Cardiovascular Profile Research Articles

Clinical and cardiovascular magnetic resonance profile of cardiomyopathy patients from South Africa: Pilot of the IMHOTEP study

BackgroundCardiomyopathy is an important cause of heart failure, however, there is notable lack of data on causes and manifestations of cardiomyopathy in Africa. AimsThe African Cardiomyopathy and Myocarditis Registry Program (IMHOTEP) aims to address the knowledge gap on etiology, treatment, and outcomes of cardiomyopathy in sub-Saharan Africa. Methods and resultsWe conducted a single-center pilot study to delineate the clinical and cardiovascular magnetic resonance (CMR) phenotypes of cardiomyopathy in South African patients. Assessment of the first 99 adult incident cases [mean age 36.8 ± 12.5 years; females 53.5%] enrolled in IMHOTEP showed that dilated cardiomyopathy (n = 77) was commonest, followed by hypertrophic (n = 13), restrictive (n = 5) and arrhythmogenic (n = 4) cardiomyopathies. A broad range of etiologies were encountered with secondary causes identified in 42% of patients. Onset of symptoms in the peripartum period was observed in 47% of women, and peripartum cardiomyopathy was diagnosed in 32.1% of women recruited. In addition to electrocardiography and echocardiography, CMR was performed in 67 cases and contributed diagnostically in a third of cases. Acute inflammation was rarely observed [2%] on CMR, however, late gadolinium enhancement (LGE) was noted in 92% of cases. ConclusionWe report a diverse spectrum of causes of cardiomyopathy in the South African population, with secondary, potentially treatable, etiologies in a significant proportion of cases. CMR was useful in delineating specific phenotypes and etiologies, influencing clinical care. A higher-than-expected burden of LGE was observed in this young patient cohort - the implications of which are yet to be determined.

Exploring the Bob Ross effect: A psychophysiological investigation

Watching news broadcasts is known to elicit psychological stress. Conversely, the iconic painter Bob Ross (BR) has risen to pop culture status and amassed a following, as many find the messages and sounds of BR to be soothing and relaxing. Though, it has yet to be directly tested if such exposure can confer psychological or physiological benefit. The purpose of this study was to compare the effects of watching BR versus streaming news on markers of cardiovascular health and profile of mood states (POMS). It was hypothesized that watching BR would increase POMS scores and heart rate variability (HRV). It was also hypothesized that watching the news would increase blood pressure (BP), vascular stiffness (VS), and heart rate (HR). MethodsIn a randomized, controlled, crossover design, 18 young (21 ± 1 yrs, 9 female, 9 male) healthy participants (172.6 ± 9.9 cm, 69 ± 18 kg) were assessed for BP, VS, HR, HRV, and POMS before and after watching an episode of BR or the News matched for time (∼27 mins). Results: A significant interaction effect on POMS scores were observed for, anxiety (p = 0.01), anger (p = 0.008), depression (p = 0.003), fatigue (p = 0.001), and confusion (p = 0.01) domains after watching BR. The LF/HF ratio, an HRV marker of sympathovagal balance, was significantly lower after watching BR (p = 0.04). There were no significant time, condition, or interaction effects on systolic BP, mean arterial pressure, and diastolic BP. ConclusionThe “Bob Ross Effect” reduces overall mood disturbance, though appears to exert little influence on the cardiovascular system in this acute paradigm.

Mechanical thrombectomy in very elderly people: shortand long-term outcomes of endovascular stroke treatment in nonagenarians.

To assess outcomes of mechanical thrombectomy (MT) in nonagenarians suffering from acute ischaemic stroke (AIS) in a 1-year follow-up. Age is a factor associated with both the occurrence of AIS and a poorer prognosis. As the population ages, the prevalence of AIS among the very old (90 and older) is expected to rise. Data on long-term outcomes of MT, being the optimal treatment of AIS caused by large vessel occlusions, is scarce in the population of nonagenarians. We analysed all AIS patients treated with MT in a single Comprehensive Stroke Centre. We compared two subgroups: nonagenarians (people aged 90-99) and controls ( < 90 years) in terms of cardiovascular risk factors profile, stroke severity, treatment course, presence of in-hospital complications, and outcomes (mortality and good functional outcome defined as modified Rankin Scale ≤ 2) at discharge and at 90- and 365-day follow-ups. Nonagenarians were more commonly female and suffering from atrial fibrillation. They more often developed urinary tract infection during hospitalisation. Stroke severity, treatment course and in-hospital outcomes were comparable between the groups. Nonagenarians had non-significantly higher 90-day and 365-day mortality, and a significantly lower rate of good functional outcomes after 90 days (25.0% vs 57.7%, p = 0.011) and 365 days (31.5% vs 61.0%, p = 0.020). Despite worse outcomes than in younger patients, 25% of nonagenarians were functionally independent three months after MT, and almost one in three of them were so a year after the procedure, thereby showing the benefits of the treatment in this group.

