Journal of Cardiovascular Development and Disease

The heart switches its main metabolic substrate from glucose to fatty acids shortly after birth, which is one of reasons for the loss of heart regeneration capability in adult mammals. On the contrary, metabolic shifts from oxidative phosphorylation to glucose metabolism promote cardiomyocyte (CM) proliferation after heart injury. However, how glucose transportation in CMs is regulated during heart regeneration is still not fully understood. In this report, we found that the expression of Glut1 (slc2a1) was upregulated around the injury site of zebrafish heart, accompanied by an increase in glucose uptake at the injury area. Knockout of slc2a1a impaired zebrafish heart regeneration. Our previous study has demonstrated that the expression of Δ113p53 is activated after heart injury and Δ113p53⁺ CMs undergo proliferation to contribute to zebrafish heart regeneration. Next, we used the Δ113p53 promoter to generate the Tg(Δ113p53:cmyc) zebrafish transgenic line. Conditional overexpression of cmyc not only significantly promoted zebrafish CM proliferation and heart regeneration but also significantly enhanced glut1 expression at the injury site. Inhibiting Glut1 diminished the increase in CM proliferation in Tg(Δ113p53:cmyc) injured hearts of zebrafish. Therefore, our results suggest that the activation of cmyc promotes heart regeneration through upregulating the expression of glut1 to speed up glucose transportation. Full article

Coronavirus disease 2019 (COVID-19) is a severe respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Heart failure (HF) is associated with a worse prognosis for patients with this viral infection, highlighting the importance of early detection and effective treatment strategies. HF can also be a consequence of COVID-19-related myocardial damage. To optimise the treatment of these patients, one needs to understand the interactions between this disease and viruses. Until now, the validity of the screening for cardiovascular complications after COVID-19 has not been confirmed. There were also no patients in whom such diagnostics seemed appropriate. Until appropriate recommendations are made, diagnosis procedures must be individualised based on the course of the acute phase and clinical symptoms reported or submitted after COVID-19. Clinical phenomena are the criteria for determining the recommended test panel. We present a structured approach to COVID-19 patients with heart involvement. Full article

Background: Surgical mortality risk scores, even if not properly designed and rarely tested in the transcatheter aortic valve implantation (TAVI) setting, still guide the heart team in managing significant aortic stenosis. Methods: After splitting 1763 consecutive patients retrospectively based on their mortality risk thresholds, the composite endpoint early safety (ES) was adjudicated according to Valve Academic Research Consortium (VARC)-2 and -3 consensus documents. Results: ES incidence was higher if VARC-2 rather than VARC-3 defined. Despite only patients showing VARC-2 ES had significantly lower absolute values of all three main risk scores, these last still failed to foresee both VARC-2 and -3 ES in intermediate-risk patients. The receiver operating characteristic analysis also showed a significant correlation, but with poor diagnostic accuracy, among the three scores and only VARC-2 ES; moreover, the absence of VARC-2 ES and low-osmolar contrast media administration were identified as independent predictors of 1-year mortality and absence of VARC-3 ES, respectively. Finally, even a single complication included in the ES definition could significantly affect 1-year mortality. Conclusion: Currently, the most used mortality risk scores do not have adequate diagnostic accuracy in predicting ES after TAVI. The absence of VARC-2, instead of VARC-3, ES is an independent predictor of 1-year mortality. Full article

Hypertension in Mexico has a prevalence of 32% and is the second most widespread cause of consultation in primary care. Only 40% of patients in treatment have a blood pressure (BP) below 140/90 mmHg. This clinical trial aimed to compare the effectiveness of the combination of enalapril and nifedipine versus the empirical treatment for hypertension in patients with uncontrolled BP in a primary care center in Mexico City. Participants were randomized to treatment with enalapril and nifedipine (combination group) or to continue with the empirical treatment. Outcome variables were BP control, therapeutic adherence, and adverse effects at 6 months of follow-up. At the end of the follow-up period, BP control (64% versus 77%) and therapeutic adherence (53% versus 93%) showed an improvement from the baseline values in the group that received the combination treatment. BP control (51% versus 47%) and therapeutic adherence (64% versus 59%) in the group who received the empirical treatment did not show improvement from the baseline to follow-up. Combined treatment was 31% more efficacious than conventional empirical treatment (odds ratio = 3.9), which yielded an incremental clinical utility of 18% with high tolerability extent among patients in primary care in Mexico City. These results contribute to the control of arterial hypertension. Full article

