Role of Cardiac Biomarkers in Monitoring Cardiotoxicity in Chemotherapy Patients.

PURPOSE: This review aims to highlight the different types of chemotherapy-induced cardiotoxicity and will discuss the evidence base behind the use of different cardiac biomarkers to predict cardiovascular complications. Additionally, we will review the use of cardiac biomarkers to monitor cardiac outcomes and the role of cardioprotective medications in reducing cardiovascular side effects. RECENT FINDINGS: Chemotherapy has been linked to an increased risk of cardiotoxicity and heart failure. Currently, patients receiving chemotherapy undergo echocardiogram before starting chemotherapy and every 6 months to monitor for any decline in cardiac function. We reviewed the current evidence and practice guidelines of monitoring chemotherapy cardiotoxicity. SUMMARY: Cardio-oncology is a rapidly evolving subspecialty in cardiology, especially with the advent of new chemotherapeutic agents, which have cardiovascular side effects. Early detection of these effects is crucial to prevent life-threatening and irreversible cardiovascular outcomes. Monitoring troponin, pro-brain natriuretic peptide, and other cardiac biomarkers during chemotherapy will help to early detect cardiotoxicity.

Same-Day Discharge After Left Bundle Area Pacing.

BACKGROUND: Left bundle area pacing (LBAP) has emerged as an area that appears to be an attractive alternative to other forms of physiological pacing owing to its ease and favorable pacing parameters. Same-day discharge after conventional pacemakers, implantable cardioverter defibrillators, and more recently leadless pacemakers have become routine, especially after the COVID-19 pandemic. With the advent of LBAP, the safety and feasibility of same-day discharge remain unclear. METHODS: This is a retrospective, observational case series of consecutive, sequential patients undergoing LBAP at Baystate Medical Center, an academic teaching hospital. We included all patients who underwent LBAP and were discharged on the same day of procedure completion. Safety parameters included any procedure-related complications including pneumothorax, cardiac tamponade, septal perforation, and lead dislodgement. Pacemaker parameters included pacing threshold, R-wave amplitude, and lead impedance pre-discharge the following day of implantation and up to 6 months of follow-up. RESULTS: A total of 11 patients were included in our analysis, the average age was 70.3 ± 6.74 years. The most common indication for pacemaker insertion was AV block (73%). No complications were seen in any of the patients. The average time between the procedure and discharge was 5.6 hours. Pacemaker and lead parameters were stable after 6 months of follow-up. CONCLUSIONS: In this case series, we find that same-day discharge after LBAP for any indication is a safe and feasible option. As this mode of pacing becomes increasingly more common, larger prospective studies evaluating the safety and feasibility of early discharge after LBAP will be needed.

A systematic review of trials currently investigating therapeutic modalities for post-acute COVID-19 syndrome and registered on WHO International Clinical Trials Platform.

BACKGROUND: Post-acute COVID-19 syndrome (PACS) is a well-recognized, complex, systemic disease which is associated with substantial morbidity. There is a paucity of established interventions for the treatment of patients with this syndrome. OBJECTIVES: To systematically review registered trials currently investigating therapeutic modalities for PACS. DATA SOURCES: A search was conducted up to the 16 September, 2022, using the COVID-19 section of the WHO Internal Clinical Trials Registry Platform. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Interventional clinical trials of any sample size examining any therapeutic modality targeting persistent symptoms among individuals after diagnosis with COVID-19. METHODS: Data on trial characteristics and intervention characteristics were collected and summarized. RESULTS: After screening 17 125 trials, 388 trials, from 42 countries, were eligible. In total, we had 406 interventions, of which 368 were mono-therapeutic strategies, whereas 38 were intervention combinations. Among 824 primary outcomes identified, there were >300 different outcomes. Rehabilitation was the most employed class of intervention in 169 trials. We encountered 76 trials examining the pharmacological agents of various classes, with the most common agent being colchicine. Complementary and alternative medicine encompassed 64 trials exploring traditional Chinese medicine, Ayurveda, homeopathic medications, naturopathic medications, vitamins, dietary supplements, and botanicals. Psychotherapeutic and educational interventions were also employed in 12 and 4 trials, respectively. Other interventions, including transcranial direct current stimulation, transcutaneous auricular vagus nerve stimulation, general electrical stimulation, cranial electrotherapy stimulation, various stem cell interventions, and oxygen therapy interventions, were also employed. CONCLUSION: We identified 388 registered trials, with a high degree of heterogeneity, exploring 144 unique mono-therapeutic interventions for PACS. Most studies target general alleviation of symptoms. There is a need for further high-quality and methodologically robust PACS treatment trials to be conducted with standardization of outcomes while following WHO's recommendation for uniform evaluation and treatment.

Human Obesity Attenuates Cardioprotection Conferred by Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells.

