital. During the above period, 192 patients with heart disease were hospitalized at this department and CHF was the cause of admission in 59.4% of them. Congenital heart disease (CHO) was the most common cause (65 cases, 57%) of heart failure in this group, followed by rheumatic heart disease (RHO) (26 cases, 23%) and cardiomyopathy (CM) (23 cases, 20%). Sixty-five patients (57%) were male and forty-nine (43%) were female (M/F = 1.3/ I). The youngest patient was 2 days old while the oldest one had 13 years. The mean age of the patients was 4.5 years. Forty-nine (43%) were under one year of age and the majority (44/49, 90%) suffered from CHO. All the children with RHO were between 6 to 13 years of age. 14 patients (12%) died. CHO was the most common cause of death. The variations in the pattern of heart failure according to different age groups in this study are compatible with those in other developing countries.

---

Heart failure is a clinical syndrome characterized by the inability of the heart to provide nutrient supply to tissues. In 75% of cases, the underlying pathology causing heart failure in patients with cardiac death is coronary heart disease. A rabbit model of heart failure with coronary ligation was produced to mimic coronary heart disease in humans. After producing the model, two arteries and two veins were investigated in the two groups (control and with coronary ligation). Arteries and veins were cut as rings and bathed in Krebs solution maintained at 37 DC, and gassed with 95% oxygen and 5% CO 2 , Then all tissues were placed under different resting tensions and allowed to equilibrate for 1 hour. Then all the tissues were contracted with U -46619 (0.1 µM) nearly ten minutes before initial application of isoprenaline. When the U -46619 (0.1 µM)-induced contraction reached a plateau, concentration-response curves to isoprenaline were obtained. Isoprenaline was chosen as a vasodilator, it's effect resulting from stimulating beta receptors in blood vessels. Isoprenaline induced relaxation in all tissues, but the renal artery was the most sensitive and showed maximum relaxation.20-26 Compared to acetylcholine, relaxation responses were small and maximum responses observed in the vena cava, aorta and renal vein were only 10 percent. In all tissues, relaxation responses to the vasodilator agent isoprenaline showed no significant difference between control and coronary ligated rabbits 8 weeks after operation.

---

Endothelial Nitric Oxide Synthase (eNOS) produces nitric oxide (NO) from L-arginine and is important for the maintenance of cardiovascular homeostasis. Congestive heart failure (CHF) generally results in increased pulmonary blood flow and if untreated leads to pulmonary hypertension and end stage heart failure. We therefore hypothesized that increased pulmonary flow without changes in pressure would result in hypertrophy of the media (middle layer of vascular wall). NO produced by the lung is regulated by systemic blood flow and in turn adjusts smooth muscle proliferation via altered expression of eNOS. To study this hypothesis, we created an artificial aortocaval shunt in order to increase pulmonary flow for 7 weeks. The shunt resulted in a significant thickening of the media. eNOS Western and Northern blot analysis demonstrated no significant alterations of eNOS protein and mRNA levels in the large-shunted group but in the small shunted one in comparison with sham. We suggested that NO in low concentrations (about > 10µM) caused weak hypertrophy of the media in the small-shunted group and in high concentrations (about> 50µM) caused S-nitrosylation of eNOS protein and deamination of eNOS mRNA and the regulatory genes in the nucleus thus the media of the vascular wall was significantly thickened in the large-shunted group. In higher concentrations, NO induces apoptosis and decreased cell viability.

---

The purpose of the work presented here was to investigate endotheliumdependent relaxations in the rabbit coronary ligation model of heart failure. We investigated endothelium-dependent relaxations at the level of larger vessels (thoracic aorta and vena cava left renal artery and left renal vein lateral saphenous artery and lateral saphenous vein and finally central ear artery and marginal ear vein) in a model devised to mimic heart failure. The model presented here i s the rabbit coronary ligation model in which myocardial infarction was produced in male New Zealand white rabbits (2.6kg-3.0kg) by ligation of the marginal branch of the left descending coronary artery. The development of chronic heart failure was allowed to proceed over eight weeks. Animals were killed by overdose with pentobarbitone sodium (i.v. injection). Arteries and veins were carefully removed with as little connective tissue as possible and placed i n cold physiological salt solution (PSS). The arterial and venous rings were mounted in 10mL isolated organ baths, bathed in Krebs maintained at 37°C and gassed with 95% 02 plus 5% CO2 , The rings were then placed under different resting tensions. Acetylcholine (ACh) was chosen as endothelium-dependent vasodilator. After initial application of tension, tissues were left to equilibrate for a 60 min period. Then all tissues were precontracted with noradrenaline (1µM) nearly ten minutes before initial application of vasodilator. This induced submaximal contraction in all vessels with the exception of the ear vein. When the noradrenaline-induced contraction reached a plateau, cumulative concentration-response curves (CCRC) to acetylcholine were obtained by increasing the concentration in half-log increments. The results led to two major conclusions with respect to the model. First, the relaxation responses to acetylcholine were not impaired. Second, the results of our experiments in this model of heart failure suggest that normal stimulation of endothelial NO is preserved in peripheral conduit and capacitance vessels.

