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1.
Herz ; 2021 Jan 12.
Artigo em Alemão | MEDLINE | ID: mdl-33433651

RESUMO

Arterial hypertension is the most important risk factor for cardiovascular diseases. Arterial hypertension is diagnosed when reproducible office resting blood pressure values are 140 mm Hg or more systolic and/or 90 mm Hg or more diastolic. A recent alternative is to base the diagnosis of hypertension on ambulatory 24 h blood pressure monitoring (ABPM) and/or home blood pressure monitoring (HBPM) if feasible. Nonpharmacological and pharmacological strategies of blood pressure management are available. Treatment decisions should involve a shared decision-making process and pharmacological agents as well as lifestyle recommendations should be tailored to the needs and comorbidities of each individual patient in a personalized approach. The target values depend on age and comorbidities. Despite clear recommendations as depicted in pertinent guidelines, blood pressure control remains inadequate in the majority of hypertensive patients. The continuous improvement of perception, diagnostics and treatment thus remain high priorities in healthcare systems worldwide. The aim of this CME article is to provide a perspective on recent developments in the management of arterial hypertension.

4.
Am J Cardiol ; 139: 71-78, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33190811

RESUMO

We aimed to evaluate the efficacy and safety of a low-dose imaging protocol to reduce intraprocedural radiation during transcatheter aortic valve implantation (TAVI). Observational analysis: 802 transfemoral TAVI patients receiving balloon-expandable devices ≥23 mm at a high-volume centre. After propensity score matching, a standard-dose group (SD, n = 333) treated between January 2014 and February 2016 was compared with a low-dose group (LD, n = 333) treated between August 2017 and March 2019 after departmental uptake of a low-dose imaging protocol (reduced field size, high table height, use of "fluoro save," 3.75 frames/second acquisition, increased filtering). Primary end point was dose-area product (DAP). Secondary safety end points were VARC-2 device success and a composite of in-hospital complications. The LD protocol was associated with lower DAP (4.64 [2.93, 8.42] vs 22.73 [12.31, 34.58] Gy⋅cm2, p <0.001) and fluoroscopy time (10.4 [8.1, 13.9] vs 11.5 [9.1, 15.3] minutes, p = 0.001). Contrast use was higher in the LD group (LD 110 [94, 130] vs SD 100 [80, 135] milliliters, p = 0.042). Device success (LD 88.3% vs SD 91.3%, p = 0.25), and the composite end point (LD 8.1% vs SD 11.4%, p = 0.19) were similar. In multivariate analysis, the low-dose protocol was associated with a 19.8 Gy⋅cm2 reduction in procedural DAP (p <0.001). In conclusion, compared with standard imaging, a low-dose protocol for TAVI significantly reduced radiation dose without compromising outcomes.

5.
J Thorac Dis ; 12(11): 6769-6779, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33282378

RESUMO

Background: This study compares two latest-generation self-expanding transcatheter heart valves (THV), the supra-annular ACURATE neo (Boston Scientific) and the intra-annular Centera THV (Edwards Lifesciences). Methods: In this single center observational cohort trial 317 patients treated with the ACURATE neo and 78 patients treated with the Centera TVH were included. The main endpoints were device success and the early safety endpoint at 30 days. Results: Besides higher incidence of diabetes mellitus and higher body mass index in patients treated with the ACURATE neo THV, there were no baseline differences between the groups. Device success was similar in both groups (neo: 91.8% vs. Centera: 93.6%; P=0.598), with numerically higher rates of moderate to severe paravalvular leakage in the ACURATE neo group (4.7% vs. 1.3%; P=0.214). At 30 days all-cause mortality rates were low in both groups (0.3% vs. 0%; P=0.620) and no difference occurred in the early safety at 30 days (19.3% vs. 16.7%; P=0.599). However, all-cause stroke rates were significantly higher in patients treated with the Centera THV (6.4 vs. 1.6%; P=0.015). Conclusions: The ACURATE neo and the Centera THV show low mortality rates as well as comparable, favorable hemodynamics. The finding of higher stroke rates at 30 days with the repositionable Centera SE-THV needs further assessment.

