Gastrointestinal bleeding in patients with continuous-flow left ventricular assist devices: A comprehensive review.

BACKGROUND: Gastrointestinal bleeding is a major cause of morbidity that plagues the quality of life of patients supported on contemporary continuous-flow left ventricular assist devices (CF-LVADs). Despite benefits in survival and the nearly 50% reduction in complications provided by CF-LVADs, bleeding remains one of the most frequent adverse events with CF-LVAD implants. The CF-LVADs cause an increased risk of bleeding mainly due to the activation of the coagulation cascade. METHODS: A literature search was done using PubMed and Google Scholar from Inception to February 2022. Qualitative analyses of the articles retrieved were used to construct this review. This review attempts to provide a comprehensive summary of the epidemiology, pathophysiology, risk stratification, and management of gastrointestinal bleeding as a complication of CF-LVAD as well as propose an algorithm for diagnosis and treatment. RESULTS: Bleeding can occur at different sites in the gastrointestinal tract, the most common underlying pathology being arteriovenous malformations located in the upper gastrointestinal tract The increased prevalence of gastrointestinal (GI) bleeding in CF-LVAD patients has been attributed to the physiology of the LVAD itself, the use of anticoagulants, as well as patient comorbidities. Management involves pharmacologic and nonpharmacologic strategies. CONCLUSIONS: CF-LVAD-supported patients have a significant risk of GI bleeding that is mainly caused by arteriovenous malformations located in the upper GI tract. The increased prevalence of GI bleeding in CF-LVAD patients is attributed to several etiologies that include factors attributed to the device itself and extrinsic factors such as the use of anticoagulation.

The influence of individual and neighborhood-level characteristics on rural-urban disparities in cardiovascular disease mortality among U.S. women diagnosed with breast and gynecologic cancers.

OBJECTIVE: Rural-urban disparities exist in cancer and cardiovascular disease (CVD) mortality. Investigations of CVD mortality among breast and gynecologic cancer (BGC) survivors from rural/urban communities are limited. We evaluated the influence of individual and neighborhood-level factors on rural-urban disparities in CVD mortality among BGC survivors. METHODS: Data were from 1,139,767 women aged ≥20 years from the Surveillance, Epidemiology, and End Results program who were diagnosed with BGC from 2000 to 2016 that was merged with Area Health Resource Files for neighborhood-level factors (smoking, cancer screening, primary care provider density and socioeconomic index). Standardized mortality ratios (SMRs) for CVD mortality were calculated and multilevel Cox models, accounting for competing events, were used to estimate hazards ratios (HR) and 95% confidence intervals (CI). RESULTS: The average age of BGC survivors was 60 years, with 10.3% of them living in rural counties. During a median follow-up of 5.1 years, 47,995 CVD deaths occured. Women with BGC had excess CVD mortality compared to general population women (SMR 6.05; CI: 6.00-6.11). This risk was highest among women aged <50 years (SMR = 27.16; CI: 25.74-28.62). In models adjusted for demographics, cancer stage and cancer therapy, women with BGC in rural communities had higher CVD deaths than those in urban communities (HR = 1.10, CI:1. 05-1.15). Additional adjustment for neighborhood-level characteristics attenuated the relation of rurality with CVD mortality (HR = 1.02, CI: 0.98-1.07). CONCLUSIONS: BGC survivors living in rural communities have elevated risk of CVD mortality. Neighborhood-level characteristics explained the rural-urban disparities in CVD mortality observed among BGC survivors.

The Joint Association of Septicemia and Cerebrovascular Diseases with In-Hospital MortalityAmong Patients with Left Ventricular Assist Device in the United States.

