J. Cardiovasc. Dev. Dis., Volume 10, Issue 7 (July 2023) – 49 articles

Cardiac fibrosis is a pathological condition characterized by excessive deposition of collagen and other extracellular matrix components in the heart. It is recognized as a major contributor to the development and progression of heart failure. Despite significant research efforts in characterizing and identifying key molecular mechanisms associated with myocardial fibrosis, effective treatment for this condition is still out of sight. In this regard, bioactive compounds have emerged as potential therapeutic antifibrotic agents due to their anti-inflammatory and antioxidant properties. These compounds exhibit the ability to modulate fibrogenic processes by inhibiting the production of extracellular matrix proteins involved in fibroblast to myofibroblast differentiation, or by promoting their breakdown. Extensive investigation of these bioactive compounds offers new possibilities for preventing or reducing cardiac fibrosis and its detrimental consequences. This comprehensive review aims to provide a thorough overview of the mechanisms underlying cardiac fibrosis, address the limitations of current treatment strategies, and specifically explore the potential of bioactive compounds as therapeutic interventions for the treatment and/or prevention of cardiac fibrosis. Full article

Background: Renal dysfunction and impaired organ perfusion are common concerns following cardiac surgery. Levosimendan, a calcium sensitizer inotropic drug, is investigated in this study for its potential to improve postoperative renal function and organ perfusion in patients with low preoperative ejection fraction and severe myocardial dysfunction after cardiac surgery. Methods: A retrospective analysis was conducted on 314 patients with preoperative heart failure who underwent cardiac surgery. Among them, 184 patients received perioperative adjunctive therapy with levosimendan, while 130 patients with similar characteristics received conventional treatment. Results: The perioperative administration of levosimendan resulted in a significantly lower need for renal replacement therapy (p < 0.001) and improvements in the serum creatinine levels, glomerular filtration rate, and creatinine clearance. Similarly, the C-reactive protein levels, blood pH, and lactic acid levels showed comparable improvements. Conclusions: The use of levosimendan was associated with a significant enhancement in postoperative renal function and a reduction in the need for renal replacement therapy. Furthermore, it resulted in a decrease in the extent of organ malperfusion. Postoperative inflammatory reactions and metabolic balance also exhibited improvements. Full article

Purpose: The benefits of sutureless compared to conventional aortic valve prosthesis replacement remain controversial. Supposed advantages of sutureless aortic valve replacement include shortened cross-clamp and implantation time, as well as improved overall safety and good post-operative performance. We aimed to compare the early outcomes and performance of sutureless aortic valve replacement (su-AVR) with the sutureless Perceval (Corcym, Milan, Italy) vs. the conventional AVR with a conventional counterpart, in this case, the Labcor Dokimos Plus (LDP) aortic bioprosthesis. Methods: We compared two types of aortic valve prostheses, the sutureless (Corcym, Milan, Italy) and the conventional valve Labcor Dokimos Plus (LDP), implanted between August 2014 and May 2019 in our Department of Cardiac Surgery at RWTH Aachen University Hospital. Data were collected from 141 patients who received the Perceval (Corcym, Milan, Italy) and 138 who received the Labcor Dokimos Plus (LDP) aortic bioprosthesis. After matching the two groups considering STS mortality risk and pre-operative LDH levels, 201 patients were included in our final study cohort. Seventy-one patients (17 from the Perceval group and 54 from the Dokimos group) were excluded due to the lack of complete data, particularly standardized echocardiographic data (n = 71). Primary endpoints were 30-day mortality, length of hospital stay, and pacemaker implantation. Secondary endpoints were echocardiographic parameters, major adverse cardiovascular events, and prosthesis failure (grade II aortic regurgitation, paravalvular leak with reintervention). Results: Bypass and cross-clamp time proved to be shorter in the Perceval group, while hospital stays were longer. The faster implantation had no effect on the 30-day mortality primary endpoint. Transvalvular gradients were significantly higher in the Perceval group, in addition to a smaller effective orifice area. The LDH values were remarkably higher post-operatively in the Perceval group. Conclusions: Regarding the clinical outcomes, Perceval was equivalent and not superior to the Dokimus bioprosthesis. The suitability of a Perceval prosthesis implantation must be determined on a case-by-case basis and reserved for elderly patients with increased comorbidity. Full article

