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1.
Coron Artery Dis ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32040026

RESUMO

BACKGROUND: In established ischemic heart disease, the relationship between lipoprotein(a) and new cardiovascular events showed contradictory results. Our aim was to assess the relationship between lipoprotein(a) and very long-term recurrent myocardial infarction (MI) after an index episode of ST-segment elevation acute myocardial infarction (STEMI). METHODS: We included 435 consecutive STEMI patients discharged from October 2000 to June 2003 in a single teaching center. The relationship between lipoprotein(a) at discharge and recurrent MI was evaluated through negative binomial regression and Cox regression analysis. RESULTS: The mean age was 65 years (55-74 years), 25.5% were women, 34.7% were diabetic, and 66% had a MI of anterior location. Fibrinolysis, rescue, or primary angioplasty was performed in 215 (49.4%), 19 (4.4%), and 18 (4.1%) patients, respectively. The median lipoprotein(a) was 30.4 mg/dL (12-59.4 mg/dL). After a median follow-up of 9.6 years (4.1-15 years), 180 (41.4%) deaths and 187 MI in 133 (30.6%) patients were recorded. After a multivariate adjustment, the risk gradient of lipoprotein(a) showed a neutral effect along most of the continuum and only extreme higher values identified those at higher risk of recurrent MI (P = 0.020). Those with lipoprotein(a) values >95th percentile (≥135 mg/dL) showed a higher risk of recurrent MI (incidence rate ratio, 2.34; 95% confidence interval, 1.37-4.02; P = 0.002). Lipoprotein(a) was not related to the risk of mortality (P = 0.245). CONCLUSIONS: After an episode of STEMI, only extreme high values of lipoprotein(a) were associated with an increased risk of long-term recurrent MI.

3.
ESC Heart Fail ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059081

RESUMO

AIMS: The objective of the present study is to assess the prognostic value of acute kidney injury (AKI) in the evolution of patients with heart failure (HF) using real-world data. METHODS AND RESULTS: Patients with a diagnosis of HF and with serial measurements of renal function collected throughout the study period were included. Estimated glomerular filtration rate (GFR) was calculated with the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). AKI was defined when a sudden drop in creatinine with posterior recovery was recorded. According to the Risk, Injury, Failure, Loss, and End-Stage Renal Disease (RIFLE) scale, AKI severity was graded in three categories: risk [1.5-fold increase in serum creatinine (sCr)], injury (2.0-fold increase in sCr), and failure (3.0-fold increase in sCr or sCr > 4.0 mg/dL). AKI incidence and risk of hospitalization and mortality after the first episode were calculated by adjusting for potential confounders. A total of 30 529 patients with HF were included. During an average follow-up of 3.2 years, 5294 AKI episodes in 3970 patients (13.0%) and incidence of 3.3/100 HF patients/year were recorded. One episode was observed in 3161 (10.4%), two in 537 (1.8%), and three or more in 272 (0.9%). They were more frequent in women with diabetes and hypertension. The incidence increases across the GFR levels (Stages 1 to 4: risk 7.6%, 6.8%, 11.3%, and 12.5%; injury 2.1%, 2.0%, 3.3%, and 5.5%; and failure 0.9%, 0.6%. 1.4%, and 8.0%). A total of 3817 patients with acute HF admission were recorded during the follow-up, with incidence of 38.4/100 HF patients/year, 3101 (81.2%) patients without AKI, 545 (14.3%) patients with one episode, and 171 (4.5%) patients with two or more. The number of AKI episodes [one hazard ratio (HR) 1.05 (0.98-1.13); two or more HR 2.01 (1.79-2.25)] and severity [risk HR 1.05 (0.97-1.04); injury HR 1.41 (1.24-1.60); and failure HR 1.90 (1.64-2.20)] increases the risk of hospitalization. A total of 10 560 deaths were recorded, with incidence of 9.3/100 HF patients/year, 8951 (33.7%) of subjects without AKI episodes, 1180 (11.17%) of subjects with one episode, and 429 (4.06%) with two or more episodes. The number of episodes [one HR 1.05 (0.98-1.13); two or more HR 2.01 (1.79-2.25)] and severity [risk 1.05 confidence interval (CI) (0.97-1.14), injury 1.41 (CI 1.24-1.60), and failure 1.90 (CI 1.64-2.20)] increases mortality risk. CONCLUSIONS: The study demonstrated the worse prognostic value of sudden renal function decline in HF patients and pointed to those with more future risk who require review of treatment and closer follow-up.