OBJECTIVES: Left ventricular assist device (LVAD) is associated with complications such as cerebrovascular diseases (CEVD) as well as septicemia which is often preventable. With their use increasing in the U.S., identifying patients with LVAD who are at high risk for short-term mortality is essential for targeted effective patient management strategies to prevent adverse outcomes. We investigated the individual and joint association of CEVD and septicemia with the risk of in-hospital mortality in patients with LVAD in the U.S. MATERIALS AND METHODS: We used data from the National Inpatient Sample from 2004 to 2015 to identify patients ≥18 years of age who underwent LVAD implantation by means of International Classification of Disease, 9th Revision, codes. Multivariable hierarchical negative binomial regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) for in-hospital mortality by CEVD-septicemia status. RESULTS: The mean age of the 4638 patients was 56 years, and 23% of them were women. Approximately 13% of patients had septicemia; 7% had CEVD and 2% had both conditions. In models adjusted for demographic, lifestyle/behavior factors and comorbid conditions, the risk of in-hospital mortality was almost threefold higher among patients with septicemia alone (RR=2.84, CI:2.24-3.60); two-and-half fold higher among patients with CEVD alone (RR=2.53, CI:1.85-3.48); and almost fourfold among patients with both septicemia and CEVD (RR=3.76, CI: 2.38-5.94, Pinteraction = <0.001) CONCLUSION: The presence of both septicemia and CEVD was associated with a substantially higher risk of in-hospital mortality among LVAD patients when compared to septicemia or CEVD alone.

Invasive Hemodynamics in Heart Failure with Preserved Ejection Fraction: Importance of Detecting Pulmonary Vascular Remodeling and Right Heart Function.

Heart failure (HF) is an ongoing crisis reaching epidemic proportions worldwide. About 50% of HF patients have a preserved ejection fraction. Invasive hemodynamics have shown varied results in patients who have HF with preserved ejection fraction (HFpEF). This article attempts to summarize the importance of detecting pulmonary vascular remodeling in HFpEF using invasive hemodynamics. Incorporating newer invasive hemodynamic parameters such as diastolic pulmonary gradient, pulmonary arterial compliance, pulmonary vascular resistance, and pulmonary arterial pulsatility index may improve patient selection for studies used in defining advanced therapies and clinical outcomes. Profiling of patients using invasive hemodynamic parameters may lead to better patient selection for clinical research.

Epidemiology and pathogenesis of heart failure with preserved ejection fraction.

Heart failure (HF) is a complex syndrome that affects approximately 6.5 million adults in the United States. About half of the 6.5 million adults with HF are estimated to be individuals with heart failure with preserved ejection fraction (HFpEF). It is a common cause for poor quality of life, increased health-care resource utilization, and early mortality. HF incidence has risen to epidemic proportions in the recent years. This review attempts to address the epidemiology and pathophysiology of HFpEF. The incidence of HFpEF increased from 48% to 57% from 2000 to 2007 with a slight decrease in 2010 to 52%. The temporal trends in heart failure show an overall stable incidence of HF over the last two decades with increasing incidence of HFpEF and decreasing HFrEF incidence. Many etiologies contribute to the development of HFpEF which makes the treatment very challenging. Pathophysiology of HFpEF is multifaceted stemming from several disease-specific aspects of inflammation and endothelial function, cardiomyocyte hypertrophy and fibrosis, ventricular-vascular uncoupling, pulmonary hypertension and chronotropic incompetence. Hence identifying the risk factors and etiologies is imperative to achieve optimal outcomes in this population. Newer insights into myocardial remodeling have led to an interesting finding of abnormal fibroblasts in HFpEF which are apoptosis resistant and initiate the development of an abnormal myocardial matrix resulting in initiation and progression of the disease. Upregulation of ROS has also been implicated in HFpEF. Further investigation could provide new avenues to target therapeutics specifically to stop initiation and progression of fibrosis.

Recurrent short-to-shield phenomenon requiring LVAD exchange: a rare complication.

