The efficacy of bone marrow mononuclear stem cell transplantation in patients with non-ischemic dilated cardiomyopathy-a meta analysis.

Cardiomyopathy refers to a wide spectrum of heart pathologies that interfere with normal heart function. Management options of patients with cardiomyopathy depended mainly on the severity of the condition. Lifestyle modifications and regular exercise together with a healthy diet is compatible for mild conditions. Severe conditions, however, rely on medications or surgery. Here, we aim to investigate the efficacy of bone marrow mononuclear stem cell transplantation in patients with dilated cardiomyopathy. We searched PubMed, Scopus, and Cochrane CENTRAL for relevant clinical trials and excluded observational studies. We performed the quality assessment of this study following GRADE guidelines. The assessment of the risk of bias was performed by the Cochrane's risk of bias tool. We present an analysis of the following outcomes: left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and six minutes walking test. Data were pooled as mean differences (MD) and relative confidence intervals (CI). The analysis of 667 patients from 11 studies receiving autologous bone marrow cell therapy for non-ischemic dilated cardiomyopathy is presented. A total of 338 patients were allocated to the treatment group, and 329 participants entered the control group. The mean age of the patients in the treatment group is 52.4 ± 4.3 years, while that of the control is 53.7 ± 3.7 years. Seven studies (14.18-23) reported transplantation through the intracoronary route. Table 1 shows a summary of the baseline characteristics of the included studies and participants, the number of injected cells, and the type of injected cells in each trial. Table 2 summarizes and illustrates the previous treatment history of included patients in each trial, as well as the baseline values of different scores used as outcome measures in this analysis. We found that bone marrow mononuclear stem cell therapy leads to significantly increased LVEF (MD = 4.54%, 95% CI [3.52, 5.56], P < 0.0001). Patients in the transplant group experienced less left ventricular end-diastolic diameter (millimeter) than the control arm (MD = -1.86 mm, 95% CI [-4.01, 0.29], P = 0.09). Additionally, Patients in the transplant group could walk 28.53 m more than the controls (MD = 28.53 m, 95% CI [2.51, 54.55], P = 0.03). Transplantation of bone marrow stem cells yields acceptable results regarding left ventricular ejection fraction and lowers the left ventricular end-diastolic diameter. Additionally, the six minutes walking test is improved in the transplant group. Table 1 Demographic data about the included participants Study Year Sample size Age, years Males, n (%) Diabetics, n (%) Route of administration Number of injected cells Type of injected cells TTT Control TTT Control TTT Control TTT Control Bartolucci 2015 12 11 58 ± 14 57 ± 11 8 (66.7) 9 (81.8) 2 (16.7) 1 (9.1) Intracoronary 1.94 × 10^6 CD34 +  Bocchi 2010 8 15 51 ± 15 NR NR NR NR Intracoronary NR NR Frljak 2018 30 30 56 ± 9 54 ± 11 27 (90) 26 (87) 3 (10) 2 (6) Trans-endocardial NR CD34 +  Hamshere 2015 15 14 57.67 ± 12.32 56.79 ± 9.8 10 12 9(59.9%) 8(57.1%) Intracoronary 4.91 × 10^6 CD34 +  Hu 2011 31 29 56.61 ± 9.72 58.27 ± 8.86 NR NR NR NR NR NR NR Matrino 2015 82 78 51 ± 11.1 49.6 ± 11.1 73.1 68.3 NR NR Intracoronary 10^8 TTT, CD45, CD105, and CD133 Sant'Anna 2014 20 10 48.3 ± 8.71 51.6 ± 7.79 13(65) 5 (50%) NR NR Intra-myocardial 1.06 × 108 CD3, CD4, CD14, CD34, CD38, and CD45 Seth 2010 41 40 45 ± 15 49 ± 9 33 35 NR NR NR 168 × 10^6 Bone marrow mononuclear cells Vrtovec 2011 28 27 52 ± 8 54 ± 7 26 (93) 23 (85) NR NR Intracoronary 123 × 10^6 CD34 +  Vrtovec 2013 55 55 53 ± 8 55 ± 7 45 (82) 44 (80) NR NR Intracoronary NR NR Xiao 2017 16 20 49.5 ± 11.6 54.4 ± 11.6 9 (56.3) 14 (70.0) 6 (37.5) 5 (29.4) Intracoronary infusion (4.9 ± 1.7) × 108 (CD29, CD34, CD44, CD45, and CD166) Data are reported as mean ± SD or n (%) unless proved otherwise TTT treatment group, NR not reported Table 2 Previous history of treatment and drug intake by the patients Study Year Medical therapy, n (%) Baseline scores, mean (SD) Beta blockers ACE inhibitors Digoxin Diuretics LVEF, % LVEDD, mm Six minutes-walk test* TTT Control TTT Control TTT Control TTT Control TTT Control TTT Control TTT Control Bartolucci 2015 10 (83.3) 8 (72.7) NR NR 3 (25) 3 (27.3) 11 (91.6) 10 (90.9) 26.8 ± 4.9 30.3 ± 6.3 NR NR NR NR Bocchi 2010 NR NR NR NR NR NR NR NR 21.8 ± 3.8 30.6 ± 7.3 79 (10) 78 (12) NR NR Frljak 2018 30 (100) 30 (100) 31 (100) 32 (100) 2 (7) 3 (10) 32 (100) 33 (100) 32.2 ± 9.3 31.1 ± 7.8 NR NR NR NR Hamshere 2015 13 14 15 13 6 2 9 8 32.93 ± 16.46 29.75 ± 9.2 NR NR NR NR Hu* 2011 NR NR NR NR NR NR NR NR NR NR NR NR 466 (402, 495) 448 (383, 497) Matrino 2015 9 (11) 8 (10.2) 53 (64.1) 48 (61.1) 63 (77) 62 (79) 74 (89.7) 69 (88.9) 23.8 ± 7.2 24.7 ± 7.0 NR NR 347.3(146.7) 349.8(139.7) Sant'Anna 2014 NR NR NR NR NR NR NR NR NR NR NR NR 358.5 (88.69) 353 (86.67) Seth 2010 29 (70) 29 (72) 41 (100) 40 (100) NR NR NR NR NR NR NR NR NR NR Vrtovec 2011 21 (75) 22 (81) NR NR 5 (18) 6 (22) 26 (93) 24 (88) 25.6 ± 5.1 26.7 ± 3.9 69 ± 10 70 ± 7 NR NR Vrtovec 2013 43 (79) 46 (84) 51 (93) 54 (98) 9 (16) 11 (20) 51 (93) 20 (91) 24.3 ± 6.5 25.7 ± 4.1 69 ± 10 70 ± 7 NR NR Xiao 2017 16 (100) 20 (100) 16 (100) 19 (95) 4 (25.0) 8 (40.0) 5 (31.3) 6 (30.0) 33.1 ± 3.9 33.7 ± 4.0 NR NR 355.0 ± 91.2 323.3 ± 89.4 Data are reported as mean ± SD or n (%) unless proved otherwise TTT treatment group, NR not reported *Data are reported as median (IQR).