4.
Eur Heart J Acute Cardiovasc Care ; : 2048872620907539, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32067483

RESUMO

BACKGROUND: Undetectable high-sensitivity cardiac troponin (hs-cTn) in a single determination upon admission may rule out acute coronary syndrome. We investigated undetectable hs-cTnT (

5.
J Am Heart Assoc ; 9(4): e014254, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32067585

RESUMO

Background Intravenous ferric carboxymaltose (FCM) improves symptoms, functional capacity, and quality of life in heart failure and iron deficiency. The mechanisms underlying these effects are not fully understood. The aim of this study was to examine changes in myocardial iron content after FCM administration in patients with heart failure and iron deficiency using cardiac magnetic resonance. Methods and Results Fifty-three stable heart failure and iron deficiency patients were randomly assigned 1:1 to receive intravenous FCM or placebo in a multicenter, double-blind study. T2* and T1 mapping cardiac magnetic resonance sequences, noninvasive surrogates of intramyocardial iron, were evaluated before and 7 and 30 days after randomization using linear mixed regression analysis. Results are presented as least-square means with 95% CI. The primary end point was the change in T2* and T1 mapping at 7 and 30 days. Median age was 73 (65-78) years, with N-terminal pro-B-type natriuretic peptide, ferritin, and transferrin saturation medians of 1690 pg/mL (1010-2828), 63 ng/mL (22-114), and 15.7% (11.0-19.2), respectively. Baseline T2* and T1 mapping values did not significantly differ across treatment arms. On day 7, both T2* and T1 mapping (ms) were significantly lower in the FCM arm (36.6 [34.6-38.7] versus 40 [38-42.1], P=0.025; 1061 [1051-1072] versus 1085 [1074-1095], P=0.001, respectively). A similar reduction was found at 30 days for T2* (36.3 [34.1-38.5] versus 41.1 [38.9-43.4], P=0.003), but not for T1 mapping (1075 [1065-1085] versus 1079 [1069-1089], P=0.577). Conclusions In patients with heart failure and iron deficiency, FCM administration was associated with changes in the T2* and T1 mapping cardiac magnetic resonance sequences, indicative of myocardial iron repletion. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03398681.

