J. Cardiovasc. Dev. Dis., Volume 10, Issue 10 (October 2023) – 33 articles

Cellular senescence (CS), classically considered a stable cell cycle withdrawal, is hallmarked by a progressive decrease in cell growth, differentiation, and biological activities. Senescent cells (SNCs) display a complicated senescence-associated secretory phenotype (SASP), encompassing a variety of pro-inflammatory factors that exert influence on the biology of both the cell and surrounding tissue. Among global mortality causes, cardiovascular diseases (CVDs) stand out, significantly impacting the living quality and functional abilities of patients. Recent data suggest the accumulation of SNCs in aged or diseased cardiovascular systems, suggesting their potential role in impairing cardiovascular function. CS operates as a double-edged sword: while it can stimulate the restoration of organs under physiological conditions, it can also participate in organ and tissue dysfunction and pave the way for multiple chronic diseases under pathological states. This review explores the mechanisms that underlie CS and delves into the distinctive features that characterize SNCs. Furthermore, we describe the involvement of SNCs in the progression of CVDs. Finally, the study provides a summary of emerging interventions that either promote or suppress senescence and discusses their therapeutic potential in CVDs. Full article

Background: Progressive myocardial remodeling (MR) in chronic heart failure (CHF) leads to aggravation of systolic dysfunction (SD) and clinical manifestations. Identification of metabolomic markers of these processes may help in the search for new therapeutic approaches aimed at achieving reversibility of MR and improving prognosis in patients with CHF. Methods: To determine the relationship between plasma acylcarnitine (ACs) levels, MR parameters and clinical characteristics, in patients with CHF of ischemic etiology (n = 79) and patients with coronary heart disease CHD (n = 19) targeted analysis of 30 ACs was performed by flow injection analysis mass spectrometry. Results: Significant differences between cohorts were found for the levels of 11 ACs. Significant positive correlations (r > 0.3) between the medium- and long-chain ACs (MCACs and LCACs) and symptoms (CHF NYHA functional class (FC); r = 0.31−0.39; p < 0.05); negative correlation (r = −0.31−0.34; p < 0.05) between C5-OH and FC was revealed. Positive correlations of MCACs and LCACs (r = 0.31−0.48; p < 0.05) with the left atrium size and volume, the right atrium volume, right ventricle, and the inferior vena cava sizes, as well as the pulmonary artery systolic pressure level were shown. A negative correlation between C18:1 and left ventricular ejection fraction (r = −0.31; p < 0.05) was found. However, a decrease in levels compared to referent values of ACs with medium and long chain lengths was 50% of the CHF-CHD cohort. Carnitine deficiency was found in 6% and acylcarnitine deficiency in 3% of all patients with chronic heart disease. Conclusions: ACs may be used in assessing the severity of the clinical manifestations and MR. ACs are an important locus to study in terms of altered metabolic pathways in patients with CHF of ischemic etiology and SD. Further larger prospective trials are warranted and needed to determine the potential benefits to treat patients with CV diseases with aberrate AC levels. Full article

(1) Background: A plethora of studies have elucidated the safety and efficacy of catheter ablation (CA) for patients afflicted with atrial fibrillation (AF) and concomitant reduction in left ventricular ejection fraction (LVEF). Nevertheless, the literature on the benefits of CA in the specific etiological context of heart failure (HF) remains limited. This study delineates a comparative assessment of outcomes for patients with AF and reduced LVEF across the primary etiologies. (2) Methods: Our inquiry encompassed 216 patients diagnosed with congestive heart failure and an LVEF of less than 50 percent who were referred to our institution for circumferential pulmonary vein isolation (CPVI) between the years 2016 and 2020. The selection criteria included a detailed medical history while excluding those suffering from valvular disease, congenital heart disease, and hypertrophic cardiomyopathy. In an effort to scrutinize varying etiologies, patients were stratified into three categories: dilated cardiomyopathy (DCM, n = 56, 30.6%), ischemic cardiomyopathy (ICM, n = 68, 37.2%), and tachycardia-induced cardiomyopathy (TIC, n = 59, 32.2%). (3) Results: Following an average (±SD) duration of 36 ± 3 months, the prevalence of sinus rhythm was 52.1% in the DCM group, 50.0% in the ICM group, and 68.14% in the TIC group (p = 0.014). This study revealed a significant disparity between the DCM and TIC groups (p = 0.021) and the ICM and TIC groups (p = 0.007), yet no significant distinction was discerned between the TIC and ICM groups (p = 0.769). Importantly, there were no significant variations in the application of antiarrhythmic drugs or recurrence of procedures among the three groups. The mortality rates were 14.29% for the DCM group and 14.71% for the ICM group, which were higher than the 3.39% observed in the TIC group (DCM vs. TIC p = 0.035 (HR = 4.50 (95%CI 1.38–14.67)), ICM vs. TIC p = 0.021 (HR = 5.00 (95%CI 1.61–15.50))). A noteworthy enhancement in heart function was evidenced in the TIC group in comparison to the DCM and ICM groups, including a higher LVEF (p < 0.001), diminution of LV end-diastolic diameter (p < 0.001), and an enhanced New York Heart Association classification (p = 0.005). Hospitalization rates for heart failure were discernibly lower in TIC patients (0.98 (0,2) times) relative to those with DCM (1.74 (0,3) times, p < 0.01) and TIC (1.78 (0,4) times, p < 0.001). Patients with paroxysmal atrial fibrillation and brief episodes were found to achieve superior clinical outcomes through a catheter ablation strategy. (4) Conclusion: Patients diagnosed with TIC demonstrated a more pronounced benefit from catheter ablation compared to those with DCM and ICM. This encompassed an augmented improvement in cardiac function, an enhanced maintenance of sinus rhythm, and a reduced mortality rate. Full article

