Genetic markers of cardiac autonomic neuropathy in the Kazakh population.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes. MATERIALS AND METHODS: A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE "Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan". 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0. RESULTS: Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09-3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63-1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04-9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19-5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09-0.68), p = 0.007, and OR 0.43, CI (0.22-0.84), p = 0.02, respectively). CONCLUSION: The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN.

Comparison of dmft and behavior rating scores between children with systemic disease and healthy children at the first dental visit.

PURPOSE: To evaluate and compare oral health and behavior scores at the first dental visit and dental treatment need using general anesthesia/sedation (GA/S) of children with systemic diseases (SD) and healthy children. METHODS: Data were obtained from healthy children (n = 87) and children with SD (n = 79), aged 4 to 6 years, presenting to a hospital dental clinic for a first dental examination. The total number of decayed, missing and filled teeth (dmft), dental behavior score using Frankl Scale, and dental treatment need using GA/S were recorded. Chi-square / Fisher's exact test and Mann-Whitney U tests were used for statistical analyses. RESULTS: The patients with SD were diagnosed with cardiac disease (61%), renal disease (9%), and pediatric cancers (30%). The median dmft values of the SD group (3.00) were significantly lower than those of healthy children (5.00) (p = 0.02) and healthy children exhibited significantly more positive behavior (90.8%) than children with SD (73.4%) (p = 0.002). The number of patients needing GA/S for dental treatment did not differ significantly between the two groups (p = 0.185). There was no relationship between dental treatment need with GA/S and dental behavior scores of the patients (p = 0.05). A statistically significant relationship was found between the patients' dmft scores and the need for dental treatment using GA/S; and the cut-off value was found to be dmft > 4 for the overall comparisons. CONCLUSION: The presence of chronic disease in children appeared to affect the cooperation negatively at the first dental visit compared to healthy controls, however, it did not affect the oral health negatively. Having a negative behavior score or SD did not necessitate the use of GA/S for dental treatment.

Recurrent intra-cardiac thrombosis: A rare manifestation of Behçet's disease.

Behçet's disease is a systemic vasculitis characterized by recurrent bipolar aphtosis and ophthalmic disorders. Cardiac involvement is rarely reported and could be associated to poor prognosis. Intracardiac thrombosis is exceptional and represents a therapeutic issue. We report the case of a young man admitted in internal medicine department for management of prolonged fever and recurrent mouth ulcers.

The value of cardiopulmonary comorbidity in patients with acute large vessel occlusion stroke undergoing endovascular thrombectomy: a retrospective, observational cohort study.

BACKGROUND: Chronic lung and heart diseases are more likely to lead an intensive end point after stroke onset. We aimed to investigate characteristics and outcomes of endovascular thrombectomy (EVT) in patients with acute large vessel occlusion stroke (ALVOS) and identify the role of comorbid chronic cardiopulmonary diseases in ALVOS pathogenesis. METHODS: In this single-center retrospective study, 191 consecutive patients who underwent EVT due to large vessel occlusion stroke in neurological intensive care unit were included. The chronic cardiopulmonary comorbidities and several conventional stroke risk factors were assessed. The primary efficacy outcome was functional independence (defined as a mRS of 0 to 2) at day 90. The primary safety outcomes were death within 90 days and the occurrence of symptomatic intracranial hemorrhage(sICH). Univariate analysis was applied to evaluate the relationship between factors and clinical outcomes, and logistic regression model were developed to predict the prognosis of ALVOS. RESULTS: Endovascular therapy in ALVOS patients with chronic cardiopulmonary diseases, as compared with those without comorbidity, was associated with an unfavorable shift in the NHISS 24 h after EVT [8(4,15.25) versus 12(7.5,18.5), P = 0.005] and the lower percentage of patients who were functionally independent at 90 days, defined as a score on the modified Rankin scale of 0 to 2 (51.6% versus 25.4%, P = 0.000). There was no significant between-group difference in the frequency of mortality (12.1% versus 14.9%, P = 0.580) and symptomatic intracranial hemorrhage (13.7% versus 19.4%, P = 0.302) or of serious adverse events. Moreover, a prediction model showed that existence of cardiopulmonary comorbidities (OR = 0.456, 95%CI 0.209 to 0.992, P = 0.048) was independently associated with functional independence at day 90. CONCLUSIONS: EVT was safe in ALVOS patients with chronic cardiopulmonary diseases, whereas the unfavorable outcomes were achieved in such patients. Moreover, cardiopulmonary comorbidity had certain clinical predictive value for worse stroke prognosis.