6.
Br J Clin Pharmacol ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068914

RESUMO

AIMS: Explore the efficacy, safety and tolerability of the dual sodium glucose co-transporter (SGLT) 1 and 2 inhibitor, licogliflozin in patients with type-2 diabetes mellitus (T2DM) and heart failure. METHODS: This multi-center, parallel-group phase IIA study randomized 125 patients with T2DM and heart failure (NYHA II-IV; plasma NT-proBNP >300 pg/mL) to licogliflozin (2.5mg, 10mg, 50mg) taken at bedtime, empagliflozin (25mg) or placebo (44 patients completed the study). The primary endpoint was change from baseline in NT-proBNP after 12 weeks. Secondary endpoints included change from baseline in glycated hemoglobin (HbA1c), fasting plasma glucose, weight, blood pressure (BP), fasting lipid profile, high-sensitivity c-reactive protein, and safety and tolerability. RESULTS: Licogliflozin 10 mg for 12 weeks significantly reduced NT-proBNP vs. placebo (Geometric mean ratio 0.56 [95% CI: 0.33, 0.95], p=0.033). A trend was observed with 50 mg licogliflozin (0.64 [95% CI: 0.40, 1.03], p=0.064), with no difference between licogliflozin and empagliflozin. The largest numerical decreases in HbA1c were with licogliflozin 50 mg (-0.58±0.34%) and empagliflozin (-0.44±1.18%) vs. placebo (-0.04±0.91%). The reduction in body weight was similar with licogliflozin 50 mg (-2.15±2.40kg) and empagliflozin (-2.25±1.89kg). A numerical reduction in systolic BP was seen with licogliflozin 50 mg (-9.54±16.88mmHg) and empagliflozin (-6.98 ±15.03mmHg) vs. placebo (-2.85±11.97mmHg). Adverse events (AEs) were mild, including hypotension (6.5%), hypoglycemia (8.1%) and inadequate diabetes control (1.6%). The incidence of diarrhea (4.9%) was lower than previously reported. CONCLUSION: The reduction in NT-proBNP with licogliflozin suggests a potential benefit of SGLT1 and 2 inhibition in patients with T2DM and heart failure.

8.
Nephrol Dial Transplant ; 35(Supplement_1): i13-i23, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32003834

RESUMO

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have clearly demonstrated their beneficial effect in diabetic kidney disease (DKD) on top of the standard of care [blood glucose control, renin-angiotensin system blockade, smoking cessation and blood pressure (BP) control], even in patients with overt DKD. However, the indication of this drug class is still blood glucose lowering in type 2 diabetic patients with estimated glomerular filtration rate >45 mL/min/1.73 m2. Based on the new evidence, several scientific societies have emphasized the preferential prescription of SGLT2i for patients at risk of heart failure or kidney disease, but still within the limits set by health authorities. A rapid positioning of both the European Medicines Agency and the US Food and Drug Administration will allow patients with overt DKD to benefit from SGLT2i. Clinical experience suggests that SGLT2i safety management may in part mirror renin-angiotensin blockade safety management in patients with overt DKD. This review focuses on the rationale for an indication of SGTL2i in DKD. We further propose clinical steps for maximizing the safety of SGLT2i in DKD patients on other antidiabetic, BP or diuretic medication.

9.
ESC Heart Fail ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32045114

RESUMO

AIM: Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor developed for the treatment of heart failure with reduced ejection fraction. Its benefits are achieved through the inhibition of neprilysin (NEP) and the specific blockade of the angiotensin receptor AT1. The many peptides metabolized by NEP suggest multifaceted potential consequences of its inhibition. We sought to evaluate the short-term changes in serum endorphin (EP) values and their relation with patients' physical functioning after initiation of sacubitril/valsartan treatment. METHODS AND RESULTS: A total of 105 patients with heart failure with reduced ejection fraction, who were candidates for sacubitril/valsartan treatment, were included in this prospective, observational, multicentre, and international study. In a first visit, and in agreement with current guidelines, treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker was replaced by sacubitril/valsartan because of clinical indication by the responsible physician. By protocol, patients were reevaluated at 30 days after the start of sacubitril/valsartan. Serum levels of α- (α-EP), γ-Endorphin (γ-EP), and soluble NEP (sNEP) were measured using enzyme-linked immunoassays. New York Heart Association (NYHA) functional class was used as an indicator of patient's functional status. Baseline median levels of circulating α-EP, γ-EP, and sNEP were 582 (160-772), 101 (37-287), and 222 pg/mL (124-820), respectively. There was not a significant increase in α-EP nor γ-EP serum values after sacubitril/valsartan treatment (P value = 0.194 and 0.102, respectively). There were no significant differences in sNEP values between 30 days and baseline (P value = 0.103). Medians (IQR) of Δα-EP, Δγ-EP, and ΔsNEP between 30 days and baseline were 9.3 (-34 - 44), -3.0 (-46.0 - 18.9), and 0 units (-16.4 - 157.0), respectively. In a pre-post sacubitril/valsartan treatment comparison, there was a significant improvement in NYHA class, with 36 (34.3%) patients experiencing improvement by at least one NYHA class category. Δα-EP and ΔsNEP showed to be significantly associated with NYHA class after 30 days of treatment (P = 0.014 and P < 0.001, respectively). Δα-EP was linear and significantly associated with NYHA class improvement after 30 days of sacubitril/valsartan treatment. CONCLUSIONS: These preliminary data suggest that beyond the haemodynamic benefits achieved with sacubitril/valsartan, the altered cleavage of endorphin peptides by NEP inhibition may participate in patients' symptoms improvement.