Ischemia–reperfusion injury (IRI) in the myocardium has been thoroughly researched, especially in acute coronary syndrome and heart transplantation. However, our understanding of IRI implications on cardiac valves is still developing. This knowledge gap becomes even more pronounced given the advent of partial heart transplantation, a procedure designed to implant isolated human heart valves in young patients. This study aims to investigate the effects of IRI on aortic valvular endothelial cells (VECs), valvular interstitial cells (VICs), and whole leaflet cultures (no separation of VECs and VICs). We employed two conditions: hypoxic cold storage reperfusion (HCSR) and normothermia (NT). Key markers, secreted protein acidic and cysteine rich (SPARC) (osteonectin), and inducible nitric oxide synthase (iNOS2) were evaluated. In the isolated cells under HCSR, VICs manifested a significant 15-fold elevation in SPARC expression compared to NT (p = 0.0016). Conversely, whole leaflet cultures exhibited a 1-fold increment in SPARC expression in NT over HCSR (p = 0.0011). iNOS2 expression in VECs presented a marginal rise in HCSR, whereas, in whole leaflet settings, there was a 1-fold ascent in NT compared to HCSR (p = 0.0003). Minor escalations in the adhesion molecules intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), E-selection, and P-selection were detected in HCSR for whole leaflet cultures, albeit without statistical significance. Additionally, under HCSR, VICs released a markedly higher quantity of IL-6 and IL-8, with respective p-values of 0.0033 and <0.0001. Interestingly, the IL-6 levels in VECs remained consistent across both HCSR and NT conditions. These insights lay the groundwork for understanding graft IRI following partial heart transplantation and hint at the interdependent dynamic of VECs and VICs in valvular tissue. Full article

To explore impact of weight change (WC) on risk of atherosclerosis measured by cIMT, 20,700 participants from the CLSA follow-up were included in analysis. WC was defined as the difference of weight measured at follow-up and baseline, then quartered into four groups (Q1–Q4). cIMT > 1.0 mm was defined as high risk for atherosclerosis. Adjusted odds ratio (OR (95% CI)) from logistic regression models were used to evaluate the association between WC and risk of atherosclerosis. At follow-up, participants had gained 0.118 kg weight, on average, and 16.4% of them were at high risk for atherosclerosis. The mean levels of cIMT were comparable between participants from Q1 to Q4. Compared to Q2 (reference), the ORs (95% CI) were 1.00 (0.86, 1.15), 1.19 (1.03,1.38), and 1.25 (1.08,1.45) for Q1, Q3, and Q4, respectively. A similar pattern was observed when analyses were conducted for ages < 65 vs. 65+ separately, but it was weaker for those aged 65+. Results from the jointed distribution analyses indicated that moderate weight loss might increase risk for atherosclerosis among participants with obese BMI at baseline, but not for those with cardiovascular event status at baseline. Weight gain, however, would increase risk for atherosclerosis regardless of cardiovascular event status, or overweight/obese BMI at baseline. Full article

Background: There are limited data on gender-based differences in atrial fibrillation (AF) treatment and prognosis. We aimed to examine gender-related differences in medical attention in an emergency department (ED) and follow-up (FU) among patients diagnosed with an AF episode and to determine whether there are gender-related differences in clinical characteristics, therapeutic strategies, and long-term adverse events in this population. Methods: We performed a retrospective observational study of patients who presented to a tertiary hospital ER for AF from 2010 to 2015, with a minimum FU of one year. Data on medical attention received, mortality, and other adverse outcomes were collected and analyzed. Results: Among the 2013 patients selected, 1232 (60%) were female. Women were less likely than men to be evaluated by a cardiologist during the ED visit (11.5% vs. 16.6%, p = 0.001) and were less likely to be admitted (5.9% vs. 9.5%, p < 0.05). Electrical cardioversion was performed more frequently in men, both during the first episode (3.4% vs. 1.2%, p = 0.001) and during FU (15.9% vs. 10.6%, p < 0.001), despite a lower AF recurrence rate in women (9.9% vs. 18.1%). During FU, women had more hospitalizations for heart failure (26.2% vs. 16.1%, p < 0.001). Conclusions: In patients with AF, although there were no gender differences in mortality, there were significant differences in clinical outcomes, medical attention received, and therapeutic strategies. Women underwent fewer attempts at cardioversion, had a lower probability of being evaluated by cardiologists, and showed a higher probability of hospitalization for heart failure. Being alert to these inequities should facilitate the adoption of measures to correct them. Full article

