Journal of Cardiovascular Development and Disease最新文献

Ischemic cardiomyopathy patients with severe left ventricular dysfunction are a specific group of patients with poor surgical outcomes. There are few surgical treatment options in practice for the treatment of these patients such as heart transplantation, coronary artery bypass surgery, surgical ventricular restoration, etc. Despite multiple treatment options, there are no explicit clinical guidelines available to guide surgeons in choosing the most appropriate option and ensuring that the specific patient can benefit from the selected surgical treatment. Heart transplantation is the gold standard treatment for ischemic cardiomyopathy patients with severe left ventricular dysfunction, but it is limited to very few highly equipped centers around the world due to donor shortages, complex perioperative and surgical management, and limited technological and human resources. It is evident from some studies that heart transplant-eligible candidates can benefit from alternative surgical options such as coronary artery bypass surgery alone or combined with surgical ventricular restoration. Therefore, alternative surgical options that are used for most of the population, especially in developing and underdeveloped countries, need to be discussed to improve their outcomes. A challenge in the recent era which has yet to find a solution is to determine which heart transplant candidate can benefit from simple revascularization compared to a complex heart transplantation procedure. Myocardial viability testing was one of the most important determinants in deciding whether a patient should undergo revascularization, but its role in guiding appropriate surgical options has been challenged. This review aims to discuss the available surgical management options and their long-term outcomes for patients with ischemic cardiomyopathy, which will eventually help surgeons when choosing a surgical procedure.

Despite the availability of affordable pharmaceuticals treating cardiovascular diseases (CVDs), many of the risk factors remain poorly controlled. Fixed-dose combinations (FDCs), a form of incremental innovation, have already demonstrated improvements over combinations of single medicines in adherence and hard clinical endpoints. Nevertheless, there are many barriers related to the wider use of FDCs in CVDs. Our aim was to identify these barriers and explore system-level facilitators from a multi-stakeholder perspective. Identified barriers include (i) hurdles in evidence generation for manufacturers, (ii) limited acceptance of adherence as an endpoint by clinical guideline developers and policymakers, (iii) limited options for a price premium for incremental innovation for healthcare payers, (iv) limited availability of real-world evidence, and (v) methodological issues to measure improved adherence. Initiatives to standardize and link healthcare databases in European countries, movements towards improved patient centricity in healthcare, and extended value assessment provide opportunities to capture the benefits of FDCs. Still, there is an emerging need to facilitate the generalizability of sporadic clinical evidence across different FDCs and to improve adherence measures. Finally, healthcare payers need to be convinced to pay a fair premium price for the added value of FDCs to incentivize incremental innovation in CVD treatment.

A novel idea is introduced regarding the statistical comparisons of endpoints in clinical trials. Currently, the (dis)similarity of measured endpoints is not assessed. Instead, statistical analysis is directly applied, which can lead to multiplicity issues, reduced statistical power, and the recruitment of more subjects. The Vector-Based Comparison (VBC) approach originates from vector algebra and considers clinical endpoints as "vectors". In the general case of N clinical endpoints, a Cartesian coordinate system is defined, and the most important primary endpoint (E1) is set. Following an explicitly defined procedure, the pairwise relationships of the remaining N-1 endpoints with E1 are estimated, and the N-1 endpoints are decomposed into axes perpendicular to E1. The angle between vectors provides insight into the level of dependency between variables. Vectors that are perpendicular to each other are considered independent, and only these are used in the statistical analysis. In this work, VBC is applied to bioequivalence studies of three anti-hypertensive drugs: amlodipine, irbesartan, and hydrochlorothiazide. The results suggest that VBC is a reproducible, easily applicable method allowing for the discrimination and utilization of the endpoint component expressing different attributes. All clinical characteristics are assessed with increased statistical power, without inflation of type I error.

Aim: To assess the acute effect of empagliflozin versus dapagliflozin administration on flow-mediated vasodilation in patients with type 2 diabetes mellitus.

