Heart Rate Research Articles

Divergent hemometabolic dynamics: understanding the differences between acute myocardial infarction and heart failure related cardiogenic shock

Abstract Background Understanding the hemodynamic trajectories between acute myocardial infarction(AMI) & non-AMI cardiogenic shock(CS) is crucial for tailored management. Purpose Describe different hemometabolic patterns in AMI vs AMI-CS, AMI vs AMI-CS survivors & AMI vs AMI-CS non-survivors. Methods 354 AMI & 81 Non-AMI CS patients with PAC-hemodynamics were included. ANOVA of repeated measures was used to compare trajectories. Cox regression analysis for hazard ratios of conventional cut-off values hemometabolic goals & ideal with Youden index for LVSWi at baseline & 24h(Fig2B/C). Results AMI-CS were older(62 vs 52,P<0.001), exhibit a higher prevalence of smoking, dyslipidemia, HTN, & DM2(P<0.05). HF history & AF were more prevalent in Non-AMI-CS(P<0.001). AMI-CS had lower heart rate, respiratory rate, BUN, pH; higher LVEF, hemoglobin, leucocytes, platelets, glucose, Cl-, Na+, AST, ALT, LDH(P<0.05). Treatment modalities, AMI-CS had higher mechanical circulatory support (P<0.001). AKI was more common in non-AMI(P=0.004). There were no differences in number of vasoactives(P=0.46), but non-AMI had more dobutamine use(P<0.001). MODS score, organ failures, VT/VF, Phenotype, SCAI, and mortality(46.9 vs 47.7% Non-AMI vs AMI-CS) had no differences(P>0.05). Dynamics congestion associated with phenotypes & SCAI are shown in Fig 2A. SBP(F=12.39,P<0.001), DBP(4.72,0.03) & MAP(9.98,0.002) (Fig1A) had differences in AMI vs non-AMI-CS, but none were seen in survivors(P>0.05), only in non-survivors (SBP 17.52, <0.001; DBP 6.59, 0.011 & MAP 13.98, <0.001). RAP(7.4,0.007) & PCWP(53.51,<0.001) (Fig1B/C) also differ among AMI vs non-AMI & non-survivors(5.69,0.018 & 28.77,<0.001); but only PCWP differs across survivors(27.49,<0.001). Cardiac output & index(Fig1D)(13.65,<0.001 & 18.88,<0.001) had both differences among survivors(4.17,0.042 & 6.67,0.01) & non-survivors(10.98,<0.001 & 13.57,<0.001). Cardiac power, index, & CPIRAP(Fig1E) also had this behavior being higher in AMI. Coronary perfusion pressure (Fig1F) differs among all 3 classes (P<0.001), AMI vs non-AMI(F=31.17), survivors(11.63) & non-survivors(25.81). Perfusion pressure only had in AMI vs non-AMI(15.91,<0.001) & non-survivors(20.39,<0.001). PAPI(Fig1G) had differences in AMI vs non-AMI(F=9.3,P=0.002) & non-survivors(8.69,<0.001). API(Fig1H) differs across all spectrums(14.87 groups, 5.89 survivors & 11.61 non-survivors). Finally, LVSWi & RVSWi(Fig1I/J) had differences among AMI vs non-AMI in all categories: groups(22.5 & 14.27 both <0.001), survivors(7.88,0.005 & 9.29,0.003) & non-survivors(21.27,<0.001 & 5.17, 0.024). In the metabolic, only lactate(Fig1K) shows differences in AMI vs non-AMI(5.46,0.02) & non-survivors(8.02,0.005); no differences were noted in survivors. Hazard ratios were assessed with the whole cohort, AMI, & non-AMI; full data is shown in Fig 2B/C. Conclusion Our investigation elucidates nuanced hemodynamic disparities between AMI vs non AMI-CS, even in survivors and non-survivors of CS.Figure 1.Hemodynamic trajectoriesFigure 2.Alluvial. B/C Baseline & 24h goals

Development of machine learning models for prediction of left ventricular systolic dysfunction in patients with isolated left ventricular dilation

Abstract Background/Introduction Isolated left ventricular dilation (ILVD), in the absence of concomitant LV systolic dysfunction, is a risk factor for new reduction in LV ejection fraction (LVEF) and adverse clinical outcomes. We assessed the performance of different machine learning (ML) models in predicting new reduction in LVEF in patients with ILVD. Methods A retrospective analysis of de-identified patient records in the Tempus Database with at least two transthoracic echocardiograms (TTE) conducted between January 2019 and December 2022 were retrospectively analyzed, with the follow up period ending in January 2023. Inclusion/exclusion criteria are shown in Figure 1A. Briefly, patients with ILVD were defined based on echocardiographic parameters as those with LVEF > 50% and LV end diastolic volume indexed (LVEDVi) > 62 mL/m2 for females and > 75 mL/m2 for males, without prior LVEF < 50% and/or grade 2/3 diastolic dysfunction. The endpoint was LVEF < 40% on future (≥90 days) TTE. Five hard voting ML models and one soft voting ensemble model were trained with data parsed from TTE reports (Figure 1B). Feature importance (SHAP) was calculated, and receiver operating characteristic (ROC) and Kaplan Meier curves evaluated the final model (Figure 1C-E). Results A total of 2,962 patients met the inclusion criteria. The median time from index to last TTE was 578 (IQR = 500) days. LVEF < 40% on follow up TTE was noted in 6% of patients (177 patients, median 478 days to endpoint, IQR = 535 days). Of the six models developed, the ensemble model had the highest ROC area under the curve (0.791, Figure 1D), precision (0.163), F1-score (0.266), and specificity (0.773). The ensemble model also had the lowest predicted prevalence (25.5%), although this was higher than the observed prevalence in the test set (5.7%). Patients predicted to develop LVEF < 40% had a 8.2x higher risk of developing LVEF < 40% within five years of index (p<0.001, Figure 1E). Feature importance showed that male gender, higher heart rate, lower LVEF at index TTE, higher LVEDVi, and lower tricuspid annular plane systolic excursion had the highest mean absolute impact on the model’s output probability (Figure 1C). Conclusion Using only data parsed from the index TTE, ensembling a model for the prediction of developing LVEF < 40% in patients with ILVD and without a history of LV diastolic or systolic dysfunction performed the best. Additional analyses including clinical variables such as comorbidities, symptoms, and medications may improve the model’s performance.

