Clonal hematopoiesis, a condition in which individual hematopoietic stem cell clones generate a disproportionate fraction of blood leukocytes, correlates with higher risk for cardiovascular disease. ...The mechanisms behind this association are incompletely understood. Here, we show that hematopoietic stem cell division rates are increased in mice and humans with atherosclerosis. Mathematical analysis demonstrates that increased stem cell proliferation expedites somatic evolution and expansion of clones with driver mutations. The experimentally determined division rate elevation in atherosclerosis patients is sufficient to produce a 3.5-fold increased risk of clonal hematopoiesis by age 70. We confirm the accuracy of our theoretical framework in mouse models of atherosclerosis and sleep fragmentation by showing that expansion of competitively transplanted Tet2−/− cells is accelerated under conditions of chronically elevated hematopoietic activity. Hence, increased hematopoietic stem cell proliferation is an important factor contributing to the association between cardiovascular disease and clonal hematopoiesis.
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•HSC proliferation is elevated in mice and humans with atherosclerosis•Increased proliferation accelerates somatic evolution and clonal hematopoiesis (CH)•Measured rates imply several-fold increased risk of CH in atherosclerosis patients•Mutant expansion is accelerated in mice with increased HSC proliferation
Heyde et al. propose that clonal hematopoiesis can be a symptom rather than a cause of atherosclerosis, since this disease increases hematopoietic stem cell division, which results in accelerated somatic evolution.
Mechanical valves in the pulmonary position: an international retrospective analysis Pragt, Hanna, MSc; van Melle, Joost P., MD, PhD; Javadikasgari, Hoda, MD ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
10/2017, Letnik:
154, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Abstract Objective Life expectancy of patients with congenital heart disease has improved over the past decades, increasing the need for a durable pulmonary prosthetic valve. Biological valves in ...various forms have become the valve of choice for pulmonary valve replacement (PVR), but structural valve deterioration is unavoidable in the long term. Use of a mechanical valve could be an alternative, but data on long-term outcome is sparse. Methods We retrospectively collected and analyzed data on 364 patients with mechanical valves implanted in the pulmonary position between 1965 and 2014. The data originates from medical centers in Barcelona (Spain), Graz (Austria), Groningen (the Netherlands), Munich (Germany), Rochester (USA), Seoul (Republic of Korea), and Tehran (Iran). Results Median follow-up duration was 4.26 (range 0-27) years, mean age at implantation was 27.16 ± (SD 12.2) years. Tetralogy of Fallot was the most common primary cardiac diagnosis with a subgroup of 69.8%. Freedom from valvar thrombosis was 91% (95%CI 87%-94%) at 5 years and 86% (95% CI 81%-91%) at 10 years post PVR. With a success rate up to 88%, thrombolysis was a successful therapy. Freedom from reoperation was 97% (95% CI 94%-99%) at 5 years post PVR and 91% (95%CI 85%-95%) at 10 years. Conclusion MPVR is associated with a limited risk of valvar thrombosis. Thrombolysis was an effective treatment in the majority.
Abstract
Background
Aortic stenosis is the most common valvulopathy in Western countries. The treatment of choice had been surgery aortic valve replacement (SAVR), but the improvement in endovascular ...approaches as transcatheter aortic valve implantation (TAVI), initially reserved for patients with very high surgical risk, has been extended to high and intermediate, and recently also to low-risk patients. Stroke and vascular cognitive impairment are the most important complications. It is not entirely clear which technique is best to avoid these complications as well as their impact. Our goal is to evaluate changes in cognitive performance in the early (1-month) and late (1-year) postoperative period in patients undergoing SAVR or TAVI, by extensive neuropsychological study (NRP) and advanced Magnetic Resonance Imaging (MRI).
Specifically, to compare early and late cognitive changes after the intervention between both groups, the occurrence of stroke during follow-up and to compare the appearance of silent vascular lesions and changes in brain activity and functional connectivity with functional MRI during follow-up between both groups.
