Ischemic Heart Failure Research Articles

The Prognostic Role of Global Longitudinal Strain and NT-proBNP in Heart Failure Patients Receiving Cardiac Resynchronization Therapy.

We aimed to evaluate whether baseline GLS (global longitudinal strain), NT-proBNP, and changes in these after cardiac resynchronization therapy (CRT) can predict long-term clinical outcomes and the echocardiographic-based response to CRT (defined by 15% relative reduction in left ventricular end-systolic volume). We enrolled 143 patients with stable ischemic heart failure (HF) undergoing CRT-D implantation. NT-proBNP and echocardiography were obtained before and 6 months after. The patients were followed up (median: 58 months) for HF-related deaths and/or HF hospitalizations (primary endpoint) or HF-related deaths (secondary endpoint). A total of 84 patients achieved the primary and 53 the secondary endpoint, while 104 patients were considered CRT responders and 39 non-responders. At baseline, event-free patients had higher absolute GLS values (p < 0.001) and lower NT-proBNP serum levels (p < 0001) than those achieving the primary endpoint. A similar pattern was observed in favor of CRT responders vs. non-responders. On Cox regression analysis, baseline absolute GLS value (HR = 0.77; 95% CI, 0.51-1.91; p = 0.002) was beneficially associated with lower primary endpoint incidence, while baseline NT-proBNP levels (HR = 1.55; 95% CI, 1.43-2.01; p = 0.002) and diabetes presence (HR = 1.27; 95% CI, 1.12-1.98; p = 0.003) were related to higher primary endpoint incidence. In HF patients undergoing CRT-D, baseline GLS and NT-proBNP concentrations may serve as prognostic factors, while they may predict the echocardiographic-based response to CRT.

RED CELL DISTRIBUTION WIDTH – AN IGNORED BUT EMERGING INDICATOR TO PREDICT ADVERSE EVENTS IN HYPERTENSIVE PATIENTS

Objectives: Hypertension (HT) is related to the development of ischemic heart disease, heart failure, stroke, and chronic kidney disease. It is one of the primary causes of long-term morbidity and mortality. Past studies showed that red blood cell (RBC) morphology plays a significant role in inflammatory conditions of HT. Hence, this study was conducted to find association of erythrocyte parameters like RBC distribution width (RDW) with arterial blood pressure in hypertensives. Methods: The study was conducted in two groups: study and control. Fifty hypertensives and 50 normotensives between 40 and 60 years, matching inclusion and exclusion criteria were involved, and blood samples were taken and analyzed. Results: Our study has found significantly low values of mean corpuscular volume and mean corpuscular hemoglobin in the study group. However, the study group shows significantly high RDW values as compared to control group. Conclusion: High RDW values in hypertensives are a strong indicator of RBC abnormality, and it is associated with various vascular complications along with end-organ damage.

Renegotiating identity. A Nordic study of adolescent's experiences of living with a parent having heart disease.

To explore adolescents' experiences of having a parent with heart disease. This qualitative study was performed with semi-structured individual interviews. Interviews were conducted with 33 adolescents between 13 and 19 years old, who either had a mother or father with one of these diagnoses: ischemic heart disease, arrhythmia, heart failure, cardiac arrest or heart valve disease. The parent had been ill for at least 6 months and up to 5 years. The study was carried out in Denmark, Norway and Sweden between 2019 and 2022. The analysis was inspired by Reflexive Methodology. Three central themes emerged: Response to parental heart disease; Growing up ahead of time; and Strategies in a changed life situation. For the adolescents, heart disease was experienced as an acute and lethal disease that put their parents' lives in danger. New routines and roles not only changed everyday life within the family but they also enhanced maturity and appreciation of life. To maintain a balance in life, the adolescents pursued normality and sought a safe space to have a normal youthful life. In a period known to be significant for development, life with parental heart disease appeared as a biographical disruption because adolescents renegotiated their identity to manage their new life situation. It is important to help younger family members adapt to parental heart disease by informing them about possible reactions and supporting them in how to adapt to their new life by seeking breaks and normality. No patient or public involvement.

Risk of cardiovascular disease in patients with multiple sclerosis treated with fingolimod compared to natalizumab: A nationwide cohort study of 2095 patients in Denmark.