The interplay between neurology and cardiology has gained significant attention in recent years, particularly regarding the shared pathophysiological mechanisms and clinical comorbidities observed in epilepsy and arrhythmias. Neuro-cardiac electrophysiology mapping involves the comprehensive assessment of both neural and cardiac electrical activity, aiming to unravel the intricate connections and potential cross-talk between the brain and the heart. The emergence of artificial intelligence (AI) has revolutionized the field by enabling the analysis of large-scale data sets, complex signal processing, and predictive modeling. AI algorithms have been applied to neuroimaging, electroencephalography (EEG), electrocardiography (ECG), and other diagnostic modalities to identify subtle patterns, classify disease subtypes, predict outcomes, and guide personalized treatment strategies. In this review, we highlight the potential clinical implications of neuro-cardiac mapping and AI in the management of epilepsy and arrhythmias. We address the challenges and limitations associated with these approaches, including data quality, interpretability, and ethical considerations. Further research and collaboration between neurologists, cardiologists, and AI experts are needed to fully unlock the potential of this interdisciplinary field. Full article

(1) Background: Epidemiological studies on the relationship between serum copper and hypertension are contradictory. We assessed the relationship between serum copper and blood pressure among adults in the United States. (2) Methods: We divided hypertension into two categories: treated hypertension and untreated hypertension. Linear or logistic regression analysis was applied to investigate the association between serum copper concentrations and blood pressure levels. (3) Results: As compared to quartile 1, the odds ratios (ORs) for untreated hypertension in quartiles 2, 3, and 4 were 1.02 (0.74–1.42), 1.23 (0.88–1.72), and 1.08 (0.74–1.58), respectively, in multivariable analysis (all p > 0.05). In non-hypertension, as compared with quartile 1, the β (95% CI) of systolic blood pressure for quartiles 2, 3, and 4 was −0.92 (−2.07–0.23), −0.05 (−1.30–1.20), and −0.48 (−1.83–0.88), respectively, in multivariable analysis (all p > 0.05). As compared to quartile 1, the ORs for treated hypertension in quartiles 2, 3, and 4 were 1.36 (0.88–2.10), 1.35 (0.87–2.09), and 1.56 (0.98–2.47), respectively, upon multivariable analysis including antihypertensive medication use as a covariate (all p > 0.05). Furthermore, 1SD increase in serum copper was non-significantly associated with 1.16 (0.97–1.37)-fold increased risk of hypertension in multivariable analysis (p = 0.096). (4) Conclusion: In the present study, we discovered that the serum copper concentration was not related with hypertension or blood pressure levels. Antihypertensive drug use may distort the correlation between copper and blood pressure levels. Information on antihypertensive drug use may be taken into account when identifying new risk factors for hypertension. Full article

Hypertension is one of the leading causes of morbidity and mortality among women related to pregnancy, childbirth and the postpartum period. The pathogenesis of gestational hypertension is complex and still not fully understood. The aim of this study was to assess the population of circulating CD4+CD25+FoxP3+ cells and its differentiation in terms of OX40 expression in two forms of hypertension: isolated hypertension developing after the 20th week of pregnancy and pre-eclampsia. The study included a group of 60 patients with hypertension and 48 healthy controls. The analysis of the percentage of Tregs was performed by flow cytometry. There was no difference in the percentage of peripheral lymphocytes between the groups. In the group of women with preeclampsia compared to the group with gestational hypertension, significantly higher percentages of CD4+CD25+FoxP3+ cells (p = 0.03) and percentages of CD4+CD25+FoxP3+ cells expressing the OX40 antigen (p = 0.001) were observed. OX40 expression on Tregs seems to be related to more serious type of hypertensive disorders in pregnant women. Full article

Background: Implantable cardioverter–defibrillators (ICDs) need to reliably detect ventricular tachycardia (VT) and ventricular fibrillation (VF) while avoiding T-wave oversensing (TWOS), which is associated with a risk of inappropriate therapies. The incidence of TWOS with endovascular ICDs appears to differ between manufacturers. Objectives: We aimed to evaluate the incidence and clinical consequences of TWOS with contemporary Medtronic and Boston Scientific ICDs. Methods: Consecutive patients implanted with a recent Medtronic or Boston Scientific ICD and remotely monitored at three French centers were included. All transmitted EGMs labelled as VF, VT, non-sustained VT (NSVT), or ventricular oversensing (Medtronic) were screened for TWOS. Results: Among 7589 transmitted episodes from 674 patients with a Boston Scientific ICD, we did not identify a single case of TWOS. Among 16,790 transmitted episodes from 1733 patients with a Medtronic ICD, we identified 60 patients (3.4%) with at least one episode of TWOS. In 46 patients, TWOS was intermittent (NSVT episodes). In the remaining 14 patients, TWOS resulted in 60 sustained episodes (completed counters). No inappropriate therapies were delivered in 12 of these patients because no therapies were programmed (in monitor zones, 11 episodes) or because therapies were inhibited by the morphology discriminator (Wavelet, 19 episodes) or by the anti-TWOS algorithm (26 episodes). Two patients received inappropriate therapies due to TWOS (0.1% of patients with Medtronic ICDs). Conclusion: On review of 24,379 transmitted episodes from 2407 patients with endovascular ICDs, we found no case of TWOS with Boston Scientific devices, whereas TWOS was not uncommon with Medtronic devices. However, the risk of inappropriate therapy with Medtronic ICDs was very low (0.1%) due to the often intermittent nature of this phenomenon, the morphology discriminator, and the anti-TWOS algorithm. Full article