Left ventricular assist device (LVAD) therapy is a common alternative approach for a patient with end-stage heart failure with HeartMate II (HM II) being one of the most common LVAD implants. The short-to-shield (STS) phenomenon is an uncommon drive-line (DL) dysfunction resulted from broken insulator causing an underlying wire to contact a metallic shield in a DL. This leads to a short circuit and a pump stoppage. We reported a case of 66-year-old man status post-implantation of HM II who presented with STS phenomenon. A tear at the distal end of the DL was found, and the patient underwent replacement of the extracorporeal part of DL twice. After the second repair, the pump functioned normally when tested in the hospital but the STS occurred again at home. The patient then underwent LVAD replacement surgery and insulation breach was found at one of the wires in intracorporeal part of the DL. After the surgery, the patient sustained recurrent episodes of STS and had to undergo a third extracorporeal DL repair surgery. Analysis of the removed DL confirmed an insulation breach. The STS has been resolved since then. Our case is unique as it is very rare to sustain another episode of STS shortly after a pump exchange. It also shows that the occurrence of STS can be intermittent and the area of insulation breach can be different from the area of the visualized tear. As a result, closed monitoring after DL repair must be strictly implemented.

Impact of preoperative atrial fibrillation in patients with left ventricular assist device: A systematic review and meta-analysis.

Atrial fibrillation (AF) is a common finding in patients evaluated for left ventricular assist device (LVAD). There is conflicting data regarding the mortality risk as well as the thromboembolic risk in patients with preoperative AF who undergo LVAD implantation. We examined these risks by performing a meta-analysis. We performed a literature search of Pubmed, EMBASE, SCOPUS, and Cochrane from inception to February 2018. The eligible studies were used to compare mortality rate and thromboembolic risk between AF and Non-AF (NAF) groups after LVAD implantation. We obtained 391 articles from our search strategy. Seven retrospective studies were included and accounted for 5823 LVAD patients (AF 1589; NAF 4234). The median follow-up duration ranged from 7-24 months. The pooled analysis revealed a significantly increased risk of mortality in preoperative AF patients who underwent LVAD operation compared to those with NAF (Risk Ratio [RR] 1.16, 95% CI 1.05-1.28, I2 = 0%). Five studies reported thromboembolism events involving 1359 preoperative AF and 3893 NAF patients. The pooled analysis did not show a statistically significant association between risk of thromboembolic event and preoperative AF (Risk Ratio [RR] 1.08, 95% CI 0.86-1.36, I2 = 76.2%). Our study shows that preoperative AF may be associated with a higher mortality rate. This study is limited by the fact that the data are pooled from retrospective studies. Further prospective studies are warranted in order to validate these results.

5- or/and 20-O-alkyl-2,3-dehydrosilybins: Synthesis and biological profiles on prostate cancer cell models.

To investigate the effects of alkylation at 5-OH and 20-OH of 2,3-dehydrosilybin on prostate cancer cell proliferation, the synthetic approaches to 5- or/and 20-O-alkyl-2,3-dehydrosilybins, through a multi-step sequence from commercially available silybin, have been successfully developed. The first three reactions in the syntheses were completed through a one-pot procedure by managing anaerobic and aerobic conditions. With these synthetic methods in hand, twenty-one 2,3-dehydrosilybins, including seven 20-O-alkyl, seven 5,20-O-dialkyl, and seven 5-O-alkyl-2,3-dehydrosilybins, have been achieved for the evaluation of their biological profiles. Our WST-1 cell proliferation assay data indicate that nineteen out of the twenty-one 2,3-dehydrosilybins possess significantly improved antiproliferative potency as compared with silybin toward both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145). 5-O-Alkyl-2,3-dehydrosilybins were identified as the optimal subgroup that can consistently inhibit cell proliferation in three prostate cancer cell models with all IC50 values lower than 8µM. Our flow cytometry-based assays also demonstrate that 5-O-heptyl-2,3-dehydrosilybin effectively arrests the cell cycle in the G0/G1 phase and activates PC-3 cell apoptosis.

Cardiac myosin-binding protein-C is a critical mediator of diastolic function.

