There is a paucity of data on the impact of complete revascularisation (CR) following percutaneous coronary intervention (PCI) among patients with diabetes with multivessel coronary disease. In this ...study, we assess the impact of CR, using a relatively simple anatomical definition, on long-term outcomes (median follow-up 7.9 years) in patients with diabetes, and compare with patients without diabetes.
5350 patients with multivessel disease (coronary stenoses ≥70% in ≥2 major epicardial arteries) who underwent PCI between January 1997 and June 2011 were included. Patients were divided into 4 groups according to diabetes and CR status (absence of residual coronary stenosis in major, predominantly proximal, epicardial segments according to Coronary Artery Surgery Study (CASS) classification).
Patients with diabetes and patients with incomplete revascularisation (IR) had more adverse clinical and angiographic characteristics. IR was frequent in patients with diabetes, and was marginally more common than in patients without diabetes (47% vs 44%, p<0.001). Patients with diabetes and patients without diabetes had higher mortality rates after IR than after CR (HR 1.56 (95% CI (1.39 to 1.85), p<0.001 for patients with diabetes and 1.70 (95% CI (1.50 to 1.92), p<0.001) in patients without diabetes). However, the absolute risk was higher for patients with diabetes (5-year mortality: IR 35.8%, CR 21.2%) than in patients without diabetes (5-year mortality: IR 22.2%, CR 14.1%). In a multivariable model, IR and diabetes mellitus were independent predictors of total mortality. This effect was present in the bare metal stent and drug-eluting stent eras and in patients with stable disease and acute coronary syndromes.
CR is associated with lower long-term mortality in patients with diabetes and patients without diabetes. However the difference was significantly greater in patients with diabetes compared with patients without diabetes.
Background
Heart failure is one of the most pressing current public health concerns. However, in Spain there is a lack of population data. We aimed to examine thirteen‐year nationwide trends in heart ...failure hospitalization, in‐hospital mortality and 30‐day readmission rates in Spain.
Methods
We conducted a retrospective observational study of patients discharged with the principal diagnosis of heart failure from The National Health System’ acute hospitals during 2003‐2015. The source of the data was the Minimum Basic Data Set. Temporal trends were modelled using Poisson regression analysis. The risk‐standardized in‐hospital mortality ratio was calculated using a multilevel risk adjustment logistic regression model.
Results
A total of 1 254 830 episodes of heart failure were selected. Throughout 2003‐2015, the number of hospital discharges with principal diagnosis of heart failure increased by 61%. Discharge rates weighted by age and sex increased during the period incidence rate ratio (IRR): 1.03; 95% confidence interval (95% CI): 1.03‐1.03; P < .001), although this increase was motivated by the increase in older age groups (≥75 years old). The crude mortality rate diminished (IRR: 0.99; 95% CI: 0.98‐1, P < .001), but 30‐day readmission rate increased (IRR: 1.05; 95% CI: 1.04‐1.06; P < .001). The risk‐standardized in‐hospital mortality ratio did not change throughout the study period (IRR: 0.997; 95% CI: 0.992‐1; P = .32).
Conclusions
From 2003 to 2015, heart failure admission rates increased significantly in Spain as a consequence of the sustained increase of hospitalization in the population ≥75 years. 30‐day readmission rates increased, but the risk‐standardized in‐hospital mortality ratio did not significantly change for the same period.
Background
Participation in cardiac rehabilitation (CR) is an essential component of care for patients with coronary artery disease. However, little is known about its benefit on cardiovascular ...outcomes in patients with diabetes mellitus (DM) who have undergone percutaneous coronary intervention. The aim of our study was to evaluate the impact of CR in this high‐risk group of patients.
Methods and Results
We performed a retrospective analysis of all patients with DM who underwent percutaneous coronary intervention in Olmsted County (Minnesota) between 1994 and 2010, assessing the impact of CR participation on clinical outcomes. CR participation was significantly lower in patients with DM (38%, 263/700) compared with those who did not have DM (45%, 1071/2379; P=0.004). Using propensity score adjustment, we found that in patients with DM, CR participation was associated with significantly reduced all‐cause mortality (hazard ratio, 0.56; 95% confidence interval, 0.39–0.80; P=0.002) and composite end point of mortality, myocardial infarction, or revascularization (hazard ratio, 0.77; 95% confidence interval, 0.60–0.98; P=0.037), during a median follow‐up of 8.1 years. In patients without DM, CR participation was associated with a significant reduction in all‐cause mortality (hazard ratio, 0.67; 95% confidence interval, 0.55–0.82; P<0.001) and cardiac mortality (hazard ratio, 0.67; 95% confidence interval, 0.47–0.95; P=0.024).