(1) Background: Chronic inflammation and fibrosis are key players in cardiac remodeling associated with left ventricular hypertrophy (LVH) and heart failure with a preserved ejection fraction (HFpEF). Monocytes and T-helpers (Th) are involved in both pro-inflammatory and fibrotic processes, while regulatory T-cells (Treg) could be considered to suppress chronic inflammation in the hypertrophied myocardium. We aimed to estimate the relationship between the frequencies of circulating CD4⁺ T-cell and monocyte subpopulations and the variables of left ventricular (LV) diastolic function in patients with LVH depending on the presence of HFpEF. (2) Methods: We enrolled 57 patients with asymptomatic hypertensive LVH (n = 21), or LVH associated with HFpEF (n = 36). A clinical assessment and echocardiographs were analyzed. CD4⁺ Treg, activated Th (Th-act), and monocyte (classical, intermediate, and non-classical) subpopulations were evaluated via direct immunofluorescence and flow cytometry. (3) Results: Patients with HFpEF had a lower Treg/Th-act ratio (p = 0.001). Though asymptomatic patients and patients with HFpEF were comparable in terms of both the total monocyte number and monocyte subsets, there were moderate correlations between intermediate monocyte count and conventional and novel echocardiographic variables of LV diastolic dysfunction in patients with HFpEF. (4) Conclusions: In patients with LVH, the clinical deterioration (transition to HFpEF) and progression of LV diastolic dysfunction are probably associated with T-cell disbalance and an increase in intermediate monocyte counts. Full article

Background: Iron overload can accelerate the accumulation of lipid oxides and contribute to the progression of atherosclerosis. Ferritin heavy chain (FT-H) exhibits oxidase activity, which inhibits the toxicity of ferrous ions and reduces oxidative damage. We investigated the effect of the intraperitoneal injection of FT-H on the progression of atherosclerosis in APOE-knockout mice (Apo-E^(−/−) mice). Methods: All mice were fed on a high-fat diet. After 10 weeks, the mice were divided into an injection group (n = 4) and a control group (n = 4). The injection group was injected intraperitoneally with FT-H (50 mg/kg, once a week), and the control group was treated with PBS buffer (at an equal volume to the injection group, once a week). After 10 weeks of intervention, MRI of the aortas was performed. Then, the animals were sacrificed, and tissues were taken. Hematoxylin–eosin (HE) staining was used for histomorphometry, Masson staining was used to quantify the collagen content in the arteries, Prussian blue staining was used to visualize iron deposition in the arteries, and MRI was used to analyze the structure of the aorta in vivo. Immunohistochemistry was performed to detect the expression of MCP-1, MMP-2, MMP-9, FT-H, FT-L, TfR1, NRF-2 and GPX-4. Results: The serological results showed that the injection group had lower levels of glucose (Glu), triacylglycerol (TG), cholesterol (CHO), low-density lipoprotein-C (LDL-C) and malondialdehyde (MDA) (p = 0.0058, p = 0.0098, p = 0.0019, p = 0.0368 and p = 0.0025, respectively), and their serum ferritin (SF) and superoxide dismutase (SOD) levels were higher (p = 0.0004 and p < 0.0001). The Masson staining and MRI results showed that the injection group had less collagen deposition (p = 0.0226), a larger arterial lumen area and arterial volume (p = 0.0006 and p = 0.0005), thinner arterial wall thickness (p = 0.0013) and a more stable arterial plaque structure (p < 0.0001). The immunohistochemical results showed reduced expression of FT-H, FT-L, TfR1, MMP-2, MMP-9, MCP-1 and NRF-2 in the injection group (p = 0.0054, p = 0.0242, p = 0.0221, p = 0.0477, p = 0.0131, p = 0.0435 and p = 0.0179). Prussian blue staining showed that the area of iron-positive areas in the aortic plaques of the control group was larger than that of injected group. The expression of GPX-4 was lower in the control group than in the injection group (p = 0.016). Conclusions: The intraperitoneal administration of FT-H to Apo-E^(−/−) mice resulted in lower blood glucose and lipid levels; reduced iron and iron metabolism protein deposition in the aorta; reduced indices of their ferroptosis, oxidation and inflammatory aggregation; and reduced collagen deposition in the aorta, which delayed the process of aortic atherosclerosis in mice. Full article

In recent years, analysis of kinetic energy (KE) and the rate of kinetic energy dissipation (KED) or energy loss (EL) within the cardiac chambers, obtained by cardiac imaging techniques, has gained increasing attention. Thus, there is a need to clarify the effect of physiological variables, specifically aging, on these energetic measures. To elucidate this aspect, we reviewed the literature on this topic. Overall, cardiac magnetic resonance and echocardiographic studies published so far indicate that aging affects the energetics of left and right intraventricular blood flow, although not all energy measures during the cardiac cycle seem to be affected by age in the same way. Current studies, however, have limitations. Additional large, multicenter investigations are needed to test the effect of physiological variables on intraventricular KE and KED/EL measures. Full article