The Risk Of Waiting Up To One Year For Cardiac Surgery.

INTRODUCTION: Cardiac disease is associated with a risk of death, both by the cardiac condition and by comorbidities. The waiting time for surgery begins with the onset of symptoms and includes referral, completion of the diagnosis and surgical waiting list (SWL). This study was conducted during the COVID-19 pandemic, which affected surgical capacity and patients' morbidities. METHODS: The cohort includes 1914 consecutive adult patients (36.6% women, mean age 67 ±11 years), prospectively registered in the official SWL from January 2019 to December 2021. We analyzed waiting times ranging from 4 days to one year to exclude urgencies and outliers. Priority was classified by the national criteria for non-oncologic or oncology surgery. RESULTS: During the study period, 74% of patients underwent surgery, 19.2% were still waiting, and 4.3% dropped out. Most cases were valvular (41.2%) or isolated bypass procedures (34.2%). Patients were classified as non-priority in 29.7%, priority in 61.8%, and high priority in 8.6%, with significantly different SWL mean times between groups (p<0.001). The overall mean waiting time was 167 ± 135 days. Mortality on SWL was 2.5%, or 1.1 deaths per patient/weeks. There were two mortality independent predictors: age (HR 1.05) and the year 2021 versus 2019 (HR 2.07) and a trend toward higher mortality in priority patients versus non-priority (p=0.065). The overall risk increased with time with different slopes for each year. Using the time limits for SWL in oncology, there would have been a significant risk reduction (p=0.011). CONCLUSION: The increased risk observed in 2021 may be related to the pandemic, either by increasing waiting time or by direct mortality. Since risk stratification is not entirely accurate, waiting time emerges as the most crucial factor influencing mortality, and implementing stricter time limits could have led to lower mortality rates.

[A Thrombus in the Right Atrium Associated with Pyogenic Liver Abscess].

Hepatic abscesses are divided into bacterial and amoebic types. Although the prognosis of bacterial liver abscesses has improved owing to progress in drainage techniques and antimicrobial agents, poor outcomes remain common. While there have been some reports of amoebic liver abscesses complicated by thrombosis, bacterial liver abscesses and subsequent thrombus in the right atrium are very rare. We herein report the case of an 82-year-old man. He had suffered acute obstructive suppurative cholangitis 10 months previously, and bile culture yielded Enterococcus faecalis. In the present case, a right atrial thrombus caused by a bacterial liver abscess was observed and the causative organism was thought to be Enterococcus faecalis, for which was detected in a blood culture was positive. The patient was successfully treated with hepatic abscess drainage and surgical right atrial thrombectomy under cardiopulmonary bypass with a beating heart.

Proteomics discovery in children and young adults with HIV identifies fibrosis, inflammatory, and immune biomarkers associated with myocardial impairment.

People with HIV are at increased risk of cardiac dysfunction; however, limited tools are available to identify patients at highest risk for future cardiac disease. We performed proteomic profiling using plasma samples from children and young adults with perinatally acquired HIV without clinical cardiac disease, comparing samples from participants with and without an abnormal myocardial performance index (MPI). We identified four proteins independently associated with subclinical cardiac dysfunction: ST2, CA1, EN-RAGE, and VSIG2.

Monocyte-Derived Macrophages Aggravate Cardiac Dysfunction After Ischemic Stroke in Mice.

