Cardiac resynchronization therapy is a treatment modality developed in the early 2000s that targets the mechanical and electrical dyssynchrony in heart failure with reduced ejection fraction patients. Appropriate patient selection conditions specified in the guidelines include measurement of left ventricular systolic dysfunction, QRS width, and assessment of functional classification. Despite consistent and increasing evidence supporting the use of cardiac resynchronization therapy in eligible patients, proportion of patients with the device is still not at the desired level. In addition, studies conducted in recent years have shown that the cardiac resynchronization therapy response of patients is quite heterogeneous and in echocardiographic follow-up, it was observed that reverse remodeling was not at the supposed level in approximately one-third of the patients. In order to change this result, which is due to many reasons, solutions such as using assistive imaging methods, providing optimal patient selection, trying different pacing techniques and post-procedural programming strategies (AV-delay and VV-delay optimization) have been the subject of debate. In this article, we aim to review the mechanisms that have been revealed regarding the differences in cardiac resynchronization therapy response and new pacing techniques—especially conduction system pacing—that may be preferred to resolve poor cardiac resynchronization therapy response.

Background: Hypertension is a vital risk factor for heart failure, while cardiac rehabilitation can effectively improve cardiac function of heart failure patients. This study aimed to determine the impact of cardiac rehabilitation on microRNA-423-5p in hypertensive patients with heart failure with a moderately reduced ejection fraction.

Methods: Sixty hypertensive patients with heart failure with a moderately reduced ejection fraction were randomly divided into cardiac rehabilitation group and positive control group with 30 cases per group, while 30 hypertensive patients without heart failure were recruited as negative control group. The cardiac rehabilitation group and positive control group were treated with 1-month cardiac rehabilitation combined with the routine treatment and routine treatment only, respectively. The New York Heart Association classification, 6-minute walking test, and color Doppler echocardiography were adopted to detect cardiac function. Meanwhile, the expression of microRNA-423-5p and N-terminal pro-B-type natriuretic peptide was determined via Real-Time Fluorescence Quantitative PCR and electrochemiluminescence immunoassay. The diagnostic potential of microR-423-5p and N-terminal pro-B-type natriuretic peptide was assessed by ROC curve analysis and multivariate linear regression model.

Results: Patients in cardiac rehabilitation group displayed significantly lower expression of microR-423-5p and better results of New York Heart Association classification, 6-minute walking test, and color Doppler echocardiography than those in positive control group (P <.05). ROC analysis showed that microR-423-5p (AUC = 0.785; 95% CI: 0.686-0.865; sensitivity = 73.33%; specificity = 73.33%) had better specificity and accuracy than N-terminal pro-B-type natriuretic peptide (AUC = 0.721; 95% CI: 0.617-0.811; sensitivity = 81.67%; specificity = 63.33%).

Conclusion: MicroR-423-5p was implicated in left ventricular hypertrophy and might be a potential biomarker for assessing the therapeutic effect of cardiac rehabilitation on hypertensive patients with heart failure with a moderately reduced ejection fraction.

Background: Myocardial infarction, a coronary heart disease, is a serious hazard to human health. Cardiomyocyte oxidative stress and apoptosis have been considered as the main causes of myocardial infarction. Here, we aimed to investigate the role of miR-615-3p in oxidative stress and apoptosis of human cardiomyocytes.

Methods: Reverse transcription-quantitative polymerase chain reaction was performed to determine miR-615-3p or MEF2A expression in human cardiomyocytes. Apoptosis and viability of human cardiomyocytes were assessed by flow cytometry analysis and CCK-8 assay. In addition, the contents of malondialdehyde, reactive oxygen species, and superoxide dismutase were detected by corresponding commercial kits. The binding of miR-615-3p and MEF2A in human cardiomyocytes was examined by luciferase reporter assay.

Results: Hypoxia/reoxygenation treatment downregulated the expression level of miR‐615-3p in human cardiomyocytes. Overexpressing miR-615-3p increased human cardiomyocyte viability and decreased human cardiomyocyte apoptosis. Moreover, miR-615-3p mimics suppressed oxidative stress in hypoxia/reoxygenation-stimulated human cardiomyocytes. MEF2A was confirmed as a target gene of miR-615-3p and was highly expressed in hypoxia/reoxygenation-stimulated human cardiomyocytes, and its upregulation partially reversed the influence of miR-615-3p mimics on oxidative stress and apop-tosis of human cardiomyocytes. Moreover, miR-615-3p inactivated the P13K/Akt pathway by inhibiting MEF2A.

Conclusions: Overexpression of miR-615-3p protects human cardiomyocytes from oxida-tive stress injury by targeting MEF2A via the PI3K/Akt signaling.