Aims: Cardiac transthyretin amyloidosis (ATTR) represents the accumulation of misfolded transthyretin in the heart interstitium. Planar scintigraphy with bone-seeking tracers has long been established as one of the three main steps in the non-invasive diagnosis of ATTR, but lately, single-photon emission computed tomography (SPECT) has gained wide recognition for its abilities to exclude false positive results and offer a possibility for amyloid burden quantitation. We performed a systematic review of the existing literature to provide an overview of the available SPECT-based parameters and their diagnostic performances in the assessment of cardiac ATTR. Methods and Methods: Among the 43 papers initially identified, 27 articles were screened for eligibility and 10 met the inclusion criteria. We summarised the available literature based on radiotracer, SPECT acquisition protocol, analysed parameters and their correlation to planar semi-quantitative indices. Results: Ten articles provided accurate details about SPECT-derived parameters in cardiac ATTR and their diagnostic potential. Five studies performed phantom studies for accurate calibration of the gamma cameras. All papers described good correlation of quantitative parameters to the Perugini grading system. Conclusions: Despite little published literature on quantitative SPECT in the assessment of cardiac ATTR, this method offers good prospects in the appraisal of cardiac amyloid burden and treatment monitoring. Full article

Background: The platelet-to-albumin ratio (PAR), leucocyte-to-albumin ratio (LAR), neutrophil percentage-to-albumin ratio (NPAR), and monocyte-to-albumin ratio (MAR) represent easily reproducible markers, which may predict the outcomes in various diseases. Early postoperative complications might appear after heart transplantation, such as infections, diabetes mellitus type 2 (DM2), acute graft rejection, and atrial fibrillation (AFib). Objective: The aim of our study was to investigate the PAR, LAR, NPAR, and MAR values before and after heart transplantation, and the associations of the preoperative levels of these markers with the presence of postoperative complications in first two months after surgery. Methods: Our retrospective research was directed from May 2014 to January 2021, with a total number of 38 patients being included. We used cut-off values for the ratios from previously published studies, as well as our own determination of these levels by using a receiver operating characteristic (ROC) curve. Results: By ROC analysis, the optimal preoperative PAR cut-off value was 38.84 (AUC: 0.771, p = 0.0039), with 83.3% sensitivity, and 75.0% specificity. Applying a Chi square (χ²) test, PAR > 38.84 represented an independent risk factor for complications, regardless of cause, and postoperative infections. Conclusions: Preoperative PAR > 38.84 was a risk factor of developing complications of any cause, and postoperative infections in the first two months after heart transplantation. Full article

Computational hemodynamic simulations are becoming increasingly important for cardiovascular research and clinical practice, yet incorporating numerical simulations of human fetal circulation is relatively underutilized and underdeveloped. The fetus possesses unique vascular shunts to appropriately distribute oxygen and nutrients acquired from the placenta, adding complexity and adaptability to blood flow patterns within the fetal vascular network. Perturbations to fetal circulation compromise fetal growth and trigger the abnormal cardiovascular remodeling that underlies congenital heart defects. Computational modeling can be used to elucidate complex blood flow patterns in the fetal circulatory system for normal versus abnormal development. We present an overview of fetal cardiovascular physiology and its evolution from being investigated with invasive experiments and primitive imaging techniques to advanced imaging (4D MRI and ultrasound) and computational modeling. We introduce the theoretical backgrounds of both lumped-parameter networks and three-dimensional computational fluid dynamic simulations of the cardiovascular system. We subsequently summarize existing modeling studies of human fetal circulation along with their limitations and challenges. Finally, we highlight opportunities for improved fetal circulation models. Full article

