J. Cardiovasc. Dev. Dis., Volume 10, Issue 3 (March 2023) – 42 articles

(1) Background: Severe left ventricular (LV) diastolic dysfunction with a restrictive diastolic pattern (LVDFP) is generally associated with a worse prognosis. Its evolution and reversibility in the short- and medium-term after aortic valve replacement (AVR) has been little-studied. We aimed to evaluate the evolution of LV remodeling and LV systolic and diastolic function after AVR in aortic stenosis (AS) patients compared to aortic regurgitation (AR). Moreover, we tried to identify the main predictive parameters for postoperative evolution (cardiovascular hospitalization or death and quality of life) and the independent predictors for the persistence of restrictive LVDFP after AVR. (2) Methods: A five-year prospective study on 397 patients undergoing AVR for AS (226 pts) or AR (171 pts), evaluated clinically and by echocardiography preoperatively and until 5 years postoperatively. (3) Results: 1. In patients with AS, early post AVR, LV dimensions decreased and diastolic filling and LV ejection fraction (LVEF) improved more rapidly compared to patients with AR. At 1 year postoperatively, persistent restrictive LVDFP was found especially in the AR group compared to the AS group (36.84% vs. 14.16%). 2. Cardiovascular event-free survival at the 5-year follow-up was lower in the AR group (64.91% vs. 87.17% in the AS group). The main independent predictors of short- and medium-term prognosis after AVR were: restrictive LVDFP, severe LV systolic dysfunction, severe pulmonary hypertension (PHT), advanced age, severe AR, and comorbidities. 3. The persistence of restrictive LVDFP after AVR was independently predicted by: preoperative AR, the E/Ea ratio > 12, the LA dimension index > 30 mm/m², an LV endsystolic diameter (LVESD) > 55 mm, severe PHT, and associated second-degree MR (p < 0.05). (4) Conclusions: AS patients had an immediate postoperative evolution in terms of LV remodeling, and LV systolic and diastolic function were more favorable compared to those with AR. The restrictive LVDFP was reversible, especially after the AVR for AS. The main prognostic predictors were the presence of restrictive LVDFP, advanced age, preoperative AR, severe LV systolic dysfunction, and severe PHT. Full article

Diagnosis of coronary artery disease is mainly based on invasive imaging modalities such as X-ray angiography, intravascular ultrasound (IVUS) and optical coherence tomography (OCT). Computed tomography coronary angiography (CTCA) is also used as a non-invasive imaging alternative. In this work, we present a novel and unique tool for 3D coronary artery reconstruction and plaque characterization using the abovementioned imaging modalities or their combination. In particular, image processing and deep learning algorithms were employed and validated for the lumen and adventitia borders and plaque characterization at the IVUS and OCT frames. Strut detection is also achieved from the OCT images. Quantitative analysis of the X-ray angiography enables the 3D reconstruction of the lumen geometry and arterial centerline extraction. The fusion of the generated centerline with the results of the OCT or IVUS analysis enables hybrid coronary artery 3D reconstruction, including the plaques and the stent geometry. CTCA image processing using a 3D level set approach allows the reconstruction of the coronary arterial tree, the calcified and non-calcified plaques as well as the detection of the stent location. The modules of the tool were evaluated for efficiency with over 90% agreement of the 3D models with the manual annotations, while a usability assessment using external evaluators demonstrated high usability resulting in a mean System Usability Scale (SUS) score equal to 0.89, classifying the tool as “excellent”. Full article

Baffle leaks are a frequently encountered and often overlooked complication after the atrial switch procedure for transposition of the great arteries. Baffle leaks are present in up to 50% of non-selected patients, and while they initially may not cause clear symptoms, they can complicate the hemodynamic course and influence the prognosis in this complex patient group. A shunt from the pulmonary venous atrium (PVA) to the systemic venous atrium (SVA) can lead to pulmonary overflow and subpulmonary left ventricular (LV) volume overload, while a shunt from the SVA to the PVA can result in (exercise-associated) cyanosis and paradoxical embolism. We report three cases of baffle leaks in patients with systemic right ventricular (sRV) failure late after the atrial switch procedure. Two symptomatic patients who presented with exercise-associated cyanosis due to SVA to PVA shunting over the baffle leak underwent successful percutaneous baffle leak closure with a septal occluder device. One patient with overt sRV failure and signs of subpulmonary LV volume overload due to PVA to SVA shunting was managed conservatively, as baffle leak closure was expected to lead to an increase in sRV end-diastolic pressure and aggravation of sRV dysfunction. These three cases illustrate the considerations made, challenges faced, and necessity of a patient-tailored approach when addressing baffle leaks. Full article