6.
Clin Res Cardiol ; 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33367949

RESUMO

AIMS: To investigate the clinical outcomes associated with an antithrombotic therapy with or without clopidogrel after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: This is a study-level meta-analysis including all randomized trials investigating antithrombotic regimens after TAVR. The protocol was registered with PROSPERO (CRD42020191036). We searched electronic scientific databases for eligible studies. The primary outcome was all-cause death. Main secondary outcome was major bleeding. Other outcomes were life-threatening (or disabling) bleeding, myocardial infarction (MI) and stroke. Six eligible trials randomly allocated 3056 TAVR patients to aspirin or oral anticoagulation (OAC) with clopidogrel (n = 1525) versus aspirin and/or OAC without clopidogrel (n = 1531). In the overall estimates, an antithrombotic therapy with clopidogrel versus without displayed a comparable risk of all-cause death [Risk Ratio-RR = 0.83, 95% Confidence intervals-CI (0.57-1.20); P = 0.25] and major bleeding [RR = 1.33, 95% CI (0.61-2.92); P = 0.39]. However, the combination of aspirin or OAC with clopidogrel doubled the risk of major bleeding as compared to aspirin or OAC without clopidogrel [RR = 2.08, 95% CI (1.27-3.42); P = 0.015, P for interaction = 0.021]. Treatment strategies did not differ with respect to the risk of life-threatening bleeding, MI and stroke. CONCLUSIONS: In patients receiving TAVR, a therapeutic strategy of aspirin or OAC with clopidogrel significantly increases the risk of major bleeding without impact on mortality and ischemic outcomes compared to aspirin or OAC without clopidogrel. The performance of different antithrombotic regimens in terms of long-term clinical outcomes and bioprosthesis valve function requires further investigation. Forest plots from pairwise and network meta-analyses associated with an antithrombotic therapy with or without clopidogrel Risk ratio for all outcomes of interest calculated with the pairwise meta-analysis (left side) and for main outcomes calculated with the network meta-analysis (right side) in patients allocated to an antithrombotic therapy with clopidogrel or without. The diamonds indicate the point estimate and the left and the right ends of the lines the [95% CI]. CI: Confidence intervals; OAC; oral anticoagulation.

7.
Basic Res Cardiol ; 115(6): 67, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33185739

RESUMO

A missense variant of the sushi, von Willebrand factor type A, EGF and pentraxin domain containing protein 1 (SVEP1) is genome-wide significantly associated with coronary artery disease. The mechanisms how SVEP1 impacts atherosclerosis are not known. We found endothelial cells (EC) and vascular smooth muscle cells to represent the major cellular source of SVEP1 in plaques. Plaques were larger in atherosclerosis-prone Svep1 haploinsufficient (ApoE-/-Svep1+/-) compared to Svep1 wild-type mice (ApoE-/-Svep1+/+) and ApoE-/-Svep1+/- mice displayed elevated plaque neutrophil, Ly6Chigh monocyte, and macrophage numbers. We assessed how leukocytes accumulated more inside plaques in ApoE-/-Svep1+/- mice and found enhanced leukocyte recruitment from blood into plaques. In vitro, we examined how SVEP1 deficiency promotes leukocyte recruitment and found elevated expression of the leukocyte attractant chemokine (C-X-C motif) ligand 1 (CXCL1) in EC after incubation with missense compared to wild-type SVEP1. Increasing wild-type SVEP1 levels silenced endothelial CXCL1 release. In line, plasma Cxcl1 levels were elevated in ApoE-/-Svep1+/- mice. Our studies reveal an atheroprotective role of SVEP1. Deficiency of wild-type Svep1 increased endothelial CXCL1 expression leading to enhanced recruitment of proinflammatory leukocytes from blood to plaque. Consequently, elevated vascular inflammation resulted in enhanced plaque progression in Svep1 deficiency.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33188598