Methyltransferases regulate transcriptome dynamics during development and aging, as well as in disease. Various methyltransferases have been linked to heart disease, through disrupted expression and activity, and genetic variants associated with congenital heart disease. However, in vivo functional data for many of the methyltransferases in the context of the heart are limited. Here, we used the Drosophila model system to investigate different histone 3 lysine 36 (H3K36) methyltransferases for their role in heart development. The data show that Drosophila Ash1 is the functional homolog of human ASH1L in the heart. Both Ash1 and Set2 H3K36 methyltransferases are required for heart structure and function during development. Furthermore, Ash1-mediated H3K36 methylation (H3K36me2) is essential for healthy heart function, which depends on both Ash1-complex components, Caf1-55 and MRG15, together. These findings provide in vivo functional data for Ash1 and its complex, and Set2, in the context of H3K36 methylation in the heart, and support a role for their mammalian homologs, ASH1L with RBBP4 and MORF4L1, and SETD2, during heart development and disease. Full article

Up to 20% of patients with ischemic stroke or transient ischemic attack have a prior history of known atrial fibrillation (AF). Additionally, unknown AF can be detected by different monitoring strategies in up to 23% of patients with cryptogenic or non-cardioembolic stroke. However, most studies had substantial gaps in monitoring time, especially early after the index event. Following this, AF rates would be higher if patients underwent continuous monitoring early after stroke, avoiding any gaps in monitoring. The few existing randomized studies focused on patients with cryptogenic stroke but did not focus otherwise specifically on prevention strategies in patients at high risk for AF (patients at higher age or with high CHA2DS2-VASC scores). Besides invasive implantable loop recorders (ILRs), external loop recorders (ELRs) and mobile cardiac outpatient telemetry (MCOT) are non-invasive tools that are commonly used for long-term ECG monitoring in cryptogenic-stroke patients in the ambulatory setting. The role of MCOT and hand-held devices within ECG smart monitoring in the detection of AF for the prevention of and after cryptogenic stroke is currently unclear. This intense review provides an overview of current evidence, techniques, and gaps in knowledge and aims to advise which patients benefit most from the current available devices. Full article

Epigenetic marks regulate the transcriptomic landscape by facilitating the structural packing and unwinding of the genome, which is tightly folded inside the nucleus. Lysine-specific histone methylation is one such mark. It plays crucial roles during development, including in cell fate decisions, in tissue patterning, and in regulating cellular metabolic processes. It has also been associated with varying human developmental disorders. Heart disease has been linked to deregulated histone lysine methylation, and lysine-specific methyltransferases (KMTs) are overrepresented, i.e., more numerous than expected by chance, among the genes with variants associated with congenital heart disease. This review outlines the available evidence to support a role for individual KMTs in heart development and/or disease, including genetic associations in patients and supporting cell culture and animal model studies. It concludes with new advances in the field and new opportunities for treatment. Full article

The incidence of heart valve disease (HVD) has been rising over the last few decades, mainly due to the increasing average age of the general population, and mitral valve (MV) disease is the second most prevalent HVD after calcific aortic stenosis, but MV disease is a heterogeneous group of different pathophysiological diseases. It is widely proven that regular physical activity reduces all-cause mortality rates, and exercise prescription is part of the medical recommendations for patients affected by cardiovascular diseases. However, changes in hemodynamic balance during physical exercise (including the increase in heart rate, preload, or afterload) could favor the progression of the MV disease and potentially trigger major cardiac events. In young patients with HVD, it is therefore important to define criteria for allowing competitive sport or exercise prescription, balancing the positive effects as well as the potential risks. This review focuses on mitral valve disease pathophysiology, diagnosis, risk stratification, exercise prescription, and competitive sport participation selection, and offers an overview of the principal mitral valve diseases with the aim of encouraging physicians to embody exercise in their daily practice when appropriate. Full article

Cardiovascular disease morbidity/mortality are increasing due to an aging population and the rising prevalence of diabetes and obesity. Therefore, innovative cardioprotective measures are required to reduce cardiovascular disease morbidity/mortality. The role of necroptosis in myocardial ischemia–reperfusion injury (MI–RI) is beyond doubt, but the molecular mechanisms of necroptosis remain incompletely elucidated. Growing evidence suggests that MI–RI frequently results from the superposition of multiple pathways, with autophagy, ferroptosis, and CypD-mediated mitochondrial damage, and necroptosis all contributing to MI–RI. Receptor-interacting protein kinases (RIPK1 and RIPK3) as well as mixed lineage kinase domain-like pseudokinase (MLKL) activation is accompanied by the activation of other signaling pathways, such as Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), NF-κB, and JNK-Bnip3. These pathways participate in the pathological process of MI–RI. Recent studies have shown that inhibitors of necroptosis can reduce myocardial inflammation, infarct size, and restore cardiac function. In this review, we will summarize the molecular mechanisms of necroptosis, the links between necroptosis and other pathways, and current breakthroughs in pharmaceutical therapies for necroptosis. Full article