Diastolic dysfunction prominently contributes to heart failure with preserved ejection fraction (HFpEF). Owing partly to inadequate understanding, HFpEF does not have any effective treatments. Cardiac myosin-binding protein-C (cMyBP-C), a component of the thick filament of heart muscle that can modulate cross-bridge attachment/detachment cycling process by its phosphorylation status, appears to be involved in the diastolic dysfunction associated with HFpEF. In patients, cMyBP-C mutations are associated with diastolic dysfunction even in the absence of hypertrophy. cMyBP-C deletion mouse models recapitulate diastolic dysfunction despite in vitro evidence of uninhibited cross-bridge cycling. Reduced phosphorylation of cMyBP-C is also associated with diastolic dysfunction in patients. Mouse models of reduced cMyBP-C phosphorylation exhibit diastolic dysfunction while cMyBP-C phosphorylation mimetic mouse models show enhanced diastolic function. Thus, cMyBP-C phosphorylation mediates diastolic function. Experimental results of both cMyBP-C deletion and reduced cMyBP-C phosphorylation causing diastolic dysfunction suggest that cMyBP-C phosphorylation level modulates cross-bridge detachment rate in relation to ongoing attachment rate to mediate relaxation. Consequently, alteration in cMyBP-C regulation of cross-bridge detachment is a key mechanism that causes diastolic dysfunction. Regardless of the exact molecular mechanism, ample clinical and experimental data show that cMyBP-C is a critical mediator of diastolic function. Furthermore, targeting cMyBP-C phosphorylation holds potential as a future treatment for diastolic dysfunction.

Artificial Intelligence Approaches for Predicting the Risks of Durable Mechanical Circulatory Support Therapy and Cardiac Transplantation.

Background: The use of AI-driven technologies in probing big data to generate better risk prediction models has been an ongoing and expanding area of investigation. The AI-driven models may perform better as compared to linear models; however, more investigations are needed in this area to refine their predictability and applicability to the field of durable MCS and cardiac transplantation. Methods: A literature review was carried out using Google Scholar/PubMed from 2000 to 2023. Results: This review defines the knowledge gaps and describes different AI-driven approaches that may be used to further our understanding. Conclusions: The limitations of current models are due to missing data, data imbalances, and the uneven distribution of variables in the datasets from which the models are derived. There is an urgent need for predictive models that can integrate a large number of clinical variables from multicenter data to account for the variability in patient characteristics that influence patient selection, outcomes, and survival for both durable MCS and HT; this may be fulfilled by AI-driven risk prediction models.

Cardiac Amyloidosis: A Contemporary Review of Medical and Surgical Therapy.

Amyloidosis is a systemic disease initiated by deposition of misfolded proteins in the extracellular space, due to which multiple organs may be affected concomitantly. Cardiac amyloidosis, however, remains a major cause of morbidity and mortality in this population due to infiltrative /restrictive cardiomyopathy. This review attempts to focus on contemporary medical and surgical therapies for the different types of cardiac amyloidosis. Amyloidosis affecting the heart are predominantly of the transthyretin type (acquired in the older or genetic in the younger patients), and the monoclonal immunoglobulin light chain (AL) type which is solely acquired. A rare form of secondary amyloidosis AA type can also affect the heart due to excessive production and accumulation of the acute-phase protein called Serum Amyloid A" (SAA) in the setting of chronic inflammation, cancers or autoinflammatory disease. More commonly AA amyloidosis is seen in the liver and kidney. Other rare types are Apo A1 and Isolated Atrial Amyloidosis (AANF). Medical therapies have made important strides in the clinical management of the two common types of cardiac amyloidosis. Surgical therapies such as mechanical circulatory support and cardiac transplantation should be considered in appropriate patients. Future research using AI driven algorithms for early diagnosis and treatment as well as development of newer genetic engineering technologies will drive improvements in diagnosis, treatment and patient outcomes.

Propensity matched post-transplant survival in durable CF-axial pump BTT patients with and without diabetes: A UNOS database analysis.