RESUMO

OBJECTIVES: In this post hoc analysis of the Ticagrelor in coronary artery bypass grafting (CABG) trial, we aimed to analyse patients treated with CABG receiving either complete revascularization (CR) or incomplete revascularization (ICR) independent from random allocation to either ticagrelor or aspirin. METHODS: Of 1859 patients enrolled in the Ticagrelor in CABG trial, 1550 patients (83.4%) received CR and 309 patients (16.6%) ICR. Outcomes were evaluated regarding all-cause mortality, cardiovascular death, myocardial infarction (MI), repeat revascularization, stroke and bleeding within 12 months after CABG. RESULTS: Baseline parameters revealed significant differences regarding clinical presentation (stable angina pectoris: CR 68.9% vs ICR 71.2%, instable angina pectoris: 14.1% vs 7.8%, non-ST elevation MI: 17.0% vs 21.0%, P ˂ 0.01), lesion characteristics (chronic total occlusion: CR 91.3% vs ICR 96.8%, P ˂ 0.01), operative technique [off-pump coronary artery bypass surgery (OPCAB): CR 3.0% vs ICR 6.1%, P ˂ 0.01] and number of utilized grafts (total number of grafts: 2.69/patient vs 2.49/patient, P ˂ 0.001). ICR patients displayed a significantly increased risk of repeat revascularization [hazard ratio (HR) 1.91, 95% confidence interval (CI) 1.16-3.16; P < 0.01] and percutaneous coronary intervention (HR 1.95, 95% CI 1.13-3.35; P < 0.05) within 12 months after CABG. Higher risk for repeat revascularization in ICR patients was independent from random allocation to either ticagrelor or aspirin and persisted after adjustment for baseline imbalances. CONCLUSIONS: Patients with ICR presented more stable at the time of admission, but received less grafts, highly likely due to a higher rate of chronic total occlusion lesions and performed OPCAB. Although mortality presented no difference between groups, our results suggest that patients benefit from CR with regard to prevention of repeat revascularization.

9.
J Am Coll Cardiol ; 76(21): 2436-2446, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33213722

RESUMO

BACKGROUND: Current guidelines recommend intensified platelet inhibition by prasugrel or ticagrelor in patients with unstable angina (UA) or non-ST-segment elevation (NSTE) myocardial infarction (MI). OBJECTIVES: This study sought to investigate the benefits and risks of ticagrelor as compared with prasugrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and planned invasive management. METHODS: This post hoc analysis combines the pre-specified subgroups of UA and NSTEMI of the randomized ISAR-REACT 5 trial. It included 1,179 patients assigned to ticagrelor and 1,186 assigned to prasugrel. Ticagrelor was started immediately after randomization and prasugrel after coronary angiography. The primary endpoint was a composite of death, MI, or stroke during 1-year follow-up, and the safety endpoint was Bleeding Academic Research Consortium class 3-5. RESULTS: The primary endpoint was reached in 101 (8.7%) patients in the ticagrelor and in 73 (6.3%) patients in the prasugrel group (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.04 to 1.90). The HR for all-cause death was 1.43 (95% CI: 0.93 to 2.21) and that for MI 1.43 (95% CI: 0.94 to 2.19). The safety endpoint occurred in 49 (5.2%) patients in the ticagrelor and in 41 (4.7%) patients in the prasugrel group (HR: 1.09; 95% CI: 0.72 to 1.65). Landmark analysis revealed persistence of the efficacy advantage with prasugrel after the first month. CONCLUSIONS: In patients with NSTE-ACS, we found that prasugrel was superior to ticagrelor in reducing the combined 1-year risk of death, MI, and stroke without increasing the risk of bleeding. Due to the post hoc nature of the analysis, these findings need confirmation by further studies. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome; NCT01944800).

