Age-dependent impact of the SYNTAX-score on longer-term mortality after percutaneous coronary intervention in an all-comer population

Background The Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery （SYNTAX）-score is a validated tool for risk stratification and revascularization strategy selection in patients with complex coronary artery disease. The aim of this study was to analyse its age-related prognostic value. Methods SYNTAX-score was calculated in 1331 all-comer patients undergoing percutaneous coronary intervention （PCI）： 463 patients ≥ 75 years and 868 patients 〈 75 years. Outcomes of interest were all-cause mortality at one and two years. Results A significant interaction of age and SYNTAX-score for mortality was observed at two-year （Pinteraction= 0.019） but not at one-year follow-up （Pinteraction= 0.594）. In multivariable analysis, SYNTAX-score independently predicted 1-year mortality in both age groups （〈 75 years, hazard ratio （HR）： 1.43, 95% confidence intervals （CI）： 1.03-2.00, P = 0.034; and 〉 75 years, HR： 1.37, 95% CI： 1.01-1.85, P = 0.042）, but only two-year mortality among younger patients （〈 75 years, HR： 1.33, 95% CI： 1.01-1.76, P = 0.041; and ≥ 75 years, HR： 1.11, 95% CI： 0.87-1.41, P = 0.394）. SYNTAX-score tertiles were useful to stratify 1-year mortality in both, patients 〈 75 years （SYNTAX-score 〈 9, 3.8%; 9-20, 5.3%; 〉 20, 10.3%; P = 0.004） and 〉 75 years （SYNTAX-score 〈 11, 5.7%; 11-22.5, 16.1%; 〉 22.5, 18.7%; P = 0.003）, but two-year mortality only among patients 〈 75 years （SYNTAX-score 〈 9, 6.5%; 9-20, 7.6%; ≥ 20, 15%; P 〈 0.001） and not among ≥ 75 years old patients （SYNTAX-score 〈 11, 19.4%; 11-22.5, 26.3%; _〉 22.5, 27.9%; P = 0.138）. Conclusions Age modi- fies the impact of the SYNTAX-score on longer-term mortality after PCI. Among patients 〈 75 years, the SYNTAX-score independently predicts the risk of death at one and two years after PCI, while among patients 〉 75 years its predictive role is limited to the first year after PCI. Further studies are needed to evaluate the value of SYNTAX-score for selecting the most appropriate revascularization strategy among elderly patients.

An unexpected cellular fountain of youth:platelets provide factors rejuvenating brain functions

In a recent manuscript published in Nature,Schroer et al.discovered that platelets and in particular platelet derived PF-4(CXCL4)are a novel factor,which can rejuvenate the mammalian neuronal system.1 These findings have the potential to trigger an entire new field of research opening new platelet-derived candidate effector molecules for supporting regeneration.

Computational Cardiology--A New Discipline of Translational Research

Over the past two decades, improved diagnosis, pharmaceutical therapies, and interventional strategies have impressively improved the armamentarium of modern cardiologists in the fight against the most incident and lethal diseases： heart failure, ischemic heart disease, and arrhythmia. The innovations in the field have mostly been enabled by inventions based on hypothesis-driven approaches. The invention and development of key cardiac biomarkers, such as natriuretic peptides and cardiac-specific troponins, may serve as examples.

Pro?ling and Validation of the Circular RNA Repertoire in Adult Murine Hearts

For several decades, cardiovascular disease has been the leading cause of death throughout all countries. There is a strong genetic component to many disease subtypes （e.g., cardiomyopa- thy） and we are just beginning to understand the relevant genetic factors. Several studies have related RNA splicing to cardiovascular disease and circular RNAs （circRNAs） are an emerging player, circRNAs, which originate through back-splicing events from primary transcripts, are resis- tant to exonucleases and typically not polyadenylated. Initial functional studies show clear phenotypic outcomes for selected circRNAs. We provide, for the first time, a comprehensive catalogue of RNase R-resistant circRNA species for the adult murine heart. This work combines state-of-the-art circle sequencing with our novel DCC software to explore the circRNA landscape of heart tissue. Overall, we identified 575 circRNA species that pass a beta-binomial test for enrichment （false discovery rate of 1%） in the exonuclease-treated sequencing sample. Several circRNAs can be directly attributed to host genes that have been previously described as associated with cardiovascular disease. Further studies of these candidate circRNAs may reveal disease-relevant properties or functions of specific circRNAs.

Hide and Seek: Protein-coding Sequences Inside ‘‘Non-coding” RNAs

Calcium homeostasis is crucial for muscle contractilityMuscle cells are critically dependent on calcium homeostasis. Without having the right amount of calcium ions just on the spot and coordinated in between muscle cells, no contraction can take place. Therefore, calcium homeostasis is one of the critical regulatory mechanisms in all muscle cells, including skeletal muscle and heart [1,2]. Ca2＋ adenosine triphosphatase the relaxation of muscle cells Sarco-endoplasmic reticulum （SERCA） is responsible for by pumping Ca2＋ into the sarcoplasmic reticulum （SR） .

The Role of Quality Control in Targeted Next-generation Sequencing Library Preparation

Next-generation sequencing （NGS） is getting routinely used in the diagnosis of hereditary diseases, such as human cardiomyopathies. Hence. it is of utter importance to secure high quality sequencing data, enabling the identification of disease-relevant mutations or the conclusion of negative test results. During the process of sample preparation, each protocol for target enrichment library preparation has its own requirements for quality control （QC）; however, there is little evi- dence on the actual impact of these guidelines on resulting data quality. In this study, we analyzed the impact of QC during the diverse library preparation steps of Agilent SureSelect XT target enrichment and lllumina sequencing. We quantified the parameters for a cohort of around 600 samples, which include starting amount of DNA, amount of sheared DNA, smallest and largest fragment size of the starting DNA; amount of DNA after the pre-PCR, and smallest and largest fragment size of the resulting DNA; as well as the amount of the final library, the corresponding smallest and largest fragment size, and the number of detected variants. Intriguingly, there is a high tolerance for variations in all QC steps, meaning that within the boundaries proposed in the current study, a considerable variance at each step of QC can be well tolerated without compromising NGS quality.

Personalized Computer Simulation of Diastolic Function in Heart Failure

The search for a parameter representing left ventricular relaxation from non-invasive and invasive diagnostic tools has been extensive, since heart failure （HF） with preserved ejection fraction （HF-pEF） is a global health problem. We explore here the feasibility using patient-specific cardiac computer modeling to capture diastolic parameters in patients suffering from different degrees of systolic HF. Fifty eight patients with idiopathic dilated cardiomyopathy have undergone thorough clinical evaluation, including cardiac magnetic resonance imaging （MRI）, heart catheterization, echocardiography, and cardiac biomarker assessment. A previously-introduced framework for creating multi-scale patient-specific cardiac models has been applied on all these patients. Novel parameters, such as global stiffness factor and maximum left ventricular active stress, representing cardiac active and passive tissue properties have been computed for all patients. Invasive pressure measurements from heart catheterization were then used to evaluate ventricular relaxation using the time constant of isovolumic relaxation Tau （τ）. Parameters from heart catheterization and the multi-scale model have been evaluated and compared to patient clinical presentation. The model parameter global stiffness factor, representing diastolic passive tissue properties, is correlated significantly across the patient population with τ. This study shows that multi-modal cardiac models can successfully capture diastolic （dys） function, a prerequisite for future clinical trials on HF-pEF.