Design: A double-blind clinical trial, at the Experimental and Clinical Therapeutics Institute, University Health Sciences Center, at the Universidad de Guadalajara, in inpatients with T2D according to the 2023 ADA criteria.

Methods: Thirty patients (15 males and 15 females), aged between 35 and 65 years, were included in this study, according to the 2023 ADA criteria. The eligible patients were randomly assigned to three groups: empagliflozin 25 mg once daily, dapagliflozin 10 mg once daily, or placebo once daily. Anthropometric parameters were taken using validated techniques. FMD was measured using a high-resolution semiautomatic ultrasound UNEX-EF 38G (UNEX Co., Ltd., Nagoya, Japan). Arterial tension was determined with the OMRON electronic digital sphygmomanometer (HEM 907 XL, Kyoto, Japan).

Results: The group of patients who received empagliflozin had a significantly lower baseline flow-mediated dilation (FMD) compared to the group receiving dapagliflozin (p = 0.017); at the end of this study, the empagliflozin group achieved a comparable FMD to the dapagliflozin group (p = 0.88).

Conclusion: After the treatment period, the empagliflozin and dapagliflozin groups achieved similar FMD, suggesting a class effect.

Background: Extracellular volume fraction (ECV), measured with contrast-enhanced magnetic resonance imaging (CE-MRI), has been utilized to study myocardial fibrosis, but its role in peripheral artery disease (PAD) remains unknown. We hypothesized that T1 mapping and ECV differ between PAD patients and matched controls.

Methods and results: A total of 37 individuals (18 PAD patients and 19 matched controls) underwent 3.0T CE-MRI. Skeletal calf muscle T1 mapping was performed before and after gadolinium contrast with a motion-corrected modified look-locker inversion recovery (MOLLI) pulse sequence. T1 values were calculated with a three-parameter Levenberg-Marquardt curve fitting algorithm. ECV and T1 maps were quantified in five calf muscle compartments (anterior [AM], lateral [LM], and deep posterior [DM] muscle groups; soleus [SM] and gastrocnemius [GM] muscles). Averaged peak blood pool T1 values were obtained from the posterior and anterior tibialis and peroneal arteries. T1 values and ECV are heterogeneous across calf muscle compartments. Native peak T1 values of the AM, LM, and DM were significantly higher in PAD patients compared to controls (all p < 0.028). ECVs of the AM and SM were significantly higher in PAD patients compared to controls (AM: 26.4% (21.2, 31.6) vs. 17.3% (10.2, 25.1), p = 0.046; SM: 22.7% (19.5, 27.8) vs. 13.8% (10.2, 19.1), p = 0.020).

Conclusions: Native peak T1 values across all five calf muscle compartments, and ECV fractions of the anterior muscle group and the soleus muscle were significantly elevated in PAD patients compared with matched controls. Non-invasive T1 mapping and ECV quantification may be of interest for the study of PAD.

Heart failure (HF) with mid-range or mildly reduced ejection fraction (HFmrEF) is a separate clinical entity in the HF spectrum, with a left ventricular ejection fraction ranging from 40 to 49%. While sodium glucose co-transporter 2 inhibitors have become the cornerstone therapy for the entire HF spectrum, there are a few clinical trials of HFmrEF. This prospective observational study was conducted at Dubrava University Hospital, Zagreb, Croatia, from May 2021 to October 2023. We recruited 137 participants diagnosed with HFmrEF at admission. The majority were male, with a median age of 72 and overweight. A total of 110 participants were followed for 6 months and LVEF remained the same in the majority of patients (n = 62, 56.4%), improved in 32 patients (29.1%), and decreased in 3 patients (2.73%). A total of 64 participants were followed for 12 months: 39 remained the same (60.94%) and 25 improved. There were 13 deaths in (9.5%). While the empagliflozin group had a lower BMI at 6-month- and lower HbA1c at 12-month follow-up, there were no differences in death, HF hospitalizations, ER visits, or urinary tract infections in between groups. Despite recent and daily advances in the treatment of all HF phenotypes, HFmrEF still represents a challenge in everyday clinical practice.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) can lead to sudden cardiac death and life-threatening heart failure. Due to its high fatality rate and limited therapies, the pathogenesis and diagnosis biomarker of ARVC needs to be explored urgently. This study aimed to explore the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network in ARVC. The mRNA and lncRNA expression datasets obtained from the Gene Expression Omnibus (GEO) database were used to analyze differentially expressed mRNA (DEM) and lncRNA (DElnc) between ARVC and non-failing controls. Differentially expressed miRNAs (DEmiRs) were obtained from the previous profiling work. Using starBase to predict targets of DEmiRs and intersecting with DEM and DElnc, a ceRNA network of lncRNA-miRNA-mRNA was constructed. The DEM and DElnc were validated by real-time quantitative PCR in human heart tissue. Protein-protein interaction network and weighted gene co-expression network analyses were used to identify hub genes. A logistic regression model for ARVC diagnostic prediction was established with the hub genes and their ceRNA pairs in the network. A total of 448 DEMs (282 upregulated and 166 downregulated) were identified, mainly enriched in extracellular matrix and fibrosis-related GO terms and KEGG pathways, such as extracellular matrix organization and collagen fibril organization. Four mRNAs and two lncRNAs, including COL1A1, COL5A1, FBN1, BGN, XIST, and LINC00173 identified through the ceRNA network, were validated by real-time quantitative PCR in human heart tissue and used to construct a logistic regression model. Good ARVC diagnostic prediction performance for the model was shown in both the training set and the validation set. The potential lncRNA-miRNA-mRNA regulatory network and logistic regression model established in our study may provide promising diagnostic methods for ARVC.

Amidst an aging population and escalating obesity prevalence, elucidating the impact of obesity on transcatheter aortic valve replacement (TAVR) outcomes becomes paramount. The so-called "obesity paradox"-a term denoting the counterintuitive association of obesity, typically a risk factor for cardiovascular diseases, with improved survival outcomes in TAVR patients relative to their leaner or normal-weight counterparts-merits rigorous examination. This review comprehensively investigates the complex relationship between obesity and the clinical outcomes associated with TAVR, with a specific focus on mortality and periprocedural complications. This study aims to deepen our understanding of obesity's role in TAVR and the underlying mechanisms of the obesity paradox, thereby optimizing management strategies for this patient demographic, tailored to their unique physiological and metabolic profiles.

Congenital heart disease (CHD) is increasingly diagnosed prenatally and the ability to screen and diagnose the genetic factors involved in CHD have greatly improved. The presence of a genetic abnormality in the setting of prenatally diagnosed CHD impacts prenatal counseling and ensures that families and providers have as much information as possible surrounding perinatal management and what to expect in the future. This review will discuss the genetic evaluation that can occur prior to birth, what different genetic testing methods are available, and what to think about in the setting of various CHD diagnoses.

Fetal cardiac intervention (FCI) is an emerging and rapidly advancing group of interventions designed to improve outcomes for fetuses with cardiovascular disease. Currently, FCI is comprised of pharmacologic therapies (e.g., trans-placental antiarrhythmics for fetal arrhythmia), open surgical procedures (e.g., surgical resection of pericardial teratoma), and catheter-based procedures (e.g., fetal aortic valvuloplasty for aortic stenosis). This review focuses on the rationale, criteria for inclusion, technical details, and current outcomes of the three most frequently performed catheter-based FCI procedures: (1) aortic valvuloplasty for critical aortic stenosis (AS) associated with evolving hypoplastic left heart syndrome (HLHS), (2) atrial septal intervention for HLHS with severely restrictive or intact atrial septum (R/IAS), and (3) pulmonary valvuloplasty for pulmonary atresia with intact ventricular septum (PA/IVS).