International journal of cardiology. Congenital heart disease最新文献

Peripartum cardiomyopathy (PPCM) is a rare, but serious condition, with a non-negligible risk of adverse events. Several risk factors for PPCM have been individuated over the years, including Afro-American ethnicity, preeclampsia, advanced maternal age, genetic predisposition, multiparity, twin pregnancy, obesity, smoking and diabetes. However, PPCM pathophysiology is still poorly understood, thus making it challenging to develop disease specific therapies. At present, Bromocriptine is the only targeted drug, but further evidence is needed to establish indication and timing of administration. Therefore, these patients are mainly treated following general heart failure guidelines. Even though in most patients left ventricular ejection fraction recovers during follow-up, cases of persistent left ventricular dysfunction are not uncommon. Moreover, all patients detain a certain risk of recurrence after subsequent pregnancies, which is difficult to estimate due to the dearth of long-term prospective data.

In this manuscript, we aim to provide an updated review of current evidence about PPCM pathophysiology, diagnosis, treatment and recurrence risk. In addition, we discuss the gaps in knowledge that should be addressed by future research.

Cardiac catheterization (CC) is essential for the diagnosis of pulmonary hypertension (PH), and for its characterisation. It allows distinction between pre- and post-capillary PH which, when integrated with other non-invasive data, facilitates classification into one of the 5 diagnostic groups defined by international PH guidelines. CC also provides valuable information for the risk stratification of patients with PH, guiding management and the type and intensity of treatment. Right heart catheterization is usually sufficient in PH practice, yet additional information can be acquired by extending the protocol to include left heart catheterization or provocation protocols.

This review provides a detailed overview of diagnostic CC as used in PH practice, including in patients with congenital heart disease, with an emphasis on fundamental concepts, tips and tricks and potential pitfalls.

Pulmonary arterial hypertension (PAH) is defined as increase in mean pulmonary arterial pressure and pulmonary vascular resistance (PVR). It can be associated with congenital heart disease (CHD) with the following subtypes: 1) uncorrected left-to-right (L-R) intracardiac shunt leading to overload of the pulmonary circulation and a progressive increase of PVR; 2) Eisenmenger syndrome, appearing when a large post-tricuspid shunt is left uncorrected and pulmonary vascular disease (PVD) is severe, so the shunt becomes bidirectional or right-to-left, causing cyanosis; 3) PAH after shunt closure, when PVR arises after a defect correction; and 4) PAH associated with small or coincidental defects. While the treatment of patients with Eisenmenger syndrome is well established, the treatment of patients with PAH in whom there is a L-R shunt (with no cyanosis) remains unclear and requires expertise. In such patients, correction of the defect may be contemplated if there is mild PVD and a significant L-R shunt. Others may benefit from a “treat and repair” strategy, which involves the use of PAH therapy to achieve a drop in PVR, with the aim of achieving operability criteria. Cardiac catheterization is at the center of the evaluation and follow-up of these patients, collecting “baseline” data and providing the opportunity to challenge the pulmonary circulation, manipulate the loading status, or temporarily occlude the defect. This article provides a detailed overview of the pathophysiology and treatment options for patients with PAH associated with a L-R congenital shunt, including current approaches to operability and the use of PAH therapies.

Pulmonary arterial Hypertension (PAH) is a progressive disease marked by significant morbidity and mortality due to pulmonary vasculopathy and right ventricular (RV) dysfunction. Despite advances in PAH medical therapies which have improved clinical outcomes and survival, patients continue to face severe complications, including a notable incidence of sudden cardiac death (SCD). The high arrhythmic burden, coupled with mechanical complications such as left main compression syndrome, pulmonary artery dissection, rupture, and severe hemoptysis, significantly contribute to the risk of SCD. Close monitoring and a meticulous diagnostic approach are essential for risk stratification and timely intervention, aiming to mitigate the risk of premature death in these patients. The aim of this review is to provide a comprehensive understanding of these risks and highlight strategies for improving patient outcomes through early identification, prevention and effective management.

Objective

Repaired Tetralogy of Fallot (rTOF), a complex congenital heart disease, exhibits substantial clinical heterogeneity. Accurate prediction of disease progression and tailored patient management remain elusive. We aimed to categorize rTOF patients into distinct phenotypes based on clinical variables and variables obtained from cardiac magnetic resonance (CMR) imaging.

