Association of Different Estimates of Renal Function With Cardiovascular Mortality and Bleeding in Atrial Fibrillation.

Background We compared different methods of estimated glomerular filtration rate (eGFR) and their association with cardiovascular death and major bleeding in 14 980 patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Methods and Results eGFR was calculated using equations based on creatinine (Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) and/or cystatin C (CKD-EPICysC and CKD-EPICysC+Creatinine). These 5 eGFR equations, as well as the individual variables that are used in these equations, were assessed for correlation and discriminatory ability for cardiovascular death and major bleeding. The median age was 70.0 years, and 35.6% were women. The median eGFR was highest with Cockcroft-Gault (74.1 mL/min) and CKD-EPICysC (74.2 mL/min), and lowest with Modification of Diet in Renal Disease (66.5 mL/min). Correlation between methods ranged from 0.49 (Cockroft-Gault and CKD-EPICysC) to 0.99 (Modification of Diet in Renal Disease and CKD-EPI). Among the eGFR equations, those based on cystatin C yielded the highest C indices for cardiovascular death and major bleeding: 0.628 (CKD-EPICysC) and 0.612 (CKD-EPICysC+Creatinine), respectively. A model based on the variables within the different eGFR equations (age, sex, weight, creatinine, and cystatin C) yielded the highest discriminatory value for both outcomes, with a C index of 0.673 and 0.656, respectively. Conclusions In patients with atrial fibrillation on anticoagulation, correlation between eGFR calculated using different methods varied substantially. Cystatin C-based eGFRs seem to provide the most robust information for predicting death and bleeding. A model based on the individual variables within the eGFR equations, however, provided the highest discriminatory value. Our findings may help refine risk stratification in patients with atrial fibrillation and define how renal function should be determined in future atrial fibrillation studies. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00412984.

Effectiveness of sacubitril-valsartan in cancer patients with heart failure.

AIMS: Current guidelines recommend sacubitril/valsartan for patients with heart failure and reduced left ventricular ejection fraction (LVEF), but there is lack of evidence of its efficacy and safety in cancer therapy-related cardiac dysfunction (CTRCD). Our aim was to analyse the potential benefit of sacubitril/valsartan in patients with CTRCD. METHODS AND RESULTS: We performed a retrospective multicentre registry (HF-COH) in six Spanish hospitals with cardio-oncology clinics including all patients treated with sacubitril/valsartan. Demographic and clinical characteristics and laboratory and echocardiographic data were collected. Median follow-up was 4.6 [1; 11] months. Sixty-seven patients were included (median age was 63 ± 14 years; 64% were female, 87% had at least one cardiovascular risk factor). Median time from anti-cancer therapy to CTRD was 41 [10; 141] months. Breast cancer (45%) and lymphoma (39%) were the most frequent neoplasm, 31% had metastatic disease, and all patients were treated with combination antitumor therapy (70% with anthracyclines). Thirty-nine per cent of patients had received thoracic radiotherapy. Baseline median LVEF was 33 [27; 37], and 21% had atrial fibrillation. Eighty-five per cent were on beta-blocker therapy and 76% on mineralocorticoid receptor antagonists; 90% of the patients were symptomatic NYHA functional class ≥II. Maximal sacubitril/valsartan titration dose was achieved in 8% of patients (50 mg b.i.d.: 60%; 100 mg b.i.d.: 32%). Sacubitril/valsartan was discontinued in four patients (6%). Baseline N-terminal pro-B-type natriuretic peptide levels (1552 pg/mL [692; 3624] vs. 776 [339; 1458]), functional class (2.2 ± 0.6 vs. 1.6 ± 0.6), and LVEF (33% [27; 37] vs. 42 [35; 50]) improved at the end of follow-up (all P values ≤0.01). No significant statistical differences were found in creatinine (0.9 mg/dL [0.7; 1.1] vs. 0.9 [0.7; 1.1]; P = 0.055) or potassium serum levels (4.5 mg/dL [4.1; 4.8] vs. 4.5 [4.2; 4.8]; P = 0.5). Clinical, echocardiographic, and biochemical improvements were found regardless of the achieved sacubitril-valsartan dose (low or medium/high doses). CONCLUSIONS: Our experience suggests that sacubitril/valsartan is well tolerated and improves echocardiographic functional and structural parameters, N-terminal pro-B-type natriuretic peptide levels, and symptomatic status in patients with CTRCD.

Tbx20 controls the expression of the KCNH2 gene and of hERG channels.