Arterial stiffness is a recognized predictor of cardiovascular morbidity and death. It is an early indicator of arteriosclerosis and is influenced by numerous risk factors and biological processes. The lipid metabolism is crucial and standard blood lipids, non-conventional lipid markers and lipid ratios are associated with arterial stiffness. The objective of this review was to determine which lipid metabolism marker has a greater correlation with vascular aging and arterial stiffness. Triglycerides (TG) are the standard blood lipids that have the strongest associations with arterial stiffness, and are often linked to the early stages of cardiovascular diseases, particularly in patients with low LDL-C levels. Studies often show that lipid ratios perform better overall than any of the individual variables used alone. The relation between arterial stiffness and TG/HDL-C has the strongest evidence. It is the lipid profile of atherogenic dyslipidemia that is found in several chronic cardio-metabolic disorders, and is considered one of the main causes of lipid-dependent residual risk, regardless of LDL-C concentration. Recently, the use of alternative lipid parameters has also been increasing. Both non-HDL and ApoB are very well correlated with arterial stiffness. Remnant cholesterol is also a promising alternative lipid parameter. The findings of this review suggest that the main focus should be on blood lipids and arterial stiffness, especially in individuals with cardio-metabolic disorders and residual cardiovascular risk. Full article

Background: Through its helical centreline geometry, the BioMimics 3D vascular stent system is designed for the mobile femoropopliteal region, aiming to improve long-term patency and the risk of stent fractures. Methods: MIMICS 3D is a prospective, European, multi-centre, observational registry to evaluate the BioMimics 3D stent in a real-world population through 3 years. A propensity-matched comparison was performed to investigate the effect of the additional use of drug-coated balloons (DCB). Results: The MIMICS 3D registry enrolled 507 patients (518 lesion, length 125.9 ± 91.0 mm). At 3 years, the overall survival was 85.2%, freedom from major amputation 98.5%, freedom from clinically driven target lesion revascularisation 78.0%, and primary patency 70.2%. The propensity-matched cohort included 195 patients in each cohort. At 3-year follow-up, there was no statistically significant difference in clinical outcomes, such as overall survival (87.9% in the DCB vs. 85.1% in the no DCB group), freedom from major amputation (99.4% vs. 97.2%), clinically driven TLR (76.4% vs. 80.3%), and primary patency (68.5% vs. 74.4%). Conclusion: The MIMICS 3D registry showed good 3-year outcomes of the BioMimics 3D stent in femoropopliteal lesions, demonstrating the safety and performance of this device under real-world conditions, whether used alone or in combination with a DCB. Full article

Acutely decompensated chronic heart failure (adCHF) is among the most important causes of in-hospital mortality. R-wave peak time (R_pT) or delayed intrinsicoid deflection was proposed as a risk marker of sudden cardiac death and heart failure decompensation. Authors want to verify if QR interval or R_pT, obtained from 12-lead standard ECG and during 5-min ECG recordings (II lead), could be useful to identify adCHF. At hospital admission, patients underwent 5-min ECG recordings, obtaining mean and standard deviation (_SD) of the following ECG intervals: QR, QRS, QT, JT, and T peak–T end (Te). The R_pT from a standard ECG was calculated. Patients were grouped by the age-stratified Januzzi NT-proBNP cut-off. A total of 140 patients with suspected adCHF were enrolled: 87 (mean age 83 ± 10, M/F 38/49) with and 53 (mean age: 83 ± 9, M/F: 23/30) without adCHF. V_5-, V_6- (p < 0.05) R_pT, and QR_SD, QRS_SD, QT_SD, JT_SD, and Te_SDp < 0.001 were significantly higher in the adCHF group. Multivariable logistic regression analysis demonstrated that the mean of QT (p < 0.05) and Te (p < 0.05) were the most reliable markers of in-hospital mortality. V₆ R_pT was directly related to NT-proBNP (r: 0.26, p < 0.001) and inversely related to a left ventricular ejection fraction (r: 0.38, p < 0.001). The intrinsicoid deflection time (obtained from V_5-6 and QR_SD) could be used as a possible marker of adCHF. Full article

Objectives. The current guidelines still do not include specific recommendations on the use of subvalvular repair (SV-r) for treatment of ischemic mitral regurgitation (IMR). Therefore, the objective of our study was to evaluate the clinical impact of mitral regurgitation (MR) recurrence and ventricular remodeling on long-term outcomes after SV-r combined with restrictive annuloplasty (RA-r). Methods. We performed a subanalysis of the papillary muscle approximation trial, studying 96 patients with severe IMR and coronary artery disease undergoing restrictive annuloplasty alongside subvalvular repair (SV-r + RA-r group) or restrictive annuloplasty alone (RA-r group). We analyzed treatment failure differences, the influence of residual MR, left ventricular remodeling, and clinical outcomes. The primary endpoint was treatment failure (composite of death; reoperation; or recurrence of moderate, moderate-to-severe, or severe MR) within 5 years of follow-up after the procedure. Results. A total of 45 patients showed failure of the treatment within 5 years, of which 16 patients underwent SV-r + RA-r (35.6%) and 29 underwent RA-r (64.4%, p = 0.006). Patients with significant residual MR presented with a higher rate of all-cause mortality at 5 years compared with trivial MR (HR 9.09, 95% CI 2.08–33.33, p = 0.003). MR progression occurred earlier in the RA-r group, as 20 patients in the RA-r group vs. 6 in SV-r + RA-r group had a significant MR 2 years after surgery (p = 0.002). Conclusions. RA-r remains a surgical mitral repair technique with an increased risk of failure and mortality at 5 years compared with SV-r. The rates of recurrent MR are higher, and recurrence occurs earlier, with RA-r alone compared to SV-r. The addition of the subvalvular repair increases the durability of the repair, thus extending all of the benefits of preventing MR recurrence. Full article