Automatic calculation of the parasympathetic, sympathetic and Baevsky stress indexes provides a more comprehensive assessment of cardiac autonomic modulation

Abstract Background Cardiac autonomic modulation (CAM) is clinically evaluated by measuring the Heart Rate Variability (HRV) parameters, related to sympathetic and parasympathetic efferences to the heart, with linear (L), nonlinear (NL), and time-varying (TV) mathematical methods. Recently, automatic calculation of the parasympathetic (PNSi), sympathetic (SNSi), and Baevsky’s stress (BSTRi) indexes [1,2], integrating some L and NL parameters, has become available for more synthetic assessment of CAM. This study aimed to evaluate in healthy subjects (HS) the normal range of PNSi, SNSi, and BSTRi and their physiological variations during daily activity (ACT) and Non-REM sleep (NREM), taking also into account aging-related changes. Methods 24-hour (H24) Holter ECG recordings of 87 HS, divided into three (Age1, Age2 and Age3) groups (16-34, 35-52, and 53-84 years old, respectively), were retrospectively analyzed with the Kubios software (version 4.0), which automatically calculates the PNSi, SNSi, and BSTRi [1], and time domain (TD), frequency domain (FD), NL and TV HRV parameters. HRV was calculated from H24 and short-term (2 minutes) intervals, selected during ACT and NREM. All HRV calculations were done after "detrending" with the "smooth priors" function (lambda=500). Statistical analysis was performed with SPSS 21. Results Average values of the three indexes and several independent L and NL parameters are summarized in Table 1. Average BSTRi values of each age group were not different between ACT and NREM, whereas significant (p<0.05) increments between Age3 and Age1 (during ACT) and between Age3 and both Age1 and 2 (during NREM and H24) were found. Average SNSi values were slightly above the normality range [1] during ACT, or normal (during NREM and H24). Average PNSi values were within the suggested normality range [1] with minimal aging-related variations. Significant aging-related decrement of the selected TD and FD parameters was found in all analysed conditions. Among NL parameters, the correlation dimension (D2) values showed significant aging-related decrement (H24 and NREM), while H24 and ACT sample entropy (SampEn) was lower in Age1 and Age2, compared with Age3 (p<0.05). An example (H24 analysis of Age3 data) of significant (p<0.01) correlation among the three indexes and the selected independent linear and non-linear parameters is shown in Figure 1. Conclusions In this study, a significant aging-related increment of BSTRi was found in all investigated conditions. PNSi and SNSi were always within the suggested normality range [1]. In spite of the significant changes of linear parameters consistent with the well-known aging-related decrement of HRV, the higher SampEn (and BSTRi) found in Age3 HS suggests that an "healthy elderly", is characterized by a more complex adaptation of CAM, likely mediated also by the observed moderate (healthy?) increment of physiological stress. However further investigation on a broader population is warranted.Table 1Figure 1

The Effect of a Biofeedback-Based Integrated Intervention for Older Adults with Orthostatic Hypotension: A Secondary Analysis on Psychological Health Outcomes in a Non-Randomized Pilot Trial

Background/Objectives: Aging-related physical changes and dysfunctions in the autonomic nervous system (ANS) often lead to orthostatic hypotension (OH) in older adults. OH negatively impacts both the physical and psychological well-being of those affected. Previous studies have demonstrated that the biofeedback-based integrated program (BBIP), a multicomponent intervention focused on heart rate variability biofeedback, effectively improves OH, as well as symptoms related to ANS function. This substudy aims to examine the effects of the BBIP on psychological health outcomes among community-dwelling older adults with OH. Methods: This study employed a non-randomized controlled trial design with a convenience sampling strategy. A total of 51 older adults with OH were recruited from two senior welfare centers and randomly assigned to either the intervention group (n = 27) or the control group (n = 24). The intervention group participated in a 12-week BBIP, which included weekly biofeedback sessions and group education on lifestyle modification to alleviate OH. Telephone counseling was also provided to promote compliance. Results: The intervention group showed significant improvements in health-related quality of life, depression, anxiety, and fall efficacy after the 12-week BBIP, whereas the control group exhibited no significant changes. There was a significant reduction in the percentage of participants in the intervention group reporting problems in all five dimensions of the EQ-5D (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Conclusions: The BBIP was effective in improving the psychological health outcomes of older adults with OH. Future studies should explore the long-term effects of the BBIP using a larger sample size and a randomized controlled trial design.