Fingolimod may be associated with risk of developing cardiovascular disease (CVD). Studies including reference groups and long follow-up are scarce. We hypothesized that patients treated with fingolimod would be at higher risk of developing CVD compared to patients treated with natalizumab. A nationwide 12-year cohort study linking individual-level data from the Danish Multiple Sclerosis Registry with health registries on 2095 adult patients with multiple sclerosis (MS) without any health records of CVD at follow-up start. Exposure to fingolimod and natalizumab was defined by the first treatment of at least 3 months. Cohort entry was from 2011 to 2018. We defined CVD as a composite measure, including hypertension, ischemic heart disease, atrial fibrillation, heart failure, and stroke. We used multivariable adjusted Cox regression. There were 28.8 and 17.4 CVD events per 1000 person-years in fingolimod and natalizumab groups, respectively. Compared to natalizumab-treated patients, fingolimod-treated patients had a higher risk of CVD (hazard ratio (HR) = 1.57; 95% confidence interval (CI) = 1.18-2.08). Hypertension comprised 200 of 244 CVD events. We found an increased risk of CVD in patients with MS treated with fingolimod. This increased risk was mainly due to hypertension.

An updated review of experimental rodent models of pulmonary hypertension and left heart disease.

Left heart disease (LHD) is the leading cause of pulmonary hypertension (PH). Its recent growth has not been matched by the design of therapeutic agents directly targeting the disease. Effective therapies approved for pulmonary arterial hypertension (PAH) have been shown to be inefficient in patients with PH-LHD. Hence, there is a need for an animal model that would closely mimic PH-LHD in preclinical experiments. The current study describes and compares a number of rodent models of left ventricular failure and their potential to induce PH. It also evaluates whether, and to what extent, common PH models could develop LV failure. Articles were identified in the Pubmed/Medline and Web of Science online electronic databases following the PRISMA Protocol between 1992 and 2022. Quality assessment was carried out using the SYRCLE risk-of-bias tool for animal studies. Publication bias across studies using Egger's regression test statistic, was performed together with sensitivity analysis. A wide spectrum of protocols-135 studies and 207 interventions, was examined, including systemic hypertensive models, pressure-overload-induced HF, model of ischemic heart failure, and metabolic approaches based on high fat diet or metabolic syndrome. The most pronounced alterations in PH-related parameters were demonstrated for the common PH models, but were also seen in animals with LV failure induced by ischemic conditions, pressure overload or metabolic conditions. Models based on aortic banding, transverse aortic constriction (TAC), or with myocardial infarction (MI) caused by coronary artery ligation, demonstrated more pronounced worsening in PH due to LV failure; however, they also demonstrated poor survival, especially the ischemic-HF model. Common PH models, excluding prolonged exposure to monocrotaline, do not promote LV hypertrophy. Prolonged exposure to a high-fat diet, or a two-hit model of an obese ZSF1 rat combined with SU5416-induced pulmonary endothelial impairment (a VEGF receptor antagonist) worsened PH and impaired diastolic dysfunction. Due to the limited number of protocols, further trials are needed to confirm the utility of such approaches for modeling PH in subjects with metabolic syndrome. This would provide a clearer insight into the complexity of LHD, PH and metabolic disorders in PH-LHD, and thus accelerate the development of new therapies in clinical trials.

LIPCAR levels in plasma-derived extracellular vesicles is associated with left ventricle remodeling post-myocardial infarction

BackgroundLong Intergenic noncoding RNA predicting CARdiac remodeling (LIPCAR) is a long noncoding RNA identified in plasma of patients after myocardial infarction (MI) to be associated with left ventricle remodeling (LVR). LIPCAR was also shown to be a predictor of early death in heart failure (HF) patients. However, no information regarding the expression of LIPCAR and its function in heart as well as the mechanisms involved in its transport to the circulation is known. The aims of this study are (1) to characterize the transporter of LIPCAR from heart to circulation; (2) to determine whether LIPCAR levels in plasma isolated-extracellular vesicles (EVs) reflect the alteration of its expression in total plasma and could be used as biomarkers of LVR post-MI.MethodsSince expression of LIPCAR is restricted to human species and the limitation of availability of cardiac biopsy samples, serum-free conditioned culture media from HeLa cells were first used to characterize the extracellular transporter of LIPCAR before validation in EVs isolated from human cardiac biopsies (non-failing and ischemic HF patients) and plasma samples (patients who develop or not LVR post-MI). Differential centrifugation at 20,000g and 100,000g were performed to isolate the large (lEVs) and small EVs (sEVs), respectively. Western blot and nanoparticle tracking (NTA) analysis were used to characterize the isolated EVs. qRT-PCR analysis was used to quantify LIPCAR in all samples.ResultsWe showed that LIPCAR is present in both lEVs and sEVs isolated from all samples. The levels of LIPCAR are higher in lEVs compared to sEVs isolated from HeLa conditioned culture media and cardiac biopsies. No difference of LIPCAR expression was observed in tissue or EVs isolated from cardiac biopsies obtained from ischemic HF patients compared to non-failing patients. Interestingly, LIPCAR levels were increased in lEVs and sEVs isolated from MI patients who develop LVR compared to patients who did not develop LVR.ConclusionOur data showed that large EVs are the main extracellular vesicle transporter of LIPCAR from heart into the circulation independently of the status, non-failing or HF, in patients. The levels of LIPCAR in EVs isolated from plasma could be used as biomarkers of LVR in post-MI patients.