Myocardial infarction is the most prevalent cardiovascular disease worldwide, and it is defined as cardiomyocyte cell death due to a lack of oxygen supply. Such a temporary absence of oxygen supply, or ischemia, leads to extensive cardiomyocyte cell death in the affected myocardium. Notably, reactive oxygen species are generated during the reperfusion process, driving a novel wave of cell death. Consequently, the inflammatory process starts, followed by fibrotic scar formation. Limiting inflammation and resolving the fibrotic scar are essential biological processes with respect to providing a favorable environment for cardiac regeneration that is only achieved in a limited number of species. Distinct inductive signals and transcriptional regulatory factors are key components that modulate cardiac injury and regeneration. Over the last decade, the impact of non-coding RNAs has begun to be addressed in many cellular and pathological processes including myocardial infarction and regeneration. Herein, we provide a state-of-the-art review of the current functional role of diverse non-coding RNAs, particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in different biological processes involved in cardiac injury as well as in distinct experimental models of cardiac regeneration. Full article

Background: Homocysteine (Hcy) is involved in various methylation processes, and its plasma level is increased in cardiac ischemia. Thus, we hypothesized that levels of homocysteine correlate with the morphological and functional remodeling of ischemic hearts. Thus, we aimed to measure the Hcy levels in the plasma and pericardial fluid (PF) and correlate them with morphological and functional changes in the ischemic hearts of humans. Methods: Concentration of total homocysteine (tHcy) and cardiac troponin-I (cTn-I) of plasma and PF were measured in patients undergoing coronary artery bypass graft (CABG) surgery (n = 14). Left-ventricular (LV) end-diastolic diameter (LVED), LV end-systolic diameter (LVES), right atrial, left atrial (LA) area, thickness of interventricular septum (IVS) and posterior wall, LV ejection fraction (LVEF), and right ventricular outflow tract end-diastolic area (RVOT EDA) of CABG and non-cardiac patients (NCP; n = 10) were determined by echocardiography, and LV mass was calculated (cLVM). Results: Positive correlations were found between Hcy levels of plasma and PF, tHcy levels and LVED, LVES and LA, and an inverse correlation was found between tHcy levels and LVEF. cLVM, IVS, and RVOT EDA were higher in CABG with elevated tHcy (>12 µM/L) compared to NCP. In addition, we found a higher cTn-I level in the PF compared to the plasma of CABG patients (0.08 ± 0.02 vs. 0.01 ± 0.003 ng/mL, p < 0.001), which was ~10 fold higher than the normal level. Conclusions: We propose that homocysteine is an important cardiac biomarker and may have an important role in the development of cardiac remodeling and dysfunction in chronic myocardial ischemia in humans. Full article

Objective: We aimed to study the long-term association of LV mass index (LV_MI) and myocardial fibrosis with ventricular arrhythmia (VA) in a population of patients with confirmed hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance imaging (CMR). Methods: We retrospectively analyzed the data in consecutive HCM patients confirmed on CMR referred to an HCM clinic between January 2008 and October 2018. Patients were followed up yearly following diagnosis. Baseline demographics, risk factors and clinical outcomes from cardiac monitoring and an implanted cardioverter defibrillator (ICD) were analyzed for association of LV_MI and LV late gadolinium enhancement (LV_LGE) with VA. Patients were then allocated to one of two groups according to the presence of VA (Group A) or absence of VA (Group B) during the follow-up period. The transthoracic echocardiogram (TTE) and CMR parameters were compared between the two groups. Results: A total of 247 patients with confirmed HCM (age 56.2 ± 16.6, male = 71%) were studied over the follow-up period of 7 ± 3.3 years (95% CI = 6.6–7.4 years). LV_MI derived from CMR was higher in Group A (91.1 ± 28.1 g/m² vs. 78.8 ± 28.3 g/m², p = 0.003) when compared to Group B. LV_LGE was higher in Group A (7.3 ± 6.3% vs. 4.7 ± 4.3%, p = 0.001) when compared to Group B. Multivariable Cox regression analysis showed LV_MI (hazard ratio (HR) = 1.02, 95% CI = 1.001–1.03, p = 0.03) and LV_LGE (HR = 1.04, 95% CI = 1.001–1.08, p = 0.04) to be independent predictors for VA. Receiver operative curves showed higher LV_MI and LV_LGE with a cut-off of 85 g/m² and 6%, respectively, to be associated with VA. Conclusions: LV_MI and LV_LGE are strongly associated with VA over long-term follow-up. LV_MI requires more thorough studies to consider it as a risk stratification tool in patients with HCM. Full article