Changes in blood metabolomes as potential biomarkers for severity and prognosis in doxorubicin-induced heart failure: a study in HER2-positive and HER2-negative breast cancer patients

Abstract Background The use of doxorubicin for breast cancer treatment is often limited due to cardiotoxicity. Doxorubicin was shown to cause the alterations of cardiac metabolome levels in doxorubicin-treated rats. Interestingly, these changes were robustly associated with the development of doxorubicin-induced heart failure. Unfortunately, measurements of cardiac metabolome levels are rarely possible in humans. Hence, non-invasive biomarkers as representatives of doxorubicin-induced heart failure are required in clinical research and practice. Human epidermal growth factor receptor 2 (HER2) is a point of interest in breast cancer treatment. HER2 is associated with tumor aggressiveness. However, it was observed that HER2 protected against systemic oxidative stress and dilated cardiomyopathy. Therefore, we hypothesized that the alterations of blood metabolome levels and cardiac functions following doxorubicin treatment were different between HER2-positive and HER2-negative breast cancer patients. Purpose We determined the potential roles of changes in blood metabolomes as severity and prognostic markers of doxorubicin-induced heart failure. In addition, the changes in blood metabolomes and cardiac parameters following doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients were compared. Methods HER2-positive (n=37) and HER2-negative (n=37) breast cancer patients were enrolled. Echocardiography, heart rate variability, and blood collection were performed at baseline and 2 weeks after completion of doxorubicin treatment in all patients, as well as at 3 months after completion of doxorubicin treatment in HER2-negative breast cancer patients. Blood obtained at all 3 time points was processed for measuring cardiac injury markers. Blood obtained at baseline and 2 weeks after completion of doxorubicin treatment was also processed for measuring oxidative stress in peripheral blood mononuclear cells using flow cytometry and 85 metabolome levels in plasma using mass spectrometry-based targeted metabolomics. Results Cardiac injury and systolic dysfunction at 2 weeks after completion of doxorubicin treatment were comparable between HER2-positive and HER2-negative breast cancer patients. However, only HER2-negative breast cancer patients exhibited increased systemic oxidative stress and cardiac autonomic dysfunction at this time point. Moreover, 33 and 29 blood metabolomes were altered at 2 weeks after completion of doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients, respectively (Figure). Interestingly, the changes in most of these metabolomes were correlated with the changes in cardiac parameters, both at 2 weeks and 3 months after completion of doxorubicin treatment (Figure). Conclusions The changes in blood metabolomes following doxorubicin treatment were dependent on HER2 status, which might be served as severity and prognostic markers of doxorubicin-induced heart failure.

User technology for AI-supported objective measurement of Work-related Quality of Life (MI-LQ)

Abstract Background Understanding and enhancing job satisfaction is crucial for improving Work-Related Quality of Life (WrQoL) in today’s office work environments. Our work uses multimodal data collection and analysis techniques to objectively assess WrQoL, thus mitigating respondent bias and survey fatigue. Leveraging machine learning (ML) and automated methods measuring WrQoL presents a promising approach in public health research, particularly concerning stress-related health outcomes. Methods Through a systematic literature search of 9,242 publications to identify WrQoL indicators, we selected over 100 publications for data extraction. A base model, including workload, commute, overtime, valence, and arousal was formulated. To amass a wide data set, Objective measurement tools (computers, smartphones, and wearables) complemented by questionnaire data. This data will inform ML algorithms to predict individual WrQoL indicators. Developed as an input/output data platform, an app-prototype will objectively assess WrQoL, facilitating a field study with office workers to refine the model. A mobile app prototype serves as a user interface and data relay for WrQoL metric analysis. Results Our research develops instruments for measuring WrQoL using smartphones, wearables, and specialized trackers for heart rate variability (HRV) analysis, alongside a software prototype for keyboard and mouse tracking for workload assessment of valence and arousal. Fitness trackers with photoplethysmography functionality are favored for HRV assessment. Conclusions The systematic search identified influences on WrQoL, translated into measurable indicators in a base model. Leveraging user tech for assessment and a ML and mobile app framework, this approach facilitates objective WrQoL determination. By presenting the relationship between digital service use and WrQoL indicators, this methodology promises new insights, informing stress and burnout prevention strategies within public health initiatives. Key messages • Progressive approach: ML-driven WrQoL assessment offers promising avenues for stress prevention in workplace health research. • Methodological Advancement: The novel framework for WrQoL assessment using digital tools contributes to effective workplace health promotion strategies, with potential for tailored interventions.

Study protocol for an observational cohort study of heat stress impacts in pregnancy in The Gambia, West Africa

Climate change has resulted in an increase in heat exposure globally. There is strong evidence that this increased heat stress is associated with poor maternal and fetal outcomes, especially in vulnerable populations. However, there remains poor understanding of the biological pathways and mechanisms involved in the impact of heat in pregnancy. This observational cohort study of 764 pregnant participants based in sub-Saharan Africa, a geographical region at risk of extreme heat events, aims to evaluate the physiological and biochemical changes that occur in pregnancy due to heat stress. The key objectives of the study are to 1) map exposure to heat stress in the cohort and understand what environmental, social and community factors increase the risk of extreme heat exposure; 2) assess the impact of heat stress on maternal health, e.g. heat strain, subjective psychological well-being, sleep and activity level; 3) evaluate how heat stress impacts placenta structure and function; 4) determine how chronic heat exposure impacts birth outcomes; and 5) explore the epigenetic changes in the placenta and infant by heat stress exposure per trimester. Pregnant women will be recruited from two distinct regions in The Gambia to exploit the naturally occurring heat gradient across the country. Microclimate mapping of the area of recruitment will give detailed exposure measurements. Participants will be asked to wear a watch-style device at 28- and 35-weeks gestational age to evaluate maternal heart rate, activity and sleep. At the end of the week, an ultrasound scan will be performed to evaluate fetal size and placental blood flow. At delivery, birth outcomes will be recorded and maternal, placental and cord samples taken for epigenetic, biochemical and histological evaluation. Evaluation of neuro-behaviour and final infant samples will be taken at 1 month following birth.