10.
Int J Cardiol ; 302: 30-33, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31924393

RESUMO

BACKGROUND: The potential sex-differential effect of frailty in patients with acute coronary syndromes (ACS) has not been well-evaluated. We sought to examine the sex-differential association between frailty status on long-term mortality in elderly patients with an ACS. METHODS AND RESULTS: This is a prospective observational single-center study that included 488 elderly patients (>65 years) hospitalized for ACS who survived the index hospitalization. Multivariate Cox regression was used to determine the association among the exposures (interaction of sex with Fried score and sex with Fried ≥ 3) and all-cause mortality. The mean age of the sample was 78 ±â€¯7 years; 41% were female and the median Fried score was higher in women [3 (2-3) vs. 2 (1-2) points, p < 0.001]. At a median follow-up of 3.12 years (IQR:1.38-5.13), 182 deaths (37.3%) were registered. The association of Fried ≥ 3 with mortality varied across sex (p-value for interaction = 0.022). In males, Fried ≥ 3 was independently associated with all-cause death (HR = 1.89; CI 95%:1.25-2.85, p = 0.003). However, it showed a neutral effect on women (HR = 0.92; CI 95%:0.57-1.49, p = 0.726). CONCLUSIONS: In this work, we found that the frailty status assessed by Fried score was independently associated with mortality in elderly males but not in females with ACS.

11.
Am J Cardiol ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31959430

RESUMO

Low lymphocyte count, as a marker of inflammation and immunosuppression, may be useful for identifying frail patients. In this work, we aimed to evaluate the association between low-relative lymphocyte count (Lymph%) and frailty status in patients >65 years old with acute coronary syndromes (ACS), and whether Lymph% is associated with morbimortality beyond standard prognosticators and frailty. In this prospective observational study, we included 488 hospital survivors of an episode of an ACS >65 years old. Total and differential white blood cells and frailty status were assessed at discharge. Frailty was evaluated using the Fried score at discharge and defined as Fried≥3. The independent association between Lymph% and Fried≥3 was evaluated by multivariate logistic regression analysis. The associations between Lymph% with long-term all-cause mortality and recurrent admission were evaluated with Cox regression and shared frailty regression, respectively. The mean age of the sample was 78 ± 7 years and 41% were females. The median (interquartile range) of the Lymph% was 21% (15 to 27) and 41% showed Fried≥3. In multivariate analysis, Lymph% was inversely related to the odds of frailty with an exponential increase risk from values below 15% (p = 0.001). Likewise, Lymph% was inverse and independently associated with a higher risk of long-term mortality (p = 0.011), recurrent all-cause (p = 0.020), and cardiovascular readmissions (p = 0.024). In conclusion, in patients >65 years with a recent ACS, low Lymph% evaluated at discharge is associated with a higher risk of frailty. Low Lymph% was also associated with a higher risk of long-term mortality and recurrent admissions beyond standard prognosticators and Fried score.