Conclusions
CR participation after percutaneous coronary intervention is associated with lower all‐cause mortality rates in patients with DM, to a similar degree as for those without DM. However, CR participation was lower in patients with DM, suggesting the need to identify and correct the barriers to CR participation for this higher‐risk group of patients.
Background
There is little evidence on the use of sodium−glucose cotransporter 2 (SGLT2) inhibitors in older patients with heart failure. This work analyzed the clinical efficacy and safety of ...empagliflozin continuation in very old patients with type 2 diabetes hospitalized for acute decompensated heart failure.
Methods
We conducted a real‐world observational study between September 2015 and June 2021. Patients ≥80 years were grouped by antihyperglycemic regimen: (1) continuation of preadmission empagliflozin combined with basal insulin regimen and (2) conventional basal‐bolus insulin regimen. A propensity score matching analysis matched patients in both groups in a 1:1 manner. The primary outcome was differences in clinical efficacy measured by the visual analogue scale dyspnea score, NT‐proBNP levels, diuretic response, and cumulative urine output. Safety endpoints such as adverse events, worsening heart failure, discontinuation of empagliflozin, length of hospital stay, and in‐hospital deaths were also analyzed.
Results
After propensity score matching, 79 patients were included in each group. At discharge, the N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels were lower in the empagliflozin continuation group than in the insulin group (1699 ± 522 vs. 2303 ± 598 pg/ml, p = 0.021). Both the diuretic response and cumulative urine output were greater in patients treated with empagliflozin than in patients with basal‐bolus insulin during the hospitalization (at discharge: −0.14 ± −0.06 vs. −0.24 ± −0.10, p = 0.044; and 16,100 ± 1510 vs. 13,900 ± 1220 ml, p = 0.037, respectively). No differences were observed in safety outcomes.
Conclusions
In very old patients with type 2 diabetes hospitalized for acute heart failure, continuing preadmission empagliflozin reduced NT‐proBNP levels and increased diuretic response and urine output compared to a basal‐bolus insulin regimen. The empagliflozin regimen also showed a good safety profile.
Marfan syndrome (MFS) is a disorder of autosomal dominant inheritance, in which aortic root dilation is the main cause of morbidity and mortality. Fibrillin-1 (FBN-1) gene mutations are found in more ...than 90% of MFS cases. The aim of our study was to summarise variants in FBN-1 and establish the genotype-phenotype correlation, with particular interest in the onset of aortic events, in a broad population of patients with an initial clinical suspicion of MFS.
This single centre prospective cohort study included all patients presenting variants in the FBN-1 gene who visited a Hereditary Aortopathy clinic between September 2010 and October 2016.
The study included 90 patients with FBN-1 variants corresponding to 58 non-interrelated families. Of the 57 FBN-1 variants found, 25 (43.9%) had previously been described, 23 of which had been identified as associated with MFS, while the the remainder are described for the first time. For 84 patients (93.3%), it was possible to give a definite diagnosis of Marfan syndrome in accordance with Ghent criteria. 44 of them had missense mutations, 6 of whom had suffered an aortic event (with either prophylactic surgery for aneurysm or dissection), whereas 20 of the 35 patients with truncating mutations had suffered an event (13.6% vs. 57.1%, p < 0.001). These events tended to occur at earlier ages in patients with truncating compared to those with missense mutations, although not significantly (41.33 ± 3.77 vs. 37.5 ± 9.62 years, p = 0.162).
Patients with MFS and truncating variants in FBN-1 presented a higher proportion of aortic events, compared to a more benign course in patients with missense mutations. Genetic findings could, therefore, have importance not only in the diagnosis, but also in risk stratification and clinical management of patients with suspected MFS.
To characterize Brn3a expression in adult albino rat retinal ganglion cells (RGCs) in naïve animals and in animals subjected to complete intraorbital optic nerve transection (IONT) or crush (IONC).