Background: We evaluated the outcome of PCI of de novo stenosis with drug-coated balloons (DCB) versus drug-eluting stents (DES) in patients with insulin-treated diabetes mellitus (ITDM) versus non-insulin-treated diabetes mellitus (NITDM). Methods: Patients were randomized in the BASKET-SMALL 2 trial to DCB or DES and followed over 3 years for MACE (cardiac death, non-fatal myocardial infarction [MI], and target vessel revascularization [TVR]). Outcome in the diabetic subgroup (n = 252) was analyzed with respect to ITDM or NITDM. Results: In NITDM patients (n = 157), rates of MACE (16.7% vs. 21.9%, hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.29–1.58, p = 0.37), death, non-fatal MI, and TVR (8.4% vs. 14.5%, HR 0.30, 95% CI 0.09–1.03, p = 0.057) were similar between DCB and DES. In ITDM patients (n = 95), rates of MACE (DCB 23.4% vs. DES 22.7%, HR 1.12, 95% CI 0.46–2.74, p = 0.81), death, non-fatal MI, and TVR (10.1% vs. 15.7%, HR 0.64, 95% CI 0.18–2.27, p = 0.49) were similar between DCB and DES. TVR was significantly lower with DCB versus DES in all diabetic patients (HR 0.41, 95% CI 0.18–0.95, p = 0.038). Conclusions: DCB compared to DES for treatment of de novo coronary lesions in diabetic patients was associated with similar rates of MACE and numerically lower need for TVR both for ITDM and NITDM patients. Full article

Tricuspid valve diseases are a heterogeneous group of pathologies that typically have poor prognoses when treated medically and are associated with significant morbidity and mortality with traditional surgical techniques. Minimal access tricuspid valve surgery may mitigate some of the surgical risks associated with the standard sternotomy approach by limiting pain, reducing blood loss, lowering the risk of wound infections, and shortening hospital stays. In certain patient populations, this may allow for a prompt intervention that could limit the pathologic effects of these diseases. Herein, we review the literature on minimal access tricuspid valve surgery focusing on perioperative planning, technique, and outcomes of minimal access endoscopic and robotic surgery for isolated tricuspid valve disease. Full article

Despite recent progress with revascularisation interventions after acute ischemic stroke, many patients remain disabled after stroke. Using data from a multi-centre, randomised, double-blind, placebo-controlled trial of a neuro-repair treatment (NeuroAiD/MLC601) with a long-term follow-up, we analysed the savings in time to functional recovery, measured by a modified Rankin Scale (mRS) score of 0 or 1, in patients receiving a 3-month oral course of MLC601. Analysis of time to recovery was assessed by a log-rank test and hazard ratios (HRs) adjusted for prognosis factors. A total of 548 patients with baseline NIHSS scores 8–14, mRS scores ≥ 2 at day 10 post-stroke, and at least one mRS assessment on or after month 1 were included in the analysis (placebo = 261; MLC601 = 287). Time to functional recovery was significantly shortened for patients receiving MLC601 versus patients receiving placebo (log-rank test: p = 0.039). This result was confirmed by Cox regression adjusting for the main baseline prognostic factors (HR: 1.30 [0.99, 1.70]; p = 0.059) and was more pronounced in patients with additional poor prognosis factors. The Kaplan–Meier plot showed that approximately 40% cumulative incidence of functional recovery was achieved within 6 months after stroke onset in the MLC601 group versus 24 months in the placebo group. The main findings are that MLC601 reduced the time to achieve functional recovery, and a 40% functional recovery rate was achieved 18 months earlier compared to placebo. Full article

(1) Background: Iron deficiency (ID) is an important adverse prognostic marker in patients with heart failure (HF); however, it is unclear whether intravenous iron replacement reduces cardiovascular mortality in this patient group. Here, we estimate the effect of intravenous iron replacement therapy on hard clinical outcomes following the publication of IRONMAN, the largest trial in this field. (2) Methods: In this systematic review and meta-analysis, prospectively registered with PROSPERO and reported according to PRISMA guidelines, we searched PubMed and Embase for randomized controlled trials investigating intravenous iron replacement in patients with HF and co-existing ID. The primary outcome was cardiovascular mortality and secondary outcomes were all-cause mortality, hospitalizations for HF and a combination of the primary outcome and hospitalizations for HF. (3) Results: A total of 1671 items were identified and after removal of duplicates we screened titles and abstracts of 1202 records. Some 31 studies were identified for full-text review and 12 studies were included in the final review. The odds ratio (OR) for cardiovascular death using a random effects model was 0.85 (95% CI 0.69 to 1.04) and for all-cause mortality it was 0.83 (95% CI 0.59 to 1.15). There was a significant reduction in hospitalizations for HF (OR 0.49, 95% CI 0.35 to 0.69) and the combination of hospitalizations for HF and cardiovascular death (OR 0.65, 95% CI 0.5 to 0.85). (4) Conclusions: This review supports the use of IV iron replacement reducing hospitalization rates for HF, however more research is required to determine the effect on cardiovascular mortality and to identify the patient population most likely to benefit. Full article