Analysis of cardiohemodynamic and electrophysiological effects of morphine along with its toxicokinetic profile using the halothane-anesthetized dogs.

Although morphine has been used for treatment-resistant dyspnea in end-stage heart failure patients, information on its cardiovascular safety profile remains limited. Morphine was intravenously administered to halothane-anesthetized dogs (n=4) in doses of 0.1, 1 and 10 mg/kg/10 min with 20 min of observation period. The low and middle doses attained therapeutic (0.13 µg/mL) and supratherapeutic (0.97 µg/mL) plasma concentrations, respectively. The low dose hardly altered any of the cardiovascular variables except that the QT interval was prolonged for 10-15 min after its start of infusion. The middle dose reduced the preload and afterload to the left ventricle for 5-15 min, then decreased the left ventricular contractility and mean blood pressure for 10-30 min, and finally suppressed the heart rate for 15-30 min. Moreover, the middle dose gradually but progressively prolonged the atrioventricular conduction time, QT interval/QTcV, ventricular late repolarization period and ventricular effective refractory period without altering the intraventricular conduction time, ventricular early repolarization period or terminal repolarization period. A reverse-frequency-dependent delay of ventricular repolarization was confirmed. The high dose induced cardiohemodynamic collapse mainly due to vasodilation in the initial 2 animals by 1.9 and 3.3 min after its start of infusion, respectively, which needed circulatory support to treat. The high dose was not tested further in the remaining 2 animals. Thus, intravenously administered morphine exerts a rapidly appearing vasodilator action followed by slowly developing cardiosuppressive effects. Morphine can delay the ventricular repolarization possibly through IKr inhibition in vivo, but its potential to develop torsade de pointes will be small.

The association of frailty on cardiac rehabilitation goal achievement.

Frailty is common among patients entering cardiac rehabilitation (CR). Frailty is associated with poor health outcomes; however, it is unclear if frailty influences achieving goals in CR. We report a secondary analysis of participants who were referred to an exercise and education-based CR program from 2005 to 2015. Frailty was measured by a 25-item accumulation of deficits frailty index (FI) ranging from 0 to 1; higher scores indicate higher frailty. Participants were categorized by admission frailty levels (FI scores: < 0.20, 0.20-0.29, 0.30-0.39, > 0.40). CR goals were determined with shared decision-making between CR staff and the patients. We conducted logistic regression analyses to examine the odds of goal attainment by CR completion, adjusting for age, sex, education, marital status, and referring diagnosis. Analyses were performed using baseline frailty as a categorical and continuous outcome, and frailty change as a continuous outcome in separate models. Of 759 eligible participants (age: 59.5 ± 9.8, 24% female), 607 (80%) participants achieved a CR goal at graduation. CR goals were categorized into similar themes: control or lose weight (n = 381, 50%), improve physical activity behaviour and fitness (n = 228, 30%), and improve cardiovascular profile (n = 150, 20%). Compared to the most severe frailty group (FI >0.40), lower levels of frailty at baseline were associated with achieving a goal at CR completion [FI < 0.20: OR = 4.733 (95% CI: 2.197, 10.194), p < .001; FI 0.20-0.29: OR = 2.116 (1.269-3.528), p = .004]. Every 1% increase in the FI was associated with a 3.5% reduction in the odds of achieving a CR goal [OR = 0.965 (0.95, 0.979), p < .001]. Participants who reduced their frailty by a minimally clinically important difference of at least 0.03 (n = 209, 27.5%) were twice as likely to achieve their CR goal [OR = 2.111 (1.262, 3.532), p = .004] than participants who increased their frailty by at least 0.03 (n = 82, 10.8%). Every 1% improvement in the FI from baseline to follow up was associated with a 2.7% increase in the likelihood of CR goal achievement [OR = 1.027 (1.005, 1.048), p = .014]. Lower admission frailty was associated with a greater likelihood of achieving CR goals. Frailty improvements were associated with CR goal achievement, highlighting the influence of frailty on goal attainment.

Incidence of Cardiovascular Complications in Pediatric Patients Treated with Anthracyclines at a Brazilian Cancer Center.

The introduction of anthracyclines in the treatment of children and adolescents with cancer has promoted a significant increase in survival, but also in morbidity and mortality rates due to cardiovascular (CV) complications. To determine the cardiovascular profile of pediatric patients treated with anthracyclines at a cancer center in Brazil and the incidence of CV complications. The following data were collected from the medical records of patients of both sexes, aged younger than 19 years - frequency and form of clinical presentation of general CV complications (G1) and CV complications related to ventricular dysfunction (G2) - and correlated with risk factors, age range and vital status, cardiovascular and cardioprotective medications. A p<0.05 was considered statistically significant. A total of 326 patients were included, 214 (65.6%) were younger than 10 years and 192 (58.9%) of male sex. G1 complications occurred in 141 (43.3%) patients, and the most frequent was systemic arterial hypertension; G2 complications occurred in 84 patients (25.8%). Cumulative dose (CD) of anthracyclines > 250mg/m2 was used in 26.7% of patients and the association of G2 complications with this CD was not statistically significant (p=0.305; OR=1.330 and [95% CI = 0.770- 2.296]). The most used cardiac medications were diuretics (34.7% of patients). In accordance with literature, the study showed a high incidence of CV complications in the treatment of children and adolescents with cancer, with general CV complications as the most prevalent.