Septic shock management in the cardiac intensive care unit (CICU) is challenging due to the complex interaction of pathophysiology between vasodilatory and cardiogenic shock, complicating how to optimally deploy fluid resuscitation, vasopressors, and mechanical circulatory support devices. Because mixed shock portends high mortality and morbidity, familiarity with quality, contemporary clinical evidence surrounding available therapeutic tools is needed to address the resultant wide range of complications that can arise. This review integrates pathophysiology principles and clinical recommendations to provide an organized, topic-based review of the nuanced intricacies of managing sepsis in the CICU. Full article

Cardiac resynchronisation therapy (CRT) has become the cornerstone of heart failure (HF) treatment. Despite the obvious benefit from this therapy, an estimated 30% of CRT patients do not respond (“non-responders”). The cause of “non-response” is multi-factorial and includes suboptimal device settings. To optimise CRT settings, echocardiography has been considered the gold standard but has limitations: it is user dependent and consumes time and resources. CRT proprietary algorithms have been developed to perform device optimisation efficiently and with limited resources. In this review, we discuss CRT optimisation including the various adopted proprietary algorithms and conduction system pacing. Full article

Introduction: The aim of this study is to assess the accuracy of the injection-based occlusion (IBO) tool utilizing saline and glucose solution in verifying pulmonary vein (PV) occlusion during cryoballoon ablation guided by a novel dielectric system (KODEX–EPD system). Methods: In this retrospective study, we enrolled 34 consecutive patients with paroxysmal atrial fibrillation (AF) who underwent their initial cryoballoon ablation procedure guided by the KODEX-EPD system. PV occlusion was firstly assessed by the IBO tool utilizing saline or glucose solution and then verified by direct contrast angiography. Patients were divided into two groups according to the fluid used in the IBO tool: the Saline Group and the Glucose Group. Results: The overall procedure time and fluoroscopy time were comparable between the Saline Group and the Glucose Group (113.7 ± 18.3 vs. 108.4 ± 15.9 min; p = 0.375 and 10.1 ± 3.7 vs. 9.3 ± 3.5 min; p = 0.559). The IBO tool was utilized a total of 138 times in the Saline Group and 135 times in the Glucose Group. When assessing PV occlusion, the IBO tool using saline demonstrated a sensitivity of 92.6% and a specificity of 95.2% compared to angiography. Similarly, the IBO tool utilizing glucose solution showed a sensitivity of 93.2% and a specificity of 96.1%. Conclusions: The IBO tool utilizing non-contrast fluid, saline and glucose solution, demonstrates a high level of sensitivity and specificity in accurately predicting PV occlusion during cryoablation procedures. Both the saline and glucose solutions used in the IBO tool show promising results in effectively assessing PV occlusion. Full article

Background: There is limited evidence on the effect of low birthweight on the use of cardiovascular medications and the role of health behaviors. This study aims to determine the independent effect of low birthweight and its combination with adult health behaviors on the number of dispensed cardiovascular medications. Methods: We included 15618 participants with information on birthweight and self-reported health behaviors. Dispensed cardiovascular medications were identified from the Prescribed Drug Register based on a three-digit level Anatomical Therapeutic Chemical classification code (C01 to C10 and B01) and categorized into 0, 1, and ≥2 different types of medications. We applied multinomial logistic regression models estimating odds ratios (ORs) and 95% confidence intervals (CIs). Results: Participants with low birthweight had a higher estimated OR of using ≥2 types of cardiovascular medications (OR = 1.46, 95% CI = 1.06, 2.01). Further, an increased risk for using ≥2 types of cardiovascular medications was found in participants with poor health behaviors for normal (OR = 2.17, 95% CI = 1.80, 2.62) and high (OR = 1.84, 95% CI = 1.29, 2.62) birthweight. The strongest effect on using ≥2 types of cardiovascular medications was found for low birthweight and poor health behaviors (OR = 3.14, 95% CI = 1.80, 5.50). Conclusion: This cohort study provides evidence that low birthweight increases the risk of using more types of cardiovascular medications in adulthood. This study also suggests that ideal health behaviors reduce this risk. Full article

Cardiac resynchronization therapy (CRT) is a cornerstone therapeutic opportunity for selected patients with heart failure. For optimal patient selection, no other method has been proven to be more effective than the 12-lead ECG, and hence ECG characteristics are extensively researched. The evaluation of particular ECG signs before the implantation may improve selection and, consequently, clinical outcomes. The definition of a true left bundle branch block (LBBB) seems to be the best starting point with which to select patients for CRT. Although there are no universally accepted definitions of LBBB, using the classical LBBB criteria, some ECG parameters are associated with CRT response. In patients with non-true LBBB or non-LBBB, further ECG predictors of response and non-response could be analyzed, such as QRS fractionation, signs of residual left bundle branch conduction, S-waves in V6, intrinsicoid deflection, or non-invasive estimates of Q-LV which are described in newer publications. The most important and recent study results of the topic are summarized and discussed in this current review. Full article