Efficacy of Cognitive Behavioral Therapy in Heart Failure Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Heart failure (HF) is a global disorder affecting around 6.2 million Americans aged 20 years and above. Neurovegetative disorders are common among such patients, and depression is a major problem that affects 20% to 40% of them. Cognitive behavioral therapy (CBT) is a type of treatment that produces the most favorable results compared to other psychotherapies, especially among patients with depression and anxiety. We aim to summarize and synthesize evidence regarding the efficacy of CBT for patients with HF. METHODS: We conducted this study by searching PubMed, Scopus, and Web of Science for relevant studies about CBT use in patients with HF. The outcomes were pooled as mean difference (MD) or standard MD with a 95% CI. The analysis was performed using the RevMan software. RESULTS: Combined data from 9 randomized controlled trials (1070 patients) revealed that CBT can alleviate both depression symptoms in HF patients when measured using different scales after 3 months of follow-up (standard MD, -0.18 [95% CI, -0.33 to -0.02]; P = 0.03) and the quality of life after 3 and 6 months of follow-up (MD, 4.92 [95% CI, 1.14-8.71]; P = 0.01 and MD, 7.72 [95% CI, 0.77-14.68]; P = 0.03, respectively). CONCLUSION: CBT is an effective type of psychotherapy for dealing with depression, mediocre quality of life, and defective physical functioning; therefore, it should be considered in HF patients' care.