Diabetes and post-transplant survival have been linked. However, the impact on post-transplant survival of patients supported on Continuous Flow (CF) axial left ventricular assist devices (LVAD) as a bridge to transplant (BTT) with diabetes has not been widely studied. This study attempts to assess the impact of diabetes type II (DM type II) as a comorbidity influencing survival patterns in the post-cardiac transplant population supported on LVADs and to test if the presence of a pre- transplant durable LVAD acts as an independent risk factor in long-term post-transplant survival. The UNOS database population from 2004 to 2015 was used to construct the cohorts. A total of 21,032 were transplanted during this period. The transplant data were further queried to extract CF-axial flow pumps BTT (HMII-BTT) patients and patients who did not have VAD support before the transplant. A total of 4224 transplant recipients had HMII at the time of transplant, and 13,131 did not have VAD support. Propensity analysis was performed, and 4107 recipients of similar patient characteristics to those in the BTT group were selected for comparison. The patients with a VAD had significantly reduced survival at 2 years post-transplant (p = 0.00514) but this trend did not persist at 5 years (p = 0.0617) and 10 years post-transplant (p = 0.183). Patients with diabetes and a VAD significantly decreased survival at 2 years (p = 0.00204), 5 years (p = 0.00029), and 10 years (p = 0.00193). The presence of a durable LVAD is not an independent risk factor for long-term survival. Diabetes has a longstanding effect on the posttransplant survival of BTT patients.

Mental Health and Substance Use Disorders in Transplant Waitlist, VAD, and Heart Transplant Patients: A TriNetX Database Analysis.

Background/Objectives: Mental health and substance use disorders (MHDs and SUDs) affect cardiac allograft and VAD recipients and impact their quality of life and compliance. Limited research currently exists on MHDs and SUDs in this population. Methods: This study compares the incidence of MHDs and SUDs in the transplant list, VAD, and post-transplant patients with that in heart failure patients. Study cohorts were derived from the TriNetX database using ICD-10 codes. Differences in incidence were examined using the log-rank test. Adults with MHDs and SUDs before the window of time were excluded. All comparisons were made between propensity-matched cohorts. Statistical significance was set at p < 0.05. Results: Transplant waitlist patients showed a significant increase in the incidence of anxiety, depression, panic, adjustment, mood, alcohol use, and eating disorders. Post-transplant patients showed a significant increase in depression and opioid use. VAD patients showed a significant increase in depression and a decrease in panic disorder and anxiety. These results allow for further investigations on prevention and coping strategies. Conclusions: The deterioration of mental health can significantly impact medication compliance, survival, and quality of life. Opioid use for pain management in the early postoperative period should be further investigated to assess its impact on long-term substance use and addiction.

Circulating miRNA as novel markers for diastolic dysfunction.

MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. Though their significance is unclear, pioneer profiling studies have attributed specific serum miRNA signatures to different disease conditions. The diagnostic potential of miRNA detection in human plasma for cardiovascular disorders is beginning to be recognized as important. In this study, we examined miRNA profiling in isolated diastolic dysfunction (DD) with preserved systolic function to identify promising candidate miRNAs. The presence of these miRNAs was tested in stable patients with isolated DD, patients with stable compensated dilated cardiomyopathy (DCM-systolic plus diastolic dysfunction) and those with decompensated congestive heart failure secondary to dilated cardiomyopathy (DCM-CHF-systolic plus diastolic dysfunction). We identified new circulating miRNAs (miR-454, miR-500, miR-1246, miR-142-3p) which showed distinct patterns of expression in patients with diastolic dysfunction. The presence or absence of systolic dysfunction does not seem to affect this trend. MiR-454 and miR-500 are downregulated in diastolic dysfunction. MiR-1246 is upregulated in diastolic dysfunction. MiR-142-3p is downregulated in DCM and DCM-CHF groups but not in the DD group. The expression of miR-124-5p is highly upregulated in DCM but not in DD and DCM-CHF groups. We therefore propose that these circulating miRNAs may serve as novel biomarkers for diastolic dysfunction because in all of these patients the only common factor was diastolic dysfunction.