12.
ESC Heart Fail ; 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31903686

RESUMO

AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for reducing plasma low-density lipoprotein cholesterol. Beyond lipid control, recent findings suggest a deleterious effect of this protein in the pathogenesis of postmyocardial infarction left ventricle remodelling and heart failure-related complications. The aim of this study was to assess the relationship between circulating PCSK9 and 6 month cardiac magnetic resonance imaging-derived left ventricular ejection fraction (LVEF) after a first ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: We prospectively evaluated 40 patients with a first STEMI, LVEF < 50% and treated with primary percutaneous coronary intervention in which PCSK9 was measured 24 h postreperfusion. All patients underwent cardiac magnetic resonance imaging 1 week and 6 months after STEMI. Baseline characteristics were compared across median values of PCSK9. The association between PCSK9 levels and LVEF at 6 months was evaluated by analysis of covariance. The mean age of the sample was 60 ± 12 years and 33 (82.5%) were male patients. The infarct location was anterior in 27 patients (67.5%), and 9 patients (22.5%) were Killip class ≥ II. The mean 1 week and 6 month LVEF were 41 ± 7% and 48 ± 10%, respectively. The mean PCSK9 was 1.93 ± 0.38 U/mL. Testing the association between serum PCSK9 and 6 month LVEF with analysis of covariance revealed an inverse relationship (r = -0.35, P = 0.028). After multivariate adjustment, circulating PCSK9 remained significant and inversely associated with 6 month LVEF (P = 0.002). CONCLUSIONS: In patients with a first STEMI with reduced ejection fraction at index admission and treated with primary percutaneous coronary intervention, circulating PCSK9 was associated with lower LVEF at 6 months.

15.
ESC Heart Fail ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31833193

RESUMO

Refractory congestive heart failure is associated with an ominous prognosis in which the treatments strategies remain scarce and not well validated. In the last years, continuous ambulatory peritoneal dialysis (CAPD) has emerged as a therapeutic alternative in this subset of patients. So far, it has been associated with a significant improvement in functional capacity and quality of life, together with a striking reduction in the risk of readmissions. We present the case of an elderly patient with severe left ventricular dysfunction and severe mitral and tricuspid regurgitation who presents recurrent admissions for anasarca. After its inclusion in a CAPD programme, the patient experienced a marked clinical and biochemical improvement despite the persistence of cardiac abnormalities. CAPD onset translates into greater sodium removal. We want to emphasize the usefulness of this therapy in the management of volume excess in patients with refractory heart failure and renal failure promoting a greater sodium removal compared with traditional diuretic strategies.

17.
Eur J Heart Fail ; 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31863682

RESUMO

AIMS: Kidney impairment has been associated with worse outcomes in acute heart failure (AHF), although recent studies challenge this association. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel biomarker of kidney tubular injury. Its prognostic role in AHF has not been evaluated in large cohorts. The present study aimed to determine if serum NGAL (sNGAL) or urine NGAL (uNGAL) is superior to creatinine for predicting short-term outcomes in AHF. METHODS AND RESULTS: The study was conducted in an international, multicentre, prospective cohort consisting of 927 patients with AHF. Admission and peak values of sNGAL, uNGAL and uNGAL/urine creatinine (uCr) ratio were compared to admission and peak serum creatinine (sCr). The composite endpoints were death, initiation of renal replacement therapy, heart failure (HF) readmission and any emergent HF-related outpatient visit within 30 and 60 days, respectively. The mean age of the cohort was 69 years and 62% were male. The median length of stay was 6 days. The composite endpoint occurred in 106 patients and 154 patients within 30 and 60 days, respectively. Serum NGAL was more predictive than uNGAL and the uNGAL/uCr ratio but was not superior to sCr (area under the curve [AUC]; admission sNGAL 0.61 [95% confidence interval (CI) 0.55-0.67] and 0.59 [95% CI 0.54-0.65], peak sNGAL 0.60 [95% CI 0.54-0.66] and 0.57 [95% CI 0.52-0.63], admission sCr 0.60 [95% CI 0.54-0.64] and 0.59 [95% CI 0.53-0.64] [area under the curve: admission sNGAL 0.61, 95% confidence interval (CI) 0.55-0.67, and 0.59, 95% CI 0.54-0.65; peak sNGAL: 0.60, 95% CI 0.54-0.66, and 0.57, 95% CI 0.52-0.63; admission sCr: 0.60, 95% CI 0.54-0.64, and 0.59, 95% CI 0.53-0.64, at 30 and 60 days, respectively], peak sCr 0.61 [95% CI 0.55-0.67] and 0.59 [95% CI 0.54-0.64] at 30 and 60 days, respectively). NGAL was not predictive of the composite endpoint in multivariate analysis. CONCLUSIONS: Serum NGAL outperformed uNGAL but neither was superior to admission or peak sCr for predicting adverse events.

