To date, no medical therapy can slow the progression of aortic stenosis. Fibrocalcific stenosis is the most frequent form in the general population and affects about 6% of the elderly population. ...Over the years, diagnosis has evolved thanks to echocardiography and computed tomography assessments. The application of artificial intelligence to electrocardiography could further implement early diagnosis. Patients with severe aortic stenosis, especially symptomatic patients, have valve repair as their only therapeutic option by surgical or percutaneous technique (TAVI). The discovery that the pathogenetic mechanism of aortic stenosis is similar to the atherosclerosis process has made it possible to evaluate the hypothesis of medical therapy for aortic stenosis. Several drugs have been tested to reduce low-density lipoprotein (LDL) and lipoprotein(a) (Lp(a)) levels, inflammation, and calcification. The Proprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9-i) could decrease the progression of aortic stenosis and the requirement for valve implantation. Great interest is related to circulating Lp(a) levels as causally linked to degenerative aortic stenosis. New therapies with ASO (antisense oligonucleotides) and siRNA (small interfering RNA) are currently being tested. Olpasiran and pelacarsen reduce circulating Lp(a) levels by 85–90%. Phase 3 studies are underway to evaluate the effect of these drugs on cardiovascular events (cardiovascular death, non-fatal myocardial injury, and non-fatal stroke) in patients with elevated Lp(a) and CVD (cardiovascular diseases). For instance, if a reduction in Lp(a) levels is associated with aortic stenosis prevention or progression, further prospective clinical trials are warranted to confirm this observation in this high-risk population.
The purpose of this study was to investigate the association between right ventricular dysfunction (RVD) and cardiovascular death after transcatheter aortic valve replacement (TAVR).
There is ...conflicting evidence on the effect of RVD on clinical outcomes after TAVR.
A total of 1,116 TAVR patients (age 82 ± 6 years; 51% female) who were consecutively enrolled into a prospective registry underwent detailed pre-operative assessment of right ventricular (RV) function and were dichotomized into 2 groups for the purposes of the present retrospective analysis. RVD was assessed using fractional area change (<35%), tricuspid annular plane systolic excursion (<1.7 cm), and systolic movement of the RV lateral wall by tissue Doppler imaging (<9.5 cm/s). RVD was found in 325 (29.1%) patients. The primary outcome was cardiovascular death at 1 year.
After adjustment for comorbidities, patients with RVD had a higher risk of cardiovascular death at 1 year compared with patients with normal RV function (20.1% vs. 7.1%; adjusted hazard ratio HRadj: 2.94; 95% confidence interval CI: 2.02 to 4.27; p < 0.001). The difference emerged within the first 30 days after TAVR (9.0% vs. 2.2%; HRadj: 4.62; 95% CI: 2.51 to 8.50; p < 0.001). Normalization of RV function after TAVR was found in 57.4% of patients with RVD at baseline. There was a gradient of increasing risk of cardiovascular death among patients with normal RV function, RVD recovery (HRadj: 2.16; 95% CI: 1.16 to 4.02), new RVD (HRadj: 3.93; 95% CI: 2.09 to 7.39), and maintained RVD (HRadj: 8.74; 95% CI: 5.33 to 14.3), respectively.
RVD at baseline was associated with a more than 2-fold increased risk of cardiovascular death at 1 year after TAVR, with a gradient of risk according to RVD recovery. (Swiss TAVI Registry; NCT01368250)
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The aim of this study was to examine the frequency, timing, and association of access-site and non–access-site bleeding with mortality in the setting of transcatheter aortic valve replacement (TAVR) ...during long-term follow-up.
Bleeding is frequent and associated with impaired prognosis in patients undergoing TAVR. It is currently unknown whether the site of bleeding differentially influences the outcomes of TAVR patients.
In total, 926 consecutive patients undergoing TAVR from 2007 through 2014 were evaluated. Bleeding was assessed according to the Valve Academic Research Consortium 2 criteria. The primary outcome of interest was all-cause mortality up to 5 years of follow-up.
A total of 285 patients (30.7%) experienced at least 1 (minor, major, or life-threatening) bleeding event up to 5 years. Compared with patients not experiencing bleeding, the adjusted risk for all-cause mortality was significantly increased among patients with access-site (hazard ratio: 1.34; 95% confidence interval: 1.01 to 1.76; p = 0.04) and non–access-site bleeding (hazard ratio: 2.08; 95% confidence interval: 1.60 to 2.71; p < 0.001). However, non–access-site bleeding conferred a significantly higher risk for mortality compared with access-site bleeding (hazard ratio: 1.56; 95% confidence interval: 1.12 to 2.18; p = 0.009). At multivariate analysis, female sex was a significant correlate of access-site bleeding, whereas chronic kidney disease and the Society of Thoracic Surgeons score were significantly associated with non–access-site bleeding.
Among patients with severe aortic stenosis undergoing TAVR, access-site and non–access-site bleeding were independently associated with an increased risk for mortality, with the greatest risk related to non–access-site bleeding during long-term follow-up.
