International Cardiovascular Research Journal
Volume:16 Issue: 4, Dec 2022

 Cardiovascular diseases, with an estimated 18.6 million deaths per year, are the leading cause of death worldwide. One of the major risk factors is elevated blood low-density lipoprotein cholesterol (LDL-C) secondary to multiple environmental and genetic factors. Genes involved in LDL-C metabolism are the targets of the most common treatment options. Advanced molecular techniques could pave the way for identifying novel targets in dyslipidemia therapies. The LIM domain and actin-binding 1 (LIMA1) gene binds to the NPC1L1 protein and facilitates its more efficient recycling to the plasma membrane. Inhibition of LIMA1 could disrupt cellular cholesterol hemostasis with a probable decrease in blood LDL-C levels. 

 The present study was designed to knock out exon 2 of the LIMA1 gene using lentiviruses as an in vitro model for reducing cholesterol absorption. 

 A CRISPR/Cas9 system with dual guide RNAs (gRNAs) was designed to completely excise exon 2 of LIMA1. Two gRNAs (gRNA1 and gRNA2) were cloned in the LentiCRISPR v2 vector. LentiCRISPR viruses were produced in the HEK293T cell line to encode the CRISPR/Cas9 complex structure. HepG2 cell lines were transduced with two different LentiCRISPR viruses simultaneously. 

 Exon 2 deletion was detected by PCR, gel electrophoresis, and subsequent Sanger sequencing of the PCR product. Exon 2 deletion caused a frameshift mutation, and the subsequent production of nonfunctional transcripts led to gene knockout. The dual gRNA CRISPR/Cas9 system could be used in gene editing setups. 

 The in vitro knockout model of LIMA1 could be considered as preliminary work to study the role and mechanism of action of the LIMA1 protein, along with its potential as a target for hypercholesterolemia therapy.

Erectile dysfunction, lower urinary tract symptoms (LUTS), and coronary artery disease (CAD) share common risk factors. Atherosclerosis, inflammation, and endothelial dysfunction with decreased nitric oxide synthase activity are the proposed etiologies for these disorders.

This study compared the prevalence and severity of erectile dysfunction and LUTS in patients with and without significant CAD.

This case-control study involved patients undergoing coronary artery angiography at Kowsar Hospital in Shiraz, Iran, between January 2019 and January 2020. Male patients aged 40 or older with or without significant coronary artery lesions diagnosed by coronary angiograms were considered the case and control groups, respectively. Both groups were asked to fill out the International Prostate Symptom Score (IPSS) and International Index of Erectile Function-5 (IIEF-5) questionnaires, which evaluate the severity of LUTS and erectile dysfunction, respectively. The prevalence and severity of erectile dysfunction and LUTS were evaluated and compared between the groups using chi-squared tests and t-tests. Also, logistic regression was performed.

A total of 352 male patients participated in this case-control study, and each group included 176 patients. Erectile dysfunction occurred in 109 patients (61.9%) in the case group vs. 63 (35.7%) in the control group (P< 0.001). The mean IIEF-5 score was 17.03 ± 7.33 in the case group vs. 20.56 ± 6.51 in the control group (P = 0.003). Ninety-five patients (54.0%) in the case group complained of LUTS, vs. 51 (29.0%) in the control group (P < 0.001). The mean IPSS score was 7.70 ± 9.28 in the case group and 3.74 ± 3.74 in the control group (P < 0.001).

Erectile dysfunction, LUTS, and CAD share common risk factors and are highly prevalent among the aging male population. As the extent of CAD increases, the prevalence and severity of erectile dysfunction and LUTS increase. We highly recommend that men older than 40 who complain of erectile dysfunction and LUTS be evaluated for CAD.

Burned-out hypertrophic cardiomyopathy (BO-HCM) is complicated by substantial adverse events. However, few studies have focused on clinical or echocardiographic features and their prognostic values among patients with BO-HCM.

This study evaluated the clinical manifestations and prognostic value of echocardiography in patients with BO-HCM.

The present retrospective study evaluated 401 consecutive patients referred to the echocardiography ward of Rajaie Cardiovascular Center for evaluation of HCM during the period from January 2010 to February 2018. Three hundred six patients who completed the follow-up were included: 78 (25.4%) had BO-HCM and an EF of < 50% (group 1), and 228 (74.5%) had a normal EF in their baseline TTE (group 2). Among the group 2 population, 183 patients had a preserved EF of > 50% (group 2B), and 45 became BO-HCM at the end of their follow-up (group 2A). Clinical data were analyzed, including medical history, electrocardiography, and echocardiography. Generalized estimating equation (GEE) regression was performed to assess the association between patient characteristics and burned-out HCM.