Incidence and risk factors of cardiovascular mortality in patients with gastrointestinal adenocarcinoma.

BACKGROUND: Gastrointestinal (GI) cancers are common and fatal. Improved cancer-directed therapies, with thier substantial role in improving cancer-specific survival, may increase non-cancer mortality-including cardiovascular mortality-in these patients. AIM: To identify the risk factors of cardiovascular mortality in GI adenocarcinoma patients. METHODS: Data of GI adenocarcinoma patients were gathered from the Surveillance, Epidemiology, and End Results database. We used Pearson's chi-square test to assess the relationships between categorical variables. We used the Kaplan-Meyer test in the univariate analysis and Cox regression test for the multivariate analysis. RESULTS: Among 556,350 included patients, 275,118 (49.6%) died due to adenocarcinoma, 64,079 (11.5%) died due to cardiovascular causes, and 83,161 (14.9%) died due to other causes. Higher rates of cardiovascular mortality were found in patients ≥ 50 years (HR, 8.476; 95% CI, 7.91-9.083), separated (HR, 1.27; 95% CI, 1.184-1.361) and widowed (HR, 1.867; 95% CI, 1.812-1.924), patients with gastric (HR, 1.18; 95% CI, 1.1-1.265) or colorectal AC (HR, 1.123; 95% CI, 1.053-1.198), and patients not undergone surgery (HR, 2.04; 95% CI, 1.958-2.126). Lower risk patients include females (HR, 0.729; 95% CI, 0.717-0.742), blacks (HR, 0.95; 95% CI, 0.924-0.978), married (HR, 0.77; 95% CI, 0.749-0.792), divorced (HR, 0.841; 95% CI, 0.807-0.877), patients with pancreatic AC (HR, 0.83; 95% CI, 0.757-0.91), and patients treated with chemotherapy (HR, 0.416; 95% CI, 0.406-0.427). CONCLUSIONS: Risk factors for cardiovascular mortality in GI adenocarcinoma include advanced age, males, whites, separated and widowed, gastric or colorectal adenocarcinoma, advanced grade or advanced stage of the disease, no chemotherapy, and no surgery. Married and divorced, and patients with pancreatic adenocarcinoma have a lower risk.

Comparative Assessment of Transvenous versus Subcutaneous Implantable Cardioverter-defibrillator Therapy Outcomes: An Updated Systematic Review and Meta-analysis.

BACKGROUND: Subcutaneous (S-ICD) and transvenous (TV-ICD) implantable cardioverter-defibrillator devices effectively reduce the incidence of sudden cardiac death in patients at a high risk of ventricular arrhythmias. This study aimed to evaluate the safe replacement of TV-ICD with S-ICD based on updated recent evidence. METHODS: We systematically searched EMBASE, JSTOR, PubMed/MEDLINE, and Cochrane Library on 30 July 2021 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: We identified 26 studies that examined 7542 (58.27%) patients with S-ICD and 5400 (41.72%) with TV-ICD. The findings indicated that, compared to patients with TV-ICD, patients with S-ICD had a lower incidence of defibrillation lead failure (odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01-0.98; p = 0.05), lead displacement or fracture (OR, 0.25; 95% CI, 0.12-0.86; p = 0.0003), pneumothorax and/or hemothorax (OR: 0.22, 95% CI 0.05, 0.97, p = 0.05), device failure (OR: 0.70, 95% CI 0.51, 0.95, p = 0.02), all-cause mortality (OR: 0.44 [95% CI 0.32, 0.60], p < 0.001), and lead erosion (OR: 0.01, 95% CI 0.00, 0.05, p < 0.001). Patients with TV-ICD had a higher incidence of pocket complications than patients with S-ICD (OR, 2.13; 95% CI, 1.23-3.69; p = 0.007) and a higher but insignificant incidence of inappropriate sensing (OR, 3.53; 95% CI, 0.97-12.86; p = 0.06). CONCLUSIONS: The S-ICD algorithm was safer and more effective than the TV-ICD system as it minimized the incidence of pocket complications, lead displacement or fracture, inappropriate sensing, defibrillation lead failure, pneumothorax/hemothorax, device failure, lead erosion, and all-cause mortality. Future studies should explore the scope of integrating novel algorithms with the current S-ICD systems to improve cardiovascular outcomes.