Skin Cancer Risk Prediction in Heart Transplant Recipients.

OBJECTIVES: This study was undertaken to derive a risk prediction model for skin cancer utilizing the United Network for Organ Sharing database population. MATERIALS AND METHODS: Of the 24734 adults (>18 years old) heart transplant recipients (2000-2015) in the United Network for Organ Sharing database, 2625 recipients developed skin cancer. Univariate and multivariate Cox regression analyses were performed; P values, hazard ratios, and confidence intervals were derived. The model was tested using receiver operating characteristics curves and area under the curves. MATLAB software (MathWorks) was used for analyses. RESULTS: Multivariate analysis showed that White patients had a hazard ratio of 31.7 compared with Black patients (P < .001). Male patients had a hazard ratio of 2.52 (P < .001) compared with female patients. Malignancy at listing showed a hazard ratio of 1.77 (P < .001). Thymoglobulin had a hazard ratio of 1.19 (P = .005) compared with other induction agents. The receiver operating characteristic curves generated for 5 years, 8 years, and 10 years after transplant showed area under the curve values of 0.78, 0.77, and 0.76, respectively, in the training set and 0.75, 0.75, and 0.74, respectively, in the validation set. CONCLUSIONS: Male sex, White ethnicity, older age, malignancy at the time of listing or at time of transplant, and thymoglobulin induction are major risk factors for skin cancers after transplant. This risk prediction model has a C statistic of 0.75. To our knowledge,this is the firsttime such a model has been generated for skin cancers in this population.

NT-proBNP and D-Dimer in acute decompensated heart failure: assessment of diagnostic accuracy and correlation with echocardiographic parameters.

PURPOSE: Abnormalities in coagulation and inflammation exist in heart failure. This study compares the diagnostic accuracy of NT-proBNP and D-Dimer and the correlation of these biomarkers with echocardiographic parameters in acute decompensated heart failure. METHODS: A retrospective cross-sectional/observational study was performed using 162 patients with acute decompensated heart failure and 253 age-matched controls. Patients were ruled out for a pulmonary embolus by CT or VQ scans. The study protocol was approved by Institutional Review Board, Lubbock, TX. Correlation of NT-proBNP and D-Dimer values was done with echocardiographic parameters. Statistical significance was assumed at p < 0.05. RESULTS: D-Dimer showed a positive correlation with NT-proBNP (r = 0.665, p = 001). The AUC for NT-proBNP, D-Dimer and a combination of D-Dimer plus NT-proBNP were 0.963, 0.928 and 0.982 respectively. The AUC value for D-Dimer versus the combination of D-Dimer and NT-roBNP was not significant (p = 0.21). Correlation of NT-proBNP was significant with the echocardiographic parameters but D-Dimer did not significantly correlate with any of the echocardiographic parameters studied. CONCLUSIONS: Comparison of the AUC values for D-Dimer versus the combination of D-Dimer and NT-proBNP showed no significance suggestive of comparable diagnostic accuracy in the study population. The lack of correlation between D-Dimer and echocardiographic parameters suggests an independent pathophysiological mechanism underlying upregulation of D-Dimer in acute decompensated heart failure. Further systematic studies are needed to define mechanism of D-Dimer increase in heart failure.

Closing the Gap: Investigation of Various Approaches in the Management of Patent Ductus Arteriosus.