An atrial fibrillation (AF) rhythm was more common in the groups with BO-HCM (groups 1 and 2A) (32.8 vs. 14%; P = 0.002), as were Frequent premature ventricular contractions (PVCs) (13.98 vs. 5%; P = 0.040). Moderate or severe systolic anterior motion (SAM) was significantly more common in group 2B (LVEF > 50%) compared with group 1 and 2A, who had an EF of ≤ 50% (32.3% vs. 7.6%; P = 0.006). The S-wave of the right ventricle was significantly lower in groups 1 and 2A (9.73 vs. 11.8 cm/s; P < 0.001). Systolic pulmonary artery pressure (SPAP) was significantly higher in groups 1 and 2A (38.28 vs. 29.74 mmHg, P < 0.001). The differences in the prevalence of asymmetrical septal hypertrophy (ASH), left ventricular outlet (LVOT) obstruction, pericardial effusion (PE), diastolic dysfunction, and mitral regurgitation (MR) were insignificant between all groups.

Among the patients suffering from HCM, the presence of AF rhythm, frequent PVCs, significant RV dysfunction, and absence of systolic anterior motion (SAM) of mitral valve leaflets have prognostic value and might be considered predictors for progression to BO-HCM.

Hypertension is a major risk factor for cardiovascular diseases and is associated with increased all-cause and cardiovascular mortality. Cardiac changes such as impaired left ventricular (LV) function, left ventricular hypertrophy (LVH), and heart failure are consequences of chronic exposure to elevated blood pressure. Speckle tracking echocardiography (STE) is a sensitive method for detecting early regional and global myocardial dysfunction missed in asymptomatic patients with cardiovascular disease by conventional modalities.

This study aimed to assess the ability of 2D-STE in assessing regional and global LV strain to diagnose subclinical LV dysfunction in patients with systemic hypertension and preserved ejection fraction.

This prospective observational study included 80 hypertensive patients and 30 healthy controls. In the hypertensive group, at least six months had passed from diagnosis of hypertension according to AHA guidelines. 2D echocardiographic LV images were acquired in apical 4, 2, and 3-chamber and parasternal short axis views. Left ventricular global longitudinal strain (LVGLS) and circumferential strain (LVGCS) were quantified in all segments using a Philips Affiniti 70 device. Differences between hypertensive patients and controls were analyzed using the independent t-test. A P-value less than 0.05 was considered statistically significant.

In comparison, LVGLS and LVGCS were significantly (P < 0.001) lower among the hypertensive group (GLS: -17.43 ± 1.71, GCS: -23.76 ± 3.35) than the control group (GLS: -20.18 ± 1.11, GCS: -27.46 ± 4.33). LVGLS was significantly (P < 0.001) lower in uncontrolled hypertension (-16.91 ± 1.70) vs. controlled hypertension (-17.96 ± 1.57). Similarly, LVGLS was significantly (P < 0.001) lower among the cases with LVH on 2D echocardiography ( 16.23 ± 1.69) compared to those without LVH ( 17.96 ± 1.6). In the hypertensive group, LVGLS was significantly lower in males (-16.84 ± 1.42) than in females (-18.02 ± 1.78; P < 0.05).

This study demonstrates the potential benefits of using STE as a non-invasive imaging technique in assessing cardiac remodeling and providing a further risk assessment of hypertensive patients.

Since cardiac involvement in scleroderma patients has a poor prognosis, studies have shown that observation of Left Ventricular (LV) deformation analysis using the sensitive speckle-tracking echocardiography (STE) method is appropriate in predicting heart failure.

This study evaluated LV function in patients with scleroderma with normal pulmonary artery pressure.

This cross-sectional study was performed on 30 scleroderma patients and 30 healthy cases by myocardial strain analysis. The frequency of left ventricular dysfunction in systemic sclerosis patients was evaluated by STE, two-dimensional (2D) echocardiography, and Tissue Doppler Imaging (TDI). The statistics analysis was done by SPSS software version 22.

The mean age was 41.07 ± 8.94 years in the case group and 39.00 ± 15.64 years in the control group. The absolute values of the global longitudinal strain (GLS) average, GLS average 3-chambers, ejection fraction, end-diastolic volume (EDV), and stroke volume were significantly lower in the case group compared with the control group (P < 0.05). The two groups were similar in other echocardiographic indicators including GLS average 2-chambers, GLS average 4-chambers, heart rate, PAP (mm), and end-systolic volume (ESV) (P > 0.05).

Heart health monitoring techniques such as Myocardial Strain Analysis are useful in the early diagnosis of systolic and diastolic disorders and can play an effective role in the early treatment of this disease and prevent permanent cardiac complications of disease or medications in systemic sclerosis patients. Finally, the STE technique can be useful in evaluating GLS to diagnose subclinical LV systolic dysfunction in scleroderma patients.