Gene therapy encoding cell cycle factors to treat chronic ischemic heart failure in rats.

Gene therapies to induce cardiomyocyte (CM) cell cycle re-entry have shown a potential to treat subacute ischaemic heart failure (IHF) but have not been tested in the more relevant setting of chronic IHF. Our group recently showed that polycistronic non-integrating lentivirus encoding Cdk1/CyclinB1 and Cdk4/CyclinD1 (TNNT2-4Fpolycistronic-NIL) is effective in inducing CM cell cycle re-entry and ameliorating subacute IHF models and preventing the subsequent IHF-induced congestions in the liver, kidneys, and lungs in rats and pigs. Here, we aim to test the long-term efficacy of TNNT2-4Fpolycistronic-NIL in a rat model of chronic IHF, a setting that differs pathophysiologically from subacute IHF and has greater clinical relevance. Rats were subjected to a 2-h coronary occlusion followed by reperfusion; 4 weeks later, rats were injected intramyocardially with either TNNT2-4Fpolycistronic-NIL or LacZ-NIL. Four months post-viral injection, TNNT2-4Fpolycistronic-NIL-treated rats showed a significant reduction in scar size and a significant improvement in left ventricular (LV) systolic cardiac function but not in the LV dilatation associated with chronic IHF. A mitosis reporter system developed in our lab showed significant induction of CM mitotic activity in TNNT2-4Fpolycistronic-NIL-treated rats. This study demonstrates, for the first time, that TNNT2-4Fpolycistronic-NIL gene therapy induces CM cell cycle re-entry in chronic IHF and improves LV function, and that this salubrious effect is sustained for at least 4 months. Given the high prevalence of chronic IHF, these results have significant clinical implications for developing a novel treatment for this deadly disease.

Cardiovascular Events According to Inhaler Therapy and Comorbidities in Chronic Obstructive Pulmonary Disease.

COPD coexists with many concurrent comorbidities. Cardiovascular complications are deemed to be major causes of death in COPD. Although inhaler therapy is the main therapeutic intervention in COPD, cardiovascular events accompanying inhaler therapy require further investigation. Therefore, this study aimed to investigate new development of cardiovascular events according to each inhaler therapy and comorbidities. This study analyzed COPD patients (age ≥ 40 years, N = 199,772) from the Health Insurance Review and Assessment Service (HIRA) database in Korea. The development of cardiovascular events, from the index date to December 31, 2020, was investigated. The cohort was eventually divided into three arms: the LAMA/LABA group (N = 28,322), the ICS/LABA group (N = 11,812), and the triple group (LAMA/ICS/LABA therapy, N = 6174). Multivariable Cox analyses demonstrated that, compared to ICS/LABA therapy, triple therapy was independently associated with the development of ischemic heart disease (HR: 1.22, 95% CI: 1.04-1.43), heart failure (HR: 1.45, 95% CI: 1.14-1.84), arrhythmia (HR: 1.72, 95% CI: 1.41-2.09), and atrial fibrillation/flutter (HR: 2.31, 95% CI: 1.64-3.25), whereas the LAMA/LABA therapy did not show a significant association. Furthermore, emergency room visit during covariate assessment window was independently associated with the development of ischemic heart disease, heart failure, arrhythmia, and atrial fibrillation/flutter (p < 0.05). Our data suggest that cardiovascular risk should be considered in COPD patients receiving triple therapy, despite the confounding bias resulting from disparities in each group.

Muscle Oxygen Dynamics Measured by NIRS.

