Comparison of Dabigatran Plus a P2Y12 Inhibitor With Warfarin-Based Triple Therapy Across Body Mass Index in RE-DUAL PCI.

BACKGROUND: Body mass index (BMI) affects drug levels of nonvitamin K antagonist oral anticoagulants. We sought to assess whether BMI affected outcomes in the RE-DUAL PCI trial. METHODS: RE-DUAL PCI (NCT02164864) evaluated the safety and efficacy of a dual-antithrombotic-therapy regimen using dabigatran (110 mg or 150 mg twice daily and a P2Y12 platelet antagonist) in comparison with triple therapy of warfarin, aspirin, and a P2Y12 platelet inhibitor in 2725 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI). We compared the risk of first International Society on Thrombosis and Haemostasis (ISTH)-defined major or clinically relevant nonmajor bleeding events (primary endpoint) and the composite of death, myocardial infarction, stroke, systemic embolism, or unplanned revascularization (main efficacy endpoint) in relation to baseline BMI. RESULTS: Median (range) BMI was 28.1 (14-66) kg/m2. Dabigatran dual therapy versus warfarin triple therapy had relevantly and similarly lower rates of bleeding at both 110 mg and 150 mg twice-daily doses, irrespective of BMI. Thromboembolic event rates appeared consistent across categories of BMI, including those <25 and ≥35 kg/m2 (P for interaction: 0.806 and 0.279, respectively). CONCLUSIONS: The reduction in bleeding with dabigatran dual therapy compared with warfarin triple therapy in patients here evaluated appears consistent across BMI categories.

Feasibility and safety of pulmonary vein isolation by high-power short-duration radiofrequency application: short-term results of the POWER-FAST PILOT study.

PURPOSE: Pulmonary vein (PV) isolation (PVI) by point-by-point radiofrequency application (PPRF) results in longer procedures than that achieved by single-shot ablation techniques. In addition, it is associated with significant risk of oesophageal injury. The POWER-FAST pilot study evaluated the feasibility and safety of PVI by high-power short-duration (HPSD) PPRF. METHODS: HPSD PPRF around the PVs was done in 48 consecutive patients with atrial fibrillation. Fifty watts was delivered until a predefined lesion index value was reached (LSI ≥ 5 or Abl-I ≥ 350) and 60 W during 7-10 s in the first 18 and last 30 patients, respectively. A control group of 47 consecutive patients who had undergone PVI before the HPSD group with conventional PPRF (30 W for 30 s) was included for reference. Echocardiography and oesophageal endoscopy was performed shortly after ablation in all patients. RESULTS: PVI of all targeted veins was achieved in 98% and 100% of patients of the conventional and HPSD groups, respectively (p = 0.59). Total radiofrequency time was 34 ± 11, 24 ± 8, and 15 ± 5 min in groups 30 W, 50 W, and 60 W (p < 0.001). Audible steam pops occurred in 4 out of 48 (8%) patients in the HPSD group, accounting for 4 (0.08%) out of 5 269 HPSD radiofrequency applications. No patient in the HPSD group developed pericardial effusion. The incidence of oesophageal lesions was 28%, 22%, and 0% in groups 30 W, 50 W, and 60 W, respectively (p = 0.007) CONCLUSIONS: PVI can be achieved with HPSD PPRF in most patients. This approach appears safe and associated with low risk of esophageal damage.

Long term clinical outcomes in survivors after out-of-hospital cardiac arrest.

INTRODUCTION AND OBJECTIVES: Information regarding long-term outcomes in patients surviving out-of-hospital cardiac arrest (OHCA) is scarce. Our aim was to study the long-term clinical outcomes of a large cohort of OHCA patients surviving until hospital discharge and to identify predictors of mortality and cardiovascular events. METHODS: Consecutive OHCA patients admitted in the Acute Cardiac Care Unit who survived at least until hospital discharge between 2007 and 2019 were included. All received therapeutic hypothermia according to the local protocol. Pre- and intra-hospital clinical and analytical variables were analyzed, as well as the clinically relevant events during follow-up. RESULTS: A total of 201 patients were included, with a mean age of 57.6 ± 14.2 years, 168 (83.6%) were male. Thirty-six (17.9%) died during a median follow-up of 40.3 months (18.9-69.1), the most frequent causes of death being cardiovascular and neurological, followed by cancer. We calculated a predictive model for mortality during follow-up using Cox regression that included the following variables: poor neurological outcome [HR 3.503 (1.578-7.777)], non-shockable rhythm [HR 2.926 (1.390-6.163)], time to onset of CPR [HR 1.063 (0.997-1.134)], older age [1.036 (1.008-1.064)) and worse ejection fraction at discharge [1.033 (1.009-1.058)]. CONCLUSIONS: Even though few patients experience recurrent cardiac arrest events, survivors after OHCA face high morbidity and mortality during long-term follow-up. Therefore, they may benefit from multidisciplinary teams providing an integral management and ensuring continuity of care.