Computed tomography perfusion (CTP) is frequently used in the triage of ischemic stroke patients for endovascular thrombectomy (EVT). We aimed to quantify the volumetric and spatial agreement of the CTP ischemic core estimated with different thresholds and follow-up MRI infarct volume on diffusion-weighted imaging (DWI). Patients treated with EVT between November 2017 and September 2020 with available baseline CTP and follow-up DWI were included. Data were processed with Philips IntelliSpace Portal using four different thresholds. Follow-up infarct volume was segmented on DWI. In 55 patients, the median DWI volume was 10 mL, and median estimated CTP ischemic core volumes ranged from 10–42 mL. In patients with complete reperfusion, the intraclass correlation coefficient (ICC) showed moderate-good volumetric agreement (range 0.55–0.76). A poor agreement was found for all methods in patients with successful reperfusion (ICC range 0.36–0.45). Spatial agreement (median Dice) was low for all four methods (range 0.17–0.19). Severe core overestimation was most frequently (27%) seen in Method 3 and patients with carotid-T occlusion. Our study shows moderate–good volumetric agreement between ischemic core estimates for four different thresholds and subsequent infarct volume on DWI in EVT-treated patients with complete reperfusion. The spatial agreement was similar to other commercially available software packages. Full article

Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting millions of people worldwide. The cardiac autonomic nervous system (ANS) is widely recognized as playing a key role in both the initiation and propagation of AF. This paper reviews the background and development of a unique cardioneuroablation technique for the modulation of the cardiac ANS as a potential treatment for AF. The treatment uses pulsed electric field energy to selectively electroporate ANS structures on the epicardial surface of the heart. Insights from in vitro studies and electric field models are presented as well as data from both pre-clinical and early clinical studies. Full article

(1) Background: The presence of restrictive left ventricular diastolic filling pattern (LVDFP) is associated with an unfavorable prognosis in many cardiac diseases, but few data are available on the prognostic implications of this pattern in patients with dilated cardiomyopathy (DCM). We aimed to establish the main prognostic predictors at the 1- and 5-year follow-ups in DCM patients and the value of restrictive LVDFP in increasing morbidity and mortality. (2) Methods: A prospective study of 143 patients with DCM divided in non-restrictive LVDFP group (95 patients) and restrictive group (47 patients). The patients were evaluated at a 5-year follow-up through an in-patient visit during the pre-pandemic period and hybrid methods (face-to-face, teleconsultation and home monitoring with a telemedicine application) during the pandemic period. Statistical analysis compared the two groups in terms of NYHA class, quality of life, hospitalizations/emergency department (ED) visits due to HF exacerbation and total mortality. (3) Results: The mortality rate in the restrictive group was markedly higher than that in the non-restrictive group at 1 year (17.02% vs. 10.59%, respectively, p < 0.05) and at 5 years (68.08% vs. 50.53%, p < 0.05). In the restrictive group, hospitalizations/ED visits due to HF decompensations at 1 year were significantly higher (85.11% vs. 57.89%, p < 0.05), with hospitalizations for ventricular arrhythmia being almost three times higher (21.28% vs. 7.37%, respectively, p < 0.05). The percentage of patients with a favorable evolution (in terms of NYHA class and quality of life) at the 1- and 5-year follow-ups were higher in the non-restrictive LVDFP group. The main prognostic predictors in patients with DCM at the 1-year follow-up were: restrictive LVDFP, age > 75 years, markedly dilated LV, comorbidities (DM, COPD), 2nd-degree mitral regurgitation and severe pulmonary hypertension (p < 0.05). (4) Conclusions: At the 1- and 5-year follow-ups, the presence of the restrictive LVDFP in DCM patients was independently associated with a poor prognosis, being the best clinical predictor for unfavorable evolution, after adjustment for other well-established predictive parameters in DCM patients. Full article