Methods/design
Prospective longitudinal cohort study. A non-selected representative sample of 80 subjects, 40 SAVR and 40 TAVI to obtain a final sample of 36 eligible subjects in each group, ranging from 70 to 85 years old, with indication for aortic replacement and intermediate or high surgical risk will be studied. At baseline, within one month before the treatment, all individuals will undergo an extensive NRP and advanced MRI study. These studies will also be performed 1-month and 1-year after treatment, to assess the appearance of new vascular lesions, as well as changes in cognitive performance with respect to baseline.
Discussion
This study aims to evaluate changes in cognitive performance as well as both clinical and silent vascular events occurring in the early (1-month) and late (1-year) periods after SAVR and TAVI. We will also analyze the correlation between neuropsychological and neuroimaging approaches in order to evaluate cognition. Therefore, it may provide high-quality data of cognitive changes and vascular events for both techniques, and be useful to tailor interventions to individual characteristics and ultimately aiding in decision-making.
Trial registration
This study is register in Clinicaltrials.gov (NCT05235529) on 11
th
February 2022.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aortic stenosis is one of the most prevalent valve diseases but is rarely accompanied by tricuspid regurgitation. Our objective was to analyze the impact of tricuspid regurgitation severity and its ...surgical treatment on prognosis of patients undergoing aortic valve replacement.
This was a retrospective cohort study including all patients presenting with aortic stenosis with some degree of tricuspid regurgitation between 2001 and 2018. Patients were grouped according to the degree of tricuspid regurgitation.
From a sample of 8080 patients with aortic stenosis, 143 (1.8%) presented with more than trace tricuspid regurgitation. Among patients with mild, moderate, or severe tricuspid regurgitation, we observed no differences in 30-day (15.1% vs 14.8% vs 8.7%; P = .727), 12-month (51.2% vs 56% vs 55%; P = .892), or 5-year (64% vs 73.3% vs 66.7%; P = .798) survival. Aortic valve replacement plus tricuspid annuloplasty, when compared with aortic valve replacement only was associated with longer intensive care unit stay (9 vs 3 days; P = .043) but not higher 30-day (0% vs 15.5%; P = .112), 12-month (38.5% vs 54.3%; P = .278), or 5-year mortality (57.1% vs 67.1%; P = .594). Only history of liver disease and postoperative major morbidity were independent predictors of survival 30 days, 12 months and 5 years after surgery.
Severity of tricuspid regurgitation in patients with aortic stenosis was not associated with increased mortality. Tricuspid annuloplasty did not improve survival in this subset of patients but was associated with increased postoperative morbidity.
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Abstract
Aims
Quantitative real-time RT-PCR (RT-qPCR) has become the method of choice for mRNA quantification, but requires an accurate normalization based on the use of reference genes showing ...invariant expression across various pathological conditions. Only few data exist on appropriate reference genes for the human heart. The objective of this study was to determine a set of suitable reference genes in human atrial and ventricular tissues, from right and left cavities in control and in cardiac diseases.
Methods and results
We assessed the expression of 16 reference genes (ACTB, B2M, GAPDH, GUSB, HMBS, HPRT1, IPO8, PGK1, POLR2A, PPIA, RPLP0, TBP, TFRC, UBC, YWHAZ, 18S) in tissues from: right and left ventricles from healthy controls and heart failure (HF) patients; right-atrial tissue from patients in sinus rhythm with (SRd) or without (SRnd) atrial dilatation, patients with paroxysmal (pAF) or chronic (cAF) atrial fibrillation or with HF; and left-atrial tissue from patients in SR or cAF. Consensual analysis (by geNorm and Normfinder algorithms, BestKeeper software tool and comparative delta-Ct method) of the variability scores obtained for each reference gene expression shows that the most stably expressed genes are: GAPDH, GUSB, IPO8, POLR2A, and YWHAZ when comparing either right and left ventricle or ventricle from healthy controls and HF patients; GAPDH, IPO8, POLR2A, PPIA, and RPLP0 when comparing either right and left atrium or right atria from all pathological groups. ACTB, TBP, TFRC, and 18S genes were identified as the least stable.