Incidência de Complicações Cardiovasculares em Pacientes Pediátricos Tratados com Antraciclinas em um Centro Oncológico Brasileiro

Abstract Background: The introduction of anthracyclines in the treatment of children and adolescents with cancer has promoted a significant increase in survival, but also in morbidity and mortality rates due to cardiovascular (CV) complications. Objectives: To determine the cardiovascular profile of pediatric patients treated with anthracyclines at a cancer center in Brazil and the incidence of CV complications. Methods: The following data were collected from the medical records of patients of both sexes, aged younger than 19 years – frequency and form of clinical presentation of general CV complications (G1) and CV complications related to ventricular dysfunction (G2) – and correlated with risk factors, age range and vital status, cardiovascular and cardioprotective medications. A p&lt;0.05 was considered statistically significant. Results: A total of 326 patients were included, 214 (65.6%) were younger than 10 years and 192 (58.9%) of male sex. G1 complications occurred in 141 (43.3%) patients, and the most frequent was systemic arterial hypertension; G2 complications occurred in 84 patients (25.8%). Cumulative dose (CD) of anthracyclines &gt; 250mg/m2 was used in 26.7% of patients and the association of G2 complications with this CD was not statistically significant (p=0.305; OR=1.330 and [95% CI = 0.770- 2.296]). The most used cardiac medications were diuretics (34.7% of patients). Conclusions: In accordance with literature, the study showed a high incidence of CV complications in the treatment of children and adolescents with cancer, with general CV complications as the most prevalent.

Challenge or Threat? The Effects of the Standard and a Second-Generation Mindfulness Intervention with Buddhist Practices on Cognitive Appraisals of Stress: Secondary Analysis of a Randomized Controlled Experiment Performed in Switzerland.

Contemplative approaches rooted in Buddhist traditions have been linked to the attenuation of response to social stress. Anticipatory cognitive appraisals of social situations potentially represent a mechanism explaining the stress-reducing effects of contemplative practices. The cognitive appraisal of threat is associated with an anticipated loss of social self-esteem. In contrast, the cognitive appraisal of challenge involves recognizing the potential for gain or growth in stressful situations and is associated with a more adaptive cardiovascular response. In this secondary analysis of a randomized controlled experiment performed in Switzerland, we evaluated the effects of two contemplative interventions on cognitive appraisals of challenge and threat and associated physiological profiles. The interventions were a standard Mindfulness-Based Stress Reduction (MBSR) program and a new program (MBSR-B), which included several elements from Buddhist practices. After an eight-week intervention, participants completed the Trier Social Stress Test (TSST) and underwent the assessment of primary cognitive appraisals and cardiovascular response to stress. The results demonstrated greater challenge appraisal in the MBSR (n = 20) and MBSR-B (n = 21) groups compared to Control (n = 24), and MBSR-B participants scored higher on the challenge than threat appraisal. At the physiological level, the groups did not differ on changes in cardiac output and total peripheral resistance. Still, an exploratory analysis demonstrated that the MBSR-B group's cardiovascular profile best resembled challenge appraisal. The results suggest that contemplative approaches foster challenge appraisal, contributing to a more adaptive response to stress.

Autonomic Dysfunction and Cardiovascular Risk in Patients with Rheumatoid Arthritis: Can Heart Rate Variability Analysis Contribute to a Better Evaluation of the Cardiovascular Profile of a Patient?

(1) Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease of autoimmune etiology. Increased scientific evidence suggests that immune-mediated inflammatory dis-eases are associated with autonomic nervous system (ANS) dysfunction. Studies proved that autonomic imbalance is correlated with RA evolution and may explain augmented cardiovascular pathology and mortality not attributable to classical risk factors. (2) Methods: 75 patients (25 males, 50 females) with RA were submitted to standard ECG recording and 24 h Holter monitoring. Twenty-five healthy patients were used as controls. Both time (SDNN, SDANN, SDANN Index, RRmed, rMSSD, and pNN50) and frequency domain (TP, VLF, HF, LF and LF/HF) heart rate variability (HRV) parameters were obtained. Parameters were compared to controls, and correlations with the QTc-interval and inflammatory status expressed through the C-reactive protein (CRP) were evaluated. (3) Results: In patients with a CRP > 5 mg/L, HRV parameters were lower compared to controls and to patients with a CRP ≤ 5 mg/L. All HRV parameters generated by Holter monitoring are negatively correlated with CRP levels and QTc values. The number of premature ventricular contractions (PVC) recorded is correlated with SDNN, SDANN, and LF/HF values. (4) Conclusions: Our study supports recent data suggesting that in RA there is an autonomic system dysfunction strongly connected with the inflammatory status of the patient. The autonomic dysfunction can contribute to the increased risk of cardiovascular death observed in patients with RA.