Case Report: Acute Abdomen Due to Ruptured Ovarian Ectopic Pregnancy at 8 Weeks

Background Ovarian pregnancy is a rare type of ectopic pregnancy, accounting for 0.5% to 1% of all ectopic pregnancies, with an incidence ranging from 1 in 2,100 to 1 in 60,000 pregnancies. Due to its rarity and the lack of common risk factors, diagnosing ovarian pregnancy is often challenging and typically occurs during surgical exploration. Case Presentation We present the case of a 40-year-old woman who experienced severe pelvic pain, light vaginal bleeding, and 8 weeks of amenorrhea. Upon arrival at the hospital, she was hemodynamically unstable, with low blood pressure and a rapid heart rate. An ultrasound revealed an empty uterus, an irregular mass on her right ovary, and free fluid in the pelvis. Her beta-hCG level was elevated, and her hemoglobin level was low. Given the suspicion of an ectopic pregnancy, she underwent emergency surgery. During the operation, the surgical team discovered a large amount of clotted blood and a ruptured mass on her left ovary measuring 10 x 9.5 cm. Due to heavy bleeding, they performed a left oophorectomy and salpingectomy. Histopathological analysis later confirmed the diagnosis of ovarian pregnancy. Conclusion This case underscores the challenges in diagnosing ovarian pregnancy and highlights the necessity for prompt surgical intervention, particularly in unstable patients. Early detection and appropriate management are critical to prevent life-threatening complications.

Exercise stress echocardiography detects patients with paroxysmal/persistent atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the most prevalent atrial tachyarrhythmia, affecting an estimated 2-4% of adults worldwide. AF is a well-recognized and treatable risk factor for stroke, but it often remains asymptomatic or subclinical, leading to underdiagnosis. This study aimed to identify distinguishing signs during exercise stress echocardiography (ESE) among patients in sinus rhythm (SR), with and without history of paroxysmal/persistent AF (PAF). Methods An international prospective cohort comprising 1035 consecutive patients was initially considered from 12 cardiology institutions. These patients were referred for clinically-driven ESE as part of the Stress Echo 2020-2030 study network. All patients underwent comprehensive ESE with the ABCDE protocol, which included assessment of B-lines, left ventricle contractile reserve (LVCR), ECG-based heart rate reserve (HRR), LV ejection fraction (EF), LV end-diastolic volume, E/e’, pulmonary artery systolic pressure estimation, tricuspid annular plane sytolic excursion (TAPSE), left atrium volume index (LAVi) and left atrium reservoir phase strain (LASr) at rest and with exercise. Results After excluding 89 patients who were in AF during the ESE, 946 patients in SR were included as the main study cohort (101 with and 845 without a history of PAF). A scoring system was then constructed using all independent variables that differentiate the two groups (those with and without history of PAF). Presence of systemic hypertension, rest LAVI>31ml/m2, rest |LASr|< 21%, stress LAVI >29 ml/m2, stress |LASr| <24%, stress E/e’ >7, ∆TAPSE <4.5 mm, HRR<1.87, and LVCR<1.6 were identified as the discriminators between patients with and without PAF. The composite score, summing all 9 items (with a total score range from 0 to 9), yielded a score of >4 as the best balance between sensitivity (87%) and specificity (60%) in predicting those with PAF. The receiver operating characteristic curve analysis of the scoring model showed an AUC of 0.79 (p-value <0.0001), Figure. Conclusion ESE evaluation can be a valuable adjunct for identifying patients in SR with history of PAF. This multifaceted approach enhances the potential for more accurate detection and clinical management of individuals in SR at risk for AF, who could be considered for aggressive monitoring programs to prevent the development of new onset AF and subsequent increase in cardiovascular risk.

Discovery of BAY 2413555, First Selective Positive Allosteric Modulator of the M2 Receptor to Restore Cardiac Autonomic Balance.

Autonomic disbalance, i.e., sympathetic overactivation and parasympathetic withdrawal, is a causal driver of disease progression in heart failure. While sympatholytic drugs are established treatments, no drug therapy restoring vagal control of cardiac function is available. We report here the HTS-based discovery of a novel class of 1,8-naphthyridin-4(1H)-one carboxamides acting as positive allosteric modulators (PAMs) of the M2 muscarinic acetylcholine receptor (M2R). M2R is the main postsynaptic myocyte receptor regulating heart rate, electrical conduction, and contractile strength. Extensive optimization of the screening hit in terms of potency, permeation, metabolic stability, and solubility ultimately resulted in the discovery of the first-in-class clinical candidate BAY 2413555 (27). With an overall technical profile compatible with once-daily oral administration in a phase 1 study, no apparent effects on blood pressure, and a mechanism that largely preserves autonomic regulatory capacity, BAY 2413555 could be the tool to finally study the restoration of autonomic balance.

National early warning score predicts 90 days all-cause mortality among patients with acute heart failure