Background: No-reflow phenomenon after primary percutaneous coronary intervention is a common condition affecting the outcomes; therefore, studying its predictive factors is helpful in identifying patients at high risk. Our objective was to investigate the impact of the total ischemia time on no-reflow phenomenon and its correlation to thrombolysis in myocardial infarction flow grade after primary percutaneous coronary intervention.

Methods: This study was conducted on 545 patients with ST-elevation myocardial infarction who underwent PPCI; the patients were divided into two groups according to the incidence of no-reflow, TIMI flow ≤2 was considered no-reflow. The time interval from chest pain onset to balloon dilatation was assessed and correlated to thrombolysis in myocardial infarction flow grade.

Results: The incidence of no-reflow was 13.9%; thrombolysis in myocardial infarction flow ≤2 occurred in 76 patients. Multivariate regression analysis showed that advanced age 65 years, the total ischemia time ˃6 h, high thrombus burden, and cardiogenic shock were the independent predictors of no-reflow phenomenon. Spearman’s correlation analysis showed a significant negative correlation between the total ischemia time and thrombolysis in myocardial infarction flow grade (r = −351 and P-value =.001).

Conclusion: The time delay is the main limitation of achieving thrombolysis in myocardial infarction 3 flow after primary percutaneous coronary intervention. The total ischemia time has a significant negative correlation with thrombolysis in myocardial infarction flow grade after primary percutaneous coronary intervention.

Background: Dysregulation of microRNAs is associated with pulmonary hypertension. The present study aimed to determine the alterations in microRNA and microRNA expressions and their role in signaling pathways and investigate the relationship with serum levels of apelin, kynurenine, and endocan in pulmonary hypertension.

Methods: The study design was prospective and single-centered. The study included 32 consecutive treatment-naive patients with precapillary pulmonary hypertension and 55 age and sex-matched healthy controls. All subjects underwent right heart catheterization. mRNA expressions of hypoxia-inducible factor-1 alpha, hypoxia-inducible factor-2 alpha, signal transducer and activator of transcription-3, fibroblast growth factor-2, fibroblast growth factor receptor-1, and poly-ADP-ribose polymerase-1 and microRNA expressions of miRNA-210, miRNA-130a, miRNA-424, miRNA-204, and miRNA-223 were determined by RT-PCR. Concentrations of kynurenine, apelin, and endocan were analyzed
by ELISA.

Results: mRNA expressions of hypoxia-inducible factor-2 alpha, signal transducer and activator of transcription-33, and FGF-2 were increased; miRNA-210 and miRNA-130a were increased; miRNA-223 and miRNA-204 were decreased in pulmonary hypertension. Apelin and kynurenine concentrations were decreased in pulmonary hypertension. There were positive correlations: hypoxia-inducible factor-2 alpha-miRNA-424, ApelinmiRNA-424, kynurenine-miRNA-210, signal transducer and activator of transcription-3-PVR, miRNA-210-right atrial pressure, and kynurenine-right atrial pressure. There were negative correlations: poly-ADP-ribose polymerase-1-miRNA-210 and poly-ADP-ribose polymerase-1-right atrial pressure. On multiple logistic regression analyses, miRNA-130a and Apelin were independent risk factors for PH.

Conclusions: We report a novel relationship between the kynurenine and poly-ADPribose polymerase-1 signaling pathways that could be mediated by miRNA-210. We also report a connection between the Apelin and hypoxia-inducible factor-2 alpha signaling pathways that could be mediated by miRNA-424. Reduced levels of Apelin and elevated levels of miRNA-130a are associated with pulmonary hypertension. We also find that elevated levels of signal transducer and activator of transcription-3, miRNA-210, and kynurenine and reduced levels of poly-ADP-ribose polymerase-1 correlate with more severe hemodynamics

Background: Antiphospholipid syndrome is an autoimmune disease characterized by the occurrence of venous and/or arterial thrombosis. Chronic thromboembolism is one of the known established pathogenesis of pulmonary hypertension, known as chronic thromboembolic pulmonary hypertension. Pulmonary endarterectomy is the treatment of choice for chronic thromboembolic pulmonary hypertension. The aim of this study is to evaluate the efficacy and risk of pulmonary endarterectomy in patients with antiphospholipid syndrome-associated chronic thromboembolic pulmonary hypertension.

Methods: Data were prospectively collected and retrospectively analyzed, for patients who underwent pulmonary endarterectomy between March 2011 and March 2020.