...Rats were divided into three groups, naïve, IONT, and IONC. Two-, 5-, 9-, or 14-day postlesion (dpl) retinas were examined for immunoreactivity for Brn3a. Before the injury, the RGCs were labeled with Fluorogold (FG; Fluorochrome, Corp. Denver, CO). Brn3a retinal expression was also determined by Western blot analysis. The proportion of RGCs double labeled with Brn3a and FG was determined in radial sections. The temporal course of reduction in Brn3a(+) RGCs and FG(+) RGCs induced by IONC or IONT was assessed by quantifying, in the same wholemounts, the number of surviving FG-labeled RGCs and Brn3a(+)RGCs at the mentioned time points. The total number of FG(+)RGCs was automatically counted in naïve and injured retinas (2 and 5 dpl) or estimated by manual quantification in retinas processed at 9 and 14 dpl. All Brn3a immunopositive RGCs were counted using an automatic routine specifically developed for this purpose. This protocol allowed, as well, the investigation of the spatial distribution of these neurons.
Brn3a(+) cells were only present in the ganglion cell layer and showed a spatial distribution comparable to that of FG(+) cells. In the naïve retinal wholemounts the mean (mean +/- SEM; n = 14) total number of FG(+)RGCs and Brn3a(+)RGCs was 80,251 +/- 2,210 and 83,449 +/- 4,541, respectively. Whereas in the radial sections, 92.2% of the FG(+)RGCs were also Brn3a(+), 4.4% of the RGCs were Brn3a(+)FG(-) and 3.4% were FG(+)Brn3a(-). Brn3a expression pattern was maintained in injured RGCs. The temporal course of Brn3a(+)RGC and FG(+)RGC loss induced by IONC or IONT followed a similar trend, but Brn3a(+)RGCs loss was detected earlier than that of FG(+)RGCs. Independent of the marker used to detect the RGCs, it was observed that their loss was quicker and more severe after IONT than after IONC.
Brn3a can be used as a reliable, efficient ex vivo marker to identify and quantify RGCs in control and optic nerve-injured retinas.
Summary
Fictitious domain methods, like the Cartesian grid finite element method (cgFEM), are based on the use of unfitted meshes that must be intersected. This may yield to ill‐conditioned systems ...of equations since the stiffness associated with a node could be small, thus poorly contributing to the energy of the problem. This issue complicates the use of iterative solvers for large problems. In this work, we present a new stabilization technique that, in the case of cgFEM, preserves the Cartesian structure of the mesh. The formulation consists in penalizing the free movement of those nodes by a smooth extension of the solution from the interior of the domain, through a postprocess of the solution via a displacement recovery technique. The numerical results show an improvement of the condition number and a decrease in the number of iterations of the iterative solver while preserving the problem accuracy.
Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains ...unclear.
The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization.
Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold.
A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.
FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.
Arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease defined by the progressive replacement of the ventricular myocardium with fibroadipose tissue, which can act as a substrate for ...arrhythmias, sudden death, or even give rise to heart failure (HF). Sudden death is frequently the first manifestation of the disease, particularly among young patients. The aim of this study is to describe a new pathogenic variant in the
.
A descriptive observational study that included eight initially non-interrelated families with a diagnosis of ACM undergoing follow-up at our HF and Familial Cardiomyopathies Unit, who were carriers of the NM_004572.3:c.775_776insG;
variant in the
. The genetic testing employed next-generation sequencing for the index cases and the Sanger method for the targeted study with family members. We compiled personal and family histories, demographic and clinical characteristics, data from the additional tests at the time of diagnosis, and arrhythmic events at diagnosis and during follow-up.
We included 47 subjects, of whom 8 were index cases (17%). Among the evaluated family members, 16 (34%) were carriers of the genetic variant, 3 of whom also had a diagnosis of ACM. The majority were women (26 patients; 55.3%), with a mean age on diagnosis of 48.9 ± 18.6 years and a median follow-up of 39 24-59 months. Worthy of note are the high incidences of arrhythmic events as the form of presentation and in follow-up (21.5% and 20.9%, respectively), and the onset of HF in 25% of the sample. The most frequent ventricular involvements were right (four patients, 16.7%) and biventricular (four patients, 16.7%); we found no statistical differences in any of the variables analysed.
This variant is a pathogenic variant of gene
that has not previously been described and is not present in the control groups associated with ACM. It has incomplete penetrance, a highly variable phenotypic expressivity, and was identified in eight families of our geographical area in Malaga (Andalusia, Spain), suggesting a founder effect in this area and describe the clinical and risk characteristics.
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