The right ventricular (RV)-pulmonary arterial (PA) coupling ratio relates the efficiency with which RV stroke work is transferred into the PA. Lower ratios indicate an inadequate RV contractile ...response to increased afterload.
This study sought to evaluate the prognostic significance of RV-PA coupling in patients with tricuspid regurgitation (TR) who were undergoing transcatheter tricuspid valve repair or replacement (TTVR).
The study investigators calculated RV-PA coupling ratios for patients enrolled in the global TriValve registry by dividing the tricuspid annular plane systolic excursion (TAPSE) by the PA systolic pressure (PASP) from transthoracic echocardiograms performed before the procedure and 30 days after the procedure. The primary endpoint was all-cause mortality at 1-year follow-up.
Among 444 patients analyzed, their mean age was 76.9 ± 9.1 years, and 53.8% of the patients were female. The median TAPSE/PASP ratio was 0.406 mm/mm Hg (interquartile range: 0.308-0.567 mm/mm Hg). Sixty-three patients died within 1 year of TTVR, 21 with a TAPSE/PASP ratio >0.406 and 42 with a TAPSE/PASP ratio ≤0.406. In multivariable Cox regression analysis, a TAPSE/PASP ratio >0.406 vs ≤0.406 was associated with a decreased risk of all-cause mortality (HR: 0.57; 95% CI: 0.35-0.93; P = 0.023). In 234 (52.7%) patients with echocardiograms 30 days after TTVR, a decline in RV-PA coupling was independently associated with reduced odds of all-cause mortality (odds ratio OR: 0.42; 95% CI: 0.19-0.93; P = 0.032). The magnitude of TR reduction after TTVR (≥1+ vs <1+; OR: 2.53; 95% CI: 1.06-6.03; P = 0.037) was independently associated with a reduction in post-TTVR RV-PA coupling.
RV-PA coupling is a powerful, independent predictor of all-cause mortality in patients with TR undergoing TTVR. These data suggest that the TAPSE/PASP ratio can inform patient selection and prognostication following TTVR.
A large database was examined to identify cardiac arrests that occurred during competitive sports. During 18.5 million person-years of observation, 16 such cardiac arrests occurred. Only 3 cases were ...considered to have been potentially identifiable by screening.
The capacity of stem and progenitor cells to stimulate cardiac regeneration has been studied for almost 20 years, with very promising preclinical data and mixed clinical results. Several cell types ...have been studied, identified by their cell surface markers, differentiation capacity and their secreted growth factors. Bone marrow derived mesenchymal stem cells (MSCs) have been found to have potent regenerative capacity, through multiple mechanisms, including mesoderm lineage differentiation, immunomodulation, and paracrine stimulation. MSCs also secrete exosomes and microvesicles, which themselves contain potent angiogenic cytokines or mRNA molecules with effects on their local milieu. This concise review summarizes the mechanisms of MSC‐based cardiac regeneration and highlighting results from molecular and preclinical studies. We also discuss clinical trial results to date, and ongoing studies. Furthermore, we discuss novel approaches for the enhancement of MSC based cardiac regeneration, such as genetic modification. Stem Cells Translational Medicine 2018;7:543–550
BACKGROUND:SGLT2 (sodium-glucose cotransporter 2) inhibitors lower cardiovascular events in type 2 diabetes mellitus but whether they promote direct cardiac effects remains unknown. We sought to ...determine if empagliflozin causes a decrease in left ventricular (LV) mass in people with type 2 diabetes mellitus and coronary artery disease.
METHODS:Between November 2016 and April 2018, we recruited 97 individuals ≥40 and ≤80 years old with glycated hemoglobin 6.5% to 10.0%, known coronary artery disease, and estimated glomerular filtration rate ≥60mL/min/1.73m. The participants were randomized to empagliflozin (10 mg/day, n=49) or placebo (n=48) for 6 months, in addition to standard of care. The primary outcome was the 6-month change in LV mass indexed to body surface area from baseline as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and -systolic volumes indexed to body surface area, ejection fraction, 24-hour ambulatory blood pressure, hematocrit, and NT-proBNP (N-terminal pro b-type natriuretic peptide).