To explore the impact of obesity on reparative potency of adipose tissue-derived mesenchymal stromal/stem cells (A-MSC) in hypertensive cardiomyopathy, A-MSC were harvested from subcutaneous fat of obese and age-matched non-obese human subjects during bariatric or kidney donation surgeries, and then injected into mice 2 weeks after inducing renovascular hypertension (RVH) or sham surgery. Two weeks later, left ventricular (LV) function and deformation were estimated in vivo by micro-magnetic resonance imaging and myocardial damage ex vivo. Blood pressure and myocardial wall thickening were elevated in RVH + Vehicle and normalized only by lean-A-MSC. Both A-MSC types reduced LV mass and normalized the reduced LV peak strain radial in RVH, yet obese-A-MSC also impaired LV systolic function. A-MSC alleviated myocardial tissue damage in RVH, but lean-A-MSC decreased oxidative stress more effectively. Obese-A-MSC also showed increased cellular inflammation in vitro. Therefore, obese-A-MSC are less effective than lean-A-MSC in blunting hypertensive cardiomyopathy in mice with RVH.

Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: a systematic review and meta-analysis.

BACKGROUND: Post-acute coronavirus 2019 (COVID-19) syndrome is now recognized as a complex systemic disease that is associated with substantial morbidity. OBJECTIVES: To estimate the prevalence of persistent symptoms and signs at least 12 weeks after acute COVID-19 at different follow-up periods. DATA SOURCES: Searches were conducted up to October 2021 in Ovid Embase, Ovid Medline, and PubMed. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Articles in English that reported the prevalence of persistent symptoms among individuals with confirmed severe acute respiratory syndrome coronavirus 2 infection and included at least 50 patients with a follow-up of at least 12 weeks after acute illness. METHODS: Random-effect meta-analysis was performed to produce a pooled prevalence for each symptom at four different follow-up time intervals. Between-study heterogeneity was evaluated using the I2 statistic and was explored via meta-regression, considering several a priori study-level variables. Risk of bias was assessed using the Joanna Briggs Institute tool and the Newcastle-Ottawa Scale for prevalence studies and comparative studies, respectively. RESULTS: After screening 3209 studies, a total of 63 studies were eligible, with a total COVID-19 population of 257 348. The most commonly reported symptoms were fatigue, dyspnea, sleep disorder, and difficulty concentrating (32%, 25%, 24%, and 22%, respectively, at 3- to <6-month follow-up); effort intolerance, fatigue, sleep disorder, and dyspnea (45%, 36%, 29%, and 25%, respectively, at 6- to <9-month follow-up); fatigue (37%) and dyspnea (21%) at 9 to <12 months; and fatigue, dyspnea, sleep disorder, and myalgia (41%, 31%, 30%, and 22%, respectively, at >12-month follow-up). There was substantial between-study heterogeneity for all reported symptom prevalences. Meta-regressions identified statistically significant effect modifiers: world region, male sex, diabetes mellitus, disease severity, and overall study quality score. Five of six studies including a comparator group consisting of COVID-19-negative cases observed significant adjusted associations between COVID-19 and several long-term symptoms. CONCLUSIONS: This systematic review found that a large proportion of patients experience post-acute COVID-19 syndrome 3 to 12 months after recovery from the acute phase of COVID-19. However, available studies of post-acute COVID-19 syndrome are highly heterogeneous. Future studies need to have appropriate comparator groups, standardized symptom definitions and measurements, and longer follow-up.

Global epigenetic alterations of mesenchymal stem cells in obesity: the role of vitamin C reprogramming.

Obesity promotes dysfunction and impairs the reparative capacity of mesenchymal stem/stromal cells (MSCs), and alters their transcription, protein content, and paracrine function. Whether these adverse effects are mediated by chromatin-modifying epigenetic changes remains unclear. We tested the hypothesis that obesity imposes global DNA hydroxymethylation and histone tri-methylation alterations in obese swine abdominal adipose tissue-derived MSCs compared to lean pig MSCs. MSCs from female lean (n = 7) and high-fat-diet fed obese (n = 7) domestic pigs were assessed using global epigenetic assays, before and after in-vitro co-incubation with the epigenetic modulator vitamin-C (VIT-C) (50 µg/ml). Dot blotting was used to measure across the whole genome 5-hydroxyemthycytosine (5hmC) residues, and Western blotting to quantify in genomic histone-3 protein tri-methylated lysine-4 (H3K4me3), lysine-9 (H3K9me3), and lysine-27 (H3K27me3) residues. MSC migration and proliferation were studied in-vitro. Obese MSCs displayed reduced global 5hmC and H3K4m3 levels, but comparable H3K9me3 and H3K27me3, compared to lean MSCs. Global 5hmC, H3K4me3, and HK9me3 marks correlated with MSC migration and reduced proliferation, as well as clinical and metabolic characteristics of obesity. Co-incubation of obese MSCs with VIT-C enhanced 5hmC marks, and reduced their global levels of H3K9me3 and H3K27me3. Contrarily, VIT-C did not affect 5hmC, and decreased H3K4me3 in lean MSCs. Obesity induces global genomic epigenetic alterations in swine MSCs, involving primarily genomic transcriptional repression, which are associated with MSC function and clinical features of obesity. Some of these alterations might be reversible using the epigenetic modulator VIT-C, suggesting epigenetic modifications as therapeutic targets in obesity.