New onset hypertension after transplantation.

It has been reported that up to 90% of organ transplant recipients have suboptimal blood pressure control. Uncontrolled hypertension is a well-known culprit of cardiovascular and overall morbidity and mortality. In addition, rigorous control of hypertension after organ transplantation is a crucial factor in prolonging graft survival. Nevertheless, hypertension after organ transplantation encompasses a broader range of causes than those identified in non-organ transplant patients. Hence, specific management awareness of those factors is mandated. An in-depth understanding of hypertension after organ transplantation remains a debatable issue that necessitates further clarification. This article provides a comprehensive review of the prevalence, risk factors, etiology, complications, prevention, and management of hypertension after organ transplantation.

Role of inflammation in atrial fibrillation: A comprehensive review of current knowledge.

BACKGROUND: Atrial fibrillation (AF) is one of the most common cardiac disorders affecting adults and is associated with significant morbidity and mortality. Efforts to manage AF through anti-arrhythmics and rate control have been largely unsatisfactory. It has become clear that AF causes structural alterations in the atrial myocardium that propagate further AF, and that some of these alterations are the result of inflammation. METHODS: An in-depth review of the available literature was undertaken using Google Scholar and keyword searches including [Atrial fibrillation] in combination with [inflammatory markers], [myocardial fibrosis], and [immunomodulators], limiting the search to English language articles. All articles were reviewed for relevance and collated by the author. RESULTS: Multiple markers of inflammation have been shown to be elevated in AF and to predict responses to treatments of AF including anti-arrhythmics and cardioversion. The nidus of inflammation is not clear but seems to be related to the pulmonary veins. CONCLUSIONS: The inflammatory cascade induces fibrotic changes in the myocardium, an arrhythmogenic process that stimulates further inflammation. Advances in treatment are focusing on biological agents and immunomodulators that inhibit the inflammatory cascade.

South Asian Health: Inflammation, Infection, Exposure, and the Human Microbiome.

This paper presents the results of the literature review conducted for the working group topic on inflammation, infection, exposure, and the human microbiome. Infection and chronic inflammation can elevate risk for cardiovascular disease and cancer. Environmental exposures common among South Asian (SA) subgroups, such as arsenic exposure among Bangladeshis and particulate matter air pollution among taxi drivers, also pose risks. This review explores the effects of exposure to arsenic and particulate matter, as well as other infections common among SAs, including human papillomavirus (HPV) and hepatitis B/C infection. Emerging research on the human microbiome, and the effect of microbiome changes on obesity and diabetes risk among SAs are also explored.

Reversal of tumorigenicity and the block to differentiation in erythroleukemia cells by GATA-1.

Oncogenic transformation usually inhibits normal cell differentiation processes. Certain chemical agents can force some tumor cells to resume their differentiation program and undergo cell cycle arrest, an approach termed differentiation therapy. Mouse erythroleukemia (MEL) cells represent an important cell culture model system for investigating the principles of differentiation therapy. MEL cells are malignant erythroblasts that are blocked from differentiating into mature erythroid cells because of inappropriate expression of the transcription factor PU.1, which binds to and represses GATA-1, a key transcriptional stimulator of red blood cell differentiation. We report here that the block to differentiation in MEL cells can be overcome by providing the cells with additional GATA-1. A conditionally active form of GATA-1 can trigger the cells to differentiate, undergo terminal cell division, and lose their tumorigenicity. We also show that the gene for the cell cycle inhibitor p21 is transcriptionally regulated by GATA-1 and is a likely downstream effector of GATA-1 that helps to promote differentiation and proliferation arrest.

CDK6 blocks differentiation: coupling cell proliferation to the block to differentiation in leukemic cells.