RESULTS:Among the 97 participants (90 men 93%, mean standard deviation age 62.8 9.0 years, type 2 diabetes mellitus duration 11.0 8.2 years, estimated glomerular filtration rate 88.4 16.9 mL/min/1.73m, LV mass indexed to body surface area 60.7 11.9 g/m), 90 had evaluable imaging at follow-up. Mean LV mass indexed to body surface area regression over 6 months was 2.6 g/m and 0.01 g/m for those assigned empagliflozin and placebo, respectively (adjusted difference −3.35 g/m; 95% CI, −5.9 to −0.81g/m, P=0.01). In the empagliflozin-allocated group, there was significant lowering of overall ambulatory systolic blood pressure (adjusted difference −6.8mmHg, 95% CI −11.2 to −2.3mmHg, P=0.003), diastolic blood pressure (adjusted difference −3.2mmHg; 95% CI, −5.8 to −0.6mmHg, P=0.02) and elevation of hematocrit (P=0.0003).
CONCLUSIONS:Among people with type 2 diabetes mellitus and coronary artery disease, SGLT2 inhibition with empagliflozin was associated with significant reduction in LV mass indexed to body surface area after 6 months, which may account in part for the beneficial cardiovascular outcomes observed in the EMPA-REG OUTCOME (BI 10773 Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial.
CLINICAL TRIAL REGISTRATION:URLhttps://www.clinicaltrials.gov. Unique identifierNCT02998970.
Although the role of inflammation in atherosclerosis is established, whether this relationship remains important after lowering low-density lipoprotein cholesterol (LDL-C) is still unclear. Recently ...in The Lancet, Ridker et al. demonstrated that residual inflammatory risk was a stronger predictor of fatal and non-fatal events compared to residual cholesterol risk, supporting the concept of inflammation testing to guide vascular risk reduction.
Although the role of inflammation in atherosclerosis is established, whether this relationship remains important after lowering low-density lipoprotein cholesterol (LDL-C) remains unclear. Recently in The Lancet, Ridker et al. demonstrated that residual inflammatory risk was a stronger predictor of fatal and non-fatal events compared to residual cholesterol risk, supporting the concept of inflammation testing to guide vascular risk reduction.
Pulmonary arterial hypertension (PAH) is a rare, but progressive and devastating vascular disease with few treatment options to prevent the advancement to right ventricular dysfunction hypertrophy ...and failure. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, enhances urinary glucose excretion as well as reduces cardiovascular events and mortality in individuals with type 2 diabetes. While empagliflozin has been reported to lower systemic hypertension due to increased diuresis, the effect of empagliflozin on PAH is unknown. We used monocrotaline (MCT)-treated Sprague-Dawley rats to determine if empagliflozin alters PAH-associated outcomes. Compared to vehicle control, daily empagliflozin administration significantly improved survival in rats with severe MCT-induced PAH. Hemodynamic assessments showed that empagliflozin treatment significantly reduced mean pulmonary artery pressure, right ventricular systolic pressure, and increased pulmonary acceleration time. Empagliflozin treatment resulted in reduced right ventricular hypertrophy and fibrosis. Histological and molecular assessments of lung vasculature revealed significantly reduced medial wall thickening and decreased muscularization of pulmonary arterioles after empagliflozin treatment compared to vehicle-treated rats. In summary, SGLT2 inhibition with empagliflozin lowered mortality, reduced right ventricle systolic pressure, and attenuated maladaptive pulmonary remodeling in MCT-induced PAH. Clinical studies evaluating the efficacy of SGLT-2 inhibition should be considered for patients with PAH.