Background: To compare the characteristics of a “real world” population included in a prospective registry to patients enrolled in a randomized, controlled trial (RCT) after endovascular revascularization (EVR) for symptomatic peripheral artery disease (PAD). Methods: The RECcording COurses of vasculaR Diseases (RECCORD) registry is an observational registry prospectively recruiting patients undergoing EVR for symptomatic PAD in Germany. VOYAGER PAD was an RCT which demonstrated the superiority of rivaroxaban and aspirin versus aspirin to reduce major cardiac and ischemic limb events following infrainguinal revascularization for symptomatic PAD. For this exploratory analysis, the clinical characteristics of 2.498 patients enrolled in RECCORD and of 4.293 patients from VOYAGER PAD who underwent EVR were compared. Results: The rate of patients aged ≥ 75 years was considerably higher in the registry (37.7 vs. 22.5%). More patients in the registry had undergone previous EVR (50.7 vs. 38.7%) or suffered from critical limb threatening ischemia (24.3 vs. 19.5%). Registry patients were more commonly active smokers (51.8 vs. 33.6%), but less frequently suffered from diabetes mellitus (36.4 vs. 44.7%). While statins (70.5 vs. 81.7%) were less frequently used, antiproliferative catheter technologies (45.6 vs. 31.4%) and postinterventional dual antiplatelet therapy (64.5 vs. 53.6%) were more commonly applied in the registry. Conclusions: There were many similarities but some clinically meaningful differences in clinical characteristics between PAD patients who underwent EVR and were included in a nationwide registry and PAD patients from the VOYAGER PAD trial. Full article

Heart failure (HF) is a complex clinical syndrome involving structural and/or functional abnormalities of the heart. Heart failure is often classified based on left ventricular ejection fraction, which serves as a predictor of mortality. The majority of the data supporting disease-modifying pharmacological therapies are from patients with reduced ejection fraction (less than 40%). However, with the recent results from the sodium glucose cotransporter-2 inhibitor trials, there is renewed interest in identifying potential beneficial pharmacological therapies. This review focuses on and includes pharmacological HF therapies across the spectrum of ejection fraction, providing an overview of the novel trials. We also examined the effects of the treatments on mortality, hospitalization, functional status, and biomarker levels to further investigate the interplay between ejection fraction and HF. Full article

Background: Although there are studies on blood pressure (BP) and autonomic cardiac control (ACC) impairments caused by ergogenic aids, research has scarcely addressed this analysis during sleep. This study analyzed BP and ACC during sleep and wake periods in three groups of resistance training (RT) practitioners: ergogenic aid non-users, thermogenic supplement (TS) self-users, and anabolic-androgenic steroid (AAS) self-users. Methods: RT practitioners were selected for the Control Group (CG; n = 15), TS self-users Group (TSG; n = 15), and AAS self-users Group (AASG; n = 15). All individuals underwent cardiovascular Holter monitoring (BP, ACC) during sleep and wake periods. Results: The maximum systolic BP (SBP) during sleep was higher in AASG (p < 0.01) than CG (p < 0.001). CG had lower mean diastolic BP (DBP) than TSG (p < 0.01) and lower mean SBP (p = 0.009) than the other groups. Additionally, CG had higher values (p < 0.01) than TSG and AASG for SDNN and pNN50 during sleep. HF, LF, and LF/HF ratio values during sleep were statistically different in CG (p < 0.001) from the other groups. Conclusions: Our findings demonstrate that high doses of TS and AAS can impair cardiovascular parameters during sleep in RT practitioners who take ergogenic aids. Full article