Background: Coronary CT angiography (CCTA) is increasingly used as a non-invasive tool to assess coronary artery disease (CAD). However, CCTA is subject to motion artifacts, potentially limiting its clinical utility. Despite faster (0.35 and 0.28 s/rot) gantry rotation times, low (60–65 bpm) heartbeat is recommended, and the use of β-blockers is often needed. Technological advancements have resulted in the development of faster rotation speeds (0.23 s/rot). However, their added value in patients not premedicated with β-blockers remains unclear. This prospective single-center, two-arm, randomized, controlled trial aims to assess the influence of fast rotation on coronary motion artifacts, diagnostic accuracy of CCTA for CAD, and patient safety. Methods: We will randomize a total of 142 patients aged ≥ 50 scheduled for an aortic stenosis work-up to receive CCTA with either a fast (0.23) or standard (0.28 s/rot) gantry speed. Primary outcome: rate of CCTAs with coronary motion artifacts hindering interpretation. Secondary outcomes: assessable coronary segments rate, diagnostic accuracy against invasive coronary angiography (ICA), motion artifact magnitude per segment, contrast-to-noise ratio (CNR), and patient ionizing radiation dose. The local ethics committee has approved the protocol. Potential significance: FAST-CCT may improve motion artifact reduction and diagnosis quality, thus eliminating the need for rate control and β-blocker administration. Clinicaltrials.gov identifier: NCT05709652. Full article

Cardiac catheter ablation (CCA) is a common method used to correct cardiac arrhythmia. Pulsed Field Ablation (PFA) is a recently-adapted CCA technology whose ablation is dependent on electrode and waveform parameters (factors). In this work, the use of the Design of Experiments (DoE) methodology is investigated for the design and optimization of a PFA device. The effects of the four factors (input voltage, electrode spacing, electrode width, and on-time) and their interactions are analyzed. An empirical model is formed to predict and optimize the ablation size responses. Based on the ranges tested, the significant factors were the input voltage, the electrode spacing, and the on time, which is in line with the literature. Two-factor interactions were found to be significant and need to be considered in the model. The resulting empirical model was found to predict ablation sizes with less than 2.1% error in the measured area and was used for optimization. The findings and the strong predictive model developed highlight that the DoE approach can be used to help determine PFA device design, to optimize for certain ablation zone sizes, and to help inform device design to tackle specific cardiac arrhythmias. Full article

Immune checkpoint inhibitors (ICIs) have emerged as a powerful and efficacious therapeutic approach for many cancer patients. Sintilimab is a fully human IgG4 monoclonal antibody that binds with programmed cell death receptor-1 (PD-1) to block its interaction with ligands, thereby enhancing the antitumor effects of T cells. However, ICIs may induce immune-related adverse events (irAEs) in various systems and organs, with fulminant myocarditis being the most severe one. We report the case of a 45-year-old female with gastric cancer who developed chest pain two weeks after chemotherapy with sintilimab; she was diagnosed with immune-associated fulminant myocarditis and experienced an Adams–Stokes syndrome attack in the hospital. Eventually, she was discharged after being treated with methylprednisolone, immunoglobulin, and an IABP. Full article

Transcatheter aortic valve implantation (TAVI) has become first-line treatment for older adults with severe aortic stenosis (AS), however, patients with bicuspid aortic valve (BAV) have been traditionally excluded from randomised trials and guidelines. As familiarity and proficiency of TAVI operators have improved, case-series and observational data have demonstrated the feasibility of successful TAVI in bicuspid aortic valve aortic stenosis (BAV-AS), however, patients with BAV-AS have several distinct characteristics that influence the likelihood of TAVI success. This review aims to summarise the pathophysiology and classification of BAV, published safety data, anatomical challenges and procedural considerations essential for pre-procedural planning, patient selection and procedural success of TAVI in BAV. Full article

Objective: Little is known about gut microbiota (GM) and cardiomyopathy. Their causal relationship was explored using two-sample Mendelian randomization (TSMR) performed by R software. Methods: The single nucleotide polymorphisms (SNPs) were further screened based on the genome-wide association studies (GWAS) of gut microbiota and cardiomyopathy obtained from an open database. TSMR was performed using an MR-Egger regression, simple estimator based on mode, weighted median method, inverse variance weighted (IVW), weighted estimator and CML-MA-BIC to explore the causal association. And the sensitivity analysis was carried out using an MR-Egger regression and the leave-one-out sensitivity test. Results: As for 211 GM taxa, IVW results confirmed that the class Actinobacteria (OR = 0.81, p = 0.021) and genus Coprobacter (OR = 0.85, p = 0.033) were protective factors for cardiomyopathy. The phylum Firmicutes (OR = 0.87, p < 0.01), family Acidaminococcaceae (OR = 0.89, p < 0.01), genus Desulfovibrio (OR = 0.92, p = 0.030) and genus Prevotella9 (OR = 0.93, p = 0.029) were protective factors for ischemic cardiomyopathy. The family Rhodospirillaceae (OR = 1.06, p = 0.036) and genus Turicibacter (OR = 1.09, p = 0.019) were risk factors for ischemic cardiomyopathy. The genus Olsenella (OR = 0.91, p = 0.032) was a protective factor for non-ischemic cardiomyopathy. The order Rhodospirillales (OR = 1.14, p = 0.024), family Rikenellaceae (OR = 1.21, p = 0.012) and genus Gordonibacter (OR = 1.12, p = 0.019) were risk factors for non-ischemic cardiomyopathy. The robustness of MR results was reflected in the heterogeneity (p > 0.05) and pleiotropy (p > 0.05) analyses. Conclusions: A potential causal relationship of cardiomyopathy with some GM taxa has been confirmed in the current study. Full article