---

We investigated neuronal uptake of noradrenaline (NA) at the level of larger vessels (thoracic aorta and vena cava left renal artery and left renal vein lateral saphenous artery and lateral saphenous vein and finally central ear artery and marginal ear vein) in a model devised to mimic heart failure. The model presented here is the rabbit coronary ligation model in which myocardial infarction was produced in male New Zealand white rabbits (2.6kg-3.0kg) by ligation of the marginal branch of the left descending coronary artery. The development of chronic heart failure was allowed to proceed over eight weeks. Animals were killed by overdose with pentobarbitone sodium (IV injection). Arteries and veins were carefully removed with as little connective tissue as possible and placed in cold physiological salt solution (PSS). The arterial and venous lings were mounted in 10mL isolated organ baths, bathed in Krebs maintained at 37°C and gassed with 95% O2 plus 5% CO2. The rings were then placed under different resting tensions. They were allowed to equilibrate for 1 hour before the experiments. Initially all tissues were exposed to cumulative concentrations of NA (lnM-300µM). Following complete washout, the preparations were left for 45 minutes to re-equilibrate. After preincubation with cocaine (10µM) for 10-15 minutes to inhibit neuronal uptake of NA, final NA cumulative concentration-response curves (CCRC) were conducted. Alierial plasma noradrenaline is 163% higher in patients with heart failure than in control patients. High plasma noradrenaline correlates directly with the hemodynamic severity of the disease and inversely with survival. Activation of the sympathetic nervous and renin-angiotensin systems may be important in the pathophysiology of heart failure associated with severity of the disease. Elevated levels of circulating noradrenaline in heart failure may result from impaired peripheral reuptake of this catecholamine. Cocaine has generally been used as the prototype drug for inhibition of neuronal uptake of catecholamines. The aim of our study was to investigate the possibility of changing reuptake of noradrenaline by using cocaine in this model of heart failure. In conclusion, effects of cocaine on noradrenaline responses were identical in sham operated compared with coronary ligated rabbits. These results suggest normal neuronal uptake of noradrenaline in this model of heart failure.

---

  Background: Sleep disorders are common among patients with chronic heart failure (HF), and it can have a significant effect on patients’ daily activities as well as their health. The purpose of this study was to assess sleep quality and its predictors in Iranian patients with chronic HF.

  Methods : This cross-sectional study was conducted on a sample of 200 patients with HF in two hospitals of Tehran University of Medical Sciences from June to November 2009. These patients completed a demographic questionnaire, and their sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). One-way analysis of variance (ANOVA), Kruskal-Wallis test, t-test and Linear regression were used for data analysis.

  Results : Seventy-nine percent of patients (n = 158) reported poor sleep quality (PSQI > 5). The range of global PSQI scores was 3–20. Also, a significant relationship was found between PSQI scores and patients’ age (p<0.004), gender (p< 0.042), educational level (p< 0.001), occupational status (p< 0.038), number of hospitalizations (p< 0.005), type of referral (p< 0.001), non-cardiac diseases (p< 0.001), diuretic use (p< 0.021) and left ventricular ejection fraction (p< 0.015). Three predictors were identified using regression analyses with stepwise methods, and included age, type of referral and educational level.

  Conclusion : The high prevalence of poor sleep quality highlighted the importance of sleep disorders in HF patients. There are many factors associated with sleep quality and sleep disorders that health providers should recognize for improved and effective management.