Cardiovascular risk and renal injury profile in subjects with type 2 diabetes and non-albuminuric diabetic kidney disease

BackgroundIn the last years, the classical pattern of diabetic kidney disease (DKD) has been partially overcome, because of the uncovering of a new DKD phenotype with significant renal dysfunction without presence of albuminuria: the non-albuminuric DKD (NA-DKD). To date, the cardiovascular risk associated with this phenotype is still debated. We investigated the cardiovascular risk and renal injury profile of NA-DKD subjects in comparison with other DKD phenotypes.MethodsPulse wave velocity (PWV), intima-media thickness, presence of carotid atherosclerotic plaque, renal resistive index (RRI), and a panel of urinary biomarkers of kidney injury were evaluated in 160 subjects with type 2 diabetes, stratified according to estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR) into four groups: controls (UACR < 30 mg/g and eGFR ≥ 60 mL/min/1.73 m2), A-DKD (Albuminuric-DKD, UACR ≥ 30 mg/g and eGFR ≥ 60 mL/min/1.73 m2), NA-DKD (UACR < 30 mg/g and eGFR < 60 mL/min/1.73 m2), AL-DKD (Albuminuric and Low eGFR-DKD; UACR ≥ 30 mg/g and eGFR < 60 mL/min/1.73 m2).ResultsSubjects with NA-DKD showed a higher PWV (11.83 ± 3.74 m/s vs. 10.24 ± 2.67 m/s, P = 0.045), RRI (0.76 ± 0.11 vs. 0.71 ± 0.09, P = 0.04), and prevalence of carotid atherosclerotic plaque (59% vs. 31%, P = 0.009) compared with controls. These characteristics were similar to those of subjects with AL-DKD, whereas the profile of A-DKD subjects was closer to controls. After multiple regression analyses, we found that RRI, that is in turn influenced by eGFR (β = − 0.01, P = 0.01), was one of the major determinants of PWV (β = 9.4, P = 0.02). Urinary TreFoil Factor 3, a marker of tubular damage, was higher in NA-DKD subjects vs. controls (1533.14 ± 878.31 ng/mL vs. 1253.84 ± 682.17 ng/mL, P = 0.047). Furthermore, after multiple regression analyses, we found that urinary osteopontin was independently associated with PWV (β = 2.6, P = 0.049) and RRI (β = 0.09, P = 0.006).ConclusionsOur data showed a worse cardiovascular and renal injury profile in NA-DKD subjects. This finding emphasizes the central role of eGFR in the definition of cardiovascular risk profile of diabetic subjects together with albuminuria.

Lipid Profile in Olympic Athletes: Proposal for a “Lipid Athlete Score” as a Clinical Tool to Identify High-Risk Athletes

Dyslipidemia is a major risk factor for atherosclerosis. Identification of dyslipidemia in athletes has raised interest in establishing preventive strategies and reducing cardiovascular (CV) events. Nowadays, targets or “scores” for athletes are undefined. The aim of our study was to create a “Lipid Athlete Score” based on lipid parameters and derive score indexes to identify high-risk athletes. We retrospectively enrolled 957 Olympic athletes practicing different sporting disciplines (power, skills, endurance, and mixed), analyzing their CV profiles and anthropometrics; 55.4% were male, the mean age was 27.1 ± 5 years, and the mean body mass index (BMI) was 23.1 ± 3.2 kg/m2. Three hundred and forty-three athletes (35.8%) were dyslipidemic (LDL ≥ 115 mg/dL or LDL/HDL ≥ 1.90). Multivariate analysis revealed the following: male p = 0.001, OR 1.88 [0.41–2.51], familiarity for dyslipidemia p = 0.001, OR 2.82 [1.72–4.59], BMI ≥ 30 kg/m2 p = 0.001, OR 2.53 [1.46–4.38], and fat mass p = 0.001, OR 2.29 [1.38–3.80] were significant. Endurance athletes presented the lowest CV risk. We proposed a lipid athlete score including major (LDL ≥ 115 mg/dL and LDL/HDL ≥ 1.90) and minor criteria (male, BMI &gt; 30 kg/m2 or fat mass &gt;22% for males and 32% for females, familiarity for dyslipidemia, and conventional CV risk factors). Twelve athletes (1.2%) were at high risk, 150 athletes (15.7%) at medium risk, 171 athletes (17.9%) at low risk, and 624 (65.2%) were at no risk. Dyslipidemia is very common in elite athletes. We have defined a specific lipid athlete score based on lipid parameters and derived score indexes for the stratification of risk. In accordance with this tool, a substantial proportion of athletes (16.9%) were at medium-to-high risk and need early preventive strategies to improve their lipid profiles and reduce the future development of atherosclerotic CV diseases.