Long QT syndrome (LQTS) exhibits great phenotype variability among family members carrying the same mutation, which can be partially attributed to genetic factors. We functionally analyzed the KCNH2 (encoding for Kv11.1 or hERG channels) and TBX20 (encoding for the transcription factor Tbx20) variants found by next-generation sequencing in two siblings with LQTS in a Spanish family of African ancestry. Affected relatives harbor a heterozygous mutation in KCNH2 that encodes for p.T152HfsX180 Kv11.1 (hERG). This peptide, by itself, failed to generate any current when transfected into Chinese hamster ovary (CHO) cells but, surprisingly, exerted "chaperone-like" effects over native hERG channels in both CHO cells and mouse atrial-derived HL-1 cells. Therefore, heterozygous transfection of native (WT) and p.T152HfsX180 hERG channels generated a current that was indistinguishable from that generated by WT channels alone. Some affected relatives also harbor the p.R311C mutation in Tbx20. In human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), Tbx20 enhanced human KCNH2 gene expression and hERG currents (IhERG) and shortened action-potential duration (APD). However, Tbx20 did not modify the expression or activity of any other channel involved in ventricular repolarization. Conversely, p.R311C Tbx20 did not increase KCNH2 expression in hiPSC-CMs, which led to decreased IhERG and increased APD. Our results suggest that Tbx20 controls the expression of hERG channels responsible for the rapid component of the delayed rectifier current. On the contrary, p.R311C Tbx20 specifically disables the Tbx20 protranscriptional activity over KCNH2 Therefore, TBX20 can be considered a KCNH2-modifying gene.

Utility of intracardiac echocardiography for catheter ablation of complex cardiac arrhythmias in a medium-volume training center.

AIMS AND OBJECTIVES: New electrophysiology tools like intracardiac echocardiography (ICE) might help to minimize and early detect complications during cardiac ablation procedures. The aim of the study was to assess the utility and vascular safety of ICE during catheter ablation of complex cardiac arrhythmias in a medium-volume training center. METHODS: Prospective, observational study consisted of consecutive patients who underwent catheter-based ablation of complex cardiac arrhythmias. All procedures were performed using three-dimensional electro-anatomical mapping and routine cannulation of right and left femoral veins. The ICE probe was initially positioned at the mid-level of the right atrium and properly moved to monitor different steps of the procedure and identify complications. All procedure-related vascular complications were registered. RESULTS: One hundred two patients (age 61.4 ± 13.1 years, 69 male) underwent 110 ablation procedures. Pulmonary vein isolation was the most common ablation substrate (55.4%). Ventricular tachycardia (17.2%) and left atrial flutter procedures (16.4%) were also common. The use of ICE enabled us to early initiate anticoagulation and to optimize the transseptal puncture. It also provided the capability to early detect life-threatening complications such as tamponade (3.6%), along with important information during the procedure such as exact catheter location, lesion formation, and stability during radiofrequency delivery. Such benefits were not associated with a higher number of vascular complications. CONCLUSION: The use of ICE during catheter-based ablation of complex cardiac substrates provides technical features that may decrease complications and increase accuracy while applying radiofrequency, especially in training centers where fellows start to perform complex procedures.

Immediate and mid-term clinical course after percutaneous closure of paravalvular leakage.

INTRODUCTION AND OBJECTIVES: Percutaneous closure of paravalvular leakage is an alternative to surgery in high-risk patients, but its use has been limited by a lack of specific devices. More appropriate devices-like the Amplatzer Vascular Plug III-have recently been developed, but information about their efficacy and safety is still scarce. The objective of the present study was to assess the mid-term results of paravalvular leakage closure with this device. METHODS: We analyzed the clinical and echocardiographic course both in-hospital and mid-term (13 [9] months) in a series of 20 consecutive patients (age, 68 years; logistic EuroSCORE, 29) with paravalvular leakage and attempted percutaneous closure. RESULTS: Closure was attempted for 23 leaks (17 mitral and 6 aortic) during 22 procedures in 20 patients. Implantation was successful in 87% of the leaks and the procedure was successful in 83%-with success being defined as a reduction in regurgitation of ≥ 1 degree. Survival at 1 year was 64.7% and survival free of the composite event of death/surgery was 58.8%. The degree of residual regurgitation was not associated with mortality but was associated with functional status. Survivors showed significant improvement in functional class. CONCLUSIONS: Percutaneous closure of leakage with the Amplatzer Vascular Plug III is safe and efficient in the mid-term. However, mortality among high-risk patients is high independently of the degree of residual regurgitation, indicating that these procedures are performed when heart disease has reached an advanced stage.

Ticagrelor versus clopidogrel in patients with acute coronary syndromes and a history of stroke or transient ischemic attack.

BACKGROUND: Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages. METHODS AND RESULTS: We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively). CONCLUSIONS: Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicatrials.gov. Unique identifier: NCT00391872.

Transcatheter aortic valve implantation: Current status and future perspectives.

Although surgical aortic valve replacement is the standard therapy for severe aortic stenosis (AS), about one third of patients are considered inoperable due to unacceptable surgical risk. Under medical treatment alone these patients have a very poor prognosis with a mortality rate of 50% at 2 years. Transcatheter aortic valve implantation (TAVI) has been used in these patients, and has shown robust results in the only randomized clinical trial of severe AS treatment performed so far. In this review, we will focus on the two commercially available systems: Edwards SAPIEN valve and CoreValve Revalving system. Both systems have demonstrated success rates of over 90% with 30-d mortality rates below 10% in the most recent transfemoral TAVI studies. Moreover, long-term studies have shown that the valves have good haemodynamic performance. Some studies are currently exploring the non-inferiority of TAVI procedures vs conventional surgery in high-risk patients, and long-term clinical results of the percutaneous valves. In this article we review the current status of TAVI including selection of patients, a comparison of available prostheses, results and complications of the procedure, clinical outcomes, and future perspectives.