11.
Circ Genom Precis Med ; 13(6): e002932, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33170024

RESUMO

BACKGROUND: Individual risk prediction based on genome-wide polygenic risk scores (PRSs) using millions of genetic variants has attracted much attention. It is under debate whether PRS models can be applied-without loss of precision-to populations of similar ethnic but different geographic background than the one the scores were trained on. Here, we examine how PRS trained in population-specific but European data sets perform in other European subpopulations in distinguishing between coronary artery disease patients and healthy individuals. METHODS: We use data from UK and Estonian biobanks (UKB, EB) as well as case-control data from the German population (DE) to develop and evaluate PRS in the same and different populations. RESULTS: PRSs have the highest performance in their corresponding population testing data sets, whereas their performance significantly drops if applied to testing data sets from different European populations. Models trained on DE data revealed area under the curves in independent testing sets in DE: 0.6752, EB: 0.6156, and UKB: 0.5989; trained on EB and tested on EB: 0.6565, DE: 0.5407, and UKB: 0.6043; trained on UKB and tested on UKB: 0.6133, DE: 0.5143, and EB: 0.6049. CONCLUSIONS: This result has a direct impact on the clinical usability of PRS for risk prediction models using PRS: a population effect must be kept in mind when applying risk estimation models, which are based on additional genetic information even for individuals from different European populations of the same ethnicity.

12.
Circulation ; 142(24): 2329-2337, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33115278

RESUMO

BACKGROUND: Data on the comparative efficacy and safety of ticagrelor versus prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention are limited. We assessed the efficacy and safety of ticagrelor versus prasugrel in a head-to-head comparison in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS: In this prespecified subgroup analysis, we included 1653 patients with ST-segment-elevation myocardial infarction randomized to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5). The primary end point was the incidence of death, myocardial infarction, or stroke at 1 year after randomization. The secondary end point was the incidence of bleeding defined as BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 1 year after randomization. RESULTS: The primary end point occurred in 83 patients (10.1%) in the ticagrelor group and in 64 patients (7.9%) in the prasugrel group (hazard ratio, 1.31 [95% CI, 0.95-1.82]; P=0.10). One-year incidence of all-cause death (4.9% versus 4.7%; P=0.83), stroke (1.3% versus 1.0%; P=0.46), and definite stent thrombosis (1.8% versus 1.0%; P=0.15) did not differ significantly in patients assigned to ticagrelor or prasugrel. One-year incidence of myocardial infarction (5.3% versus 2.8%; hazard ratio, 1.95 [95% CI, 1.18-3.23]; P=0.010) was higher with ticagrelor than with prasugrel. BARC type 3 to 5 bleeding occurred in 46 patients (6.1%) in the ticagrelor group and in 39 patients (5.1%) in the prasugrel group (hazard ratio, 1.22 [95% CI, 0.80-1.87]; P=0.36). CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, there was no significant difference in the primary end point between prasugrel and ticagrelor. Ticagrelor was associated with a significant increase in the risk for recurrent myocardial infarction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

14.
JACC Cardiovasc Interv ; 13(19): 2238-2247, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33032712

RESUMO

OBJECTIVES: The aim of this study was to assess the efficacy and safety of ticagrelor versus prasugrel in patients with diabetes mellitus (DM) presenting with acute coronary syndromes (ACS) in whom invasive therapy was planned. BACKGROUND: The efficacy and safety of ticagrelor versus prasugrel in patients with ACS with DM undergoing invasive treatment remain unknown. METHODS: This pre-specified analysis of the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial included 892 patients with ACS with DM and 3,124 patients with ACS without DM randomized to prasugrel or ticagrelor. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding (both assessed 12 months after randomization). RESULTS: The primary endpoint occurred in 51 patients (11.2%) in the ticagrelor group and 55 patients (13.0%) in the prasugrel group in the DM cohort (hazard ratio: 0.84; 95% confidence interval: 0.58 to 1.24; p = 0.383) and in 132 patients (8.6%) in the ticagrelor group and 81 patients (5.2%) in the prasugrel group in the non-DM cohort (hazard ratio: 1.70; 95% confidence interval: 1.29 to 2.24; p < 0.001). There was a significant treatment arm-by-diabetic status interaction (pint = 0.0035). Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 27 patients (6.9%) in the ticagrelor group and 19 patients (5.5%) in the prasugrel group (p = 0.425) in the DM cohort and in 68 patients (5.2%) in the ticagrelor group and 60 patients (4.6%) in the prasugrel group in the non-DM cohort (p = 0.500). CONCLUSIONS: DM seems to affect the efficacy of ticagrelor and prasugrel in patients with ACS. In patients with DM, the efficacy of ticagrelor was comparable with that of prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800).