Novel perspective on cardiovascular adverse event profiles due to treatment with sodium-glucose transport protein 2 (SGLT2) inhibitors in the Japanese Adverse Drug Event Report (JADER) database

Novel perspective on cardiovascular adverse event profiles due to treatment with sodium-glucose transport protein 2 (SGLT2) inhibitors in the Japanese Adverse Drug Event Report (JADER) database

Short-term effects of heatwaves on clinical and subclinical cardiovascular indicators in Chinese adults: A distributed lag analysis

AimsPrevious studies have related heat waves to morbidity and mortality of cardiovascular diseases; however, potential mechanisms remained limited. Our aims were to investigate the short-term effects of heat waves on a series of clinical/subclinical indicators associated with cardiovascular health. MethodsOur study used 80,574 health examination records from the Health Management Center of Nanjing Zhongda Hospital during the warm seasons of 2019–2021, including 62,128 participants. A total of 11 recognized indicators of cardiovascular risk or injury were assessed. Air pollution and meteorological data were obtained from the Nanjing Ecological Environment Bureau and the China Meteorological Data Network, respectively. Heat waves were defined as a daily average temperature over the 95th percentile for three or more consecutive days from May to September. We used a combination of linear mixed effects models and distributed lag nonlinear models to assess the lagged effects of heat waves on clinical and subclinical cardiovascular indicators. Stratified analyses based on individuals' characteristics, including gender, age, body mass index (BMI), diabetes, and hypertension, were also performed. ResultsHeat waves were related to significant changes in most indicators, with the magnitude of effects generally peaking at a lag of 0 to 3 days. Moreover, the cumulative percentage changes over lag 0–7 days were –0.82 % to –2.55 % in blood pressure, 1.32 % in heart rate, 0.20 % to 2.66 % in systemic inflammation markers, 0.36 % in a blood viscosity parameter, 9.36 % in homocysteine, and 1.35 % to 3.25 % in injuring myocardial enzymes. Interestingly, females and males showed distinct susceptibilities in different indicators. Stronger effects were also found in participants aged 50 years or over, individuals with abnormal BMI status, and patients with diabetes. ConclusionShort-term exposure to heat waves could significantly alter clinical/subclinical cardiovascular indicator profiles, including blood pressure changes, increased heart rate, acute systemic inflammation, elevated blood viscosity, and myocardial injury.

Cardiovascular Safety of Ozanimod in Patients With Ulcerative Colitis: True North and Open-Label Extension Analyses

Evaluating cardiovascular safety of sphingosine 1-phosphate (S1P) receptor modulators is warranted due to S1P receptor expression on cardiomyocytes and vascular endothelial cells. This analysis reports the cardiovascular safety of ozanimod, an S1P receptor modulator, in patients with moderately to severely active ulcerative colitis from the phase 3 True North (TN) and open-label extension (OLE). All patients who received ozanimod in TN (n= 796) and all eligible TN patients who entered the OLE (n= 823) were included. Cardiovascular-related adverse events were evaluated in patients with up to 146 weeks of ozanimod exposure (2219 patient-years), which included 52 weeks during TN. On TN day 1, first-dose ozanimod resulted in a 0.2 beats per minute mean decrease in heart rate from pretreatment to hour 6; 2 patients experienced bradycardia, which resolved without treatment modification. Mean systolic and diastolic blood pressure increases of 5.1 and 2.2 mm Hg, respectively, were observed at TN week 52. No second-degree Mobitz type II atrioventricular block events were reported; 1 third-degree atrioventricular block unrelated to ozanimod occurred in the OLE. Cardiac and vascular treatment-emergent adverse events were infrequent (3.8% [31 of 823] and 8.5% [70 of 823]); no ozanimod-related cardiovascular deaths occurred. The incidences of deep-vein thrombosis (0.2%; 2 of 823), pulmonary embolism (0.2%; 2 of 823), and ischemic stroke (0.4%; 3 of 823) in the OLE were low. No new cardiovascular safety signals were identified, consistent with findings from previous ozanimod studies. There were few major adverse cardiovascular events or thromboembolic events, which were unrelated or unlikely related to ozanimod. Ozanimod has a well-tolerated cardiovascular safety profile when prescribed in accordance with the label. Clinical trial registry website and trial numbers: ClinicalTrials.gov numbers: NCT02435992 and NCT02531126.