Near-infrared spectroscopy (NIRS) has been used to measure skeletal muscle oxidative function for more than 30years. Several indicators evaluate muscle oxidative function using NIRS during exercise, such as deoxygenation rate at the start of exercise (Deoxy-rate), changes in deoxygenation during exercise (ΔDeoxy), and reoxygenation speed after exercise (T1/2 reoxy, reoxy rate). Previous studies have reported that these muscle NIRS indicators are significantly correlated with muscle fibre type, phosphocreatine recovery rate, and peak oxygen uptake. In addition, muscle NIRS indicators have been applied to the study of a number of chronic health conditions, including patients with ischaemic heart failure. Recently, wearable NIRS devices monitor muscle function continuously and freely in the field, and we predict that NIRS devices will be widely applied to our lifestyles more than ever before. However, there are some critical problems with measuring muscle oxidative function using NIRS devices. We have previously reported that subcutaneous adipose tissue thickness (SATT) greatly influences the light pathlength and makes it difficult to quantify tissue deoxygenation, especially in the measurements of muscle deoxygenation from the skin surface. The effects of SATT need to, therefore, be corrected when using NIRS devices, especially when comparing differences in sex, age, and trainability, as the subjects' SATT could differ significantly. In addition, we have more recently reported that assuming constant mean pathlength (MPL) in NIRS leads to an inaccurate interpretation of muscle deoxygenation, since there are greater changes in MPL during incremental cycling exercise, especially at shorter wavelengths in the NIRS region. In this mini-review, we will summarise the indicators of muscle oxidative function using NIRS and the challenges of using an NIRS apparatus, especially during exercise.

Multimodal ultrasound imaging of a rat model with ischemic heart failure and its relationship to histopathology.

To investigate the value of multimodal ultrasound imaging in assessing ischemic heart failure, and to analyze the relationship between ultrasound parameters and histopathology. Thirty male healthy SD rats were randomly divided into a control (n = 10) and a model group (n = 20). The rat model of ischemic heart failure (IHF) was established by the ligation of left anterior descending artery for 4 weeks. Left ventricular ejection fraction (LVEF) and left ventricular cardiac output (LVCO) were determined with routine echocardiography. Global longitudinal strain (GLS) and global circumferential strain (GCS) were determined with Speckle Tracking. Myocardial oxygen saturation (sO2) was measured with photoacoustic (PA) imaging. Hematoxylin and eosin (H&E) staining, transmission electron microscopy, and Masson staining were performed to determine mitochondrial damage and myocardial fibrosis. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum levels of cardiac troponin I (cTNT) and N-terminal B-type natriuretic peptide (NT-pro BNP). Pearson correlation analysis was employed to analyze the correlation among LVEF, LVCO, GLS, GCS, sO2, mitochondrial impairment, fibrosis, cTNT and NT-pro BNP. Echocardiography revealed significant systolic function changes in the model group as compared to the control group, characterized by decreased LVEF and CO. The serum levels of cTn-T and NT-proBNP were increased, suggesting myocardial injury and functional impairment. GLS and GCS in the model group was reduced as compared to the control group. Concurrently, a marked reduction in sO2 was observed in the anterior wall of the model rats, whereas that in the posterior wall showed no significant change. Histopathologic examinations unveiled pronounced cellular and subcellular damage, such as disorganization of myocardial fibers and mitochondrial impairment, with the model group presenting a higher Flameng score. Masson's trichrome staining revealed increased myocardial fibrosis. Correlation analyses pinpointed significant associations between echocardiographic parameters, degree of mitochondrial damage, fibrosis, and the levels of cTn-T and NT-proBNP in the model group. This indicated the interrelated nature of structural changes and functional impairment in IHF. Notably, GLS showed the strongest correlations with indicators of myocardial injury. However, anterior wall sO2 did not demonstrate a significant correlation with either histopathologic damage or serum biomarker levels. Myocardial GLS is a sensitive indicator of pathological myocardial remodeling in heart failure. The multimodal ultrasound can be applied to assess pathologic remodeling in IHF rats.

Incidence Rate of Cardiovascular Events in Rheumatoid Arthritis: An Observational Cohort Study in Saudi Arabia.