Patients with cardiovascular disease (CVD) and chronic kidney disease (CKD) show high rates of cardiorenal outcomes. In addition, the progression towards renal failure and cardiovascular events rises as CKD worsens. Several studies suggest that the activation of the mineralocorticoid receptor (MR) induces cardiac and renal injury, including inflammation and fibrosis. Finerenone is a novel, nonsteroidal, selective MR antagonist (MRA) which has demonstrated anti-inflammatory and anti-fibrotic effects in pre-clinical studies. Moreover, two large trials (FIDELIO-DKD and FIGARO-DKD) investigated the renal and cardiovascular outcomes in patients with mild to severe CKD in type 2 diabetes which received finerenone. On these bases, this comprehensive review aims to summarize the current knowledge regarding finerenone and its effects on CKD and the cardiovascular system, emphasizing its role in modifying cardiorenal outcomes. Full article

Coronary sinus reducer (CSR) implantation is a new treatment option for patients with refractory angina pectoris. However, there is no evidence from a randomized trial that would show an improvement in exercise capacity after this treatment. The aim of this study was to evaluate the influence of CSR treatment on maximal oxygen consumption and compare it to a sham procedure. Twenty-five patients with refractory angina pectoris (Canadian Cardiovascular Society (CCS) class II–IV) were randomized to a CSR implantation (n = 13) or a sham procedure (n = 12). At baseline and after 6 months of follow-up, the patients underwent symptom-limited cardiopulmonary exercise testing with an adjusted ramp protocol and assessment of angina pectoris using the CCS scale and Seattle angina pectoris questionnaire (SAQ). In the CSR group, maximal oxygen consumption increased from 15.56 ± 4.05 to 18.4 ± 5.2 mL/kg/min (p = 0.03) but did not change in the sham group (p = 0.53); p for intergroup comparison was 0.03. In contrast, there was no difference in the improvement of the CCS class or SAQ domains. To conclude, in patients with refractory angina and optimized medical therapy, CSR implantation may improve oxygen consumption beyond that of optimal medical therapy. Full article

Unrepairable congenital heart valve disease is an unsolved problem in pediatric cardiac surgery because there are no growing heart valve implants. Partial heart transplantation is a new type of transplant that aims to solve this problem. In order to study the unique transplant biology of partial heart transplantation, animal models are necessary. This study aimed to assess the morbidity and mortality of heterotopic partial heart transplantation in rodent models. This study assessed two models. The first model involved transplanting heart valves from donor animals into the abdominal aortic position in the recipient animals. The second model involved transplanting heart valve leaflets into the renal subcapsular position of the recipient animals. A total of 33 animals underwent heterotopic partial heart transplantation in the abdominal aortic position. The results of this model found a 60.61% (n = 20/33) intraoperative mortality rate and a 39.39% (n = 13/33) perioperative mortality rate. Intraoperative mortality was due to vascular complications from the procedure, and perioperative mortality was due to graft thrombosis. A total of 33 animals underwent heterotopic partial heart transplantation in the renal subcapsular position. The results of this model found a 3.03% (n = 1/33) intraoperative mortality rate, and the remaining 96.97% survived (n = 32/33). We conclude that the renal subcapsular model has a lower mortality rate and is technically more accessible than the abdominal aortic model. While the heterotopic transplantation of valves into the abdominal aortic position had significant morbidity and mortality in the rodent model, the renal subcapsular model provided evidence for successful heterotopic transplantation. Full article