Growth Differentiation Factor 15 at 1 Month After an Acute Coronary Syndrome Is Associated With Increased Risk of Major Bleeding.

BACKGROUND: Growth differentiation factor-15 (GDF-15) is related to major bleeding when measured at initial presentation in patients with acute coronary syndromes (ACSs) treated with dual antiplatelet therapy. It is unknown whether follow-up measurements provide additional information. The objective of this study was to investigate whether GDF-15 measured 1 month after an ACS provides additional information beyond the baseline levels with regard to the risk of major bleeding. METHODS AND RESULTS: GDF-15 was measured at baseline and at 1 month after an ACS in 4049 patients included in the PLATelet inhibition and patient Outcomes (PLATO) trial. The association between 1-month GDF-15 level and non-coronary artery bypass grafting surgery-related major bleeding was assessed by a multivariable Cox model, adjusting for baseline GDF-15, age, anemia, impaired renal function, history of gastrointestinal bleeding, and sex. Elevated GDF-15 (>1800 ng/L) at 1 month was associated with an increased risk of non-coronary artery bypass grafting-related major bleeding (3.9% versus 1.2%; hazard ratio, 3.38; 95% CI, 1.89-6.06), independent of baseline GDF-15. Patients who had elevated GDF-15 levels at baseline and subsequent nonelevated GDF-15 at 1 month had a similar risk as patients who had nonelevated levels at both measurements. CONCLUSIONS: GDF-15 at 1 month after an ACS is related to the risk of bleeding during DAPT and provides additional information on the bleeding risk beyond baseline GDF-15 levels. GDF-15 levels may therefore be useful as part of decision support concerning long-term antithrombotic treatment in patients post-ACS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Percutaneous balloon pericardiotomy: Treatment of choice in patients with advanced oncological disease and severe pericardial effusion.

INTRODUCTION AND OBJECTIVES: Malignant pericardial effusion has a high recurrence rate after pericardiocentesis. We sought to confirm the efficacy and feasibility of percutaneous balloon pericardiotomy (PBP) as the initial treatment of choice for these effusions. METHODS: Retrospective analysis of the clinical, echocardiographic, and follow-up characteristics of a consecutive series of PBP carried out in a single-center in patients with advanced cancer. RESULTS: Forty PBPs were performed in 35 patients with a mean age of 61.8years (55% females). Thirty-four patients had pathologically confirmed metastatic neoplastic disease (26 patients with tumoral cells in the pericardial liquid), 7 had previously required pericardiocentesis, and in the remaining patients PBP was the first treatment for the effusion. All patients had a severe circumferential effusion (29mm by mean on transthoracic echocardiography [TTE]), and most presented evidence of hemodynamic compromise on TTE. In all cases, the procedure was successful, there were no acute complications, and it was well tolerated at the first attempt. There were no infectious complications during follow-up. One patient developed a pseudoaneurysm in the right ventricle, even though no further treatment was required. Eight patients needed a new pericardial procedure: 3 had elective pericardial window surgeries and 5 had a second PBP. Eighty percent of patients died during follow-up (57days by mean from the PBP) regarding their oncological disease. CONCLUSION: PBP is a simple and safe technique that can be effective in the prevention of recurrence in many patients with severe malignant pericardial effusion. The characteristics of this procedure make it particularly useful in this group of patients to avoid more aggressive, poorly tolerated approaches, since they have a very poor prognosis regarding to their oncological disease.

Extensive Chest Wall Destruction Secondary to a Large Ventricle Pseudoaneurysm: A Surgical Challenge.