Rheumatoid arthritis (RA) doubles the morbidity of cardiovascular disease (CVD) and leads to a 50% increase in mortality compared to the general population. This study aims to estimate the CVD incidence among RA patients in Saudi Arabia (SA), vital for assessing CVD burdens within this group. This retrospective study took place at two centers in the Eastern Province of SA, including all adult RA patients who visited the rheumatology clinic from 2016 to 2021 and were prescribed disease-modifying antirheumatic drugs (DMARDs). CVD incidence was determined by the diagnosis of ischemic heart disease (IHD), stroke/transient ischemic attack (TIA), venous thromboembolism (VTE), heart failure (HF), and arrhythmia post-RA diagnosis. Additional data collected included demographics, CVD risk factors, comorbidities, RA-related factors, and medication usage. The study comprised 651 patients, 80.5% of whom were females with an average age of 51. The overall CVD incidence was 11.2 per 1000 person-years, with males experiencing five times more incidents than females. The prevalence of CVD risk factors included 18.7% with hypertension, 7.8% with hyperlipidemia, 18.9% with diabetes, and 42.9% with obesity. Significant predictors of CVD were male gender and RA duration, with adjusted odds ratios (aOR) of 3.17 (95% CI 1.10 to 9.14, P=0.033) and 64.81 (95% CI 3.68 to 1140.6, P=0.004), respectively. This unique study from SA examined the CVD incidence in RA patients, identifying long disease duration and male gender as significant predictors. Effective reduction of CVD risk in RA patients requires aggressive management of modifiable risk factors and regular risk assessments.

Association of D-dimer to albumin ratio with adverse cardiovascular outcomes in ischaemic heart failure patients with diabetes mellitus: a retrospective cohort study

ObjectiveTo determine the association of D-dimer to albumin ratio (DAR) with major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) in ischaemic heart failure patients with diabetes mellitus.DesignA retrospective...

A Retrospective Cohort Study of the 2018 Angiotensin Receptor Blocker Recalls and Subsequent Drug Shortages in Patients With Hypertension.

Valsartan was recalled by the US Food and Drug Administration in July 2018 for carcinogenic impurities, resulting in a drug shortage and management challenges for valsartan users. The influence of the valsartan recall on clinical outcomes is unknown. We compared the risk of adverse events between hypertensive patients using valsartan and a propensity score-matched group using nonrecalled angiotensin receptor blockers and angiotensin-converting enzyme inhibitors. We used Optum's deidentified Clinformatics Datamart (July 2017-January 2019). Hypertensive patients who received valsartan or nonrecalled angiotensin receptor blockers/angiotensin-converting enzyme inhibitors for 1 year before and on the recall date were compared. Primary outcomes were measured in the 6 months following the recall and included: (1) a composite measure of all-cause hospitalization, all-cause emergency department visit, and all-cause urgent care visit, and (2) a composite cardiac event measure of hospitalizations for acute myocardial infarction and hospitalizations/emergency department visits/urgent care visits for stroke/transient ischemic attack, heart failure, or hypertension. We compared the risk of outcomes between treatment groups using Cox proportional hazard models. Of the hypertensive patients, 76 934 received valsartan, and 509 472 received a nonrecalled angiotensin receptor blocker/angiotensin-converting enzyme inhibitor. Valsartan use at the time of recall was associated with a higher risk of all-cause hospitalization, emergency department use, or urgent care use (hazard ratio [HR], 1.02 [95% CI, 1.00-1.04]) and the composite of cardiac events (HR, 1.22 [95% CI, 1.15-1.29]) within 6 months after the recall. The valsartan recall and shortage affected hypertensive patients. Local- and national-level systems need to be enhanced to protect patients from drug shortages by providing safe and reliable medication alternatives.

Clinical efficacy and safety of adjunctive treatment of chronic ischemic heart failure with Qishen Yiqi dropping pills: a systematic review and meta-analysis.