Cell proliferation and differentiation are highly coordinated during normal development. Many tumor cells exhibit both uncontrolled proliferation and a block to terminal differentiation. To understand the mechanisms coordinating these two processes, we have investigated the relation between cyclin-dependent kinase (CDK) activities and the block to differentiation in murine erythroleukemia (MEL) cells. We found that CDK6 (but not CDK4) is rapidly downregulated as MEL cells are induced to re-enter erythroid differentiation and that maintenance of CDK6 (but not CDK4) activity by transfection blocks differentiation. Moreover, we found that PU.1, an Ets transcription factor that is oncogenic in erythroid cells and also can block their differentiation, controls the synthesis of CDK6 mRNA. These results suggest a mechanism for coupling proliferation and the block to differentiation in these leukemic cells through the action of an oncogenic transcription factor (PU.1) on a key cell cycle regulator (CDK6). Our findings suggest that studying the relative roles of CDK6 and CDK4 in other types of malignant cells will be important in designing approaches for cell cycle inhibition and differentiation therapy in cancer.

Trazodone and omeprazole interaction causing frequent second-degree Mobitz type 1 atrioventricular (AV) block (Wenckebach phenomenon) and syncope: a case report and literature review.

BACKGROUND: This case report highlights serious cardiovascular adverse effects with a conventional dose of trazodone as a result of its potential interaction with omeprazole. CASE REPORT: A 54-year-old man who was a former smoker, with dyslipidemia, coronary artery disease, and anxiety disorder developed lightheadedness and syncope the morning of admission. He was taking trazodone 50 mg daily, omeprazole 20 mg daily, and simvastatin 20 mg at bedtime. He doubled the dose of trazodone 50 mg on the night prior to presentation to calm his anxiety. An electrocardiogram revealed sinus rhythm at 60 beats per minute and second-degree Mobitz type 1 atrioventricular (AV) block with 5:4 AV conduction. Results of basic metabolic panel, thyroid-stimulating hormone, and chest radiograph were normal. A transthoracic echocardiogram revealed aortic valve sclerosis. We tested for Lyme disease given his history of hunting in the woods 8 months prior to presentation, but the titer was negative. Trazodone and omeprazole were discontinued. By the 3rd day of medication discontinuation, all symptoms had resolved and the frequency of second-degree AV Mobitz type 1 AV block had decreased to once per hour. CONCLUSIONS: Due diligence and meticulous attention to detail needs to be exercised to uncover drug interactions as potential causes of lethal and nonlethal patient symptomatology, as in this case of syncope caused by concomitant use of trazodone and a widely prescribed medication, omeprazole.

Urinary bladder paraganglioma presenting as micturition-induced palpitations, dyspnea, and angina.

BACKGROUND: Sympathetic urinary bladder paragangliomas are rare catecholamine-secreting neuroendocrine tumors arising from neural crest cells. They are uncommon urinary bladder neoplasms. Symptoms classically include micturition-related or unrelated palpitations and syncope with hypertension, headaches, diaphoresis, and hematuria. Other than being attributable to vasovagal reactions, micturition-induced cardiovascular symptoms should prompt a search for catecholamine-secreting tumors such as a urinary bladder paraganglioma, as in this case. CASE REPORT: A 45-year-old asthmatic African-American female presented with episodic hematuria that began 4 years ago and episodes of micturition-induced palpitations, dyspnea, substernal tightness, sweating, and throbbing headaches. Computed tomography with contrast revealed an enhancing mass along the anterior urinary bladder wall, measuring 2.4×3.5 cm. On Positron emission Tomography with [18F] fluorodeoxyglucose integrated with computed tomography (18F-FDG PET/CT), the urinary bladder mass was 18F-FDG avid. Serum normetanephrine and supine plasma norepinephrine were significantly elevated and there was mild elevation of supine plasma epinephrine. Transurethral resection of the bladder mass revealed a neoplasm with microscopic features and immunohistochemical profile positive for synaptophysin and chromogranin, with negative screening cytokeratin AE1/AE3, suggesting a paraganglioma. Following resection of the paraganglioma, there was complete resolution of micturition-induced cardiovascular symptoms on long-term follow-up. CONCLUSIONS: Micturition-related cardiovascular symptoms are commonly attributed to vasovagal reactions. However, urinary bladder pathologies must be ruled out as a cause, as in this rare case of a urinary bladder paraganglioma exhibiting catecholaminergic symptoms.

Left ventricular non-compaction cardiomyopathy.

In this article, we describe three patients with heart failure whose 2D echocardiograms showed left ventricular non-compaction cardiomyopathy characterized by prominent trabeculation with deep intertrabecular spaces in the myocardium.