Background—Coronary endarterectomy (CEA) has been introduced to allow revascularization in end-stage coronary artery disease (CAD). After CEA, the injured remnants of the vessel’s media could result in fast neo intimal tissue ingrowth, which require an anti-proliferation agent (antiplatelet therapy (APT). We aimed to review outcomes of patients undergoing CEA within bypass surgery who received either single-APT (SAPT) or dual-APT (DAPT). Methods—We retrospectively evaluated 353 consecutive patients undergoing CEA within isolated coronary artery bypass grafting (CABG) in the period 01/2000–07/2019. After surgery, patients received either SAPT (n = 153), or DAPT (n = 200) for six months then lifelong SAPT. Endpoints included early, late survival, and freedom from major-adverse-cardiac and cerebrovascular events (MACCE), which were defined as incidence of stroke, myocardial infarction, need for coronary intervention (PCI or CABG) or death for any cause. Results—Patients’ mean age was 67 ± 9.3 years; they were predominantly male 88.1%. Both DAPT- and SAPT-groups had the same extent of CAD (mean SYNTAX-Score-II: 34.1 ± 11.6 vs. 34.4 ± 17.2, p = 0.91). Postoperatively, no difference between DAPT- and SAPT-groups was reported in the incidence of low-cardiac-output syndrome (5% vs. 9.8%, p = 0.16), revision for bleeding (5% vs. 6.5% p = 0.64), 30-day mortality (4.5% vs. 5.2%, p = 0.8) or MACCE (7.5% vs. 11.8%, p = 0.19). Imaging follow-up reported significantly higher CEA and total grafts patency (90% vs. 81.5% and 95% vs. 81%, p = 0.017) in DAPT patients. Late outcomes within 97.4 ± 67.4 months show lower incidence of overall mortality (19 vs. 51%, p < 0.001) and MACCE (24.5 vs. 58.2%, p < 0.001) in the DAPT patients when compared with SAPT patients. Conclusions—Coronary endarterectomy allows revascularization in end-stage CAD when the myocardium is still viable. The use of dual APT after CEA for at least six months seems to improve mid-to-long-term patency rates and survival, and reduced the incidence of major adverse cardiac and cerebrovascular events. Full article

Hypoplastic Left Heart Syndrome (HLHS) is a congenital heart defect that requires a three-stage surgical palliation to create a single ventricle system in the right side of the heart. Of patients undergoing this cardiac palliation series, $25\%$ will develop tricuspid regurgitation (TR), which is associated with an increased mortality risk. Valvular regurgitation in this population has been extensively studied to understand indicators and mechanisms of comorbidity. In this article, we review the current state of research on TR in HLHS, including identified valvular anomalies and geometric properties as the main reasons for the poor prognosis. After this review, we present some suggestions for future TR-related studies to answer the central question: What are the predictors of TR onset during the three palliation stages? These studies involve (i) the use of engineering-based metrics to evaluate valve leaflet strains and predict tissue material properties, (ii) perform multivariate analyses to identify TR predictors, and (iii) develop predictive models, particularly using longitudinally tracked patient cohorts to foretell patient-specific trajectories. Regarded together, these ongoing and future efforts will result in the development of innovative tools that can aid in surgical timing decisions, in prophylactic surgical valve repair, and in the refinement of current intervention techniques. Full article

Objectives: Calcific aortic valve disease (CAVD) is most common in the aging population and is without effective medical treatments. Brain and muscle ARNT-like 1 (BMAL1) is related to calcification. It has unique tissue-specific characteristics and plays different roles in different tissues’ calcification processes. The purpose of the present study is to explore the role of BMAL1 in CAVD. Methods: The protein levels of BMAL1 in normal and calcified human aortic valves and valvular interstitial cells (VICs) isolated from normal and calcified human aortic valves were checked. HVICs were cultured in osteogenic medium as an in vitro model, and BMAL1 expression and location were detected. TGF-β and RhoA/ROCK inhibitors and RhoA-siRNA were applied to detect the mechanism underlying the source of BMAL1 during HVICs’ osteogenic differentiation. ChIP was applied to check whether BMAL1 could directly interact with the runx2 primer CPG region, and the expression of key proteins involved in the TNF signaling pathway and NF-κ B pathway was tested after silencing BMAL1. Results: In this study, we found that BMAL1 expression was elevated in calcified human aortic valves and VICs isolated from calcified human aortic valves. Osteogenic medium could promote BMAL1 expression in HVICs and the knockdown of BMAL1 induced the inhibition of HVICs’ osteogenic differentiation. Furthermore, the osteogenic medium promoting BMAL1 expression could be blocked by TGF-β and RhoA/ROCK inhibitors and RhoA-siRNA. Meanwhile, BMAL1 could not bind with the runx2 primer CPG region directly, but knockdown of BMAL1 led to decreased levels of P-AKT, P-IκBα, P-p65 and P-JNK. Conclusions: Osteogenic medium could promote BMAL1 expression in HVICs through the TGF-β/RhoA/ROCK pathway. BMAL1 could not act as a transcription factor, but functioned through the NF-κ B/AKT/MAPK pathway to regulate the osteogenic differentiation of HVICs. Full article