BACKGROUND: Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral-cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke-induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear. METHODS AND RESULTS: In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1GFPCcr2RFP mice and NLRP3-deficient mice in combination with Smart-seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke-induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte-derived macrophages into the heart. Subsequently, we identified that cardiac monocyte-derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3-deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte-derived macrophages and subsequent cardiac dysfunction. CONCLUSIONS: Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve-monocyte-derived macrophage axis.

Beneficial Effects of Oral Carbon Monoxide on Doxorubicin-Induced Cardiotoxicity.

BACKGROUND: Doxorubicin and other anthracyclines are crucial cancer treatment drugs. However, they are associated with significant cardiotoxicity, severely affecting patient care and limiting dosage and usage. Previous studies have shown that low carbon monoxide (CO) concentrations protect against doxorubicin toxicity. However, traditional methods of CO delivery pose complex challenges for daily administration, such as dosing and toxicity. To address these challenges, we developed a novel oral liquid drug product containing CO (HBI-002) that can be easily self-administered by patients with cancer undergoing doxorubicin treatment, resulting in CO being delivered through the upper gastrointestinal tract. METHODS AND RESULTS: HBI-002 was tested in a murine model of doxorubicin cardiotoxicity in the presence and absence of lung or breast cancer. The mice received HBI-002 twice daily before doxorubicin administration and experienced increased carboxyhemoglobin levels from a baseline of ≈1% to 7%. Heart tissue from mice treated with HBI-002 had a 6.3-fold increase in CO concentrations and higher expression of the cytoprotective enzyme heme oxygenase-1 compared with placebo control. In both acute and chronic doxorubicin toxicity scenarios, HBI-002 protected the heart from cardiotoxic effects, including limiting tissue damage and cardiac dysfunction and improving survival. In addition, HBI-002 did not compromise the efficacy of doxorubicin in reducing tumor volume, but rather enhanced the sensitivity of breast 4T1 cancer cells to doxorubicin while simultaneously protecting cardiac function. CONCLUSIONS: These findings strongly support using HBI-002 as a cardioprotective agent that maintains the therapeutic benefits of doxorubicin cancer treatment while mitigating cardiac damage.

Factors Associated with Neonatal Arterial Hypertension: Case and Control Study.

Background. Neonatal high blood pressure has been diagnosed more frequently in recent years, and its impact extends to adulthood. However, the knowledge gaps on associated factors, diagnosis, and treatment are challenging for medical personnel. The incidence of this condition varies depending on neonatal conditions. Patients in the Newborn Unit are at increased risk of developing high blood pressure. The persistence of this condition beyond the neonatal stage increases the risk of cardiovascular disease and chronic kidney disease in childhood and adulthood. Methodology. A case-control study was carried out. It included hospitalized patients with neonatal hypertension as cases. Three controls were randomly selected for each case and matched by gestational age. The variables were analyzed based on their nature. Multivariate analysis was performed using a multivariate conditional regression model to identify variables associated with the outcome. Finally, the model was adjusted for possible confounders. Results. 37 cases were obtained and matched with 111 controls. In the univariate analysis, heart disease (OR 2.86; 95% CI 1.22-6.71), kidney disease (OR 7.24; 95% CI 1.92-28.28), bronchopulmonary dysplasia (OR 6.62; 95% CI 1.42-50.82) and major surgical procedures (OR 3.71; 95% CI 1.64-8.39) had an association with neonatal arterial hypertension. Only the latter maintained this finding in the multivariate analysis (adjusted OR 2.88; 95% CI 1.14-7.30). A significant association of two or more comorbidities with neonatal arterial hypertension was also found (OR 3.81; 95% CI 1.53-9.49). Conclusions. The study analyzed the factors related to high blood pressure in hospitalized neonates, finding relevant associations in the said population. The importance of meticulous neonatal care and monitoring of risk factors such as birth weight and major surgeries is highlighted.

Evaluation of medication use and polypharmacy in postoperative cardiac patients: The clinical pharmacist's imperative in a public institute of Pakistan.