---

Background: The aim of this study was to investigate the effectiveness of bone marrow-derived cells (BMC) technology in patients with heart failure and compare it with alternative therapies, including drug therapy, cardiac resynchronization therapy pacemaker (CRT-P), cardiac resynchronization therapy defibrillator (CRT-D).
    Methods: A systematic review study was conducted to identify all clinical studies published by 2017. Using keywords such as “Heart Failure, BMC, Drug Therapy, CRT-D, CRT-P” and combinations of the mentioned words, we searched electronic databases, including Scopus, Cochrane Library, and PubMed. The quality of the selected studies was assessed using the Cochrane Collaboration's tool and the Newcastle-Ottawa. The primary and secondary end-points were left ventricular ejection fraction (LVEF) (%), failure cases (Number), left ventricular end-systolic volume (LVES) (ml), and left ventricular end-diastolic volume (LVED) (ml). Random-effects network meta-analyses were used to conduct a systematic comparison. Statistical analysis was done using STATA.
   Results: This network meta-analysis covered a total of 57 final studies and 6694 patients. The Comparative effectiveness of BMC versus CRT-D, Drug, and CRT-P methods indicated the statistically significant superiority of BMC over CRT-P (6.607, 95% CI: 2.92, 10.29) in LVEF index and overall CRT-P (-13.946, 95% CI: -18.59, -9.29) and drug therapy (-4.176, 95% CI: -8.02, -.33) in LVES index. In addition, in terms of LVED index, the BMC had statistically significant differences with CRT-P (-10.187, 95% CI: -18.85, -1.52). BMC was also dominant to all methods in failure cases as a final outcome and the difference was statistically significant i.e. BMC vs CRT-D: 0.529 (0.45, 0.62) and BMC vs Drug: 0.516 (0.44, 0.60).
In none of the outcomes, the other methods were statistically more efficacious than BMC. The BMC method was superior or similar to the other methods in all outcomes.
   Conclusion: The results of this study showed that the BMC method, in general, and especially in terms of failure cases index, had a higher level of clinical effectiveness. However, due to the lack of data asymmetry, insufficient data and head-to-head studies, BMC in this meta-analysis might be considered as an alternative to existing treatments for heart failure.

---

Background: Ischemic cardiomyopathies are the leading causes of mortality and morbidity. Stem cell therapy using amniotic membrane mesenchymal stem cells have emerged as a promising cardiac regeneration modality. They have shown great immunological advantage when used in allogeneic or xenogeneic transplantation. The aim of the current study is to accumulate evidence from published preclinical studies on the application of amniotic membrane derived mesenchymal stem cells (AMSCs) in the treatment of ischemic cardiomyopathies including myocardial ischemia and heart failure. The aim is to define if there is enough high-quality current evidence to support starting the use of these cells in clinical trials.
   Methods: PubMed, SCOPUS, EMBASE, and ISI Web of Science databases were searched without temporal and language restrictions. Data were extracted from selected studies. The primary outcomes were left ventricular ejection fraction (LVEF) and LV fibrosis. The risk of bias (ROB) assessment was performed using SYRCLE’s ROB tool. After qualitative synthesis, provided that data meets the criteria for quantitative analysis, a meta-analysis was performed using Stata software V12 to investigate the heterogeneity of the data and to get an overall estimate of the effect size of the treatment on each outcome.
   Results: On primary search, 438 citations were retrieved. After screening, three studies were selected for quantitative analysis of each of the outcomes LVEF and LV fibrosis. Their administration in acute and chronic MI alleviates heart failure and improves LVEF (SMD=3.56, 95% CI: 2.24-4.87, I-squared=83.1%, p=0.003) and reduces infarct size (SMD= -4.41, 95% CI: (-5.68)-(-3.14), I-squared=79.0%, p=0.009). These observations were achieved in the acute MI model, HF following ischemia due to coronary artery stenosis and coronary artery occlusion with the early restoration of the perfusion.
   Conclusion: Present low and medium quality evidence from preclinical studies confirm the efficacy of the AMSCs in the preclinical models of acute MI and HF following ischemia due to coronary artery stenosis and permanent/temporary coronary artery occlusion. High-quality preclinical studies are indicated to bridge the gaps in translation of the current findings of AMSCs research for the treatment of patients with acute and chronic myocardial ischemia and heart failure.