Methods

A retrospective observational cohort study of rTOF patients with at least two CMR assessments between 2005 and 2022 was performed. From patient records, clinical variables, CMR measurements, and electrocardiogram data were collected and processed. Baseline and follow-up variables between subsequent CMR studies were used to assess both inter- and intrapatient disease heterogeneity. Subsequently, unsupervised machine learning was performed, involving dimensionality reduction using principal component analysis and K-means clustering to identify different phenotypic clusters.

Results

In total, 155 patients (54.2 % male, median 14.9 years) were included and followed for a median duration of 9.9 years. A total of 459 CMR studies were included in analysis for the identification of phenotypic clusters. Following analysis, we identified four distinct rTOF phenotypes: (1) stable/slow deteriorating, (2) deteriorating, structural remodeling, (3) deteriorated indicated for pulmonary valve replacement, and lastly (4) younger patients with coexisting anomalies. These phenotypes exhibited differential clinical profiles (p < 0.01), cardiac remodeling patterns (p < 0.01), and intervention rates (p < 0.01).

Conclusions

Unsupervised machine learning analysis unveiled four discrete phenotypes within the rTOF population, elucidating the substantial disease heterogeneity on both a population- and patient-level. Our study underscores the potential of unsupervised machine learning as a valuable tool for characterizing complex congenital heart disease and potentially tailoring interventions.

Pulmonary hypertension (PH) encompasses a group of conditions which ultimately lead to elevated pulmonary arterial pressure. PH is classified into five subgroups, of which Group 1 pulmonary arterial hypertension (PAH), is the most extensively studied. Numerous causal genes have been identified in PAH, most notably germline mutations in bone morphogenetic protein receptor type 2 (BMPR2) and the wider BMP pathway. Often when considering the genetics of PH, sporadic idiopathic and heritable PAH dominates the discussion. There are a number of reviews that elegantly describe the ‘state of the art’ in respect to group 1 PAH, however this focus misses the wider context of genetic conditions where PH is a feature, but outside of the framework of classical ‘idiopathic or heritable’ PAH. In addition to variants in genes within the TGF-β/BMP signaling pathway, genes which regulate ion channels, the extracellular matrix, inflammation, angiogenesis, and mitochondrial dysfunction have been shown to play a significant role in PH pathogenesis across different PH groups. In this review, we aim to cast the net wider to understand what we can learn from the spectrum of genetic conditions where PH is an acknowledged feature or complication, and what this tells us about the important cellular, molecular and systems physiology features that predispose to PH and consequently might be treatment targets.

Background

The prevalence of vitamin D deficiency and secondary hyperparathyroidism (sHPT) in adult Fontan patients remains unstudied, and the role of vitamin D and parathyroid hormone (PTH) levels in assessing heart and circulatory failure in these patients is unclear.

Methods

We compared vitamin D deficiency and sHPT prevalence in adult Fontan patients (n = 35; mean age 33 ± 7.5 years) to adults with mild congenital heart disease (ACHD, n = 14). We analyzed associations between laboratory measurements, patient characteristics, and clinical events.

Findings

Vitamin D deficiency was highly prevalent in both Fontan patients and ACHD controls (76.5 % vs. 71.4 %, p = 0.726). sHPT was exclusively present in Fontan patients (31.4 %). PTH levels correlated with NYHA class (r = 0.412), O2 saturation (r = −0.39), systemic ventricular function (r = 0.465), and NT-proBNP levels (r = 0.742). 25-hydroxyvitamin D showed an inverse correlation with NYHA class and systemic ventricular function (both r ≤ −0.38). Fontan patients with sHPT had a higher incidence of prior hospitalization for worsening heart failure and atrial arrhythmias compared to Fontan patients without HPT or ACHD controls. (Hospitalization: Fontan with HPT vs. Fontan without HPT: OR 5.46 [95 % CI 1.25–23.86], p = 0.021; arrhythmia: Fontan with HPT vs. Fontan without HPT: OR 1.96 [95 % CI 1.13–3.4], p = 0.035; ACHD: OR 11.45 [95 % CI 1.7–77.28], p=<0.001). PTH showed significant correlation with inflammatory markers, particularly with GDF-15 (r = 0.8).

Conclusion

Our study is the first to demonstrate a high prevalence of vitamin D deficiency and sHPT in adult Fontan patients. As PTH strongly correlates with heart failure severity, it seems to be a promising biomarker in Fontan patients.