Our study was to evaluate the effect of Qishen Yiqi Dropping Pills(QSYQ) on the prognosis of chronic ischemic heart failure(CIHF) and its safety. Databases including CNKI, Wanfang, VIP, CBM, PubMed, Web of Science, The Cochrane Library and EMbase were searched from their inception to April 2023 to screen relevant randomized controlled trials (RCTs). Primary indicators included readmission rates, rates of major adverse cardiovascular events (MACE), and all-cause mortality rates. The quality of the literature was assessed according to the Cochrane Reviewers' Handbook 5.0 and the Modified Jadad Scale (with a score of 4-7 rated as high quality). Meta-analysis was performed using the meta-package created by R software version 4.2.3, continuous data were compared using SMDs, and dichotomous and ordered data were compared using ORs; and the I2 test was used to assess the heterogeneity. Fifty-nine studies out of 1,745 publications were finally included, totalling 6,248 patients. Most studies were poorly designed and had some publication bias, with only 26 high-quality papers (Jadad score ≥4). Meta-analysis showed that the combined application of QSYQ was able to reduce the readmission rate [OR = 0.42, 95% CI (0.33, 0.53), P < 0.001], all-cause mortality rate [OR = 0.43, 95% CI (0.27, 0.68), P < 0.001], and the incidence of MACE [OR = 0.42, 95% CI (0.31, 0.56), P < 0.001]. Also, the treatment method can improve clinical effectiveness [OR = 2.25, 95% CI (1.97, 2.58), P < 0.001], increase 6-min walking distance (6MWD) [SMD = 1.87, 95% CI (1.33, 2.41), P < 0.0001] and left ventricular ejection fraction (LVEF) [SMD = 1.08, 95% CI (0.83, 1.33), P < 0.0001], and decrease the Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores [SMD = -2.03, 95% CI (-3.0, -1.07), P < 0.0001], BNP levels [SMD = -2.07, 95% CI (-2.81, -1.33), P < 0.0001] and NT-ProBNP levels [SMD = -2.77, 95% CI (-4.90, -0.63), P < 0.05]. A total of 21 studies (n = 2,742) evaluated their adverse effects, of which 13 studies reported no adverse effects and 8 studies reported minor adverse effects. Our results suggest that the combined application of QSYQ can further improve patients' cardiac function and exercise tolerance, improve their quality of life, and ultimately improve patients' prognosis with a favorable safety profile. Nonetheless, limited by the quality and high heterogeneity of the literature, we must be conservative and cautious about the present results. PROSPERO (CRD42023449251).

JCL roundtable: Evolution of preventive cardiology and clinical lipidology

It's a privilege to discuss preventive cardiology with 3 of the foremost U.S. leaders in this growing subspecialty. Preventive cardiology is the practice of primordial, primary, and secondary prevention of cardiovascular disease. It employs an integrated team of clinicians committed to preventing all forms of cardiovascular disease, including ischemic heart disease, heart failure, atrial fibrillation, and other conditions. Thus, contemporary preventive cardiology extends management beyond dyslipidemic risk reduction and now commonly includes treatment of hypertension, diabetes and other related cardiometabolic disorders, novel cardiovascular risk factors, thrombotic risk, some cardiac genetic disorders, and cardiac disorders specific to women's health, as well as attention to tobacco- and drug-related risks. Preventive cardiologists may simultaneously manage cardiac rehabilitation programs. Among significant innovations are the launch of the American Journal of Preventive Cardiology in 2020, increasing validation and use of coronary artery calcium scoring, prescription of obesity and diabetes pharmaceuticals by cardiologists, and focus on pregnancy as a natural cardiovascular stress test for women with implications for future cardiovascular events. A continuing major barrier is that reimbursement for preventive cardiology services currently does not match the value benefit which accrues to patients and society. Preventive care too often is added late in the course of disease management. In addition to ongoing pharmaceutical and lifestyle research, future directions include incorporation of specific training goals for preventive cardiology in general clinical cardiology training programs and support for registered dietician reimbursement for services to patients with clinically manifest atherosclerosis.

Primary Care Utilization and Cardiovascular Screening in Adult Survivors of Childhood Cancer