15.
JACC Cardiovasc Interv ; 13(19): 2266-2274, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33032714

RESUMO

OBJECTIVES: The aim of this study was to evaluate the prognostic impact of target lesion revascularization (TLR) of the unprotected left main coronary artery (ULMCA) after stent failure. BACKGROUND: Although drug-eluting stents are safe and effective for treatment of the ULMCA, increased rates of repeat revascularization have been observed. METHODS: This is a patient-level pooled analysis of the randomized ISAR-LEFT-MAIN (Drug-Eluting-Stents for Unprotected Left Main Stem Disease) and ISAR-LEFT-MAIN-2 (Drug-Eluting Stents to Treat Unprotected Coronary Left Main Disease) trials, in which patients underwent stenting of the ULMCA. The present analysis includes patients who underwent angiography during follow-up. Patients with TLR were compared with those without. Additional long-term clinical follow-up after TLR was conducted, and its influence on mortality was evaluated. Mortality was calculated using the Kaplan-Meier method. Predictors of mortality were assessed in a multivariate analysis. RESULTS: A total of 1,001 patients were eligible, of whom 166 experienced TLR. The 5-year mortality rate was 30.2% in patients with TLR compared with 17.3% in those without TLR (p < 0.001). In the multivariate analysis, glomerular filtration rate (-30 ml/min; hazard ratio [HR]: 2.25; 95% confidence interval [CI]: 1.54 to 3.27; p < 0.001), chronic obstructive pulmonary disease (HR: 4.95; 95% CI: 1.33 to 18.42; p = 0.02), and body mass index (+5 kg/m2; HR: 1.61; 95% CI: 1.12 to 2.32; p = 0.01) were independent predictors of mortality after TLR due to left main stent failure. The type of repeat revascularization and the underlying stent did not influence the mortality after TLR of the ULMCA. CONCLUSIONS: Mortality after TLR for left main stent failure is high. Patient-related factors seem to have a greater impact on mortality after TLR than other variables.

16.
Atherosclerosis ; 311: 84-90, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32949947

RESUMO

BACKGROUND AND AIMS: Very rare loss-of-function mutations in the apolipoprotein C3 (APOC3) gene have been associated with low circulating apoC-III, low triglycerides, and reduced cardiovascular risk. We aimed to analyze the impact of common APOC3 variants on key parameters of lipid metabolism and coronary artery disease in the largest sample so far. METHODS: Common variants in APOC3 were tested for associations with circulating apoC-III, lipids, and apolipoprotein B (apoB) in 3041 participants of the LUdwigshafen RIsk and Cardiovascular health study (LURIC). These variants were then tested for associations with coronary artery disease in a meta-analysis comprising up to 332,389 participants of the CARDIOGRAMplusC4D consortium and the UK Biobank. RESULTS: The mean (standard deviation) apoC-III concentration was 14.6 (5.1) mg/dl. Seven common variants in APOC3 (rs734104, rs4520, rs5142, rs5141, rs5130, rs5128, and rs4225) were associated with circulating apoC-III (all p < 0.05). The alleles that modestly raised apoC-III were also associated with markedly higher total triglycerides and very low density lipoprotein (VLDL) triglycerides and cholesterol (all p < 0.05), but not with low density lipoprotein (LDL) cholesterol and total apoB (all p > 0.05). These variants were not associated with coronary artery disease in the CARDIOGRAMplusC4D consortium and the UK Biobank (all p > 0.1). CONCLUSIONS: Modest, genetically caused elevations of apoC-III are associated with a marked increase of triglyceride-rich lipoproteins but not with an increase of LDL cholesterol, total apoB, and coronary artery disease. Whether effective inhibition of apoC-III production with antisense oligomers will be instrumental to reduce cardiovascular risk remains to be demonstrated.