Safety Profile in Patients with Chronic Lymphocytic Leukemia Undergoing Treatment with 1st and 2nd Generation Bruton Tyrosine Kinase Inhibitors: Multicentric Real-World Experience

INTRODUCTION Chronic lymphocytic leukemia (CLL) is the most frequent leukemia, being more frequent in older adults. Bruton's tyrosinkinase inhibitors (BTKi) have revolutionized the treatment, displacing immunochemotherapy treatment in all patient profiles. The selectivity profile in the action of these drugs means that the toxicity of first and second generation BTKi is different, resulting in higher rates of atrial fibrillation and arterial hypertension, mainly in patients treated in the second line or later, while maintaining their efficacy. Real-life studies are needed to be able to demonstrate the effects in first-line treatment in a more heterogeneous patient profile, without the strict exclusion and inclusion criteria used in clinical trials. METHODS An observational, retrospective, multicenter, retrospective study was performed. Patients with in treatment with Ibrutinib or Acalabrutinib in first line or later were included. Demographic data, comorbidity, cytogenetic and mutational disease data, adverse effect profile, comprehensive geriatric assessment (if applicable) and treatment response evaluation data are collected. RESULTS A total of 91 patients were included with a median age of 73.22 years SD 11.06. Fifty-three (58.2%) were male. Fifty-three (58.2%) were treated in frontline, 31.9% (29) in second line and 9.9% (9) in subsequent lines. Acalabrutinib was used in 25 (27.5%) patients and Ibrutinib in 66 (72.5%). Patient characteristics are shown in Table 1. Differences were revealed between these two BTKis in terms of line of treatment, with the majority being treated first (P=0.006) and Rai stage, with Rai II predominating (P=0.014). No differences were found between the two BTKis according to the rest of the characteristics. In terms of toxicity, 14 (15.4%) of patients treated with Ibrutinib developed arterial hypertension, compared to no patients in the Acalabrutinib arm (p=0.009). With respect to the development of cardiac toxicity, 19 (20.9%) patients suffered some cardiotoxic event, 3 (3.3%) in patients on acalabrutinb and 16 (17.6%) on ibrutinib, with no significant differences found between the two drugs (p=0.2). No significant differences were found with respect to other toxicities (hematologic, digestive, bleeding and infections). Table 2 No differences were found in terms of progression-free survival or overall survival. CONCLUSIONS The iBTKs have changed the treatment of CLL, although the second-generation iBTKs have a safer cardiovascular profile and are just as effective in our cohort, even in the frontline.

Sex-specific cardiovascular protein levels and their link with clinical outcome in heart failure.

This study aims to provide insight into sex-specific cardiovascular protein profiles and their associations with adverse outcomes, which may contribute to a better understanding of heart failure (HF) pathophysiology and the optimal use of circulating proteins for prognostication in women and men. In 250 stable patients with HF with reduced ejection fraction (HFrEF), we performed trimonthly blood sampling (median follow-up: 26 [17-30] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or one sample closest to censoring and applied the Olink Cardiovascular III panel. We used linear regression to study sex-based differences in baseline levels and joint models to study differences in the prognostic value of serially measured proteins. In 66 women and 184 men (mean age of 66 and 67years, respectively), 21% and 28% reached the PEP, respectively. Mean baseline levels of fatty acid-binding protein 4, secretoglobin family 3A member 2, paraoxonase 3, and trefoil factor 3 were higher in women (Pinteraction : 0.001, 0.007, 0.018, and 0.049, respectively), while matrix metalloproteinase-3, interleukin 1 receptor-like 1, and myoglobin were higher in men (Pinteraction : <0.001, 0.001, and 0.049, respectively), independent of clinical characteristics. No significant differences between sexes were observed in the longitudinal associations of proteins with the PEP. Only peptidoglycan recognition protein 1 showed a suggestive interaction with sex for the primary outcome (Pinteraction =0.028), without multiple testing correction, and was more strongly associated with adverse outcome in women {hazard ratio [HR] 3.03 [95% confidence interval (CI), 1.42 to 6.68], P=0.008} compared with men [HR 1.18 (95% CI, 0.84 to 1.66), P=0.347]. Although multiple cardiovascular-related proteins show sex differences at baseline, temporal associations with the adverse outcome do not differ between women and men with HFrEF.