•There are few treatment options available for pulmonary arterial hypertension (PAH).•We used a monocrotaline (MCT) PAH rat model to determine if empagliflozin alters PAH-related outcomes.•Empagliflozin lowered mortality in MCT-induced PAH.•Empagliflozin reduced right ventricle systolic pressure in MCT-induced PAH.•Empagliflozin attenuated maladaptive pulmonary remodeling in MCT-induced PAH.
Diabetes mellitus (DM) is a major cause of heart failure in the Western world, either secondary to coronary artery disease or from a distinct entity known as “diabetic cardiomyopathy.” Furthermore, ...heart failure with preserved ejection fraction (HFpEF) is emerging as a significant clinical problem for patients with DM. Current clinical data suggest that between 30% and 40% of patients with HFpEF suffer from DM. The typical structural phenotype of the HFpEF heart consists of endothelial dysfunction, increased interstitial and perivascular fibrosis, cardiomyocyte stiffness, and hypertrophy along with advanced glycation end products deposition. There is a myriad of mechanisms that result in the phenotypical HFpEF heart including impaired cardiac metabolism and substrate utilization, altered insulin signalling leading to protein kinase C activation, advanced glycated end products deposition, prosclerotic cytokine activation (eg, transforming growth factor-β activation), along with impaired nitric oxide production from the endothelium. Moreover, recent investigations have focused on the role of endothelial-myocyte interactions. Despite intense research, current therapeutic strategies have had little effect on improving morbidity and mortality in patients with DM and HFpEF. Possible explanations for this include a limited understanding of the role that direct cell-cell communication or indirect cell-cell paracrine signalling plays in the pathogenesis of DM and HFpEF. Additionally, integrins remain another important mediator of signals from the extracellular matrix to cells within the failing heart and might play a significant role in cell-cell cross-talk. In this review we discuss the characteristics and mechanisms of DM and HFpEF to stimulate potential future research for patients with this common, and morbid condition.
Le diabète est une cause majeure d'insuffisance cardiaque dans les pays occidentaux, qu'il soit consécutif à une coronaropathie ou attribuable à une entité clinique distincte appelée « cardiomyopathie diabétique ». De plus, l'insuffisance cardiaque à fraction d'éjection préservée (ICFEP) est un nouveau problème clinique de plus en plus important chez les patients atteints de diabète. D'après les données cliniques actuelles, de 30 à 40 % des patients atteints d'ICFEP sont diabétiques. La dysfonction endothéliale, l'intensification de la fibrose interstitielle et périvasculaire, la rigidité et l'hypertrophie des cardiomyocytes et le dépôt de produits de la glycation avancée constituent le phénotype structurel caractéristique du cœur dans l'ICFEP. Il existe une multitude de mécanismes qui aboutissent à l'apparition du phénotype du coeur ICFEP, y compris l'altération du métabolisme cardiaque et de l'utilisation des substrats, l'altération de la signalisation insulinique menant à l'activation de la protéine kinase C, le dépôt de produits de la glycation avancée, l'activation de la cytokine prosclérotique (p. ex., activation du facteur de croissance transformant β), et l'altération de la production d'oxyde nitrique dans l'endothélium. De plus, des études récentes ont porté sur le rôle des interactions entre cellules endothéliales et myocytes. Malgré des recherches intensives, les stratégies thérapeutiques actuelles se sont avérées peu efficaces pour améliorer la morbidité et la mortalité chez les patients diabétiques atteints d'ICFEP. Cette situation pourrait notamment s'expliquer par notre compréhension incomplète du rôle joué par la communication directe cellule-cellule et la signalisation paracrine dans la pathogenèse du diabète et de l'ICFEP. De plus, l'intégrine demeure un autre médiateur important des signaux de la matrice extracellulaire vers les cellules dans le cœur insuffisant et pourrait jouer un rôle important dans le dialogue entre les cellules. Dans cette revue, nous présentons les caractéristiques et les mécanismes du diabète et de l'ICFEP afin de stimuler les recherches futures dans l’intérêt des patients atteints de cette affection fréquente et invalidante.
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