Background: New-onset postoperative atrial fibrillation (PoAF) is one of the most frequent yet serious complications following cardiac surgery. Long-term consequences have not been thoroughly investigated, and studies have included different cardiac operations. The objectives were to report the incidence and short- and long-term outcomes in patients with PoAF after mitral valve surgery. Methods: This is a retrospective cohort study of 1401 patients who underwent mitral valve surgery from 2009 to 2020. Patients were grouped according to the occurrence of PoAF (n = 236) and the nonoccurrence of PoAF (n = 1165). Long-term outcomes included mortality, heart failure rehospitalization, stroke, and mitral valve reinterventions. Results: The overall incidence of PoAF was 16.8%. PoAF was associated with higher rates of operative mortality (8.9% vs. 3.3%, p < 0.001), stroke (6.9% vs. 1.5%, p < 0.001), and dialysis (13.6% vs. 3.5%, p < 0.001). ICU and hospital stays were significantly longer in patients with PoAF (p < 0.001 for both). PoAF was significantly associated with an increased risk of mortality [HR: 1.613 (95% CI: 1.048–2.483); p = 0.03], heart failure rehospitalization [HR: 2.156 (95% CI: 1.276–3.642); p = 0.004], and stroke [HR: 2.722 (95% CI: 1.321–5.607); p = 0.007]. However, PoAF was not associated with increased mitral valve reinterventions [HR: 0.938 (95% CI: 0.422–2.087); p = 0.875]. Conclusions: Atrial fibrillation after mitral valve surgery is a common complication, with an increased risk of operative mortality. PoAF was associated with lower long-term survival, increased heart failure rehospitalization, and stroke risk. Future studies are needed to evaluate strategies that can be implemented to improve the outcomes of these patients. Full article

Liver fibrosis scores, indicative of hepatic scarring, have recently been linked to coronary artery disease (CAD). We investigated the association between CAD and the fibrosis-4 index (FIB-4I) in patients who underwent coronary computed tomography angiography (CCTA). This study included 1244 patients who were clinically suspected of having CAD. The presence or absence of CAD was the primary endpoint. FIB-4I was higher in the CAD group than in the non-CAD group (1.95 ± 1.21 versus [vs.] 1.65 ± 1.22, p < 0.001). FIB-4I was also higher in the hypertension (HTN) group than in the non-HTN group (1.90 ± 1.32 vs. 1.60 ± 0.98, p < 0.001). In all patients, high FIB-4I (≥2.67) was a predictor of presence of CAD (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.30–2.83, p = 0.001), and low FIB-4I (≤1.29) was proven to be a predictor of absence of CAD (OR: 0.65, 95% CI: 0.48–0.88, p = 0.006). In the HTN group, high and low FIB-4I levels, were found to be predictors for CAD (OR: 2.01, 95% CI: 1.26–3.21, p < 0.001 and OR: 0.65, 95% CI: 0.45–0.94, p < 0.022, respectively), in particular. FIB-4I may serve as a diagnostic indicator of the presence or absence of CAD in hypertensive patients undergoing CCTA. Full article

The relationship between poorer cardiovascular health metrics (CVHM) plus low-grade inflammation (LGI) and hypertension-mediated organ damage (HMOD) and hypertension-related comorbidities (HRC) in hypertensive populations with an overweight/obese (Ow/Ob) hypertension-related phenotype is understudied. We examined the relationship between the CVHM score and the presence of LGI and Ow/Ob hypertension-associated phenotype morbidities and mortality in 243 hypertensive patients from an urban primary care center. We recorded the baseline CVHM score plus clinical data, including hs-C-reactive protein (CRP) and prevalent and incident HMOD-HRC and death. A total of 26 (10.7%) had a body mass index (BMI) < 25 kg/m², 95 (31.1%) were overweight (BMI 25–29.9 kg/m²), and 122 (50.2%) were obese (BMI ≥ 30 kg/m²). There were 264 cases of HMOD-HRC and 9 deaths. Higher hs-CRP levels were observed as BMI increased. Linear regression analysis showed a significant correlation between BMI and hs-CRP, adjusted for confounders. Additionally, individuals with a higher hs-CRP tertile had a significant increase in BMI. Significantly lower log hs-CRP levels were found as the number of ideal CVHM scores rose. Multivariate binary logistic regression found the risk of HMOD-HRC increased significantly as the ideal CVHM scores decreased, and hs-CRP levels also correlated with HMOD-HRC in the whole cohort and in the Ow and Ob subpopulations. These findings highlight the need for early intervention targeting ideal CVHMs among hypertensive individuals with an Ow/Ob phenotype in order to attenuate the inflammatory state and prevent cardiovascular disease. Full article