Introduction: Patient-specific computational models are a powerful tool for planning cardiovascular interventions. However, the in vivo patient-specific mechanical properties of vessels represent a major source of uncertainty. In this study, we investigated the effect of uncertainty in the elastic module (E) on a Fluid–Structure Interaction (FSI) model of a patient-specific aorta. Methods: The image-based $\chi$-method was used to compute the initial E value of the vascular wall. The uncertainty quantification was carried out using the generalized Polynomial Chaos (gPC) expansion technique. The stochastic analysis was based on four deterministic simulations considering four quadrature points. A deviation of about ±20% on the estimation of the E value was assumed. Results: The influence of the uncertain E parameter was evaluated along the cardiac cycle on area and flow variations extracted from five cross-sections of the aortic FSI model. Results of stochastic analysis showed the impact of E in the ascending aorta while an insignificant effect was observed in the descending tract. Conclusions: This study demonstrated the importance of the image-based methodology for inferring E, highlighting the feasibility of retrieving useful additional data and enhancing the reliability of in silico models in clinical practice. Full article

Compared with conventional right ventricular septal pacing (RVSP), several studies have shown a net clinical benefit of left bundle branch area pacing (LBBAP) in terms of ejection fraction preservation and reduced hospitalizations for heart failure. The purpose of this study was to compare acute depolarization and repolarization electrocardiographic parameters between LBBAP and RVSP in the same patients during the LBBAP implant procedure. We prospectively included 74 consecutive patients subjected to LBBAP from 1 January to 31 December 2021 at our institution in the study. After the lead was placed deep into the ventricular septum, unipolar pacing was performed and 12-lead ECGs were recorded from the distal (LBBAP) and proximal (RVSP) electrodes. QRS duration (QRSd), left ventricular activation time (LVAT), right ventricular activation time (RVAT), QT and JT intervals, QT dispersion (QTd), T-wave peak-to-end interval (Tpe), and Tpe/QT were measured for both instances. The final LBBAP threshold was a 0.7 ± 0.31 V at 0.4 ms duration with a sensing threshold of 10.7 ± 4.1 mV. RVSP produced a significantly larger QRS complex than the baseline QRS (194.88 ± 17.29 ms vs. 141.89 ± 35.41 ms, p < 0.001), while LBBAP did not significantly change the mean QRSd (148.10 ± 11.52 ms vs. 141.89 ± 35.41 ms, p = 0.135). LVAT (67.63 ± 8.79 ms vs. 95.89 ± 12.02 ms, p < 0.001) and RVAT (80.54 ± 10.94 ms vs. 98.99 ± 13.80 ms, p < 0.001) were significantly shorter with LBBAP than with RVSP. Moreover, all the repolarization parameters studied were significantly shorter in LBBAP than in RVSP (QT—425.95 ± 47.54 vs. 487.30 ± 52.32; JT—281.85 ± 53.66 vs. 297.69 ± 59.02; QTd—41.62 ± 20.07 vs. 58.38 ± 24.44; Tpe—67.03 ± 11.19 vs. 80.27 ± 10.72; and Tpe/QT—0.158 ± 0.028 vs. 0.165 ± 0.021, p < 0.05 for all), irrespective of the baseline QRS morphology. LBBAP was associated with significantly better acute depolarization and repolarization electrocardiographic parameters compared with RVSP. Full article

Objective: Outcomes after surgical aortic root replacement using different valved conduits are rarely reported. The present study shows the experience of a single center with the use of the partially biological LABCOR (LC) conduit and the fully biological BioIntegral (BI) conduit. Special attention was paid to preoperative endocarditis. Methods: All 266 patients who underwent aortic root replacement by an LC conduit (n = 193) or a BI conduit (n = 73) between 01/01/2014 and 31/12/2020 were studied retrospectively. Dependency on an extracorporeal life support system preoperatively and congenital heart disease were exclusion criteria. For patients with (n = 67) and without (n = 199) preoperative endocarditis subanalyses were made. Results: Patients treated with a BI conduit were more likely to have diabetes mellitus (21.9 vs. 6.7%, p < 0.001), previous cardiac surgery (86.3 vs. 16.6%; p < 0.001), permanent pacemaker (21.9 vs. 2.1%; p < 0.001), and had a higher EuroSCORE II (14.9 vs. 4.1%; p < 0.001). The BI conduit was used more frequently for prosthetic endocarditis (75.3 vs. 3.6%; <0.001), and the LC conduit was used predominantly for ascending aortic aneurysms (80.3 vs. 41.1%; <0.001) and Stanford type A aortic dissections (24.9 vs. 9.6%; p = 0.006). The LC conduit was used more often for elective (61.7 vs. 47.9%; p = 0.043) and emergency (27.5 vs. 15.1%; p = 0–035) surgeries, and the BI conduit for urgent surgeries (37.0 vs. 10.9%; p < 0.001). Conduit sizes did not differ significantly, with a median of 25 mm in each case. Surgical times were longer in the BI group. In the LC group, coronary artery bypass grafting and proximal or total replacement of the aortic arch were combined more frequently, whereas in the BI group, partial replacement of the aortic arch were combined. In the BI group, ICU length of stay and duration of ventilation were longer, and rates of tracheostomy and atrioventricular block, pacemaker dependence, dialysis, and 30-day mortality were higher. Atrial fibrillation occurred more frequently in the LC group. Follow-up time was longer and rates of stroke and cardiac death were less frequent in the LC group. Postoperative echocardiographic findings at follow-up were not significantly different between conduits. Survival of LC patients was better than that of BI patients. In the subanalysis of patients with preoperative endocarditis, significant differences between the used conduits were found with respect to previous cardiac surgery, EuroSCORE II, aortic valve and prosthesis endocarditis, elective operation, duration of operation, and proximal aortic arch replacement. For patients without preoperative endocarditis, significant differences were observed concerning previous cardiac surgery, pacemaker implantation history, duration of procedure, and bypass time. The Kaplan–Meier curves for the subanalyses showed no significant differences between the used conduits. Conclusions: Both biological conduits studied here are equally suitable in principle for complete replacement of the aortic root in all aortic root pathologies. The BI conduit is often used in bail-out situations, especially in severe endocarditis, without being able to show a clinical advantage over the LC conduit in this context. Full article