Left ventricular pseudoaneurysms have become a rare complication of acute myocardial infarction, occurring in approximately 2% of cases and even less frequently when primary percutaneous intervention can be performed. Regardless of treatment strategy, left ventricle pseudoaneurysms are associated with a high mortality rate. We report on the extremely rare occurrence of a patient surviving two episodes of free wall rupture associated with extensive chest wall destruction and secondary traumatic rib fractures. The key to success in this case is related to both the cardiac and chest wall repair.

Challenges in Oral Lipid-lowering Therapy: Position Document of the Spanish Society of Cardiology.

Lipid-lowering therapy is one of the cornerstones of cardiovascular prevention and is one of the most effective strategies in the secondary prevention of ischemic heart disease. Nevertheless, the current treatment of lipid disorders, together with lifestyle changes, fails to achieve the targets recommended in clinical guidelines in a substantial proportion of patients. PCSK9 inhibitors have demonstrated safety and efficacy in the treatment of dyslipidemia. Due to their ability to reduce low-density lipoprotein cholesterol levels, these drugs have recently been approved for clinical use by Spanish regulatory agencies, with the aim of reducing cardiovascular risk in selected patient groups.

[Cardiovascular management of patients with chronic myeloid leukemia from a multidisciplinary perspective, and proposing action protocol by consensus meeting]. / Gestión cardiovascular de los pacientes con leucemia mieloide crónica desde una perspectiva multidisciplinar, y propuesta de protocolo de actuación por reunión de consenso.

INTRODUCTION AND OBJECTIVES: The second generation tyrosine kinase inhibitors (TKI, dasatinib and nilotinib) used in chronic myeloid leukemia (CML) treatment have shown a benefit compared to imatinib in responses achieved and disease progression. However, both have been related to some cardiovascular toxicity, being more frequent in patients with cardiovascular risk factors (CVRFs). Nowadays, due to the lack of recommendations for CML patients, CVRF management is carried out heterogeneously. The aim of this work is to develop recommendations on the prevention and monitoring of cardiovascular events (CVD) in patients with CML treated with TKIs. MATERIAL AND METHODS: Experts from the Spanish Group of Chronic Myeloid Leukemia together with experts in cardiovascular risk have elaborated, after a consensus meeting, recommendations for the prevention and follow-up of CVE in patients with CML treated with TKI. RESULTS: Recommendations regarding the necessary information to be collected on clinical history, treatment decisions, as well as treatment and monitoring of CVRFs are shown in this document. CONCLUSIONS: TKI treatment requires comprehensive patient management from a multidisciplinary approach, in which both the prevention and management of CVRFs are essential.

Prognostic impact of decisions taken by the heart team in patients evaluated for transcatheter aortic valve implantation.

OBJECTIVE: To analyze long-term survival and predictors of mortality in patients evaluated for transcatheter aortic valve implantation (TAVI) depending on the decision taken by the heart team. METHODS: All patients with severe aortic stenosis and high surgical risk evaluated for TAVI between June 2008 and June 2012 were included. Patients were grouped according to the therapeutic strategy decided by the heart team. Mean follow-up was 16.6 months (maximum 55.3). RESULTS: A total of 149 patients were evaluated: 79 were accepted for TAVI, 12 had no current indication for valve replacement and were deferred, 13 were redirected to conventional surgery and 45 received medical treatment. The evaluated patients had a mean age of 83.7 years and a mean EuroSCORE of 19.8±12.3. Median survival free from all-cause death was 34.7 months (95% CI 27.1-42.3) in the TAVI group, 47.4 months (95% CI 0-97.4) in the deferred intervention group, not available in the surgery group and 8.2 months (95% CI 5.6-10.9) in the medical treatment group (log-rank p<0.001). After multivariable adjustment, only treatment group remained as an independent predictor of mortality. Considering the TAVI group as the reference category, the adjusted hazard ratio for all-cause death was 0.70 (95% CI 0.24-2.04) for the deferred intervention group, 0.16 (95% CI 0.02-1.19) for the surgery group and 2.47 (95% CI 1.46-4.18) for the medical treatment group. CONCLUSION: The decision taken by the heart team on potential candidates for TAVI has a decisive prognostic significance, as those who are unsuitable for any kind of valve replacement have a significantly higher mortality.

Heart failure years after cancer treatment.