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Objectives The purpose of this paper was to determine whether microRNAs (miRNAs) involved in myocardial remodeling were differentially expressed in the blood of hypertrophic cardiomyopathy (HCM) ...patients, and whether circulating miRNAs correlated with the degree of left ventricular hypertrophy and fibrosis. Background miRNAs—small, noncoding ribonucleic acids (RNAs) that regulate gene expression by inhibiting RNA translation—modulate cellular function. Myocardial miRNAs modulate processes such as cardiomyocyte (CM) hypertrophy, excitation–contraction coupling, and apoptosis; non–CM-specific miRNAs regulate myocardial vascularization and fibrosis. Recently, the possibility that circulating miRNAs may be biomarkers of cardiovascular disease has been raised. Methods Forty-one HCM patients were characterized with conventional transthoracic echocardiography and cardiac magnetic resonance. Peripheral plasma levels of 21 miRNAs were assessed by quantitative real-time polymerase chain reaction and were compared with levels in a control group of 41 age- and sex-matched blood donors. Results Twelve miRNAs (miR-27a, -199a-5p, -26a, -145, -133a, -143, -199a-3p, -126-3p, -29a, -155, -30a, and -21) were significantly increased in HCM plasma. However, only 3 miRNAs (miR-199a-5p, -27a, and -29a) correlated with hypertrophy; more importantly, only miR-29a correlated also with fibrosis. Conclusions Our data suggest that cardiac remodeling associated with HCM determines a significant release of miRNAs into the bloodstream: the circulating levels of both cardiac- and non–cardiac-specific miRNAs are significantly increased in the plasma of HCM patients. However, correlation with left ventricular hypertrophy parameters holds true for only a few miRNAs (i.e., miR-199a-5p, -27a, and -29a), whereas only miR-29a is significantly associated with both hypertrophy and fibrosis, identifying it as a potential biomarker for myocardial remodeling assessment in HCM.
The dual-antiplatelet therapy (DAPT) score was developed to identify patients more likely to derive harm (score <2) or benefit (score ≥2) from prolonged DAPT after percutaneous coronary intervention ...(PCI).
To evaluate the safety and efficacy of DAPT duration according to DAPT score.
Retrospective assessment of DAPT score-guided treatment duration in a randomized clinical trial. (ClinicalTrials.gov: NCT00611286).
PCI patients.
1970 patients undergoing PCI.
DAPT (aspirin and clopidogrel) for 24 versus 6 months.
Primary efficacy outcomes were death, myocardial infarction, or cerebrovascular accident. The primary safety outcome was type 3 or 5 bleeding according to the Bleeding Academic Research Consortium definition. Outcomes were assessed between 6 and 24 months.
884 patients (44.9%) had a DAPT score of at least 2, and 1086 (55.1%) had a score less than 2. The reduction in the primary efficacy outcome with 24- versus 6-month DAPT was greater in patients with high scores (risk difference RD for score ≥2, -2.05 percentage points 95% CI, -5.04 to 0.95 percentage points; RD for score <2, 2.91 percentage points CI, -0.43 to 6.25 percentage points; P = 0.030). However, the difference by score for the primary efficacy outcome varied by stent type; prolonged DAPT with high scores was effective only in patients receiving paclitaxel-eluting stents (RD, -7.55 percentage points CI, -12.85 to -2.25 percentage points). The increase in the primary safety outcome with 24- versus 6-month DAPT was greater in patients with low scores (RD for score ≥2, 0.20 percentage point CI, -1.20 to 1.60 percentage points; RD for score <2, 2.58 percentage points CI, 0.71 to 4.46 percentage points; P = 0.046).
Retrospective calculation of the DAPT score.
Prolonged DAPT resulted in harm in patients with low DAPT scores undergoing PCI but reduced risk for ischemic events in patients with high scores receiving paclitaxel-eluting stents. Whether prolonged DAPT benefits patients with high scores treated with contemporary drug-eluting stents requires further study.
None.
To analyse reasons, timing and predictors of hospital readmissions after transcatheter aortic valve implantation (TAVI).
Patients included in the Bern TAVI Registry between August 2007 and June 2014 ...were analysed. Fine and Gray competing risk regression was used to identify factors predictive of hospital readmission within 1 year after TAVI with bootstrap analysis for internal validation. Of 868 patients alive at discharge, 221 (25.4%) were readmitted within 1 year. Compared with patients not requiring readmission, those with at least one readmission more frequently were male and more often had atrial fibrillation and higher creatinine values (P < 0.05 for all cases). For overall 308 readmissions, cardiovascular causes accounted for 46.1% with heart failure as the most frequent indication; non-cardiovascular readmissions occurred for surgery (11.7%), gastrointestinal disorders (9.7%), malignancy (4.9%), respiratory diseases (4.6%) and chronic kidney failure (2.6%). Male gender (subhazard ratio, SHR, 1.33, 95% confidence intervals, CI, 1.02-1.73, P = 0.035) and stage 3 kidney injury (SHR 2.04, 95% CI 1.12-3.71, P = 0.021) were found independent risk factors for any hospital readmission, whereas previous myocardial infarction (SHR 1.88, 95% CI 1.22-2.90, P = 0.004) and in-hospital life-threatening bleeding (SHR 2.18, 95%CI 1.24-3.85, P = 0.007) were associated with cardiovascular readmissions. The event rate for mortality was significantly increased after readmissions for any cause (RR 4.29, 95% CI 2.86-6.42, P < 0.001).