18.
Sci Rep ; 9(1): 20017, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882712

RESUMO

Delayed enhancement cardiovascular magnetic resonance (MR) is the gold-standard for non-invasive assessment after myocardial infarction (MI). MR microscopy (MRM) provides a level of detail comparable to the macro objective of light microscopy. We used MRM and correlative histopathology to identify infarct and remote tissue in contrast agent-free multi-sequence MRM in swine MI hearts. One control group (n = 3 swine) and two experimental MI groups were formed: 90 min of ischemia followed by 1 week (acute MI = 6 swine) or 1 month (chronic MI = 5 swine) reperfusion. Representative samples of each heart were analysed by contrast agent-free multi-sequence (T1-weighting, T2-weighting, T2*-weighting, T2-mapping, and T2*-mapping). MRM was performed in a 14-Tesla vertical axis imager (Bruker-AVANCE 600 system). Images from MRM and the corresponding histopathological stained samples revealed differences in signal intensities between infarct and remote areas in both MI groups (p-value < 0.001). The multivariable models allowed us to precisely classify regions of interest (acute MI: specificity 92% and sensitivity 80%; chronic MI: specificity 100% and sensitivity 98%). Probabilistic maps based on MRM images clearly delineated the infarcted regions. As a proof of concept, these results illustrate the potential of MRM with correlative histopathology as a platform for exploring novel contrast agent-free MR biomarkers after MI.

19.
Eur J Heart Fail ; 21(12): 1553-1560, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31769140

RESUMO

AIMS: In acute heart failure (AHF), relationships between changes in B-type natriuretic peptide (BNP) and worsening renal function (WRF) and its prognostic implications have not been fully determined. We investigated the relationship between WRF and a decrease in BNP with in-hospital and 1-year mortality in AHF. METHODS AND RESULTS: The Acute Kidney Injury NGAL Evaluation of Symptomatic heart faIlure Study (AKINESIS) was a prospective, international, multicentre study of AHF patients. Severe WRF (sWRF) was a sustained increase of ≥44.2 µmol/L (0.5 mg/dL) or ≥50% in creatinine, non-severe WRF (nsWRF) was a non-sustained increase of ≥26.5 µmol/L (0.3 mg/dL) or ≥50% in creatinine, and WRF with clinical deterioration was nsWRF with renal replacement therapy, inotrope use, or mechanical ventilation. Decreased BNP was defined as a ≥30% reduction in the last measured BNP compared to admission BNP. Among 814 patients, the incidence of WRF was not different between patients with or without decreased BNP (nsWRF: 33% vs. 31%, P = 0.549; sWRF: 11% vs. 9%, P = 0.551; WRF with clinical deterioration: 8% vs. 10%, P = 0.425). Decreased BNP was associated with better in-hospital and 1-year mortality regardless of WRF, while WRF was associated with worse outcomes only in patients without decreased BNP. In multivariate Cox regression analysis, decreased BNP, sWRF, and WRF with clinical deterioration were significantly associated with 1-year mortality. CONCLUSIONS: Decreased BNP was associated with better in-hospital and long-term outcomes. WRF was only associated with adverse outcomes in patients without decreased BNP.

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