Atrial septal defect with severe pulmonary hypertension in elderly patients: usefulness of transient balloon occlusion.

In patients with an atrial septal defect and severe pulmonary hypertension, it is important to determine whether the latter is reversible before percutaneous or surgical closure. In addition to determining pulmonary resistance, one simple technique is to transiently occlude the septal defect using a balloon catheter and to evaluate the hemodynamic response. We defined a positive response as a > or = 25% reduction in mean pulmonary artery pressure during occlusion relative to the basal level, without a fall in systemic pressure or an increase in ventricular end-diastolic pressure. The study included five patients aged over 60 years with an atrial septal defect and severe pulmonary hypertension who were referred for percutaneous closure. In one patient, the test gave a negative result and closure of the atrial septal defect was not performed. In the remaining four, closure was indicated. In three patients, closure was performed percutaneously, while the fourth underwent surgery. The drop in pulmonary pressure observed during the test was maintained over the long term at a mean follow-up time of 22 months.

Safety and efficacy of drug-eluting stents versus bare-metal stents in saphenous vein grafts lesions: a meta-analysis.

AIMS: Controversy exists about the safety and efficacy of drug-eluting stents (DES) in saphenous vein bypass grafts (SVGs). The aim of this study was to perform a meta-analysis of all published studies comparing DES and bare-metal stents (BMS) in patients with SVGs disease. METHODS AND RESULTS: We included 22 studies comparing DES versus BMS in 5,543 patients with SVGs disease. The primary efficacy endpoint was target vessel revascularisation (TVR). The primary safety endpoint was mortality. Other outcomes of interest were cardiac mortality, myocardial infarction, target lesion revascularisation (TLR), stent thrombosis and a combined of major adverse cardiac events (MACE). DES significantly reduced the risk of TVR, OR=0.56 (95% CI, 0.41-0.76, p=0.0003) and TLR, OR=0.58 (95% CI, 0.41-0.81; p=0.001). Total mortality and cardiac mortality were significantly lower in DES versus BMS, OR=0.69 (95% CI, 0.49-0.98, p=0.04) and OR=0.71 (95% CI, 0.51-0.99; p=0.04), respectively. The overall risk of stent thrombosis, and myocardial infarction were not significantly different for patients receiving DES vs. BMS. Total MACE were significantly lower in patients receiving DES, OR=0.55 (95% CI, 0.42-0.71; p<0.00001). CONCLUSIONS: This meta-analysis suggests that the use of DES in patients with SVG lesions is associated with a reduction of the need of reintervention and mortality compared with BMS.

[Percutaneous implantation of aortic valve prosthesis in patients with symptomatic severe aortic stenosis rejected for surgical valve replacement]. / Implantación percutánea de prótesis valvulares aórticas en pacientes con estenosis aórtica severa sintomática rechazados para cirugía de sustitución valvular.

Percutaneous implantation of aortic valve prostheses has recently emerged as a therapeutic option for patients with severe symptomatic aortic stenosis for whom surgical valve replacement is not suitable. We describe our initial experience with this technique at our institution. Percutaneous implantation of an Edwards Sapiens aortic prosthesis was performed using the transfemoral approach in four patients with severe symptomatic aortic stenosis for whom surgery was not suitable (mean EuroSCORE, 23%). The procedure was successful in all patients, with optimal implantation of the prosthesis and no complications. By 1 month of follow-up, no patient had experienced an event and all had improved their functional class.

[Secondary prevention program: impact on cardiovascular risk]. / Programa de prevención secundaria: influencia sobre el riesgo cardiovascular.

The aims of this study were to determine the effect of a secondary prevention program on the treatment and control of coronary risk factors and to assess whether it improves functional capacity. The study involved 401 patients with coronary heart disease (mean age 57.1 years; 89% men). Clinical and anthropometric data, including blood pressure, were recorded, and electrocardiography, laboratory analysis and exercise testing were performed before and after the program, which lasted 2-3 months. The therapeutic intervention comprised pharmacological treatment of coronary risk factors and the encouragement of life-style changes, including a recommended medically supervised physical exercise regime. By the end of the program, lipid and lipoprotein levels had improved significantly (P< .001 for all). The proportion of smokers decreased from 37.4% to 3.6% (P< .001). Functional capacity increased by 26% (P< .001). In conclusion, patients who took part in the secondary prevention program experienced improvements in cardiovascular risk profile and functional capacity.

Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation.

BACKGROUND: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death. METHODS: We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel (300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin (dispensed according to body weight) and were scheduled to undergo angiography 48 to 192 hours after the start of study medication. The primary efficacy end point was a composite of an occluded infarct-related artery (defined by a Thrombolysis in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography. RESULTS: The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy (95 percent confidence interval, 24 to 47 percent; P<0.001). By 30 days, clopidogrel therapy reduced the odds of the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent (from 14.1 to 11.6 percent, P=0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups. CONCLUSIONS: In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications.