J. Cardiovasc. Dev. Dis., Volume 11, Issue 6 (June 2024) – 16 articles

Fetal cardiology has evolved over the last 40 years and changed the timing of diagnosis and counseling of congenital heart disease, decision-making, planning for treatment at birth, and predicting future surgery from the postnatal to the prenatal period. Ethical issues in fetal cardiology transect multiple aspects of biomedical ethics including improvement in prenatal detection and diagnostic capabilities, access to equitable comprehensive care that preserves a pregnant person’s right to make decisions, access to all reproductive options, informed consent, complexity in shared decision-making, and appropriate use of fetal cardiac interventions. This paper first reviews the literature and then provides an ethical analysis of accurate and timely diagnosis, equitable delivery of care, prenatal counseling and shared decision-making, and innovation through in utero intervention. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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). Full article

The congenital Gerbode defect is defined as an abnormal communication between the left ventricle and the right atrium. This review aimed to summarize existing evidence, shed light on the clinical implications, and identify knowledge gaps. The systematic literature search was conducted in the PubMed and Google Scholar medical databases using specifically selected keywords. The inclusion of each publication was assessed according to predefined eligibility criteria based on the PICOM (Population, Phenomenon of Interest, Context, Methodology) schema. Titles and abstracts were screened independently by two authors. Available full-text versions of included publications were reviewed and relevant information was extracted. A total of 78 reports were included. The compilation of all congenital Gerbode defect cases described in the literature revealed a variety of clinical presentations comprising dyspnea, palpitations, growth retardation, and asymptomatology. A suitable multimodal diagnostic approach for newborns consists of auscultation, TTE, and optionally TEE and MRI. Because of its rarity, diversity of findings, unknown pathophysiology, and similarity to more common cardiac diseases, the diagnostic challenge remains significant. To prevent untreated long-term sequelae, early individualized treatment is recommended. Surgical defect closure is preferred to device closure for evidence reasons, although major developments are currently taking place. In conclusion, the congenital Gerbode defect provides a diagnostic challenge for pediatricians to allow early diagnosis and intervention in order to improve patients’ quality of life. Full article

Abstract: Elevated serum uric acid (sUA) is associated with the risk of developing cardiovascular disease (CVD). Here, we examined the prognostic significance of sUA and exercise capacity in 411 Japanese adults (age, ≥65; mean, 81 years) hospitalized for worsening CVD. When the patients were stratified by sUA into three groups (<5.3, 5.4–6.9, >7.0 mg/dL), the high-sUA group had a significantly worse peak VO₂ and composite endpoint (rehospitalization due to worsening CVD and all-cause mortality) compared with low- and moderate-sUA groups (p < 0.001). When the patients were stratified by sUA into five groups (sUA < 3.9, 4.0–5.9, 6.0–7.9, 8.0–8.9, and >10.0 mg/dL), the incidence of the composite endpoint was significantly higher in the highest sUA group compared with that in the reference group, but only in women. Univariate Cox regression analysis, but not a multivariate analysis, indicated that sUA was significantly associated with the composite endpoint. Although sUA and exercise capacity may have some degree of prognostic significance in older patients with CVD, this significance may differ between men and women. Full article

Culturally and linguistically diverse (CALD) communities are growing globally. Understanding patterns of cerebrovascular disease in these communities may improve health outcomes. We aimed to compare the rates of transient ischaemic attack (TIA), ischaemic stroke (IS), intracerebral haemorrhage (ICH), intracranial atherosclerosis (ICAD), and stroke risk factors in Vietnamese-born residents of South-Western Sydney (SWS) with those of an Australian-born cohort. A 10-year retrospective analysis (2011–2020) was performed using data extracted from the Health Information Exchange database characterising stroke presentations and risk factor profiles. The rates of hypertension (83.7% vs. 70.3%, p <0.001) and dyslipidaemia (81.0% vs. 68.2%, p < 0.001) were significantly higher in Vietnamese patients, while the rates of ischaemic heart disease (10.4% vs. 20.3%, p < 0.001), smoking (24.4% vs. 40.8%, p < 0.001), and alcohol abuse (>1 drink/day) (9.6% vs. 15.9%, p < 0.001) were lower. The rates of ICAD and ICH were higher in Vietnamese patients (30.9% vs. 6.9%, p < 0.001 and 24.7% vs. 14.4%, p = 0.002). Regression analysis revealed that diabetes (OR: 1.86; 95% CI: 1.14–3.04, p = 0.014) and glycosylated haemoglobin (OR: 1.51; 95% CI: 1.15–1.98, p = 0.003) were predictors of ICAD in Vietnamese patients. Vietnamese patients had higher rates of symptomatic ICAD and ICH, with unique risk factor profiles. Culturally specific interventions arising from these findings may more effectively reduce the community burden of disease. Full article

Diagnosis and management of fetal arrhythmias have changed over the past 40–50 years since propranolol was first used to treat fetal tachycardia in 1975 and when first attempts were made at in utero pacing for complete heart block in 1986. Ongoing clinical trials, including the FAST therapy trial for fetal tachycardia and the STOP-BLOQ trial for anti-Ro-mediated fetal heart block, are working to improve diagnosis and management of fetal arrhythmias for both mother and fetus. We are also learning more about how “silent arrhythmias”, like long QT syndrome and other inherited channelopathies, may be identified by recognizing “subtle” abnormalities in fetal heart rate, and while echocardiography yet remains the primary tool for diagnosing fetal arrhythmias, research efforts continue to advance the clinical envelope for fetal electrocardiography and fetal magnetocardiography. Pharmacologic management of fetal arrhythmias remains one of the most successful achievements of fetal intervention. Patience, vigilance, and multidisciplinary collaboration are key to successful diagnosis and treatment. Full article

Aortic stenosis (AS) is the most prevalent degenerative valvular disease in western countries. Transthoracic echocardiography (TTE) is considered, nowadays, to be the main imaging technique for the work-up of AS due to high availability, safety, low cost, and excellent capacity to evaluate aortic valve (AV) morphology and function. Despite the diagnosis of AS being considered straightforward for a very long time, based on high gradients and reduced aortic valve area (AVA), many patients with AS represent a real dilemma for cardiologist. On the one hand, the acoustic window may be inadequate and the TTE limited in some cases. On the other hand, a growing body of evidence shows that patients with low gradients (due to systolic dysfunction, concentric hypertrophy or coexistence of another valve disease such as mitral stenosis or regurgitation) may develop severe AS (low-flow low-gradient severe AS) with a similar or even worse prognosis. The use of complementary imaging techniques such as transesophageal echocardiography (TEE), multidetector computed tomography (MDTC), or cardiac magnetic resonance (CMR) plays a key role in such scenarios. The aim of this review is to summarize the diagnostic challenges associated with patients with AS and the advantages of a comprehensive multimodality cardiac imaging (MCI) approach to reach a precise grading of the disease, a crucial factor to warrant an adequate management of patients. Full article

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation. The purpose of this systematic review is to evaluate the effectiveness of exercise training on functional capacity and quality of life (QoL) in patients with RA. We performed a search in four databases, selecting clinical trials that included community or outpatient exercise training programs in patients with RA. The primary outcome was functional capacity assessed by peak VO₂ or the 6 min walking test, and the secondary outcome was QoL assessed by questionnaires. Seven studies were finally included, identifying a total number of 448 patients. The results of the present systematic review show a statistically significant increase in peak VO₂ after exercise training in four out of seven studies. In fact, the improvement was significantly higher in two out of these four studies compared to the controls. Six out of seven studies provided data on the patients’ QoL, with five of them managing to show statistically significant improvement after exercise training, especially in pain, fatigue, vitality, and symptoms of anxiety and depression. This systematic review demonstrates the beneficial effects of exercise training on functional capacity and QoL in patients with RA. Full article

We characterized the performance, as well as the safety, of a second-generation thin-strut sirolimus-eluting stent with a biodegradable polymer, Alex Plus (Balton, Poland), implanted in patients with type 2 diabetes (DM) with a 4-year follow-up. We defined the primary endpoint as the 48-month rate of major cardiovascular adverse events (MACE), including cardiac death, myocardial infarction (MI), or target lesion revascularization (TLR). The secondary endpoints were all-cause death, cardiac death, MI, and TLR rates at 12, 24, 36, and 48 months. We enrolled 232 patients in whom 282 stents were implanted, including 97 DM and 135 non-DM patients. The mean age of the DM patients was 69.5 ± 10.1 years and females accounted for 30% of the patients. DM patients had higher rates of arterial hypertension (97% vs. 88%, p = 0.016), dyslipidemia (86% vs. 70%, p = 0.005), prior MI (61% vs. 40%, p = 0.002), prior PCI (65% vs. 50%, p = 0.020), and prior CABG (14% vs. 5.9%, p = 0.029). We recorded statistically significant differences for MACE (HR 1.85, 95% CI 1.01–3.41, p = 0.046), cardiac death (HR 4.46, 95% CI 1.44–13.8, p = 0.010), and MI (HR 3.17, 95% CI 1.10–9.12, p = 0.033), but not for TLR, between DM and non-DM patients in terms of the analyzed endpoints at 4 years. Our study showed that Alex Plus was efficient and safe in a contemporary cohort of real-world DM patients undergoing percutaneous revascularization. Full article

Background: The region of the tricuspid valve is an important area for various cardiac interventions. In particular, the spatial relationships between the right coronary artery and the annulus of the tricuspid valve should be considered during surgical interventions. The aim of this study was to provide an accurate description of the clinical anatomy and topography of this region. Methods: We analyzed 107 computed tomography scans (44% female, age 62.1 ± 9.4 years) of the tricuspid valve region. The circumference of the free wall of the tricuspid valve annulus was divided into 13 annular points and measurements were taken at each point. The prevalence of danger zones (distance between artery and annulus less than 2 mm) was also investigated. Results: Danger zones were found in 20.56% of the cases studied. The highest prevalence of danger zones and the smallest distances were found at the annular points of the tricuspid valve located at the posterior insertion of the leaflets, without observed sex-specific differences. Conclusion: The highest risk of iatrogenic damage to the right coronary artery is in the posterior part of the tricuspid valve annulus. Full article

Background: Percutaneous left-atrial appendage closure (LAAC) is an established method for preventing strokes in patients with atrial fibrillation, offering an alternative to oral anticoagulation. Various occluder devices have been developed to cater to individual anatomical needs and ensure a safe and effective procedure. In this retrospective, monocentric cohort study, we compare different LAAO devices with respect to clinical outcomes, LAA sealing properties, and device-related complications. Methods: We conducted a retrospective analysis of 270 patients who underwent percutaneous LAA closure in our center between 2009 and 2023. Patient data were extracted from medical records, including gender, age at implantation, indication, device type and size, laboratory values, LAA anatomy, periprocedural complications, ECG parameters, transthoracic and transesophageal echocardiography parameters (TTE and TEE), as well as medication at discharge. Moreover, fluoroscopy time and implantation duration, as well as post-implantation clinical events up to 1 year, were collected. Endpoints were bleeding events, recurrent stroke, thrombi on devices, and death. Results: The implanted devices were the Watchman 2.5, Watchman FLX, Amplatzer Cardiac Plug (ACP), and Amulet. The procedural success rate was 95.7% (n = 265), with cactus anatomy posing the most challenges across all devices. The mean patient age was 75.5 ± 7.7 years, with 64.5% being male. The median CHA2DS2-VASc score was 4.8 ± 1.5 and the median HAS-BLED score was 3.8 ± 1.0. Indications for LAA closure included past bleeding events and elevated bleeding risk. Periprocedural complications were most commonly bleeding at the puncture site, particularly after ACP implantation (p = 0.014). Significant peridevice leaks (PDL) were observed in 21.4% of simple sealing mechanism devices versus 0% in double sealing mechanism devices (p = 0.004). Thrombi were detected on devices in six patients, with no subsequent ischemic stroke or thromboembolic event. Comparative analysis revealed no significant differences in the occurrence of stroke, transient ischemic attack (TIA), thromboembolic events, device-related thrombi, or mortality among different device types. A 62.3% relative risk reduction in thromboembolic events and 38.6% in major bleedings could be observed over 568.2 patient years. Conclusions: In summary, our study highlights the efficacy and safety of LAA closure using various occluder devices despite anatomical challenges. Our long-term follow-up findings support LAA closure as a promising option for stroke prevention in selected patient cohorts. Further research is needed to refine patient selection criteria and optimize outcomes in LAA closure procedures. Full article

Objective: The aim of the present study was to investigate the possible relationship between the segmental burden of lower limb atherosclerosis and Major Adverse Cardiovascular Events (MACEs). Methods: All the consecutive symptomatic peripheral artery disease (PAD) patients admitted for digital subtraction angiography (DSA) at Turku University Hospital department of Vascular Surgery between 1 January 2009 and 30 July 2011 were retrospectively analyzed. Angiography due to symptomatic PAD was used as the index date for the inclusion in the study. The segmental burden of atherosclerosis based on DSA was divided into three categories according to the highest disease burden of the defined artery segment: aorto-iliac, femoropopliteal, or tibial segments. The major association for the study was MACEs (defined as a cerebrovascular event, heart failure (HF) and myocardial infarction requiring hospital admission). Demographic data and MACEs were obtained from the hospital electronic medical records system. Results. The lower limb atherosclerosis burden of tibial vessels was related to an increased probability for HF (OR 3.9; 95%CI 2.4–6.5) and for MACEs overall (OR 2.3; 95%CI 1.4–3.6). The probability of both HF and MACEs overall rose with the increasing severity of the atherosclerosis burden. Moreover, the more severe the tibial vessel atherosclerosis, the higher the risk of HF and MACEs. The most extensive tibial atherosclerosis patients had an OR 4.5; 95%CI 2.6–8.0 for HF and an OR 3.1; and 95%CI 1.7–5.6 for MACEs overall. The femoropopliteal disease burden was also associated with an increased risk of HF (OR 2.3; 95%CI 1.6–3.2) and MACE (OR 1.9; 95%CI 1.3–2.7). However, the increasing extent of atherosclerosis of the femoropopliteal segment solely increased the risk of MACEs. Conclusions: PAD patients with severe tibial atherosclerosis are likely to present with MACEs. The risk is further enhanced as the extent of tibial vessel atherosclerosis is increased. An association between MACE and severe atherosclerosis on the aortoiliac segment was not detected. However, when the femoropopliteal segment was the most affected artery segment, the risk of MACEs was increased. Full article