Disease-specific therapy for the treatment of the cardiovascular manifestations of Fabry disease: a systematic review.

OBJECTIVE: The cardiovascular manifestations of Fabry disease are common and represent the leading cause of death. Disease-specific therapy, including enzyme replacement therapy (ERT) and chaperone therapy (migalastat), is recommended for patients exhibiting cardiovascular involvement, but its efficacy for modulating cardiovascular disease expression and optimal timing of initiation remains to be fully established. We therefore aimed to systematically review and evaluate the effectiveness of disease-specific therapy compared with placebo, and to no intervention, for the cardiovascular manifestations of Fabry disease. METHODS: Eight databases were searched from inception using a combination of relevant medical subject headings and keywords. Randomised, non-randomised studies with a comparator group and non-randomised studies without a comparator group were included. Studies were screened for eligibility and assessed for bias by two independent authors. The primary outcome comprised clinical cardiovascular events. Secondary outcomes included myocardial histology and measurements of cardiovascular structure, function and tissue characteristics. RESULTS: 72 studies were included, comprising 7 randomised studies of intervention, 16 non-randomised studies of intervention with a comparator group and 49 non-randomised studies of intervention without a comparator group. Randomised studies were not at serious risk of bias, but the others were at serious risk. Studies were highly heterogeneous in their design, outcome measurements and findings, which made assessment of disease-specific therapy effectiveness difficult. CONCLUSION: It remains unclear whether disease-specific therapy sufficiently impacts the cardiovascular manifestations of Fabry disease. Further work, ideally in larger cohorts, with more standardised clinical and phenotypic outcomes, the latter measured using contemporary techniques, are required to fully elucidate the cardiovascular impact of disease-specific therapy. PROSPERO REGISTRATION NUMBER: CRD42022295989.

Inflammatory Fabry Cardiomyopathy Demonstrated Using Simultaneous [18F]-FDG PET-CMR.

Using hybridized [18F]-fluorodeoxyglucose positron emission tomography with cardiac magnetic resonance, we identify active myocardial inflammation and demonstrate its relationship with late gadolinium enhancement, in Fabry disease. We demonstrate that late gadolinium enhancement represents, at least in part, active myocardial inflammation and identify an early inflammatory phenotype that may represent a therapeutic window before irreversible tissue injury and adaptation occur. (Level of Difficulty: Intermediate.).

Validated Model for Prediction of Adverse Cardiac Outcome in Patients With Fabry Disease.

BACKGROUND: The cardiac manifestations of Fabry disease are the leading cause of death, but risk stratification remains inadequate. Identifying patients who are at risk of adverse cardiac outcome may facilitate more evidence-based treatment guidance. Contemporary cardiovascular cardiac magnetic resonance biomarkers have become widely adopted, but their prognostic value remains unclear. OBJECTIVES: The objective of this study was to develop, internally validate, and evaluate the performance of, a prognostic model, including contemporary deep phenotyping, which can be used to generate individual risk estimates for adverse cardiac outcome in patients with Fabry disease. METHODS: This longitudinal prospective cohort study consisted of 200 consecutive patients with Fabry disease undergoing clinical cardiac magnetic resonance. Median follow-up was 4.5 years (IQR: 2.7-6.3 years). Prognostic models were developed using Cox proportional hazards modeling. Outcome was a composite of adverse cardiac events. Model performance was evaluated. A risk calculator, which provides 5-year estimated risk of adverse cardiac outcome for individual patients, including men and women, was generated. RESULTS: The highest performing, internally validated, parsimonious multivariable model included age, native myocardial T1 dispersion (SD of per voxel myocardial T1 relaxation times), and indexed left ventricular mass. Median optimism-adjusted c-statistic across 5 imputed model development data sets was 0.77 (95% CI: 0.70-0.84). Model calibration was excellent across the full risk profile. CONCLUSIONS: This study developed and internally validated a risk prediction model that accurately predicts 5-year risk of adverse cardiac outcome for individual patients with Fabry disease, including men and women, which could easily be integrated into clinical care. External validation is warranted.

The Journal of cardiovascular computed tomography: A year in review 2021.

This review aims to summarize original articles published in the Journal of Cardiovascular Computed Tomography (JCCT) for the year 2021, focusing on those that had the most scientific and educational impact. The JCCT continues to expand; the number of submissions, published manuscripts, cited articles, article downloads, social media presence, and impact factor continues to increase. The articles selected by the Editorial Board of the JCCT in this review focus on coronary artery disease, coronary physiology, structural heart disease, and technical advances in cardiovascular CT. In addition, we highlight key consensus documents and guidelines published in the Journal in 2021. The Journal recognizes the tremendous work done by each author and reviewer this year - thank you.

Unraveling an Unusual Phenocopy of Hypertrophic Cardiomyopathy: MELAS Syndrome.

The mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is an uncommon cause of cardiac hypertrophy, fibrosis, and dysfunction. It shares similar features to numerous other causes of left ventricular hypertrophy, and therefore, because of its rarity, may not be immediately considered as a diagnosis. Prompt recognition of clinical and cardiac imaging features may expedite diagnosis and management. We report the case of a 38-year-old man admitted with neurological symptoms and in whom the diagnostic workup led to the diagnosis of MELAS syndrome with cardiac involvement.

CT-Derived Fractional Flow Reserve (FFRCT): From Gatekeeping to Roadmapping.

Coronary computed tomography angiography (CCTA) has emerged as the preferred modality in the diagnosis of coronary artery disease, but it is limited by modest specificity. By applying principles of computational fluid dynamics, flow fraction reserve, a measure of lesion-specific ischemia that is used to guide revascularization, can be noninvasively derived from CCTA, the so-called computed tomography-derived flow fractional reserve (FFRCT). The accuracy of FFRCT in discriminating ischemia has been extensively validated, and it has been shown to improve the specificity of CCTA. Compared to other stress myocardial perfusion imaging, FFRCT has superior or comparable accuracy. Clinical studies have provided strong evidence that FFRCT has significant prognostic implications and informs clinical decisions for revascularization, serving as a gatekeeper to invasive coronary angiography. In addition, FFRCT-based tools can be used to simulate the physiological consequences of different revascularization strategies, thus providing the roadmap to achieve complete revascularization. Although challenges remain, ongoing research and randomized controlled trials are expected to address current limitations and better define its role in clinical practice.

The Value of Cardiovascular Magnetic Resonance in Heart Transplant Patients.

Heart transplant patients present a unique set of anatomical and pathophysiological considerations. Patients often present non-specifically, requiring a low index for further investigation. Accurate assessment with standard imaging modalities can be difficult, and cardiovascular magnetic resonance (CMR) is becoming an increasingly useful modality in the assessment of heart transplant patients. This review describes the anatomy of the transplanted heart and typical CMR appearances and discusses the role of CMR in heart transplant disease.