Conclusions
The overall most stable reference genes across different heart cavities and disease conditions were GAPDH, IPO8, POLR2A and PPIA. YWHAZ or GUSB could be added to this set for some specific experiments. This study should provide useful guidelines for reference gene selection in RT-qPCR studies in human heart.
This study reports long-term clinical outcomes-up to 17 years-among patients undergoing mitral valve replacement with the On-X bileaflet mechanical valve. Prior data regarding long-term outcomes with ...the On-X mitral valve have been limited.
This retrospective observational study included all patients who underwent mitral valve replacement with the On-X (Standard or Conform-X) valve at 2 major Spanish cardiac surgery centres between 2001 and 2018. The primary study end point was freedom from death. The secondary study end points included surgical mortality and freedom from any valve-related events. Data were obtained from an institutional database, medical records review, direct telephone interviews or the Spanish population registry. Statistical and Kaplan-Meier analyses were performed.
A total of 661 patients (mean age 63.1 ± 10.9 years, 63% female) were followed for a mean of 5.6 years (range, 0-17.4 years). Survival at 5, 10 and 15 years was 85%, 71% and 63%, respectively. Surgical mortality was 7.3% (48/661). The linearized rate of global mortality was 1.3% patient-year. Freedom from reoperation was 97%, 95% and 92% at 5, 10 and 15 years, respectively; freedom from anticoagulation-related events was 94%, 89% and 89%, respectively. Multivariable analysis showed that mortality increased with total length of stay, age, smoking history, severe pulmonary hypertension and a permanent pacemaker. Patients who received the On-X 25 -mm valve had decreased long-term survival relative to patients who received other On-X valve sizes, possibly due to underlying risk factors.
Patients in this study showed good long-term survival and freedom from valve-related events.
The impact of frailty in aortic valve surgery Berastegui Garcia, Elisabet; Camara Rosell, Maria Luisa; Moret Ruiz, Enrique ...
BMC geriatrics,
10/2020, Letnik:
20, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Frailty is a geriatric syndrome that diminishes potential functional recovery after any surgical procedure. Preoperative surgical risk assessment is crucial to calibrate the risk and benefit of ...cardiac surgery. The aim of this study was to test usefulness of FRAIL Scale and other surgical-risk-scales and individual features of frailty in cardiac aortic valve surgery.
Prospective study. From May-2014 to February-2016, we collected 200 patients who underwent aortic valve replacement, either surgically or transcatheter. At 1-year follow-up, quality of life measurements were recorded using the EQ-5D (EuroQol). Univariate and multivariate analyses correlated preoperative condition, features of frailty and predicted risk scores with mortality, morbidity and quality of life at 1 year of follow-up.
Mean age 78.2y, 56%male. Mean-preoperative-scores: FRAIL scale 1.5(SD 1.02), STS 2.9(SD 1.13), BI 93.8(SD 7.3), ESlog I 12.8(SD 8.5) and GS 7.3 s (SD 1.9). Morbidity at discharge, 6 m and 1 year was 51, 14 and 28%. Mortality 4%. Survival at 6 m/ 1-y was 97% / 88%. Complication-rate was higher in TAVI group due to-vascular complications. Renal dysfunction, anemia, social dependence and GS slower than 7 s were associated with morbidity. On multivariate analysis adjusted STS, BI and GS speed were statistically significant. Quality of life at 1-year follow-up adjusted for age and prosthesis type showed a significant association with STS and FRAIL scale scores.
Frailty increases surgical risk and is associated with higher morbidity. Preoperative GS slower 7 s, and STS and FRAIL scale scores seem to be reliable predictors of quality of life at 1-year follow-up.
Abstract
Aims
Single nucleotide polymorphisms on chromosome 4q25 have been associated with risk of atrial fibrillation (AF) but the exiguous knowledge of the mechanistic links between these risk ...variants and underlying electrophysiological alterations hampers their clinical utility. Here, we tested the hypothesis that 4q25 risk variants cause alterations in the intracellular calcium homoeostasis that predispose to spontaneous electrical activity.