Abstract Background Acute heart failure (AHF) is defined as new-onset or worsening of symptoms and signs of heart failure including symptoms or signs related to congestion and volume overload. Patients presenting with AHF are a heterogeneous group as AHF is not a specific disease but a shared clinical presentation of different cardiac abnormalities. Due to the heterogeneity of the patient population, a prognostic tool is needed to identify AHF patients with a high risk of death. The National Early Warning Score (NEWS) is a system for scoring the vital signs that are measured at the patient's bedside and is developed to predict acute mortality within 24 hours. The NEWS has previously been used to evaluate all cost mortality for patients admitted to the Emergency Department (ED). There is limited data regarding the role of the NEWS in predicting adverse outcomes in patients with acute heart failure. Purpose To evaluate NEWS measured at the ED and clinical outcomes in patients with AHF. Methods This prospective, observational cohort study included consecutive patients with AHF admitted through the emergency department (ED) at a large public hospital from 10 March 2020 to 31 March 2022 and had a follow-up period of 365 days. Trained cardiologists assessed all patients for the presence of AHF. According to the cut-off value for the NEWS, high-risk groups are defined by a NEWS score > 7. The patients were categorized into two groups, high-risk and low-risk, depending on the scores they received from the NEWS assessment. The primary outcome was all-cause mortality at 90 days. We used multivariable Cox regression (hazard ratios [HRs]) to compare survival, adjusting for age, sex, smoking, known heart failure (HF), and lactate levels at admission. Results In the study period from March 10, 2020, to March 31, 2022, 408 patients were identified with AHF. Upon arrival to the ED, the median first NEWS was 4 (IQR 2-6). 323 patients were categorized in the low-risk group and 69 patients in the high-risk group. 16 patients had missing values upon arrival at the ED. The high-risk group exhibited significantly faster heart rate, lower saturation, and higher oxygen demand compared. A Kaplan-Meier plot revealed a statistically significant difference in all-cause mortality over 90 days between low-risk and high-risk groups among AHF patients (log rank, p-value < 0.001). After multivariable adjustment, NEWS>7 (HR, 1.69; CI, 1.18 to 2.45) (p-value= 0.004) and higher age (HR, 1.04; CI 1.03 to 1.07) were statistically associated with higher all-cause mortality (p <0.001). Conclusion In this prospective, observational cohort study of AHF patients presenting at the ED an initial NEWS >7 was associated with a significant all-cause mortality after 90 days.GRAPHIC ABSTRACT

Leveraging mixed reality in mitraclip implantation: A preliminary case series toward a pilot study

Abstract Introduction The advent of mixed reality (MR) technology, particularly when combined with Hololens 2.0 and specialized software for three-dimensional DICOM image visualization, offers a promising avenue for enhancing the precision and spatial awareness in interventional cardiology procedures. This case series aims to preliminarily evaluate the impact of MR on MitraClip implantation processes, setting a foundation for an ensuing comprehensive pilot study. Methods We conducted a comparative analysis within a case series of four MitraClip implantations, categorizing them into two groups based on the utilization of MR support. We examined procedural efficiency, radiation metrics (SKIA and DAP), and operator stress indicators, including cortisol levels, heart rate variability, QTc interval, and subjective assessments through NASA TLX, STAI Y, and SSQ questionnaires. Results Initial findings from the MR-assisted procedures suggest a notable improvement in procedural efficiency and a reduction in operator stress. Specifically, MR use was associated with shorter procedural times (ranging from 60 to 130 minutes) and lower radiation exposure, with SKIA durations between 15.5 and 40.5 minutes. Moreover, operators in the MR group showed reduced cortisol levels (8.2-9.2 mmol/L), indicating decreased physiological stress. Heart rate variability analysis further supported superior stress management among MR-supported operators. Subjective evaluations reinforced these physiological findings. NASA TLX scores in the MR group (13-20) markedly contrasted with those in the control group (30-45), signifying a significant reduction in perceived workload. SSQ scores remained minimal, implying good MR tolerability, and STAI Y scores (30-35) were lower than those in the control group (40-50), highlighting reduced anxiety levels during MR-assisted procedures. Conclusion This explorative case series lays the groundwork for a forthcoming pilot study, revealing MR's potential to not only streamline MitraClip implantation but also to alleviate operator stress. Both objective and subjective data advocate for expanded research to definitively ascertain MR's benefits in cardiac interventions, promising to refine procedural workflows and enhance patient outcomes. This series acts as a stepping stone towards a larger-scale evaluation that could solidify MR's role in the future of interventional cardiology.Operator's View and Technology PreviewFunction diagram

Effect of Propofol and Isoflurane on Hemodynamic changes during Spinal Surgery Under General Anesthesia

Background: Hemodynamic stability are vital requirements of up-to-date anesthesia. Both propofol and isoflurane meet these criteria though the clinical effects like postoperative nausea vomiting after administering propofol and isoflurane have been studied in various surgeries but have not been much evaluated or studied in patients undergoing major surgical procedures like spine surgeries, There’ is definite advantage of one technique over the other. Isoflurane has a low blood gas partition coefficient, which contributes to rapid induction and emergence from anaesthesia than with other volatile anesthetics in current clinical use. Propofol has been established as the intravenous agent that provides faster and smoother recovery & peri operative hemodynamic stability. Objective: To compare the effects of isoflurane and propofol regarding hemodynamic status in spinal surgery under general anaesthesia. Methods: After getting ethical approval, a randomized controlled trial study design was performed where patients were selected in the pre-anesthetic checkup room based on inclusion and exclusion criteria for those who were scheduled for spine surgeries under general anesthesia is admitted in the Department of Neurosurgery in East West Medical College from January 2023 – December 2024. A total number of 40 patients were selected. 20 patients were enrolled each in group A and group B by lottery method in a sealed envelope. They were divided into two groups by randomization; Group A and Group B. A written informed consent was taken from all selected patients. Patients were advised to fast for at least 8 hours before intervention. In Group A, anesthesia is maintained with propofol infusion, nitrous oxide (66%), and oxygen (33%) while in Group B, anesthesia is maintained with Isoflurane, nitrous oxide (66%), and oxygen (33%). All patients were given N2O in oxygen and 1.25% inspired concentration of Isoflurane (MAC -1.15). In Group A propofol infusion at rate of 80 μg/kg/min (fixed from the beginning). All data was collected at –Just after starting, 15 minutes, 30-minute, 1 hour, and >1 hour interval per operatively. Data was compiled, edited and plotted in tabular and figure form. P value was determined as significant when it was <0.05. Results: 40 patients yielded the following results. The mean age of Group A and B were 32.56±12.55 years and 34.6±12.5 years. Mean difference of heart rate was lower in Group A than that of Group B. Other parameters in both groups were confined to good and acceptable categories. But interestingly, there was a statistically significant difference found between Group A and Group B in Systolic Blood Pressure (SBP) & Diastolic Blood Pressure (DBP). The scoring was far better in Group A than Group B. Mean SBP was higher in Group B than Group A (p= >0.05). Similarly, mean DBP was also higher in Group B than Group A (p = >0.05). Conclusion: Propofol is better for maintaining hemodynamic status than Isoflurane for Spine surgery under General anaesthesia. EWMCJ Vol. 12, No. 1&2, January-July 2024: 21-26