In preterm newborns with extremely low birth weights, patent ductus arteriosus (PDA), which is defined as a remnant connection between the aorta and pulmonary artery after 72 hours of birth, is frequently linked to substantial morbidity and mortality. If left untreated, a hemodynamically significant PDA (hsPDA) increases the risk for bronchopulmonary dysplasia, necrotizing enterocolitis, and intraventricular hemorrhage among other morbidities, and can even lead to death. While instances of patent ductus arteriosus (PDA) resolving on their own are frequent, the primary approach for managing PDA closure in premature infants involves pharmacological interventions, commonly utilizing indomethacin, ibuprofen, or paracetamol. However, with these pharmacological treatment options, there is an increased risk of renal toxicity, gastrointestinal bleeding, and reopening of PDA among other complications. If pharmacological interventions are not successful or contraindicated, PDA can be closed via transcatheter closure or surgical ligation. As with any medically invasive procedure, it is not without risks and can lead to long-term complications. This review explores the different management options and the benefits and outcomes of conservative management vs. active management in order to get one step closer to standardizing the treatment for PDA. With so much controversy surrounding the best management option, there is a lack of evidence to support one treatment method superior to the other in reducing overall mortality, and this needs to be explored further.

Correction: Closing the Gap: Investigation of Various Approaches in the Management of Patent Ductus Arteriosus.

[This corrects the article DOI: 10.7759/cureus.45009.].

Effects of Methimazole vs Propylthiouracil in Newborns: A Comparative Review.

Hyperthyroidism is more common in women and the sensitivity of thyroid function changes during pregnancy. Excess levels of thyroid hormones and thioamides have a major impact on maternal and fetal outcomes. Our aim was to perform an extensive literature review and provide relevant details concerning the analytical and clinical aspects of the potential effects of the two main drugs used (methimazole and propylthiouracil) in newborns. A thorough literature review was conducted using PubMed and Google Scholar databases. In total, 10 relevant studies were identified and data from these studies were extracted and then extrapolated into results after analysis. Three out of four studies that used methimazole and carbimazole, one and two, respectively, showed adverse fetal outcomes requiring surgical management for congenital anomalies like aplasia cutis, patent vitellointestinal duct, and gastroschisis. Out of the three studies that used propylthiouracil, one baby underwent surgery for bilateral pyelectasis, vesicovaginal fistula, anal stenosis, and polydactyly. The findings of the aforementioned studies provide enough evidence to imply that the use of methimazole and carbimazole to treat antenatal hyperthyroidism has worse fetal outcomes than the use of propylthiouracil. Also, given the paucity of data in the existing literature regarding propylthiouracil's effects on newborns, further studies in this demographic are needed.

Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction.

Cardiac myosin binding protein-C (cMyBP-C) is a thick filament assembly protein that stabilizes sarcomeric structure and regulates cardiac function; however, the profile of cMyBP-C degradation after myocardial infarction (MI) is unknown. We hypothesized that cMyBP-C is sensitive to proteolysis and is specifically increased in the bloodstream post-MI in rats and humans. Under these circumstances, elevated levels of degraded cMyBP-C could be used as a diagnostic tool to confirm MI. To test this hypothesis, we first established that cMyBP-C dephosphorylation is directly associated with increased degradation of this myofilament protein, leading to its release in vitro. Using neonatal rat ventricular cardiomyocytes in vitro, we were able to correlate the induction of hypoxic stress with increased cMyBP-C dephosphorylation, degradation, and the specific release of N'-fragments. Next, to define the proteolytic pattern of cMyBP-C post-MI, the left anterior descending coronary artery was ligated in adult male rats. Degradation of cMyBP-C was confirmed by a reduction in total cMyBP-C and the presence of degradation products in the infarct tissue. Phosphorylation levels of cMyBP-C were greatly reduced in ischemic areas of the MI heart compared to non-ischemic regions and sham control hearts. Post-MI plasma samples from these rats, as well as humans, were assayed for cMyBP-C and its fragments by sandwich ELISA and immunoprecipitation analyses. Results showed significantly elevated levels of cMyBP-C in the plasma of all post-MI samples. Overall, this study suggests that cMyBP-C is an easily releasable myofilament protein that is dephosphorylated, degraded and released into the circulation post-MI. The presence of elevated levels of cMyBP-C in the blood provides a promising novel biomarker able to accurately rule in MI, thus aiding in the further assessment of ischemic heart disease.