Abdominal aortic aneurysm (AAA) is a critical health disorder, where the abdominal aorta dilates more than 50% of its normal diameter. Enlargement in abdominal aorta alters the hemodynamics and flow-induced forces on the AAA wall. Depending on the flow conditions, the hemodynamic forces on the wall may result in excessive mechanical stresses that lead to AAA rupture. The risk of rupture can be predicted using advanced computational techniques such as computational fluid dynamics (CFD) and fluid–structure interaction (FSI). For a reliable rupture risk assessment, formation of intraluminal thrombus (ILT) and uncertainty in arterial material properties should be taken into account, mainly due to the patient-specific differences and unknowns in AAAs. In this study, AAA models are computationally investigated by performing CFD simulations combined with FSI analysis. Various levels of ILT burdens are artificially generated in a realistic AAA geometry, and the peak effective stresses are evaluated to elucidate the effect of material models and ILT formation. The results indicate that increasing the ILT burden leads to lowered effective stresses on the AAA wall. The material properties of the artery and ILT are also effective on the stresses; however, these effects are limited compared to the effect of ILT volume in the AAA sac. Full article

Background. Cardiac side effects associated with anthracycline-based treatment may seriously compromise the prognosis of patients with breast cancer (BC). Evidence shows that genes that operate in drug metabolism can influence the risk of anthracycline-induced cardiotoxicity (AIC). ATP-binding cassette (ABC) transporters could serve as one of the potential biomarkers for AIC risk stratification. We aimed to determine the link between single-nucleotide polymorphisms (SNPs) in several ABC genes (ABCB1 rs1045642, ABCC1 rs4148350, ABCC1 rs3743527) and cardiotoxicity. Methods. The study included 71 patients with BC, who were treated with doxorubicin-based chemotherapy. Two-dimensional echocardiography and speckle-tracking echocardiography were performed. AIC was defined as a new decrease of 10 percentage points in the left ventricular ejection fraction (LVEF). SNPs in ABCB1 and ABCC1 genes were evaluated using real-time PCR. Results. After a cumulative dose of 236.70 mg/m² of doxorubicin, 28.2% patients met the criteria of AIC. Patients who developed AIC had a larger impairment in left ventricular systolic function compared to those who did not develop AIC (LVEF: 50.20 ± 2.38% vs. 55.41 ± 1.13%, p < 0.001; global longitudinal strain: −17.03 ± 0.52% vs. −18.40 ± 0.88%, p < 0.001). The ABCC1 rs4148350 TG genotype was associated with higher rates of cardiotoxicity (TG vs. GG OR = 8.000, 95% CI = 1.405–45.547, p = 0.019). Conclusions. The study showed that ABCC1 rs4148350 is associated with AIC and could be a potential biomarker to assess the risk of treatment side effects in patients with BC. Full article

(1) Background: Little is known about how left ventricular systolic dysfunction (LVSD) affects functional and clinical outcomes in acute ischemic stroke (AIS) patients undergoing thrombolysis; (2) Methods: A retrospective observational study conducted between 2006 and 2018 included 937 consecutive AIS patients undergoing thrombolysis. LVSD was defined as left ventricular ejection fraction (LVEF) < 50%. Univariate and multivariate binary logistic regression analysis was performed for demographic characteristics. Ordinal shift regression was used for functional modified Rankin Scale (mRS) outcome at 3 months. Survival analysis of mortality, heart failure (HF) admission, myocardial infarction (MI) and stroke/transient ischemic attack (TIA) was evaluated with a Cox-proportional hazards model; (3) Results: LVSD patients in comparison with LVEF ≥ 50% patients accounted for 190 and 747 patients, respectively. LVSD patients had more comorbidities including diabetes mellitus (100 (52.6%) vs. 280 (37.5%), p < 0.001), atrial fibrillation (69 (36.3%) vs. 212 (28.4%), p = 0.033), ischemic heart disease (130 (68.4%) vs. 145 (19.4%), p < 0.001) and HF (150 (78.9%) vs. 46 (6.2%), p < 0.001). LVSD was associated with worse functional mRS outcomes at 3 months (adjusted OR 1.41, 95% CI 1.03–1.92, p = 0.030). Survival analysis identified LVSD to significantly predict all-cause mortality (adjusted HR [aHR] 3.38, 95% CI 1.74–6.54, p < 0.001), subsequent HF admission (aHR 4.23, 95% CI 2.17–8.26, p < 0.001) and MI (aHR 2.49, 95% CI 1.44–4.32, p = 0.001). LVSD did not predict recurrent stroke/TIA (aHR 1.15, 95% CI 0.77–1.72, p = 0.496); (4) Conclusions: LVSD in AIS patients undergoing thrombolysis was associated with increased all-cause mortality, subsequent HF admission, subsequent MI and poorer functional outcomes, highlighting a need to optimize LVEF. Full article