Obesity is reported to have a protective effect on mortality in pulmonary hypertension (PH), a phenomenon known as obesity paradox. However, the data are conflicting, with some studies showing decreased mortality while other studies found no effect of obesity on mortality. Therefore, we performed a systematic review and meta-analysis to examine whether there is an association between obesity and mortality in PH. Only patients with PH diagnosed by right heart catheterization were included. We also performed a sub-group analysis of subjects with pre-capillary PH only. A total of six studies met the inclusion criteria, with a sample size of 13,987 patients. Obese subjects had lower mortality compared to non-obese subjects in the combined pre- and post-capillary PH group (hazard ratio 0.79, 95% CI 0.66–0.95, p = 0.01). While obesity was associated with reduction in mortality in the pre-capillary PH group (hazard ratio 0.77, 95% CI 0.60 to 0.98, p = 0.03), this was not uniform across all studies. Full article

1. Background: We sought to determine acute and subacute changes in cardiac function after proton beam (PBT) and photon beam (PhT) radiotherapy (RT) using conventional and two-dimensional speckle tracking echocardiography (2D-STE) in patients with malignant breast and thoracic tumors. 2. Methods: Between March 2016 and March 2017, 70 patients with breast or thoracic cancer were prospectively enrolled and underwent transthoracic echocardiography with comprehensive strain analysis at pretreatment, mid-treatment, end of treatment, and 3 months after RT. 3. Results: PBT was used to treat 44 patients; PhT 26 patients. Mean ± SD age was 55 ± 12 years; most patients (93%) were women. The median (interquartile range) of the mean heart dose was lower in the PBT than the PhT group (47 [27–79] vs. 217 [120–596] cGy, respectively; p < 0.001). Ejection fraction did not change in either group. Only the PhT group had reduced systolic tissue Doppler velocities at 3 months. 2D-STE showed changes in endocardial and epicardial longitudinal, radial, and circumferential early diastolic strain rate (SRe) in patients undergoing PhT (global longitudinal SRe, pretreatment vs. end of treatment (p = 0.04); global circumferential SRe, pretreatment vs. at 3-month follow-up (p = 0.003); global radial SRe, pretreatment vs. at 3-month follow-up (p = 0.02) for endocardial values). Epicardial strain values decreased significantly only in patients treated with PhT. Patients in the PhT group had a significant decrease in epicardial global longitudinal systolic strain rate (GLSRs) (epicardial GLSRs, at baseline vs. at end of treatment [p = 0.009]) and in GCSRe and GRSRe (epicardial GCSRe, at baseline vs. at 3-month follow-up (p = 0.02); epicardial GRSRe, at baseline vs. at 3-month follow-up (p = 0.03)) during treatment and follow-up. No changes on 2D-STE were detected in the PBT group. 4. Conclusions: Patients who underwent PhT but not PBT had reduced tissue Doppler velocities and SRe values during follow-up, suggesting early myocardial relaxation abnormalities. PBT shows promise as a cardiac-sparing RT technology. Full article

Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, and are the cornerstone of lipid-lowering treatment. They significantly reduce cardiovascular morbidity and mortality. However, musculoskeletal symptoms are observed in 7 to 29 percent of all users. The mechanism underlying these complaints has become increasingly clear, but less is known about the effect on cardiac muscle function. Here we discuss both adverse and beneficial effects of statins on the heart. Statins exert pleiotropic protective effects in the diseased heart that are independent of their cholesterol-lowering activity, including reduction in hypertrophy, fibrosis and infarct size. Adverse effects of statins seem to be associated with altered cardiomyocyte metabolism. In this review we explore the differences in the mechanism of action and potential side effects of statins in cardiac and skeletal muscle and how they present clinically. These insights may contribute to a more personalized treatment strategy. Full article