As a major concern in the healthcare sector, polypharmacy is correlated with an increased risk of potential drug-drug interactions (pDDIs), treatment costs and adverse drug reactions (ADR). To assess the prevalence of polypharmacy and its associated factors among postoperative cardiac patients admitted to the National Institute of Cardiovascular Diseases (NICVD), a hospital-based cross-sectional study was conducted between November 2021 and April 2022. Medication charts of postoperative patients were reviewed for medication utilization and polypharmacy. Data was collected using a form approved by the Ethical Review Committee (ERC) regarding patient's clinical and demographic characteristics and medications administered. Statistical analysis was performed using the SPSS software version 25.0. Patients were taking an average of 10.3±1.7 medications. The minimum number of drugs taken per patient was 5, while the maximum was 15 drugs. Only 114 (29.7%) received polypharmacy (5-9 drugs) and hyper-polypharmacy (≥10 drugs) was 270 (70.3%). The mean±SD cardiovascular drugs used were 5.45±1.18 and the mean±SD non-cardiovascular drugs were 4.83±1.18. The prevalence of hyper-polypharmacy suggests a critical need for optimized medication management strategies in this population. Incorporating clinical pharmacists within public healthcare institutions can address polypharmacy-related challenges and enhance medication safety, adherence and patient outcomes.

Placental senescence pathophysiology is shared between peripartum cardiomyopathy and preeclampsia in mouse and human.

Peripartum cardiomyopathy (PPCM) is an idiopathic form of pregnancy-induced heart failure associated with preeclampsia. Circulating factors in late pregnancy are thought to contribute to both diseases, suggesting a common underlying pathophysiological process. However, what drives this process remains unclear. Using serum proteomics, we identified the senescence-associated secretory phenotype (SASP), a marker of cellular senescence associated with biological aging, as the most highly up-regulated pathway in young women with PPCM or preeclampsia. Placentas from women with preeclampsia displayed multiple markers of amplified senescence and tissue aging, as well as overall increased gene expression of 28 circulating proteins that contributed to SASP pathway enrichment in serum samples from patients with preeclampsia or PPCM. The most highly expressed placental SASP factor, activin A, was associated with cardiac dysfunction or heart failure severity in women with preeclampsia or PPCM. In a murine model of PPCM induced by cardiomyocyte-specific deletion of the gene encoding peroxisome proliferator-activated receptor γ coactivator-1α, inhibiting activin A signaling in the early postpartum period with a monoclonal antibody to the activin type II receptor improved heart function. In addition, attenuating placental senescence with the senolytic compound fisetin in late pregnancy improved cardiac function in these animals. These findings link senescence biology to cardiac dysfunction in pregnancy and help to elucidate the pathogenesis underlying cardiovascular diseases of pregnancy.

4-phenylbutyric acid improves sepsis-induced cardiac dysfunction by modulating amino acid metabolism and lipid metabolism via Comt/Ptgs2/Ppara.

INTRODUCTION: Cardiac dysfunction after sepsis the most common and severe sepsis-related organ failure. The severity of cardiac damage in sepsis patients was positively associated to mortality. It is important to look for drugs targeting sepsis-induced cardiac damage. Our previous studies found that 4-phenylbutyric acid (PBA) was beneficial to septic shock by improving cardiovascular function and survival, while the specific mechanism is unclear. OBJECTIVES: We aimed to explore the specific mechanism and PBA for protecting cardiac function in sepsis. METHODS: The cecal ligation and puncture-induced septic shock models were used to observe the therapeutic effects of PBA on myocardial contractility and the serum levels of cardiac troponin-T. The mechanisms of PBA against sepsis were explored by metabolomics and network pharmacology. RESULTS: The results showed that PBA alleviated the sepsis-induced cardiac damage. The metabolomics results showed that there were 28 metabolites involving in the therapeutic effects of PBA against sepsis. According to network pharmacology, 11 hub genes were found that were involved in lipid metabolism and amino acid transport following PBA treatment. The further integrated analysis focused on 7 key targets, including Comt, Slc6a4, Maoa, Ppara, Pparg, Ptgs2 and Trpv1, as well as their core metabolites and pathways. In an in vitro assay, PBA effectively inhibited sepsis-induced reductions in Comt, Ptgs2 and Ppara after sepsis. CONCLUSIONS: PBA protects sepsis-induced cardiac injury by targeting Comt/Ptgs2/Ppara, which regulates amino acid metabolism and lipid metabolism. The study reveals the complicated mechanisms of PBA against sepsis.