---

Background: Chronic Stable Angina (CSA) does not respond to clinical interventions always. Therefore, enhanced external counter pulsation (EECP) has been approved by the Food and Administration Drug (FDA) as an effective technology. This study aimed to synthesize evidence on the economic evaluation of EECP in managing CSA through a systematic approach.
   Methods: In this systematic review study, PubMed/Medline, Cochrane Library, Web of Sciences, Scopus, National Institute for Health Research Journals Library, and the University of York Centre for Review and Dissemination (CRD) were searched. The targeted population was people who suffered from CSA, and the main therapeutic intervention was EECP. The comparators were not limited to any particular ones. Outcomes were changes in the Canadian Cardiovascular Society grading of angina pectoris, quality of life, and any other investigated relevant outcomes in the retrieved studies. The quality of studies was assessed through Philips et al and Joanna Briggs Institute Critical Appraisal tools. We synthesized data through a narrative approach.
   Results: We retrieved 7821 studies; among which 3 studies were included in the final phase. Two studies were systematic reviews and the Markov model economic evaluation. Another study was a partial economic evaluation.
   Conclusion: All studies only considered direct costs. EECP is a cost-effective technology in managing CSA, however, the sensitivity analysis of the studies showed the cost-effectiveness ratio is varied considerably and further studies are needed to extrapolate its economic value.
 

---

Background: Heart Failure (HF) imposes a relevant burden and a considerable health concern, with high prevalence and mortality rates. This study was conducted to assess the cost-effectiveness of remote cardiac monitoring with the CardioMEMS Heart Failure System.
   Methods: In the present systematic review, several scholarly databases were searched and updated from inception up to September 20, 2022. The objective of the present review was formulated according to the patient/population, intervention, comparison and outcomes format. Mortality rate, hospitalization rate, quality-adjusted life year (QALY), total costs, and the incremental cost-effectiveness ratio regarding the use of the CardioMEMS System were the key outcomes of the present study. The quality of included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS) checklist.
   Results: Finally, 5 articles were retained and analyzed in the present systematic review. All studies employed the Markov and decision tree models. Results show that the CardioMEMS system reduced mortality and hospitalization rate and created a higher QALY. In all selected countries the CardioMEMS method is a more expensive method than the standard of care (SoC), with the highest cost in the United States (US) ($201,437) and the lowest cost in the United Kingdom ($25,963), respectively. the highest willingness to pay in the US and the lowest in Italy ($100,000 and $33,000 per QALY), respectively. Results showed that the most cost per QALY for the CardioMEMS system was in the US and the lowest was in the Netherlands ($46,622 and $26,615 per QALY), respectively.
   Conclusion: In all selected countries, CardioMEMS is a cost-effective method for monitoring and managing pulmonary artery pressures in HF patients. Strategies such as CardioMEMS, which decrease the rate of hospitalization, are likely to be only more cost-effective in the future.
 

---

Background: Diabetes is associated with left ventricular remodeling. Myocardial wall stress is a measurable factor connected to the ventricular breadth and force and is related to myocardial thickness; it can be measured by echocardiography. The present study aimed to assess the link between heart failure (HF) and echocardiography-derived myocardial wall stress in diabetic patients with ST elevation myocardial infarction (STEMI) who were managed with revascularization.
   Methods: This study was a comparative prospective study that took place between February 2022 and February 2023. It included 100 diabetic patients presented with STEMI and managed by percutaneous coronary intervention (PCI). Patients were selected from the cardiology departments at Al-Azhar University Hospital, Damietta, Egypt. During the hospital stay, patients were checked for HF symptoms and signs. They were also observed for 3 months after discharge for detection of HF. Those who did not develop HF were assigned to group I, and those with HF were assigned to group II. 
   Results: The mean value of end-systolic wall stress (ESWS) was 77.09 ± 12.22 and 97 ± 13.44, and the mean value of end-diastolic wall stress (EDWS) was 12.61 ± 2.76 and 15.87 ± 2.86 in groups I and II respectively, with significant differences between the 2 groups. The cutoff point to detect HF was 88 KPa for ESWS and 13.5 KPa for EDWS, with a sensitivity of 70% and 79% and a specificity of 80% and 61% for ESWS and EDWS, respectively.
   Conclusion: Elevated left ventricle (LV) myocardial stress is related to increased HF in diabetic patients whose HF was managed by PCI after STEMI. LV wall stress is a potentially helpful risk stratification tool using routine echocardiography to determine the treatment plane according to the risk status.