Cholesterol-laden macrophages are recognized as a major contributor to atherosclerosis. However, recent evidence indicates that vascular smooth muscle cells (VSMC) that accumulate cholesterol and transdifferentiate into a macrophage-like cell (MLC) phenotype also play a role in atherosclerosis. Therefore, removing cholesterol from MLC may be a potential atheroprotective strategy. The two transporters which remove cholesterol from cells are ABCA1 and ABCG1, as they efflux cholesterol to apoAI and HDL, respectively. In this study, the well-characterized immortalized VSMC line MOVAS cells were edited to generate ABCA1- and ABCG1-knockout (KO) MOVAS cell lines. We cholesterol-loaded ABCA1-KO MOVAS cells, ABCG1-KO MOVAS cells, and wild-type MOVAS cells to convert cells into a MLC phenotype. When we measured apoAI- and HDL-mediated cholesterol efflux in these cells, we observed a drastic decrease in apoAI-mediated cholesterol efflux within ABCA1-KO MOVAS MLC, but HDL-mediated cholesterol efflux was only partially reduced in ABCG1-KO MOVAS cells. Since SR-BI also participates in HDL-mediated cholesterol efflux, we assessed SR-BI protein expression in ABCG1-KO MOVAS MLC and observed SR-BI upregulation, which offered a possible mechanism explaining why HDL-mediated cholesterol efflux remains maintained in ABCG1-KO MOVAS MLC. When we used lentivirus for shRNA-mediated knockdown of SR-BI in ABCG1-KO MOVAS MLC, this decreased HDL-mediated cholesterol efflux when compared to ABCG1-KO MOVAS MLC with unmanipulated SR-BI expression. Taken together, these major findings suggest that SR-BI expression in MLC of a VSMC origin plays a compensatory role in HDL-mediated cholesterol efflux when ABCG1 expression becomes impaired and provides insight on SR-BI demonstrating anti-atherogenic properties within VSMC/MLC. Full article

Although fibronectin has been associated with the pathogenesis of atherosclerosis, little is currently known about the relationship between plasma fibronectin and coronary heart disease (CHD). This retrospective study aimed to determine the predictive value of plasma fibronectin for CHD and its severity. A total of 1644 consecutive patients who underwent selective coronary angiography were recruited into the present study. The characteristics and results of the clinical examination of all patients were collected. Logistic regression analyses were performed to determine the predictive value of plasma fibronectin for the presence and severity of CHD. Compared with non-CHD patients, the CHD patients showed significantly higher plasma levels of troponin I and creatine kinase isoenzyme, along with lower plasma levels of fibronectin. However, no significant differences were detected in plasma fibronectin among patients with different grades of CHD. The logistic regression model showed that plasma fibronectin remained an independent predictor of CHD after adjustment with a 1.39-fold increased risk for every 1 SD decrease in plasma fibronectin. Nevertheless, plasma fibronectin could not predict the severity of CHD determined by the number of stenosed vessels and the modified Gensini score. This study demonstrated that lower plasma fibronectin might be an independent predictor of CHD, but it may be of no value in predicting the severity of CHD. Full article

This study aimed to delineate the effect of sodium chloride on the induction of inflammatory responses and the development of hypertension in Dahl salt-sensitive (SS) and salt-resistant (SR) rats. Splenocytes were isolated from the spleens of SS and SR rats, and cultured on anti-CD3-coated plates for 5 days. The cultured splenic T-cells were challenged with a hypertonic salt solution (0, 20, or 40 mM) in the absence or presence of IL-6 (0, 20, or 60 ng/mL), TGF-β (0, 5, or 15 ng/mL), or IL-23 (0, 10, or 30 ng/mL), and analyzed via ELISA, flow cytometry, and immunofluorescence. The hypertonic salt solution potentiated IL-17A production, as well as the differentiation of Th17 cells via IL-6/TGF-β/IL-23, exclusively in SS rats. However, it did not affect IL-10 production or the differentiation of Treg cells in any of the groups. Furthermore, it potentiated the signal of RORγt in IL-6-treated splenic T-cells from SS rats. To summarize, cultured splenic T-cells exhibited enhanced inflammatory responses on exposure to a hypertonic salt solution in SS rats only, which indicated that sodium chloride and inflammatory cytokines synergistically drove the induction of pathogenic Th17 cells and the development of hypertension in this group only. Full article

Background: Hedinger syndrome (HS) or carcinoid heart disease (CD) is a rare and challenging manifestation of malignant neuroendocrine tumours (NETs) involving the heart. We aimed to report our experience with surgical strategies and midterm results in HS patients. Methods: Eleven patients (58 ± 11 (range 41 to 79 years); 5 females) with HS who underwent cardiac surgery in our department between 07/2005 and 05/2023 were analysed. Results: All patients showed a New York Heart Association (NYHA) class III–IV and in all the tricuspid valve (TV) was involved. Four patients received a TV replacement, and three TV reconstruction. Recently, to preserve the geometry and function of the compromised right ventricle (RV), we have applied the TV “bio-prosthesis in native-valve” implantation technique with the preservation of the valve apparatus (tricuspid valve implantation: TVI) in four cases. Concomitant procedures included pulmonary valve replacement in four, pulmonary implantation in one, and aortic valve replacement in three cases. To treat RV failure, we adapted a combined TandemHeart^®-CytoSorb^® haemoperfusion strategy in Patient #10 and venoarterial extracorporeal membrane oxygenation (V-A ECMO) support avoidance, after experiencing an ECMO-induced carcinoid-storm-related death in Patient #8. Mortality at 30 days was 18% (2/11). The median follow up was 2 ± 2.1 years (range 1 month to 6 years) with an overall mortality during the follow-up period of 72.7% (8/11). Conclusions: HS surgery, despite being a high-risk procedure, can efficiently prolong survival, and represents a safe and feasible procedure. However, patient selection seems to be crucial. Further follow up and larger cohorts are needed. Full article