Background—Radiotherapy (RT) for breast cancer (BC) can lead to an increased risk of coronary artery disease several years after RT. The aim of this study was to evaluate the development of overall, non-calcified and calcified atherosclerotic plaques over 2 years after BC for RT and associations with cardiac exposure. Methods—The study included 101 left- or right-sided BC patients treated with RT without chemotherapy. A coronary CT angiography was performed before and 2 years after RT. Plaque development thorough the entire coronary network was defined as an increased number of plaques. Cardiac exposure was quantified with mean doses to the heart, left ventricle, and coronary arteries. Logistic regression models were used to assess association with doses. Results—At inclusion, 37% of patients had plaques, increasing to 42% two years after RT. Overall plaque development was observed in seven patients: five with calcified plaque development and four with non-calcified plaque development. The risk of overall plaque development was significantly associated with doses to the Left Main and Circumflex coronary arteries (OR at 1 Gy = 2.32, p = 0.03 and OR at 1 Gy = 2.27, p = 0.03, respectively). Specific analyses for calcified and non-calcified plaque development showed similar results. Conclusion—Our study suggests an association between coronary arteries exposure and the risk of developing both calcified and non-calcified atherosclerotic plaques over 2 years after BC RT. Trial registration number: NCT02605512. Full article

The life course development of cardiovascular diseases (CVDs) and the undergoing epidemiological transition in Mozambique highlight the importance of monitoring the cardiovascular risk profile in young adults. Therefore, this study aims to estimate the prevalence of CVD risk factors in a population aged 18–25 years living in Mozambique. A total of 776 young adults from a nationally representative sample were evaluated in 2014/2015 following the World Health Organization’s STEPwise approach to chronic disease risk factor surveillance. Current smoking was the most prevalent among rural men (10.8%, 95%CI: 6.3–17.8), and drinking was most prevalent among urban men (38.6%, 95%CI: 29.3–48.8). The proportion of young adults not engaging in at least 75 min of vigorous physical activity per week ranged between 14.5% in rural men and 61.6% in urban women. The prevalence of being overweight/obese and hypertension were highest among urban women (21.6%, 95%CI: 14.7–30.6) and urban men (25.2%, 95%CI: 15.9–37.6), respectively. Education >8 years (vs. none) was independently associated with lower odds of being a current smoker, and increased monthly household income was associated with increased odds of low levels of physical activity. This study shows that important CVD risk factors are already common in the young adult population of Mozambique. Full article

Cardiac damage has been attributed to SARS-CoV-2-related pathology contributing to increased risk of vascular events. Heart rate variability (HRV) is a parameter of functional neurocardiac integrity with low HRV constituting an independent predictor of cardiovascular mortality. Whether structural cardiac damage translates into neurocardiac dysfunction in patients infected with SARS-CoV-2 remains poorly understood. Hypothesized mechanisms of possible neurocardiac dysfunction in COVID-19 comprise direct systemic neuroinvasion of autonomic control centers, ascending virus propagation along cranial nerves and cardiac autonomic neuropathy. While the relationship between the autonomic nervous system and the cytokine cascade in general has been studied extensively, the interplay between the inflammatory response caused by SARS-CoV-2 and autonomic cardiovascular regulation remains largely unclear. We reviewed the current literature on the potential diagnostic and prognostic value of autonomic neurocardiac function assessment via analysis of HRV including time domain and spectral analysis techniques in patients with COVID-19. Furthermore, we discuss potential therapeutic targets of modulating neurocardiac function in this high-risk population including HRV biofeedback and the impact of long COVID on HRV as well as the approaches of clinical management. These topics might be of particular interest with respect to multimodal pandemic preparedness concepts. Full article

The successful outcome of a cardiac surgery procedure is significantly dependent on the management of cardiopulmonary bypass (CPB). Even if a cardiac operation is technically well-conducted, a patient may suffer CPB-related complications that could result in severe comorbidities, reduced quality of life, or even death. However, the role of clinical perfusionists in perioperative patient care, which is critical, is often overlooked. Therefore, the European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Cardiothoracic Anaesthesiology (EACTA), and the European Board of Cardiovascular Perfusion (EBCP) have agreed to develop joint clinical practice guidelines (CPGs) for CPB due to its significant impact on patient care and significant variations in practice patterns between countries. The European guidelines, based on the EACTS standardized framework for the development of CPGs, cover the entire spectrum of CPB management in adult cardiac surgery. This includes training and education of clinical perfusionists, machine hardware, disposables, preparation for initiation of CPB, a complete set of procedures during CPB to help maintain end-organ function and anticoagulation, weaning from CPB, and the gaps in evidence and future research directions. This comprehensive coverage ensures that all aspects of CPB management are addressed, providing clinicians with a standardized approach to CPB management based on the latest evidence and best practices. To ensure better integration of these evidence-based recommendations into daily practice, this review aims to provide a general understanding of guideline development and an overview of essential treatment recommendations for CPB management. Full article