Hospital readmission was observed in one out of four patients during the first year after TAVI and was associated with a significant increase in mortality.
This study sought to determine the impact of left ventricular diastolic dysfunction (LVDD) on clinical outcomes in patients undergoing transcatheter aortic valve replacement (TAVR).
Left ventricular ...(LV) hypertrophy in response to afterload increase promotes the development of LVDD and represents an early stage in the progression to valvular heart failure.
In a consecutive cohort of 777 aortic stenosis patients undergoing TAVR, LVDD was categorized according to the latest guidelines. The primary endpoint was 1-year all-cause mortality.
There were 545 (70.1%) patients with LVDD. Ninety-eight (18.0%), 198 (36.3%), and 104 (19.1%) patients were classified as LVDD grades I, II, and III, respectively. In 145 (26.6%) patients, LVDD grade could not be determined because of only 1 or 2 discrepant variables. One-year all-cause mortality was higher in patients with LVDD grades I (16.3%; adjusted hazard ratio HRadj: 2.32; 95% confidence interval CI: 1.15 to 4.66), II (17.9%; HRadj: 2.58; 95% CI: 1.43 to 4.67), and III (27.6%; HRadj: 4.21; 95% CI: 2.25 to 7.86) than in those with normal diastolic function (6.9%). The difference in clinical outcome emerged within 30 days, was driven by cardiovascular death, and maintained in a sensitivity analysis of patients with normal systolic LV function. Furthermore, LVDD grades I (HRadj: 2.36; 95% CI: 1.17 to 4.74), II (HRadj: 2.58; 95% CI: 1.42 to 4.66), and III (HRadj: 4.41; 95% CI: 2.37 to 8.20) were independent predictors of 1-year mortality.
Advancing stages of LVDD are associated with an incremental risk of all-cause mortality after TAVR, driven by cardiovascular death and taking effect as early as 30 days after the intervention.
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Transcatheter aortic valve implantation (TAVI) is an effective alternative therapy in selected patients with severe aortic stenosis. The role and effects of coexistent moderate to severe mitral ...regurgitation (msMR) in patients who undergo TAVI remain unclear. Thirteen studies enrolling 4,839 patients who underwent TAVI, including patients with msMR, were considered in a meta-analysis and analyzed for all-cause-mortality; a further meta-analysis was performed to assess mitral regurgitation (MR) evolution after TAVI. In patients with msMR, all-cause-mortality after TAVI was significantly increased at 30-day (effect size ES −0.18, 95% confidence interval CI −0.31 to −0.04, I2 = 46.51, Q = 7.48), 1-year (ES −0.22, 95% CI −0.36 to −0.08, I2 = 56.20, Q = 11.41), and 2-year (ES −0.15, 95% CI −0.27 to −0.02, I2 = 0.00, Q = 2.64) follow-up compared with patients with absent or mild MR, independent of baseline left ventricular ejection fraction. Interestingly, the impact of msMR on outcomes was statistically stronger when the CoreValve system was used. TAVI was also associated with an improvement in MR entity at 3- and 6-month follow-up (overall ES −0.19, 95% CI −0.37 to −0.01, I2 = 61.52, Q = 10.39). In conclusion, the presence of preoperative msMR in patients with severe, symptomatic aortic stenosis who undergo TAVI negatively affects outcomes after TAVI. In addition, in the same group of patients, a trend toward a reduction in MR severity was observed. Whether the decrease in MR severity affects mortality after TAVI remains to be defined.
Objectives This study sought to identify proteins from the cardiomyocyte (CM) secretome that are directly targeted by the muscle-specific microRNA-1 (miR-1), and thus reflect the pathophysiological ...state of the CM. Background MicroRNAs play critical regulatory roles during myocardial remodeling and progression to heart failure. However, it remains unknown whether secreted microRNA-targeted proteins can be used as indicators of myocardial microRNA expression and function. Methods A proteomic analysis based on multidimensional protein identification technology was performed on supernatants from cultured CMs overexpressing miR-1. Biochemical assays and an inducible cardiac-specific transgenic mouse model overexpressing miR-1 were used to demonstrate that heart-type fatty acid-binding protein-3 (FABP3) is a target of miR-1. Levels of miR-1 and FABP3 in cardiac tissue and plasma samples from mouse models as well as human patients were quantified by quantitative reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The study included wild-type mice subjected to ventricular pressure overload or fasting, as well as patients diagnosed with ventricular hypertrophy due to valvular aortic stenosis, acromegaly, or growth hormone deficiency, conditions associated with altered miR-1 expression. Results An inverse relationship between myocardial expression of miR-1 and circulating levels of FABP3 was found both in vitro and in vivo under various pathological conditions. Conclusions Assessment of FABP3 plasma levels in human patients might be used for indirectly measuring cardiac miR-1 activity.
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