17.
Nutr Metab Cardiovasc Dis ; 30(12): 2335-2342, 2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-32917497

RESUMO

BACKGROUND AND AIMS: Evidence on the association between aspartate aminotransferase (AST) activity and mortality of patients with ischemic heart disease (IHD) is limited. We investigated whether there is an association between AST activity and mortality in IHD patients. METHODS AND RESULTS: The study included 6857 patients with coronary angiography-proven IHD and AST activity within the reference range. AST activity measurements were available in all patients. The primary outcome was 3-year cardiac mortality. Patients were categorized in groups according to the AST activity tertiles: a group with AST within the 1st tertile (AST < 17.0 U/L), a group with AST within the 2nd tertile (AST > 17-24.5 U/L) and a group with AST within the 3rd tertile (AST > 24.5 U/L). Cardiac death (n = 297) occurred in 109, 69 and 119 patients in the 1st to 3rd AST tertiles (Kaplan-Meier estimates of mortality: 5.3%, 3.6% and 5.9%; univariable hazard ratio [HR] = 1.75, 95% confidence interval [CI] 1.30-2.36, P < 0.001 for tertile 3 vs. 2; HR = 1.13 [0.87-1.46], P = 0.370 for tertile 3 vs. 1; and HR = 0.65 [0.48-0.87], P = 0.004 for tertile 2 vs. 1). The association between AST and cardiac mortality was U-shaped. AST values <15 U/L (HR = 1.118 [1.009-1.238]) and >23 U/L (HR = 1.029 [1.003-1.056]) were associated with higher cardiac mortality compared with the reference value (21 U/L). After adjustment, the association between AST and cardiac mortality was attenuated (P = 0.133) but remained non-linear (P = 0.047). CONCLUSIONS: In patients with IHD, AST activity was associated with the risk of cardiac mortality with a U-shaped relationship. After adjustment, the association between AST and mortality was attenuated.


Assuntos
Aspartato Aminotransferases/sangue , Ensaios Enzimáticos Clínicos , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/mortalidade , Idoso , Biomarcadores/sangue , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/terapia , Intervenção Coronária Percutânea/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo , Resultado do Tratamento
18.
Circ Genom Precis Med ; 13(5): 417-423, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32862661

RESUMO

BACKGROUND: Familial sitosterolemia is a rare Mendelian disorder characterized by hyperabsorption and decreased biliary excretion of dietary sterols. Affected individuals typically have complete genetic deficiency-homozygous loss-of-function (LoF) variants-in the ABCG5 or ABCG8 genes and have substantially elevated plasma sitosterol and LDL (low-density lipoprotein) cholesterol (LDL-C) levels. The impact of partial genetic deficiency of ABCG5 or ABCG8-as occurs in heterozygous carriers of LoF variants-on LDL-C and risk of coronary artery disease (CAD) has remained uncertain. METHODS: We first recruited 9 sitosterolemia families, identified causative LoF variants in ABCG5 or ABCG8, and evaluated the associations of these ABCG5 or ABCG8 LoF variants with plasma phytosterols and lipid levels. We next assessed for LoF variants in ABCG5 or ABCG8 in CAD cases (n=29 321) versus controls (n=357 326). We tested the association of rare LoF variants in ABCG5 or ABCG8 with blood lipids and risk for CAD. Rare LoF variants were defined as protein-truncating variants with minor allele frequency <0.1% in ABCG5 or ABCG8. RESULTS: In sitosterolemia families, 7 pedigrees harbored causative LoF variants in ABCG5 and 2 pedigrees in ABCG8. Homozygous LoF variants in either ABCG5 or ABCG8 led to marked elevations in sitosterol and LDL-C. Of those sitosterolemia families, heterozygous carriers of ABCG5 LoF variants exhibited increased sitosterol and LDL-C levels compared with noncarriers. Within large-scale CAD case-control cohorts, prevalence of rare LoF variants in ABCG5 and in ABCG8 was ≈0.1% each. ABCG5 heterozygous LoF variant carriers had significantly elevated LDL-C levels (25 mg/dL [95% CI, 14-35]; P=1.1×10-6) and were at 2-fold increased risk of CAD (odds ratio, 2.06 [95% CI, 1.27-3.35]; P=0.004). By contrast, ABCG8 heterozygous LoF carrier status was not associated with increased LDL-C or risk of CAD. CONCLUSIONS: Although familial sitosterolemia is traditionally considered as a recessive disorder, we observed that heterozygous carriers of an LoF variant in ABCG5 had significantly increased sitosterol and LDL-C levels and a 2-fold increase in risk of CAD.