Utilization of high-quality clinical practice guidelines has the potential to positively impact health outcomes. This study aimed to assess the quality and content concordance of national and international recommendations on hypertensive disorders of pregnancy (HDPs). Searches were conducted of the MEDLINE database and reference lists generated from national and international agencies. Covidence software was used for the management of the systematic review process, the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool was used to assess guidelines for quality, and three reviewers independently screened records. The research team identified and screened a total of 399 records of which 10 were deemed high quality. Guidelines were assessed and compared regarding the treatment, prevention, and categorization of disorders. The quality of guidelines varied across different domains, with significant variation in domain scores even within individual guidelines. Not all recommendations showed a high level of methodologic rigor, and the highest-rated guidelines were from the American Heart Association, the World Health Organization, and South Africa national guidelines. Classification of hypertension differed among the guidelines, particularly in defining chronic hypertension, severe hypertension, and preeclampsia. Prevention modalities varied across guidelines, with recommendations for aspirin, calcium supplementation, and against the use of certain approaches. Treatment modalities highlighted the importance of delivery as the definitive way to terminate hypertensive disorders of pregnancy, with other management strategies provided for symptom control. The variability in guidelines and consensus statements across different contexts may reflect regional differences in healthcare practices, available resources, and research evidence. There is potential to harmonize guidelines for HDP globally while considering the unique needs of individual countries. Where guidelines may be synthesized and condensed into an accessible format, doing so could improve their use in clinical decision-making. Full article

Background: Left ventricular global longitudinal strain (LV GLS) is a superior predictor of adverse cardiac events in patients with myocardial infarction and heart failure. We investigated the ability of morphological features of infarcted myocardium to detect acute left ventricular (LV) dysfunction and predict LV functional recovery after three months in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: Sixty-six STEMI patients were included in the C-reactive protein (CRP) apheresis in Acute Myocardial Infarction Study (CAMI-1). LV ejection fraction (LVEF), LV GLS, LV global circumferential strain (LV GCS), infarct size (IS), area-at-risk (AAR), and myocardial salvage index (MSI) were assessed by CMR 5 ± 3 days (baseline) and 12 ± 2 weeks after (follow-up) the diagnosis of first acute STEMI. Results: Significant changes in myocardial injury parameters were identified after 12 weeks of STEMI diagnosis. IS decreased from 23.59 ± 11.69% at baseline to 18.29 ± 8.32% at follow-up (p < 0.001). AAR and MVO also significantly reduced after 12 weeks. At baseline, there were reasonably moderate correlations between IS and LVEF (r = −0.479, p < 0.001), LV GLS (r = 0.441, p < 0.001) and LV GCS (r = 0.396, p = 0.001) as well as between AAR and LVEF (r = −0.430, p = 0.003), LV GLS (r = 0.501, p < 0.001) and weak with LV GCS (r = 0.342, p = 0.020). At follow-up, only MSI and change in LV GCS over time showed a weak but significant correlation (r = −0.347, p = 0.021). Patients with larger AAR at baseline improved more in LVEF (p = 0.019) and LV GLS (p = 0.020) but not in LV GCS. Conclusion: The CMR tissue characteristics of myocardial injury correlate with the magnitude of LV dysfunction during the acute stage of STEMI. AAR predicts improvement in LVEF and LV GLS, while MSI is a sensitive marker of LV GCS recovery at three months follow-up after STEMI. Full article

Background: The incidence of delirium is high in older patients undergoing cardiovascular surgery with cardiopulmonary bypass (CPB). Intraoperative tissue hypoperfusion and re-reperfusion injury, which generate reactive oxygen species (ROS), are suggested to induce delirium. Ascorbic acid is an excellent antioxidant and may reduce organ damage by inhibiting the production of ROS. This prospective observational study aimed to measure pre- and postoperative plasma ascorbic acid levels and examine their association with delirium. Methods: Patients older than 70 years of age scheduled for elective cardiovascular surgery using CPB were enrolled. From September 2020 to December 2021, we enrolled 100 patients, and the data of 98 patients were analyzed. Results: In total, 31 patients developed delirium, while 67 did not. Preoperative plasma ascorbic acid levels did not differ between the non-delirium and delirium groups (6.0 ± 2.2 vs. 5.5 ± 2.4 µg/mL, p = 0.3). Postoperative plasma ascorbic acid levels were significantly different between the groups (2.8 [2.3–3.5] vs. 2.3 [1.6–3.3] µg/mL, p = 0.037). Conclusions: In patients who undergo cardiovascular surgery with CPB, lower postoperative plasma ascorbic acid levels may be associated with the development of delirium. Full article