Natural history of cardiac involvement in myotonic dystrophy type 1 - Emphasis on the need for lifelong follow-up.

BACKGROUND: Cardiac involvement represents a major cause of morbidity and mortality in patients with myotonic dystrophy type 1 (DM1) and prevention of sudden cardiac death (SCD) is a central part of patient care. We investigated the natural history of cardiac involvement in patients with DM1 to provide an evidence-based foundation for adjustment of follow-up protocols. METHODS: Patients with genetically confirmed DM1 were identified. Data on patient characteristics, performed investigations (12 lead ECG, Holter monitoring and echocardiography), and clinical outcomes were retrospectively collected from electronic health records. RESULTS: We included 195 patients (52% men) with a mean age at baseline evaluation of 41 years (range 14-79). The overall prevalence of cardiac involvement increased from 42% to 66% after a median follow-up of 10.5 years. There was a male predominance for cardiac involvement at end of follow-up (74 vs. 44%, p < 0.001). The most common types of cardiac involvement were conduction abnormalities (48%), arrhythmias (35%), and left ventricular systolic dysfunction (21%). Only 17% of patients reported cardiac symptoms. The standard 12­lead ECG was the most sensitive diagnostic modality and documented cardiac involvement in 24% at baseline and in 49% at latest follow-up. However, addition of Holter monitoring and echocardiography significantly increased the diagnostic yield with 18 and 13% points at baseline and latest follow-up, respectively. Despite surveillance 35 patients (18%) died during follow-up; seven due to SCD. CONCLUSIONS: In patients with DM1 cardiac involvement was highly prevalent and developed during follow-up. These findings justify lifelong follow-up with ECG, Holter, and echocardiography. CLINICAL PERSPECTIVE: What is new? What are the clinical implications?

Fabry disease in W162C mutation: a case report of two patients and a review of literature.

BACKGROUND: Fabry disease is a multisystemic disorder characterized by deposition of globotriaosylceramide (Gb3) and its deacylated form in multiple organs, sometimes localized in specific systems such as the nervous or cardiovascular system. As disease-modifying therapies are now available, early diagnosis is paramount to improving life quality and clinical outcomes. Despite the widespread use of non-invasive techniques for assessing organ damage, such as cardiac magnetic resonance imaging (MRI) for patients with cardiac disease, organ biopsy remains the gold standard to assess organ involvement. CASE PRESENTATION: The cases of two patients, father and daughter with a W162C mutation, are described. The father presented with late-onset, cardiac Fabry disease, subsequently developing systolic dysfunction and heart failure. His daughter, while asymptomatic and with normal cardiac assessment (except for slightly reduced native T1 values by cardiac MRI), had already initial myocyte Gb3 deposits on the endomyocardial biopsy, allowing her to start therapy precociously and potentially modifying the course of her disease. A review of the literature concerning the W162C mutation is then provided, showing that it is usually associated to classic, multisystemic Fabry disease rather than the cardiac-restricted form as in these two cases. CONCLUSIONS: Three main points can be concluded from this report. First, the W162C mutation can present with a more variegate phenotype than that predicted on a molecular basis. Second, endomyocardial biopsy was shown in this case to precede non-invasive investigation in determining organ involvement, justifying further studies on this potentially reliable technique, Third, difficulties can arise in the management of asymptomatic female carriers.