Low chronotropic response in post-myocardial infarction exercise test predicts worse prognosis in patients with preserved or mildly reduced left ventricular ejection fraction

Abstract Background Chronotropic incompetence is common in post-myocardial infarction (MI) patients and is associated with reduced exercise capacity. However, its prognostic significance and a determination of threshold values for prognosis remain unclear. Methods & Results We assessed 96 post-MI patients 4 weeks after their initial event with left ventricular ejection fraction (LVEF) ≥ 40%. All patients underwent combined stress echocardiography and cardiopulmonary exercise tests. The chronotropic response was measured as a percent of the maximal predicted heart rate at peak exercise (%MPHR). Exclusion criteria included patients with exercise limitations for pulmonary or peripheral reasons and those who declined to complete the study. Follow-up was conducted in 86 patients. The primary outcome measured was a composite of all-cause mortality or hospitalization for ischemic heart disease events (acute MI, unstable angina, or revascularization procedures) or heart failure exacerbation. The median follow-up duration was 4.0 (IQR 2, 5.6) years. The median patient age was 60 (IQR 53, 65) years, 64% of patients were males, and 84% were on beta-blockers. Median LVEF was 57 (IQR 51, 62)%, and median peak VO2 was 19 (IQR 15, 22) mL/kg/min. There were 15 composite end-point events, including 3 deaths, during the follow-up period. The %MPHR threshold of 67% had the best predictive value with an area under the curve (AUC) of 77% for predicting the primary outcome (PPV 31%, NPV 97%, sensitivity 93%, specificity 55%). A significant difference (p = 0.0022) in the occurrence of the composite end-point was noted between patients with a %MPHR below versus above this threshold (Figure. Kaplan-Meier curves for survival free of primary outcome). In the multivariate Cox regression analysis adjusting for demographic, clinical variables, and beta-blocker doses, only chronotropic response and current smoking correlated with the primary end-point (Table. The Cox proportional hazards regression model for prediction of the primary outcome). Conclusions A low chronotropic response to exercise is a negative prognostic marker in post-myocardial infarction patients with either preserved or mildly reduced left ventricular ejection fraction.Figure.Table.

Study on Fetal and Maternal Outcome of Postdated Pregnancy

Postdated pregnancy is not so uncommon in obstetric practice. When a pregnancy crosses the expected date of delivery (beyond 280 days) it is called postdated pregnancy. The incidence is about 7% of all pregnancies. This prospective observational study was carried out in 165 postdated pregnancies admitted in the Department of Obstetrics & Gynaecology, during a period of 3 years from January 2021 to December 2023 . Majority of the patients were below 25 years of age (47.88%) and primigravida (41.82%). Most of the patients belonged to rural areas (55.75%) and were middle socio-economic status group (45.45%). The majority of these postdated women were delivered by NVD (52.12%), followed by LSCS (32.72%) and instrumental (15.15%). Postdated pregnancy was associated with perinatal complications like meconium aspiration syndrome, oligohydramnios, fetal birth injuries, septicemia, shoulder dystocia, non-reassuring fetal heart rate status, fetal distress in labour. There was an increased risk of maternal complications like increased caesarean section rate, post-partum hemorrhage (PPH) ,cervical tear, perineal tear. Management of postdated pregnancy is challenging. Careful advice and timely interventions can reduce fetomaternal complications. EWMCJ Vol. 12, No. 1&2, January-July 2024: 94-98

Assessment of body composition in young adulthood and its associations to early changes in cardiovascular phenotypes: a cross-sectional study

Abstract Introduction Obesity in young adulthood is associated with various cardiovascular structural and functional changes, commonly used as markers of early subclinical cardiovascular disease. Whether these changes occur predominantly in relation to increased fat mass (FM) or are instead more closely related to simultaneous increases in underlying fat-free mass (FFM) that are known to occur in obesity, is incompletely understood. Purpose To investigate associations between both FM and FFM and a wide range of cardiac (left ventricular mass, LVM; end-diastolic volume, EDV; cardiac output, CO; stroke volume, SV), vascular (systolic blood pressure, SBP; diastolic blood pressure, DBP; mean arterial pressure, MAP; systemic vascular resistance, SVR) and autonomic (heart rate variability triangular index, HRVTI; baroreceptor reflex sensitivity, BRS) phenotypes commonly used to monitor the early evolution of subclinical CVD. Methods The study used data from extensive adipose and cardiovascular phenotyping of 408 healthy young adults (mean age 21 years) participating in a sub-study of the long-running ALSPAC birth cohort. We performed cross-sectional analysis using multiple imputation, multivariable linear regression and interaction testing to assess the association between both FM and FFM and cardiovascular phenotypes. Results Our study revealed that FFM resulted in a much greater increase in CO (difference in outcome per 1-SD difference in exposure β=0.58L/min, p<0.01, 95% CI=0.38, 0.77) than FM (β=0.20L/min, p=0.01, 95% CI=0.05, 0.36), following adjustment for both tissue types. FFM was also associated with an increase in LVM (β=19.1g, p<0.01, 95% CI=16.61, 21.58), EDV (β=22ml, p<0.01, 95% CI=18.18, 25.13) and SV (β=13ml, p<0.01, 95% CI=10.96, 15.75). FFM was also associated with improved autonomic and peripheral vascular function, including lower HR (β=-4bpm, p<0.01, 95% CI=-6.12, -1.95), higher HRVTI (β=2.1, p<0.01, 95% CI=0.72, 3.48) and lower SVR (β=-1.1, p<0.01, 95% CI=-2.12, -1.07), resulting in unchanged MAP despite elevations in CO. On the contrary, FM was not associated with LVM (β=-0.91g, p=0.35, 95% CI=-2.85, 1.02), and was associated with lower EDV (β=-4.62ml, p<0.01, 95% CI=-7.34, -1.88) and reduced autonomic function, as seen with HRVTI (β=-1.83, p<0.01, 95% CI=-3.02, -0.64) and BRS (β=-2.47, p=0.01, 95% CI=-4.27, -0.67). FM was also associated with increased HR (β=3.26bpm, p<0.01, 95% CI=1.57, 4.94) and increased SBP (β=2.14mmHg, p<0.01, 95% CI=1.01, 3.27) DBP (β=2.68mmHg, p<0.01, 95% CI=1.60, 3.77), and MAP (β=2.34mmHg, p<0.01, 95% CI=1.34, 3.34). Conclusion In young adults, changes in surrogate clinical markers of cardiac, vascular, and autonomic function commonly attributed solely to increases in fat mass should be interpreted with caution as they may be associated with underlying changes in FFM. Future work should focus on longitudinal studies of this cohort to confirm remodelling patterns based on these clinical markers.