(1) Background: Disparity in clinical care on the basis of gender, socioeconomic status, ethnic and racial variation is an established phenomenon. The focus on health disparities was led on by the report of the Secretary’s Task Force on Black & Minority Health, which emphasized that the burden of death and illness was in excess among black people and other minorities. In Saudi Arabia, cardiac health care is being provided to a heterogeneous group of patients during pilgrimage time. This mixed population comprises different socio-economic backgrounds, demographics, ethnicities and languages. This study was carried out to assess for any disparities in cardiac surgical outcomes after isolated CABG surgery between Saudi citizens and non-Saudi patients. (2) Methods: The data of 2178 patients who underwent isolated coronary artery bypass surgery at King Abdullah Medical City from December 2014 to July 2020 were extracted. Patient demographics, clinical features, comorbidities, diagnoses, surgical procedures, complications, length of hospital stay and mortality were included in the data. The primary outcome was mortality after coronary artery bypass grafting surgery. (3) Results: A total of 2178 isolated CABG procedures were conducted during the study period with almost 57.5% of patients being Saudi citizens in comparison with 42.5% of non-Saudi citizens. The male gender represented the majority of the population, with a total of 1584 patients, representing 72.7% of the total study population. The rate of mortality had no statistical significance with the mortality rate of 5% vs. 5.3% (p < 0.786). The postoperative morbidities were comparable for all the parameters except for postoperative extracorporeal membrane oxygenation (ECMO). (4) Conclusions: In the present study, the chances of survival and postoperative outcomes are not associated with nationality per se, but with underlying comorbidities. Full article

Background: Transthoracic impedance values have not been widely used to measure extravascular pulmonary water content due to accuracy and complexity concerns. Our aim was to develop a foundational model for a novel system aiming to non-invasively estimate the intrathoracic condition of heart failure patients. Methods: We employed multi-frequency bioelectrical impedance analysis to simultaneously measure multiple frequencies, collecting electrical, physical, and hematological data from 63 hospitalized heart failure patients and 82 healthy volunteers. Measurements were taken upon admission and after treatment, and longitudinal analysis was conducted. Results: Using a light gradient boosting machine, and a decision tree-based machine learning method, we developed an intrathoracic estimation model based on electrical measurements and clinical findings. Out of the 286 features collected, the model utilized 16 features. Notably, the developed model demonstrated high accuracy in discriminating patients with pleural effusion, achieving an area under the receiver characteristic curves (AUC) of 0.905 (95% CI: 0.870–0.940, p < 0.0001) in the cross-validation test. The accuracy significantly outperformed the conventional frequency-based method with an AUC of 0.740 (95% CI: 0.688–0.792, and p < 0.0001). Conclusions: Our findings indicate the potential of machine learning and transthoracic impedance measurements for estimating pleural effusion. By incorporating noninvasive and easily obtainable clinical and laboratory findings, this approach offers an effective means of assessing intrathoracic conditions. Full article

The aim of cardiopulmonary bypass is the maintenance of a sufficient whole body perfusion and gas exchange during open or closed heart surgery procedure (coronary artery bypass grafting, valve repair and replacement, surgical intervention on the ascending aorta and/or aortic arch, repair of congenital malformations, and finally implantation of ventricular assist devices or cardiac transplantation). The main components of cardiopulmonary bypass are the pump that supplies the circulation and the oxygenator that regulates gas exchange. However, even though this technology has been extensively developed and improved over the last decades, one of the major drawbacks—which is the fact that blood has to flow through tubing systems with foreign surfaces—persists so far. Nevertheless, interesting innovations have been made more recently in order to better control the side-effects that culminate into a major activation of the coagulation and inflammatory systems: among them, miniaturization of the circuits, together with reduction of the priming volume and a simplified cardioplegia concept. All of these lead to a significant decrease of hemodilution and thereby a significant reduction of volume overload during surgery. In this brief review we will present some of these most interesting topics around minimized circuits and the simplified low-volume cardioplegia and discuss their potential benefits on the clinical outcome. Full article

Fontan patients undergo multiple cardiothoracic surgeries in childhood. Following these procedures, ventricular function is temporarily decreased, and recovers over months. This is presumably related to cardiopulmonary bypass, but this is incompletely understood. Throughout the Fontan palliation, cardiac function is also affected by volume unloading. We aimed to gain insight into the biological processes related to impaired ventricular function and recovery following Fontan palliations using a panel of biomarkers. Furthermore, we described changes in ventricular function across the Fontan palliation due to volume unloading. We performed a prospective multicenter observational study in patients undergoing partial (PCPC) or total cavo-pulmonary connection (TCPC). Patients underwent assessment—including echocardiography and blood sampling—before surgery (T1), at first follow-up (T2), and 1 year after their procedures (T3). Blood samples were analyzed using a biomarker panel (OLINK CVD-III). Ninety-two biomarkers were expressed as principal components (PC) to limit multiple statistical testing. We included 32 PCPC patients aged 7.2 [5.3–10.3] months, and 28 TCPC patients aged 2.7 [2.2–3.8] years. The single ventricular longitudinal strain (SV GLS) temporarily decreased for PCPC patients at T2 (−15.1 ± 5.6 (T1) to −13.5 ± 5.2 (T2) to −17.3 ± 4.5 (T3), p < 0.047 for all differences), but not following TCPC. The serum biomarkers were expressed as 4 PCs. PC1, including biomarkers of cell–cell adhesion, was not related to any patient characteristic. PC2, including biomarkers of superoxide anion regulation, increased at T2. PC3, including biomarkers of cardiovascular development, related to the stage of Fontan palliation. PC4 was of uncertain biological or clinical significance. No PC was found that related to ventricular performance. The SV GLS was temporarily diminished following PCPC, but not following TCPC. Several biomarkers were related to post-operative stress and adaptation to the PCPC or TCPC circulation, but none were related to the outcome. Full article