19.
Circ Arrhythm Electrophysiol ; 13(10): e008461, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32903044

RESUMO

BACKGROUND: Recent data demonstrate promising effects on left ventricular dysfunction and left ventricular ejection fraction (LVEF) improvement following ablation for atrial fibrillation (AF) in patients with heart failure. We sought to study the relationship between LVEF, New York Heart Association class on presentation, and the end points of mortality and heart failure admissions in the CASTLE-AF study (Catheter Ablation for Atrial Fibrillation With Heart Failure) population. Furthermore, predictors for LVEF improvement were examined. METHODS: The CASTLE-AF patients with coexisting heart failure and AF (n=363) were randomized in a multicenter prospective controlled fashion to ablation (n=179) versus pharmacological therapy (n=184). Left ventricular function and New York Heart Association class were assessed at baseline (after randomization) and at each follow-up visit. RESULTS: In the ablation arm, a significantly higher number of patients experienced an improvement in their LVEF to >35% at the end of the study (odds ratio, 2.17; P<0.001). Compared with the pharmacological therapy arm, both ablation patient groups with severe (<20%) or moderate/severe (≥20% and <35%) baseline LVEF had a significantly lower number of composite end points (hazard ratio [HR], 0.60; P=0.006), all-cause mortality (HR, 0.54; P=0.019), and cardiovascular hospitalizations (HR, 0.66; P=0.017). In the ablation group, New York Heart Association I/II patients at the time of treatment had the strongest improvement in clinical outcomes (primary end point: HR, 0.43; P<0.001; mortality: HR, 0.30; P=0.001). CONCLUSIONS: Compared with pharmacological treatment, AF ablation was associated with a significant improvement in LVEF, independent from the severity of left ventricular dysfunction. AF ablation should be performed at early stages of the patient's heart failure symptoms.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32888121

RESUMO

BACKGROUND: The value of antiarrhythmics to maintain normal sinus rhythm in patients with atrial fibrillation (AF) and heart failure (HF) is still being debated. We aimed to determine whether rhythm control using antiarrhythmic drugs (AADs) is more effective than rate control in improving outcomes in this population. METHOD: In this sub-analysis of the CASTLE-AF study, we included patients that were treated pharmacologically either to maintain sinus rhythm or to achieve rate control. The primary endpoint was defined as a composite of death from any cause or worsening of HF that led to an unplanned overnight hospitalization. RESULT: Among 210 patients (mean age of 64.1 ± 10.8 years, 83.3% male) treated pharmacologically, 60 patients were in the rhythm control group and 150 were in the rate control group. Patients in the rhythm control group were less likely to be assigned a beta-blocker (53 (88.3%) vs 141 (97.9%), P = 0.004) and digitalis (8 (13.3%) vs 53 (36.8%), P < 0.001). Over a median follow-up of 3.76 (95% confidence interval (CI), 3.23, 4.48) years, the primary composite endpoint of all-cause mortality and HF admissions occurred in 23 patients (38.3%) in the rhythm control arm vs 67 (44.7%) in the rate control arm (hazard ratio, 0.99; 95% CI, 0.62 to 1.60; P = 0.976). CONCLUSION: In CASTLE-AF among AF patients with HF, rhythm control with AADs did not significantly reduce the primary composite endpoint of all-cause mortality and HF hospitalization when compared with a pharmacological rate control strategy.

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