Transcatheter aortic valve implantation (TAVI) is now a commonly used therapy in patients with severe aortic stenosis, even in those patients at low surgical risk. The indications for TAVI have broadened as the therapy has proven to be safe and effective. Most challenges associated with TAVI after its initial introduction have been impressively reduced; however, the possible need for post-TAVI permanent pacemaker implantation (PPI) secondary to conduction disturbances continues to be on the radar. Conduction abnormalities post-TAVI are always of concern given that the aortic valve lies in close proximity to critical components of the cardiac conduction system. This review will present a summary of noteworthy pre-and post-procedural conduction blocks, the best use of telemetry and ambulatory device monitoring to avoid unnecessary PPI or to recognize the need for late PPI due to delayed high-grade conduction blocks, predictors to identify those patients at greatest risk of requiring PPI, important CT measurements and considerations to optimize TAVI planning, and the utility of the MInimizing Depth According to the membranous Septum (MIDAS) technique and the cusp-overlap technique. It is stressed that careful membranous septal (MS) length measurement by MDCT during pre-TAVI planning is necessary to establish the optimal implantation depth before the procedure to reduce the risk of compression of the MS and consequent damage to the cardiac conduction system. Full article

It is common for a cardiac mass to be discovered accidentally during an echocardiographic examination. Following the relief of a cardiac mass, being able to evaluate and characterize it using non-invasive imaging methods is critical. Echocardiography, computed tomography (CT), cardiac magnetic resonance imaging (CMR), and positron emission tomography (PET) are the main imaging modalities used to evaluate cardiac masses. Although multimodal imaging often allows for a better assessment, CMR is the best technique for the non-invasive characterization of tissues, as the different MR sequences help in the diagnosis of cardiac masses. This article provides detailed descriptions of each CMR sequence employed in the evaluation of cardiac masses, underlining the potential information it can provide. The description in the individual sequences provides useful guidance to the radiologist in performing the examination. Full article

Background: Transcatheter aortic valve implantation (TAVI) has developed as an alternative to surgery for symptomatic high-risk patients with aortic stenosis (AS). An important complication of TAVI is acute kidney injury. The purpose of the study was to investigate if the Mehran Score (MS) could be used to predict acute kidney injury (AKI) in TAVI patients. Methods: This is a multicenter, retrospective, observational study including 1180 patients with severe AS. The MS comprised eight clinical and procedural variables: hypotension, congestive heart failure class, glomerular filtration rate, diabetes, age >75 years, anemia, need for intra-aortic balloon pump, and contrast agent volume use. We assessed the sensitivity and specificity of the MS in predicting AKI following TAVI, as well as the predictive value of MS with each AKI-related characteristic. Results: Patients were categorized into four risk groups based on MS: low (≤5), moderate (6–10), high (11–15), and very high (≥16). Post-procedural AKI was observed in 139 patients (11.8%). MS classes had a higher risk of AKI in the multivariate analysis (HR 1.38, 95% CI, 1.43–1.63, p < 0.01). The best cutoff for MS to predict the onset of AKI was 13.0 (AUC, 0.62; 95% CI, 0.57–0.67), whereas the best cutoff for eGFR was 42.0 mL/min/1.73 m² (AUC, 0.61; 95% CI, 0.56–0.67). Conclusions: MS was shown to be a predictor of AKI development in TAVI patients. Full article