Cardiovascular disease is the leading noncancer cause of premature death among survivors of childhood cancer. Adult survivors of childhood cancer are largely managed by primary care practitioners (PCPs), and health care utilization patterns related to cardiovascular screening are not well described. To examine screening and health care utilization among survivors of childhood cancer at high risk for cardiovascular complications. This multicenter cross-sectional study included participants enrolled in a randomized clinical trial from 2017 to 2021. Abstracted documentation of participants' cancer history, cardiotoxic treatment exposures, and survivorship care plans were obtained from participants' PCPs spanning 2 years preceding trial enrollment. Participants were members of the Childhood Cancer Survivor Study cohort at elevated risk for ischemic heart disease or heart failure, enrolled in a randomized trial focused on improving cardiovascular risk factor control. Data were analyzed from November 2022 to July 2023. Outcomes of interest were numbers of PCP and specialist visits, cardiovascular risk factors (hypertension, dyslipidemia, and diabetes), risk factor screening, and cardiac testing. Multivariable logistic regression assessed characteristics associated with up-to-date cardiac testing at enrollment. Of 347 enrolled participants, 293 (84.4%) had evaluable medical records (median [range] age, 39.9 [21.5-65.0] years; 149 [50.9%] male) and were included in analyses. At baseline, 238 participants (81.2%) had a documented PCP encounter; 241 participants (82.3%) had undergone blood pressure screening, 179 participants (61.1%) had undergone lipid testing, and 193 participants (65.9%) had undergone diabetes screening. A total of 63 participants (21.5%) had echocardiography completed or planned. Only 198 participants (67.6%) had records referencing a cancer history. PCP documentation of prior cardiotoxic exposures was low compared with known exposures, including radiation therapy (103 participants [35.2%] vs 203 participants [69.3%]; P < .001) and anthracycline chemotherapy (27 participants [9.2%] vs 222 participants [75.8%]; P = .008). Few records referenced a need for cancer-related late effects surveillance (95 records [32.4%]). Independent factors associated with cardiac screening included documentation of increased cardiovascular disease risk (odds ratio [OR], 11.94; 95% CI, 3.37-42.31), a late-effects surveillance plan (OR, 3.92; 95% CI, 1.69-9.11), and existing cardiovascular risk factors (OR per each additional factor, 2.09; 95% CI, 1.32-3.31). This cross-sectional study of adult survivors of childhood cancer at increased risk of cardiovascular disease found low adherence to recommended cardiac testing and documentation of risk for these individuals. Improving accuracy of reporting of survivors' exposures and risks within the medical record may improve screening.

Cumulative Diastolic Blood Pressure Burden in Normal Systolic Blood Pressure and Cardiovascular Disease.

The clinical significance of isolated diastolic hypertension defined by the 2017 American College of Cardiology/American Heart Association blood pressure (BP) guidelines remains inconsistent. We examined whether long-term diastolic burden predicts the first major adverse cardiovascular event in participants with sustained and untreated normal systolic BP. The Mass General Brigham Biobank is a New England health care-based cohort recruited between 2010 and 2021. A total of 15 979 participants aged 18 to 64 years and without prior cardiovascular disease, antihypertensives, or high systolic BP were studied. The cumulative diastolic burden was determined as the area under the curve for diastolic BP (DBP) ≥80 mm Hg over 5 years before enrollment. Major adverse cardiovascular event was defined as a composite of first incident ischemic heart disease, stroke, heart failure, or all-cause death. Of the 15 979 participants, mean (SD) age at enrollment was 47.6 (14.3) years, 11 950 (74.8%) were women, and the mean (SD) systolic BP and DBP were 118.0 (12.9) and 72.2 (9.3) mm Hg, respectively. Over a median (interquartile range) follow-up of 3.5 (1.8-5.4) years, 2467 (15.4%) major adverse cardiovascular events occurred. Using Cox proportional hazards regression, each SD increase in cumulative DBP was independently associated with a hazard ratio (95% CI) of 1.06 (1.02-1.10) without effect modification by sex (P=0.65), age (P=0.46), or race/ethnicity (P=0.24). In addition to traditional risk factors, cumulative DBP modestly improved the discrimination C index (95% CI) from 0.74 (0.72-0.75) to 0.75 (0.74-0.76; likelihood ratio test, P=0.037). Among individuals with normal systolic BP, cumulative DBP may augment cardiovascular disease risk stratification beyond a single DBP measure and traditional risk factors.

Social determinants of health and clinical outcomes among patients with atrial fibrillation: evidence from a global federated health research network.