Cardiovascular Outcomes of α-Blockers vs 5-α Reductase Inhibitors for Benign Prostatic Hyperplasia

The most prescribed class of medications for benign prostatic hyperplasia (BPH) is α-blockers (ABs). However, the cardiovascular safety profile of these medications among patients with BPH is not well understood. To compare the safety of ABs vs 5-α reductase inhibitors (5-ARIs) for risk of adverse cardiovascular outcomes. This active comparator, new-user cohort study was conducted using insurance claims data from a 20% random sample of Medicare beneficiaries from 2007 to 2019 to evaluate the 1-year risk of adverse cardiovascular outcomes. Males aged 66 to 90 years were indexed into the cohort at new use of an AB or 5-ARI. Twelve months of continuous enrollment and at least 1 diagnosis code for BPH within 12 months prior to initiation were required. Data were analyzed from January 2007 through December 2019. Exposure was defined by a qualifying prescription fill for an AB or 5-ARI after at least 12 months without a prescription for these drug classes. Follow-up began at a qualified refill for the study drug. Primary study outcomes were hospitalization for heart failure (HF), composite major adverse cardiovascular events (MACE; hospitalization for stroke, myocardial infarction, or death), composite MACE or hospitalization for HF, and death. Inverse probability of treatment and censoring-weighted 1-year risks, risk ratios (RRs), and risk differences (RDs) were estimated for each outcome. Among 189 868 older adult males, there were 163 829 patients initiating ABs (mean [SD] age, 74.6 [6.2] years; 579 American Indian or Alaska Native [0.4%], 5890 Asian or Pacific Islander [3.6%], 9179 Black [5.6%], 10 610 Hispanic [6.5%], and 133 510 non-Hispanic White [81.5%]) and 26 039 patients initiating 5-ARIs (mean [SD] age, 75.3 [6.4] years; 76 American Indian or Alaska Native [0.3%], 827 Asian or Pacific Islander [3.2%], 1339 Black [5.1%], 1656 Hispanic [6.4%], and 21 605 non-Hispanic White [83.0%]). ABs compared with 5-ARIs were associated with an increased 1-year risk of MACE (8.95% [95% CI, 8.81%-9.09%] vs 8.32% [95% CI, 7.92%-8.72%]; RR = 1.08 [95% CI, 1.02-1.13]; RD per 1000 individuals = 6.26 [95% CI, 2.15-10.37]), composite MACE and HF (RR = 1.07; [95% CI, 1.03-1.12]; RD per 1000 individuals = 7.40 [95% CI, 2.88-11.93 ]), and death (RR = 1.07; [95% CI, 1.01-1.14]; RD per 1000 individuals = 3.85 [95% CI, 0.40-7.29]). There was no difference in risk for HF hospitalization alone. These results suggest that ABs may be associated with an increased risk of adverse cardiovascular outcomes compared with 5-ARIs. If replicated with more detailed confounder data, these results may have important public health implications given these medications' widespread use.

Celebrating Versatility: Febuxostat's Multifaceted Therapeutic Application.

Febuxostat, initially developed as a xanthine oxidase inhibitor to address hyperuricemia in gout patients, has evolved into a versatile therapeutic agent with multifaceted applications. This review provides a comprehensive overview of febuxostat's mechanism of action, its effectiveness in gout management, its cardiovascular safety profile, renal and hepatic effects, musculoskeletal applications, safety considerations, and emerging research prospects. Febuxostat's primary mechanism involves selective inhibition of xanthine oxidase, resulting in reduced uric acid production. Its pharmacokinetics require personalized dosing strategies based on individual characteristics. In gout management, febuxostat offers a compelling alternative, effectively lowering uric acid levels, relieving symptoms, and supporting long-term control, especially for patients intolerant to allopurinol. Recent studies have demonstrated its cardiovascular safety, and it exhibits minimal hepatotoxicity, making it suitable for those with liver comorbidities. Febuxostat's potential nephroprotective effects and kidney stone prevention properties are noteworthy, particularly for gout patients with renal concerns. Beyond gout, its anti-inflammatory properties hint at applications in musculoskeletal conditions and a broader spectrum of clinical contexts, including metabolic syndrome. Emerging research explores febuxostat's roles in cardiovascular health, neurological disorders, rheumatoid arthritis, and cancer therapy, driven by its anti-inflammatory and antioxidative properties. Future directions include personalized medicine, combination therapies, mechanistic insights, and ongoing long-term safety monitoring, collectively illuminating the promising landscape of febuxostat's multifaceted therapeutic potential.