Exercise gas exchange phenotyping according to body mass index: a population-based study in an apparently healthy population

Abstract Background Obesity is a widespread medical condition consisting in a BMI > 30 kg/m2. The link between BMI, exercise performance and cardiovascular risk is not well defined on large set of apparently healthy subjects. Aim In this population-based trial of apparently healthy individuals we aimed at defining the exercise gas exchange phenotype by cardiopulmonary exercise testing (CPET) according to BMI strata. Methods 932 subjects (54.7% females) presenting with none to five major cardiovascular risk factors (MCVRFs; hypertension, diabetes, tabagism, dyslipidaemia, BMI> 25), underwent CPET and were divided in 3 categories (normal weight; NW, overweight; OW and obese; Ob). Cohort analysis was carried out by dividing and analysing patients into groups based on BMI, sex, and number of MCVRFs. Peak VO2 was considered normal for a predicted value > 80%. Composite endpoint was defined as the combination of the following events: cardiovasular mortality, cardiovascular hospitalization, coronary artery disease (CAD), heart failure (HF), atrial fibrillation (AF), percutaneous coronary intervention (PCI), TAVI (Transcatheter aortic valve implantation), cardiac surgery, acute pulmonary oedema or stroke/transient ischemic attack (TIA). Results the number of MCVRFs significantly increased (CI 95%, p-value 0,009) through BMI strata being in NW, OW and Ob 1.6, 2.7, 2.9 respectively. Peak VO2 significantly (CI 95%, p-value <0,001) decreased with rise in BMI (21.8ml/min/kg, 18.7 ml/min/kg, 15.5 ml/min/kg for NW, OW and Ob, respectively; p-value <0,001). A significant correlation between the increase in number of MCRVFs and the decrease in peak VO2 was documented for BMI<30 (-0.44 for NW and -0.30 for OW; p-value <0,001), whereas Ob exhibited the lowest mean peak VO2 which was unaffected by the increasing number of MCVRFs. (figure 1). HRR (Heart rate reserve) was significantly lower in Ob subjects compared to OW and NW (respectively 0.59, 0.68, 0.72 p-value <0,001). Regression models showed that neither risk factors nor CPET variables were predictive for composite endpoint in NW. Interestingly, peak VO2 (OR 0,93 [CI 0,86-0,99] p-value 0,039) and VE/VCO2 slope (OR 1,06 [CI 1,00-1,11] p-value 0,047) were predictive of composite endpoint just in OW with Ob subjects showing similar trend not reaching statistical power; Diabetes was predictive of composite endpoint in Ob cohort. KM curves reported higher event rates in OW subjects with higher VE/VCO2 slope and lower peak VO2. (figure 2) Conclusions As far as obesity is concerned, regardless of the number of MCVRFs, BMI is the single strong determinant of exercise performance and gas exchange phenotype. In OW and NW cohorts, the cumulative number of MCVRFs impacts on worse exercise performance and gas exchange inefficiency. Lower peak VO2 and higher VE/VCO2 slope are predictive of CV composite endpoint in OW and a similar trend was observed in Ob.BMI and peak VO2KM BMI 25-30

Arrhythmogenic effects of DEHP exposure: insights into cardiac electrophysiology and myocardial cells

Abstract Introduction Hemodialysis patients, who are exposed to plasticizers through the hemodialysis circuit, face a high risk of cardiovascular disease (CVD). Plasticizers, such as the endocrine-disrupting compound Di(2-ethylhexyl) phthalate (DEHP), have emerged as potential contributors to CVD. This study explores the impact of DEHP on cardiac electrophysiology and myocardial cells, providing insights into its cardiotoxic effects. Methods We employed optical mapping techniques to assess cardiac electrophysiology in Langendorff-perfused rat hearts exposed to DEHP, comparing them to a control group. Additionally, we evaluated the effect of DEHP on cardiac muscle cells using H9C2 rat cardiomyoblasts. Results Prolonged DEHP exposure resulted in elevated heart rate, increased electrocardiographic variability, and higher low-frequency values, indicative of sympathetic nervous system overactivity. Action potential duration at APD80 increased, leading to greater action potential triangulation. Electrical alternans observed in the DEHP-treated group heightened the risk of arrhythmias. Single-cell analysis revealed severe mitochondrial damage, myocardial cell apoptosis, and disrupted calcium ion balance. Conclusion This study highlights DEHP's cardiotoxicity, suggesting its potential role in arrhythmogenesis and cardiac dysfunction. Environmental pollutants like DEHP warrant consideration as contributors to cardiovascular diseases, emphasizing the need for further research on preventive strategies.