Results: Seventeen patients (4 male and 13 female) were identified. Thirteen patients had primary antiphospholipid syndrome and 4 had secondary antiphospholipid syndrome. The mean age was 34.82 ± 10.07 years and the mean time interval between the diagnosis and surgery was 26.94 ± 17.35 months. Dyspnea on exertion was the main symptom in all patients. Seven patients had previous deep vein thrombosis, 5 patients had a history of recurrent abortions, and 2 patients had hemoptysis. Following surgery, mean pulmonary artery pressure decreased from 47.82 ± 13.11 mm Hg to 22.24 ± 4.56 mm Hg (P <.001),
and pulmonary vascular resistance improved from 756.50 ± 393.91 dyn/s/cm−5 to 298.31 ± 132.84 dyn/s/cm−5 (P <.001). There was no in-hospital mortality with a mean follow-up of 75.29 ± 40.21 months. The functional capacity of all patients improved from 269.46 ± 111.7 m to 490 ± 105.34 m on a 6-minute walking test.

Conclusions: Pulmonary endarterectomy is a safe and curative treatment in patients with antiphospholipid syndrome-associated chronic thromboembolic pulmonary hypertension. It has a favorable outcome by increasing the quality of life. A multidisciplinary
experienced chronic thromboembolic pulmonary hypertension team is critical in the management of these unique patients.

Background: Venous diseases encompass a large spectrum of abnormalities in the venous system with complaints, such as aching and swelling. Enhanced external counterpulsation, proven safe and effective in patients with coronary artery disease and chronic heart failure, is a technique that increases venous return and augments diastolic blood pressure. This study assessed the effects of enhanced external counterpulsation on symptoms of venous disease using the Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms questionnaire.

Methods: This study was designed prospectively for evaluating venous symptoms before and after enhanced external counterpulsation treatment. The study population consisted of 30 consecutive patients who were admitted to the cardiology clinic. The Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms questionnaire was applied to assess venous symptoms one day before and after enhanced external counterpulsation treatment.

Results: The mean age of the patients was 64.62 ± 9.67 years. After 35 hours of enhanced external counterpulsation, 28 patients (93%) had at least 1 New York Heart Association functional class reduction compared with baseline and 43% of patients had 2 New York Heart Association functional classes improvement. The New York Heart Association class significantly decreased after enhanced external counterpulsation treatment (P<.001). There was a significant improvement in their swelling and night cramps symptoms compared with baseline (P<.001 and P =.05, respectively). Also, The left ventricular ejection fraction significantly increased after the enhanced external counterpulsation treatment (P =.02).

Conclusions: The findings obtained in the present study suggested that patients treated with enhanced external counterpulsation showed a significant reduction in swelling and night cramps symptoms. Although the total VEIN score did not change after the enhanced external counterpulsation procedure, improvement in swelling and night cramps underlines the beneficial effects of enhanced external counterpulsation through the venous vascular territory.

In patients with persistent atrial fibrillation (AF) with a high risk of bleeding, left atrial appendage closure (LAAC) has gradually become the best alternative to long-term oral anticoagulant therapy in preventing stroke.1 However, in some patients, the occlusion device falls off because of various reasons, such as improper selection or unstable preinstallation, and constitutes one of the most serious complications of LAAC.2 Here, we report a case of an elderly patient with AF. On the second day after the surgery, her Watchman device fell off. The detached device was retrieved using the double transseptal sheaths technique, and the LAmbre device was installed.

Fabry disease is a progressive and rare storage disease that occurs due to low or complete deficiency of lysosomal alpha galactosidase-A (α-GLA) enzyme activity. Low alpha galactosidase-A enzyme activity causes progressive accumulation of globotriaosylceramide in various tissues and organs including the myocardium, kidney, and nervous system. Left ventricular hypertrophy (LVH) is the most common cause of cardiac involvement in patients with Fabry disease. Over a thousand different mutations have been identified in the GLA gene up to now. We describe a case of a 54-year-old male with Fabry disease due to a novel GLA gene mutation.

Tricuspid valve disease, particularly tricuspid regurgitation (TR), has been a “neglected valvulopathy” for many years. In patients with left heart pathologies, chronic pressure overload on the right ventricle causes functional TR and is associated with a poor prognosis.1 Treatment of severe symptomatic TR has usually been restricted to diuretics and mostly remained ineffective.2 Moreover, patients undergoing surgical repair of isolated tricuspid valve disease have the highest mortality of all valves, due to advanced right ventricular dysfunction and coexisting comorbidities.3 Thus, transcatheter tricuspid valve therapy (TTVT) has emerged as a novel strategy for patients with high or prohibitive surgical risk. In this case, we performed bicaval valve implantation using TricValve to reduce caval backflow on a symptomatic patient with severe functional TR and successfully managed device migration complications.