Few studies have investigated the role of social determinants of health (SDoH) in patients with atrial fibrillation (AF). To investigate the relationship between SDoH and adverse events in a large multinational AF cohort. Retrospective study utilizing a global federated health research network (TriNetX). Patients with AF were categorized as socially deprived defined according to ICD codes based on three SDoHs: (i) extreme poverty; (ii) unemployment; and/or (iii) problems related with living alone. The outcomes were the 5-year risk of a composite outcomes of all-cause death, hospitalization, ischemic heart disease (IHD), stroke, heart failure (HF) or severe ventricular arrhythmias. Cox regression was used to compute hazard rate ratios (HRs) and 95% confidence intervals (CIs) following 1:1 propensity score matching (PSM). The study included 24 631 socially deprived (68.8 ± 16.0 years; females 51.8%) and 2 462 092 non-deprived AF patients (75.5 ± 13.1 years; females 43.8%). Before PSM, socially deprived patients had a higher risk of the composite outcome (HR 1.9, 95% CI 1.87-1.93), all-cause death (HR 1.34, 95% CI 1.28-1.39), hospitalization (HR 2.01, 95% CI 1.98-2.04), IHD (HR 1.67, 95% CI 1.64-1.70), stroke (HR 2.60, 95% CI 2.51-2.64), HF (HR 1.91, 95% CI 1.86-1.96) and severe ventricular arrhythmias (HR 1.83, 95% CI 1.76-1.90) compared to non-deprived AF patients. The PSM-based hazard ratios for the primary composite outcome were 1.54 (95% CI 1.49-1.60) for the unemployed AF patients; 1.39 (95% CI 1.31-1.47) for patients with extreme poverty or with low income; and 1.42 (95% CI 1.37-1.47) for those with problems related with living alone. In patients with AF, social deprivation is associated with an increased risk of death and adverse cardiac events. The presence of possible unmeasured bias associated with the retrospective design requires confirmation in future prospective studies.

Influence of cigarette smoking on the Index of Cardiac Electrophysiological Balance in apparently healthy Angolans.

Background: Tobacco use accelerates atherosclerosis and is one of the predictors of death from ischemic heart disease, arrhythmias, heart failure, and sudden death. A new non-invasive parameter, the Index of Cardiac Electrophysiological Balance (iCEB) between depolarization and repolarization of the action potential, was considered a new biomarker for the identification of patients at increased arrhythmic risk. Objectives: We aimed to evaluate the iCEB in apparently healthy Angolans with habitual cigarette smoking compared to non-smokers. Subjects and methods: Data were obtained from the CardioBengo study, a cross-sectional community-based study in which a random sample of individuals aged between 15 and 84 years was selected. In total, 214 apparently healthy subjects, 102 smokers, and 112 non-smokers in the same age group were included in the final analysis. Results: The average age of the participants was 42.17±13.04 years old and 26.6% of the sample was female. Smoking subjects had higher iCEB and corrected Index of Cardiac Electrophysiological Balance (iCEBc) values compared with non-smoking controls (4.39 vs. 4.25; p = 0.024, respectively), and (4.74 vs. 4.57; p = 0.030, respectively). Conclusions: In summary, iCEB and iCEBc were significantly higher in habitual smokers than in nonsmokers, which represents an increased risk of ventricular arrhythmogenesis in healthy habitual smokers. To the best of our knowledge, this is the first study performed in Africa to evaluate iCEB in smokers, making this type of study very important in low- and middle-income countries in the context of epidemiological transition.

The prognostic value of beta-1 blockers in patients with non-small-cell lung carcinoma treated with pembrolizumab

BackgroundImmune checkpoint inhibitors (ICIs) such as pembrolizumab have revolutionized the treatment of metastatic non-small cell lung cancer (mNSCLC). Beta-adrenergic activation contributes to cancer initiation and progression. While non-selective beta-blocker were found to improve the efficacy of ICIs therapy, the role of beta-1 (β1)-selective -blocker (β1B) in lung cancer patients is unknown. ObjectiveTo evaluate the effect of β1B on overall survival (OS) and progression-free survival (PFS) in patients diagnosed with mNSCLC and treated with pembrolizumab. MethodsWe performed a retrospective analysis of patients diagnosed with mNSCLC and treated with first-line pembrolizumab at our center. ResultsOf 200 eligible patients, 53 (27%) were pretreated with β1B. Patients in the β1B cohort were older (73 ± 8 vs. 67 ± 10 years, p < 0.001) with a higher prevalence of cardiac risk factors and cardiovascular (CV) diseases including ischemic heart disease (32% vs. 16%, p = 0.010), heart failure (9% vs. 3%, p = 0.043) and atrial fibrillation (23% vs. 3%, p < 0.001). Compared to the non-β1B group, patient pretreated with β1B had a significant shorter median OS (12 vs. 24 months, p = 0.004) and PFS (6 vs. 8 months, p < 0.001). In a multivariate analysis, including all CV risk factors and diseases, the use of baseline β1B was a strong and independent predictor for accelerated disease progression (HR 1.92, 95%CI 1.32–2.79, p < 0.001) and shorter OS (HR 1.8, 95%, CI 1.18–2.75, p = 0.007). ConclusionsThe use of baseline β1B showed a strong and independent association for shorter OS and PFS in patients diagnosed with mNSCLC and treated with pembrolizumab.