Methods and results
Western blotting, confocal calcium imaging, and patch-clamp techniques were used to identify mechanisms linking the 4q25 risk variants rs2200733T and rs13143308T to defects in the calcium homoeostasis in human atrial myocytes. Our findings revealed that the rs13143308T variant was more frequent in patients with AF and that myocytes from carriers of this variant had a significantly higher density of calcium sparks (14.1 ± 4.5 vs. 3.1 ± 1.3 events/min, P = 0.02), frequency of transient inward currents (ITI) (1.33 ± 0.24 vs. 0.26 ± 0.09 events/min, P < 0.001) and incidence of spontaneous membrane depolarizations (1.22 ± 0.26 vs. 0.56 ± 0.17 events/min, P = 0.001) than myocytes from patients with the normal rs13143308G variant. These alterations were linked to higher sarcoplasmic reticulum calcium loading (10.2 ± 1.4 vs. 7.3 ± 0.5 amol/pF, P = 0.01), SERCA2 expression (1.37 ± 0.13 fold, P = 0.03), and RyR2 phosphorylation at ser2808 (0.67 ± 0.08 vs. 0.47 ± 0.03, P = 0.01) but not at ser2814 (0.28 ± 0.14 vs. 0.31 ± 0.14, P = 0.61) in patients carrying the rs13143308T risk variant. Furthermore, the presence of a risk variant or AF independently increased the ITI frequency and the increase in the ITI frequency observed in carriers of the risk variants was exacerbated in those with AF. By contrast, the presence of a risk variant did not affect the amplitude or properties of the L-type calcium current in patients with or without AF.
Conclusions
Here, we identify the 4q25 variant rs13143308T as a genetic risk marker for AF, specifically associated with excessive calcium release and spontaneous electrical activity linked to increased SERCA2 expression and RyR2 phosphorylation.
To obtain a quantitative expression profile of the main genes involved in the cAMP-signaling cascade in human control atria and in different cardiac pathologies.
Expression of 48 target genes playing ...a relevant role in the cAMP-signaling cascade was assessed by RT-qPCR. 113 samples were obtained from right atrial appendages (RAA) of patients in sinus rhythm (SR) with or without atrium dilation, paroxysmal atrial fibrillation (AF), persistent AF or heart failure (HF); and left atrial appendages (LAA) from patients in SR or with AF. Our results show that right and left atrial appendages in donor hearts or from SR patients have similar expression values except for AC7 and PDE2A. Despite the enormous chamber-dependent variability in the gene-expression changes between pathologies, several distinguishable patterns could be identified. PDE8A, PI3Kγ and EPAC2 were upregulated in AF. Different phosphodiesterase (PDE) families showed specific pathology-dependent changes.
By comparing mRNA-expression patterns of the cAMP-signaling cascade related genes in right and left atrial appendages of human hearts and across different pathologies, we show that 1) gene expression is not significantly affected by cardioplegic solution content, 2) it is appropriate to use SR atrial samples as controls, and 3) many genes in the cAMP-signaling cascade are affected in AF and HF but only few of them appear to be chamber (right or left) specific.
Genetic changes in human diseased atria.
The cyclic AMP signaling pathway is important for atrial function. However, expression patterns of the genes involved in the atria of healthy and diseased hearts are still unclear. We give here a general overview of how different pathologies affect the expression of key genes in the cAMP signaling pathway in human right and left atria appendages. Our study may help identifying new genes of interest as potential therapeutic targets or clinical biomarkers for these pathologies and could serve as a guide in future gene therapy studies.
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•cAMP-signaling related genes were studied in human atrial appendages and different pathologies.•Gene expression is not significantly affected by cardioplegic solution content.•It is appropriate to use atrial samples from patients in sinus rhythm as controls.•AC7 and PDE2A have a higher expression in the left versus right non-diseased atrium.•PI3Kγ, PDE8 and Epac2 expression is increased in atrial fibrillation.
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