Background: Different methods are established for the changes in aortic valve stenosis with cardiac computed tomography angiography (CCTA), but the effect of the grade of stenosis on contrast densities around the valve has not been investigated. Aims/methods: Using the information from flow dynamics in cases of increased velocity through narrowed lumen, the hypothesis was formed that flow changes can alter the contrast densities in stenotic post-valvular regions, and the density changes might correlate with the grade of stenosis. Forty patients with severe aortic stenosis and fifteen with a normal aortic valve were enrolled. With echocardiography, the peak/mean transvalvular gradients, peak transvalvular velocity, and aortic valve opening area were obtained. With CCTA, densities 4–5 mm above the aortic valve; at the junction of the left, right, and noncoronary cusp to the annulus; at the middle level of the left, right, and noncoronary sinuses of Valsalva in the center and the lateral points; at the sinotubular junction; and 4 cm from the sinotubular junction at the midline were measured. First, a comparison of the densities between the normal and stenotic valve was performed, and then possible correlations between echocardiography and CCTA values were investigated in the stenotic group. Results: In all CCTA regions, significantly lower-density values were detected among stenotic valve patients compared to the normal aortic valve population. Additionally, in both groups, higher densities were measured in the peri-jet regions than in the lateral ones. Furthermore, a good correlation was found between the aortic valve opening area and the densities in almost all perivalvular areas. With regard to the densities at the junction of the non-coronary leaflet to the fibrotic annulus and at the most lateral point of the right sinus of Valsalva, a high level of correlation was found between all echocardiography and CCTA parameters. Lastly, with receiver operating characteristic curve measurements, area under the curve values were between 0.857 and 0.930. Conclusion: Certain CCTA density values, especially 4–5mm above the valve opening, can serve as auxiliary information to echocardiography when the severity of aortic valve stenosis is unclear. Full article

Hypertrophic cardiomyopathy (HCM) is a congenital heart disease characterized by thickening of the heart’s left ventricle (LV) wall that can lead to cardiac dysfunction and heart failure. Ventricular wall thickening affects the motion of cardiac walls and blood flow within the heart. Because abnormal cardiac blood flow in turn could lead to detrimental remodeling of heart walls, aberrant ventricular flow patterns could exacerbate HCM progression. How blood flow patterns are affected by hypertrophy and inter-patient variability is not known. To address this gap in knowledge, we present here strategies to generate personalized computational fluid dynamics (CFD) models of the heart LV from patient cardiac magnetic resonance (cMR) images. We performed simulations of CFD LV models from three cases (one normal, two HCM). CFD computations solved for blood flow velocities, from which flow patterns and the energetics of flow within the LV were quantified. We found that, compared to a normal heart, HCM hearts exhibit anomalous flow patterns and a mismatch in the timing of energy transfer from the LV wall to blood flow, as well as changes in kinetic energy flow patterns. While our results are preliminary, our presented methodology holds promise for in-depth analysis of HCM patient hemodynamics in clinical practice. Full article

Background: The aim of this pilot study was to determine the potential prognostic relevance of novel multidirectional myocardial and volumetric echocardiographic parameters in patients with non-ischemic dilated cardiomyopathy (NIDCM). Methods: Multidirectional myocardial parameters (longitudinal, radial, and circumferential left-ventricular (LV) strain using speckle tracking echocardiography) and a new volumetric parameter (the sum of the mitral and tricuspid regurgitation volume (mitral–tricuspid regurgitation volume) were assessed. The cardiovascular (CV) outcome was a composite of cardiac death and hospitalization for heart failure (HF) at 1 year. Results: Approximately 102 patients were included in this pilot study. The mean LV ejection fraction (LVEF) was 28.4 ± 8.9%. During a follow-up of 1 year, the CV outcome occurred in 39 patients (10 HF deaths, and 36 hospitalizations for HF). The LV global longitudinal systolic strain (GLS) and mitral–tricuspid regurgitation volume were the main parameters that were seen to be significantly altered in the comparison of patients with events vs. those without events (GLS (absolute values) 7.4 ± 2.7% vs. 10.3 ± 2.6%; mitral–tricuspid regurgitation volume 61.1 ± 20.4 mL vs. 40.9 ± 22.9 mL, respectively; p-value < 0.01). In line with these findings, in a multivariate continuous logistic regression analysis, the GLS and mitral–tricuspid regurgitation volume were the main parameters associated with worse CV outcomes (GLS: OR 0.77 (95%CI 0.65–0.92); mitral–tricuspid regurgitation volume OR 1.09 (95%CI 1.01–1.25)), whereas the radial and circumferential LV global strain and mitral regurgitation volume and tricuspid regurgitation volume were not linked to the CV outcome. Furthermore, in a receiver operating characteristic curve analysis, a GLS cutoff of <7.5% and mitral–tricuspid regurgitation volume > 60 mL were the identified values for the parameters associated with worse CV outcomes. Conclusions: The findings of this pilot study suggest that the GLS and a novel volumetric parameter (the sum of the mitral and tricuspid regurgitation volume) are linked to worse CV outcomes in patients with non-ischemic dilated cardiomyopathy. Hence, these promising results warrant further validation in larger studies. Full article