Beta-blocker use and outcomes in patients with heart failure and mildly reduced and preserved ejection fraction

Abstract Background Concerns have been raised about the appropriateness of use and safety of beta-blockers (BBs) in patients with heart failure and mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF). However, randomized trial evidence is still lacking. Purpose To perform an observational analysis of the association between BB use and clinical outcomes in a large dataset of patients with HFmrEF and HFpEF. Methods We pooled individual patient data from four large HFmrEF/HFpEF trials (I-Preserve, TOPCAT, PARAGON-HF, and DELIVER). The associations between baseline BB use and outcomes were analyzed. The primary outcome was the composite of cardiovascular death or HF hospitalization. Results Among the 16,951 patients included, the mean left ventricular ejection fraction (LVEF) was 56.8%, and 13,400 (79.1%) had HFpEF (LVEF ≥50%). Overall, 12,812 patients (75.6%) received a BB. The median bisoprolol-equivalent dose of BB was 5.0 (Q1-Q3: 2.5-5.0) mg with BB continuation rates of 95.1% at 1 year and 93.1% at 2 years (in patients who survived more than 1 and 2 years, respectively). Overall, the hazard ratio (HR) for the primary outcome did not differ between BB users and non-users (HR: 0.98 [95% CI: 0.91-1.05]) but among patients with HFmrEF, BB users had a lower HR (0.84 [95% CI 0.71-0.98]), whereas in HFpEF the HR was similar BB users and non-users (0.99 [95% CI 0.92-1.08]). However, after comprehensive adjustment for known prognostic variables, including NT-proBNP, BB use was associated with a better outcome in the overall cohort (HR 0.81 [0.74-0.88]), and this association was maintained across the range of LVEF (Figure 1). In subgroup analyses, the risk of the primary outcome was similar in BB users and non-users with or without a history of myocardial infarction, with or without a history of hypertension, or with or without a baseline heart rate <70 bpm. By contrast, a better outcome with BB use was seen in patients with atrial fibrillation compared to those without atrial fibrillation (Figure 2). Conclusions Although this is an observational analysis of non-randomized treatment, there was no suggestion that BB use was associated with worse HF outcomes even after extensive adjustment for other prognostic variables. Figure Legends Figure 1. Association between beta-blocker use and outcomes across the range of LVEF. Risk in beta-blocker users versus non-users is shown as an adjusted continuous hazard ratio Figure 2. Association between beta-blocker use and non-use in the overall population and clinically relevant patient subgroups, shown as an adjusted hazard ratio (HR). The outcome analyzed was the composite of CV death or HF hospitalization (primary outcome)Figure 1Figure 2

Chronotropic incompetence predictors in a Cardiac Rehabilitation Program following myocardial infarction

Abstract Background Chronotropic incompetence (CI) has been described in many patients after myocardial infarction (MI) and can negatively affect physical capacity, especially if negative chronotropic therapy (NCT) is prescribed. Prediction of CI after MI could be useful for tailored medical therapy and exercise training prescription. Purpose We aim to predict CI on initial exercise ECG testing (ExECG) in MI patients submitted to a Cardiac Rehabilitation Program (CRP). Methods Patients with ST-segment elevation MI (STEMI) or occlusion MI (OMI) submitted to our CRP were prospectively included. After an initial follow-up phase of clinical stabilization and medical therapy optimization, ExECG (conventional or cardiopulmonary) was performed. Peak VO2 and chronotropic reserve index [(maximum heart rate – resting heart rate) / ([220-age] – resting heart rate)] were measured. Chronotropic incompetence was defined as <80% chronotropic reserve index (≤62% in patients treated with NCT). Pharmacological therapy with NCT was registered in absolute and equivalent doses per bisoprolol 2.5mg units (B2.5EU). The effect of NCT on CI was studied by ANOVA test, and predictors of CI by binary logistic regression analysis. The model was tested by area under the curve (AUC) analysis in receiver operating characteristic curves. A p<0.05 was considered statistically significant. Results The cohort comprised 143 patients, mostly middle-aged (mean 60.3±15.8 years) males (85.3%) with anterior or inferior MI (44.8% and 44.8%, respectively). Mean left ventricular ejection fraction (LVEF) was 52.4±10.6% and 36.4% depicted LVEF<50%. NCT was prescribed in most patients (n=125, 87.4%), and median equivalent dose was 1 [0.5-1] B2.5EU. CI was noted on more than half of the population on initial ExECG (n=75, 52.4%). Higher NCT doses per B2.5EU associated with worse mean chronotropic reserve indexes: 72.8±24.4% in patients without NCT; 71.7±18.7% in patients with 0.5 B2.5EU; 62.8±18.2% in patients with 1 B2.5EU; and 58.7±16.9% in patients with ≥2 B2.5EU (ANOVA p=0.04). On binary logistic regression analysis, only two variables were independent predictors of CI: diabetes mellitus (HR 3.02 [1.26-7.23], p=0.01) and LVEF (0.97 [0.94-0.99] per increased %, p=0.04). However, the predictive power of the model was poor (AUC 0.62 [0.53-0.71], p=0.01). Conclusions Chronotropic incompetence after a MI is associated with lower LVEF, diabetes mellitus, and higher doses of NCT. Although significant interindividual variability exists in chronotropic response in the post-infarction period, these factors could be taken into consideration for tailored prescription (or deprescription), especially in patients who may not derive any prognostic benefit from NCT.Chronotropic incompetence in CRP