Cardioprotection beyond the guidelines: the SAFE trial results

Abstract ESC 2022 Guidelines suggest that low-risk patients receiving anthracyclines and/or anti-HER2 therapies can be followed within the oncology program with appropriate referral to cardio-oncology if cancer therapy-related cardiovascular toxicity or new or uncontrolled cardiovascular risks emerges. ACE-I or ARB and beta-blockers should not be considered for primary prevention. Design The SAFE trial is a four-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study conducted at eight oncology departments in Italy. Between July 2015 and June 2020 patients with breast cancer were recruited and considered eligible for trial inclusion if they had indicated primary or postoperative systemic therapy using an anthracycline-based regimen. Patients with a prior diagnosis of cardiovascular disease or high-risk features were excluded. Cardioprotective therapy (bisoprolol (B), ramipril (R), or both drugs, as compared to placebo (P)) was administered for 1 year since the initiation of chemotherapy or until the end of trastuzumab therapy in the case of HER2 positive patients. All drugs were systematically titrated, up to the target daily dose of B (5 mg, OD), R (5 mg, OD), and P, if tolerated. The primary endpoint was defined as the detection of any subclinical impairment (worsening ≥10%) in left ventricular ejection fraction measured with 3-dimensional echocardiography (3DLVEF), and in global longitudinal strain (GLS) at the end-of-therapy (EOT) and at 2-year follow-up (EOF). Results 262 women (median age, 48 years; range, 24-75 years) were enrolled and treated. We analyzed 222 patients who had completed the pre-planned cardiological assessment at 24 months. Baseline demographic, tumor and cardiovascular profiles were similar between groups. All patients received anthracyclines, 215 at least three cycles (range 1-6), 217 patients also received taxane, and 77 adjuvant trastuzumab. Forty-nine patients were treated with neoadjuvant chemotherapy, 154 had adjuvant endocrine therapy, and 124 had postoperative radiation therapy. 3DLVEF and GLS data are reported in the Table as means±SE (95% CI). Statistical analysis was performed by ANCOVA. The percent changes from the baseline are reported in the Figure. At EOF GLS worsened by 10% or greater in 65 % of patients enrolled in the P arm, in 13%, 9%, and 10% of patients enrolled in the R, B, and R+B arms, respectively (P &amp;lt; 0.05). A reduction of 10% or greater in 3DLVEF was observed in 49% in the P arm, 4% in the R arm, 2% in the B arm, and 5% in the R+B arm (P &amp;lt; 0.05). Study drugs were well tolerated with no serious adverse events, the R+B arm showed significantly more side effects and had a significantly higher rate of allocated treatment discontinuation/reduction as compared to the other arms. Conclusion The results of the SAFE trial suggest that primary prevention should be considered also in low-risk breast cancer receiving anthracyclines and/or anti-HER2 therapies.TableFigure

Diastolic function is more sensitive than GLS in identifing cardiotoxicity. The SAFE trial results

Abstract Echocardiographic measures of diastolic dysfunction are associated with an increased risk of incident heart failure. Previous studies have shown that changes in diastolic function occur with anthracycline cancer therapy. However, they did not incorporate the newest classification of diastolic function nor evaluated the association with subsequent declines in systolic function. Design The SAFE trial is a four-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study. Recruitment was conducted between July 2015 and June 2020. Patients with breast cancer were eligible if they had indication to primary or postoperative systemic therapy using an anthracycline-based regimen. Known cardiovascular disease or high-risk features were exclusion criteria. Cardioprotective therapy (bisoprolol(B), ramipril(R), or both drugs, as compared to placebo(P)) was administered for 1 year since chemotherapy initiation or until the end of trastuzumab therapy in the case of HER2-positive patients. Each drug was systematically titrated, up to the target dose of B(5 mg OD), R(5 mg OD), if tolerated. The primary endpoint was defined as any subclinical impairment (worsening ≥10%) of 3D left ventricular ejection fraction and global longitudinal strain (GLS) at the end-of-therapy (EOT) and at 2-year follow-up (EOF). Individual measures indicative of diastolic function (mitral E/A ratio, septal and lateral e’ velocities, indexed LA volume, TR velocity, and E/e’ ratio) were recorded and diastolic function was graded according to the 2016 ASE/EACVI guidelines. Results Out of 262 women (median age 48 years; range, 24-75 years) enrolled and treated, 222 patients completed the pre-planned cardiological assessment at 24 months. Baseline demographic, tumor, and cardiovascular profiles were similar between the study arms. All patients received anthracyclines, 217 also received taxane, and 77 adjuvant trastuzumab. Forty-nine patients were treated with neoadjuvant chemotherapy, 154 with adjuvant endocrine therapy, and 124 had postoperative radiation therapy. At EOT GLS worsened by 10% or greater in 57% of patients in the P arm, 20%, 13%, and 18% in the R, B, and R+B arms, respectively (P&amp;lt; 0.05). At EOF GLS worsened by 10% or greater in 65 % of patients in the P arm, 13%, 9%, and 10% in the R, B, and R+B arms, respectively (P&amp;lt; 0.05). In all patients, diastolic function was normal at baseline. Changes in any diastolic parameter were not significant (Table). AT EOT 9% of the patients with &amp;lt;10% GLS decrease showed diastolic dysfunction (22% in P arm, 8%, 6%, and 4% in the R, B, and R+B arms, respectively, P&amp;lt;0.05). At EOF 78% of patients with ≥10% GLS decrease showed diastolic dysfunction (Figure). Our findings provide evidence that 1. abnormal diastolic function precedes systolic dysfunction, 2 there are significant changes in diastolic function grade over time, 3. cardioprotective therapy may be useful in low-risk breast cancer patients.TableFigure