As heart transplantation continues to be the gold-standard therapy for end-stage heart failure, the supply-demand imbalance of available organs worsens. Until recently, there have been no advances in increasing the donor pool, as prolonged cold ischemic time excludes the use of certain donors. The TransMedics Organ Care System (OCS) allows for ex-vivo normothermic perfusion, which allows for a reduction of cold ischemic time and allows for long-distance procurements. Furthermore, the OCS allows for real-time monitoring and assessment of allograft quality, which can be crucial for extended-criteria donors or donation after cardiac death (DCD) donors. Conversely, the XVIVO device allows for hypothermic perfusion to preserve allografts. Despite their limitations, these devices have the potential to alleviate the supply-demand imbalance in donor availability. Full article

Background: Atrial fibrillation (AF) is the most common arrhythmia and typically occurs in elderly patients with other cardiovascular and extracardiac diseases. However, up to 15% of AF develops without any related risk factors. Recently, the role of genetic factors has been highlighted in this particular form of AF. Aims: The aims of this study were to determine the prevalence of pathogenic variants in early-onset AF in patients without known disease-related risk factors and to identify any structural cardiac abnormalities in these patients. Materials and Methods: We conducted exome sequencing and interpretation in 54 risk factor-free early-onset AF patients and further validated our findings in a similar AF patient cohort from the UK Biobank. Results: Pathogenic/likely pathogenic variants were found in 13/54 (24%) patients. The variants were identified in cardiomyopathy-related and not arrhythmia-related genes. The majority of the identified variants were TTN gene truncating variants (TTNtvs) (9/13 (69%) patients). We also observed two TTNtvs founder variants in the analysed population—c.13696C>T p.(Gln4566Ter) and c.82240C>T p.(Arg27414Ter). Pathogenic/likely pathogenic variants were found in 9/107 (8%) individuals from an independent similar AF patient cohort from the UK Biobank. In correspondence with our Latvian patients, only variants in cardiomyopathy-associated genes were identified. In five (38%) of the thirteen Latvian patients with pathogenic/likely pathogenic variants, dilation of one or both ventricles was identified on a follow-up cardiac magnetic resonance scan. Conclusions: We observed a high prevalence of pathogenic/likely pathogenic variants in cardiomyopathy-associated genes in patients with risk factor-free early-onset AF. Moreover, our follow-up imaging data indicate that these types of patients are at risk of developing ventricular dilation. Furthermore, we identified two TTNtvs founder variants in our Latvian study population. Full article

Background: Although several studies suggest that heparins prevent arrhythmias caused by acute myocardial infarction (AMI), the molecular mechanisms involved remain unclear. To investigate the involvement of pharmacological modulation of adenosine (ADO) signaling in cardiac cells by a low-molecular weight heparin (enoxaparin; ENOX) used in AMI therapy, the effects of ENOX on the incidences of ventricular arrhythmias (VA), atrioventricular block (AVB), and lethality (LET) induced by cardiac ischemia and reperfusion (CIR) were evaluated, with or without ADO signaling blockers. Methods: To induce CIR, adult male Wistar rats were anesthetized and subjected to CIR. Electrocardiogram (ECG) analysis was used to evaluate CIR-induced VA, AVB, and LET incidence, after treatment with ENOX. ENOX effects were evaluated in the absence or presence of an ADO A1-receptor antagonist (DPCPX) and/or an inhibitor of ABC transporter-mediated cAMP efflux (probenecid, PROB). Results: VA incidence was similar between ENOX-treated (66%) and control rats (83%), but AVB (from 83% to 33%) and LET (from 75% to 25%) incidences were significantly lower in rats treated with ENOX. These cardioprotective effects were blocked by either PROB or DPCPX. Conclusion: These results indicate that ENOX was effective in preventing severe and lethal arrhythmias induced by CIR due to pharmacological modulation of ADO signaling in cardiac cells, suggesting that this cardioprotective strategy could be promising in AMI therapy. Full article