While investigating the outcomes of balloon dilatation procedures in patients with congenital obstructive lesions of the heart, several parallel observations were made. The purpose of this review is to present these observations/phenomena/innovations related to balloon dilatation of pulmonary stenosis (PS), aortic stenosis (AS), and aortic coarctation (AC). In subjects who had balloon pulmonary valvuloplasty (BPV), development of infundibular obstruction, electrocardiographic (ECG) changes, changes in right ventricular filling, role of balloon/annulus ratios on the results of BPV, and double balloon vs. single balloon BPV will be reviewed. In patients who had balloon aortic valvuloplasty (BAV), causes of aortic insufficiency and trans-umbilical venous approach for BAV are tackled. In children who had balloon angioplasty (BA) of AC, aortic remodeling and biophysical response after BA of AC are discussed. Full article

In dilated cardiomyopathy (DCM), where the heart muscle becomes stretched and thin, heart failure (HF) occurs, and the cardiomyocytes suffer from an energetic inefficiency caused by an abnormal cardiac metabolism. Although underappreciated as a potential therapeutic target, the optimal metabolic milieu of a failing heart is still largely unknown and subject to debate. Because glucose naturally has a lower P/O ratio (the ATP yield per oxygen atom), the previous studies using this strategy to increase glucose oxidation have produced some intriguing findings. In reality, the vast majority of small-scale pilot trials using trimetazidine, ranolazine, perhexiline, and etomoxir have demonstrated enhanced left ventricular (LV) function and, in some circumstances, myocardial energetics in chronic ischemic and non-ischemic HF with a reduced ejection fraction (EF). However, for unidentified reasons, none of these drugs has ever been tested in a clinical trial of sufficient size. Other pilot studies came to the conclusion that because the heart in severe dilated cardiomyopathy appears to be metabolically flexible and not limited by oxygen, the current rationale for increasing glucose oxidation as a therapeutic target is contradicted and increasing fatty acid oxidation is supported. As a result, treating metabolic dysfunction in HF may benefit from raising ketone body levels. Interestingly, treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) improves cardiac function and outcomes in HF patients with or without type 2 diabetes mellitus (T2DM) through a variety of pleiotropic effects, such as elevated ketone body levels. The improvement in overall cardiac function seen in patients receiving SGLT2i could be explained by this increase, which appears to be a reflection of an adaptive process that optimizes cardiac energy metabolism. This review aims to identify the best metabolic therapeutic approach for DCM patients, to examine the drugs that directly affect cardiac metabolism, and to outline all the potential ancillary metabolic effects of the guideline-directed medical therapy. In addition, a special focus is placed on SGLT2i, which were first studied and prescribed to diabetic patients before being successfully incorporated into the pharmacological arsenal for HF patients. Full article

Background: Although physical activity (PA) has been shown to enhance hypertension control, the impact of exercise on the potential decrease of the use of antihypertensive medications remains inadequately researched. Aim: The aim was to assess the impact of a two-year PA on the medication requirements of individuals with hypertension. Methods: A clinical trial was conducted, involving 130 participants with essential hypertension who took at least one antihypertensive medication. Participants were randomly assigned to either a control group (CG n = 65) or an experimental group (EG n = 65) that underwent a 24-month supervised PA program based on a combination of aerobic and resistance training. The antihypertensive drug load for each participant was determined by adding the ratios of the prescribed daily dose (PDD) to the defined daily dose (DDD) for all antihypertensive medications taken by the participants. The outcome measures were evaluated at 0, 6, 12, 18, and 24 months. Results: A total of 76 participants completed the 24-month assessment, and RM-ANOVA revealed a significantly lower antihypertensive drug load in the EG compared to the CG at 18 (p < 0.017) and 24 months (p < 0.003). Conclusion: A long-term PA program can decrease the antihypertensive drug load in older adults with essential hypertension. The trend of improvement regarding the EG drug load intake and the trend of CG drug load increase, although not significant over time, results in a significant difference between the groups at 18 months and an even greater difference at 24 months. This trend certifies the protective value of PA against the aging process and its related health risk factors. Full article