Progress in cancer treatment has significantly improved survival of patients with cancer. However, the incidence of cardiovascular diseases such as left ventricular dysfunction (LVD) and chronic heart failure (HF) is increasing due to the long-term toxic effects of chemotherapy and radiotherapy. Cardio-oncology teams are necessary to ensure the implementation of primary prevention strategies and screening protocols for early recognition of LVD. Moreover, early administration of advanced treatment for HF is crucial to achieve left ventricular recovery. In this article we will focus on the prevalence of chronic HF among cancer survivors, the main risk factors of LVD and chronic HF, the prevention strategies and management based on the current evidence and, finally, the future perspectives in this field.

Antiplatelet and anticoagulation agents in acute coronary syndromes: what is the current status and what does the future hold?

Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y12 receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio.

Trehalose improves human fibroblast deficits in a new CHIP-mutation related ataxia.

In this work we investigate the role of CHIP in a new CHIP-mutation related ataxia and the therapeutic potential of trehalose. The patient's fibroblasts with a new form of hereditary ataxia, related to STUB1 gene (CHIP) mutations, and three age and sex-matched controls were treated with epoxomicin and trehalose. The effects on cell death, protein misfolding and proteostasis were evaluated. Recent studies have revealed that mutations in STUB-1 gene lead to a growing list of molecular defects as deregulation of protein quality, inhibition of proteasome, cell death, decreased autophagy and alteration in CHIP and HSP70 levels. In this CHIP-mutant patient fibroblasts the inhibition of proteasome with epoxomicin induced severe pathophysiological age-associated changes, cell death and protein ubiquitination. Additionally, treatment with epoxomicin produced a dose-dependent increase in the number of cleaved caspase-3 positive cells. However, co-treatment with trehalose, a disaccharide of glucose present in a wide variety of organisms and known as a autophagy enhancer, reduced these pathological events. Trehalose application also increased CHIP and HSP70 expression and GSH free radical levels. Furthermore, trehalose augmented macro and chaperone mediated autophagy (CMA), rising the levels of LC3, LAMP2, CD63 and increasing the expression of Beclin-1 and Atg5-Atg12. Trehalose treatment in addition increased the percentage of immunoreactive cells to HSC70 and LAMP2 and reduced the autophagic substrate, p62. Although this is an individual case based on only one patient and the statistical comparisons are not valid between controls and patient, the low variability among controls and the obvious differences with this patient allow us to conclude that trehalose, through its autophagy activation capacity, anti-aggregation properties, anti-oxidative effects and lack of toxicity, could be very promising for the treatment of CHIP-mutation related ataxia, and possibly a wide spectrum of neurodegenerative disorders related to protein disconformation.

Implantation of cardioverter defibrillators with minimal fluoroscopy using a three-dimensional navigation system: a feasibility study.

AIMS: Fluoroscopy is necessary to implant cardioverter defibrillators using the conventional approach. Modern electroanatomic navigation systems allow the visualization of multiple catheters and, as they are capable of rendering precise geometrical reconstructions of cardiac chambers, have been used for fluoroscopy-free electrophysiological procedures. The aim of our study was to assess the feasibility of non-fluoroscopic implants using a three-dimensional navigation system. METHODS AND RESULTS: The NavX system was used to create the virtual anatomies of heart chambers and thoracic veins. Defibrillator leads were placed at stable positions using exclusively the electrical and anatomical information provided by the navigator. A single fluoroscopy shot confirmed final lead positions. Thirty-five consecutive patients had 30 single-chamber and 5 dual-chamber defibrillators implanted. Cardiac chambers geometries were developed in 10 ± 4.3 min. Ventricular and atrial leads were implanted, with suitable positions and electrical parameters being achieved, in 18 ± 22 and 16 ± 9 min, respectively. The final confirmatory shot was the only fluoroscopy needed in 31 (89%) cases. Two patients needed fluoroscopy-guided relocation of the ventricular lead due to high defibrillation threshold and a breakdown of the active-fixation mechanism, respectively. In one patient the ventricular lead was totally extracted and reimplanted because a loop has formed in the vena cava, and one patient required fluoroscopy-guided subclavian puncture. In five cases (16%), the position of the proximal defibrillation coil was minimally modified with fluoroscopy due to incomplete geometric reconstruction of the superior vena cava. CONCLUSION: Fluoroscopy-free defibrillators implantation is feasible using a navigation system. Suitable placement of the proximal coil is a critical stage and requires a reliable and complete reconstruction of the superior vena cava.

Left atrial myxofibrosarcoma: Diagnostic approach through imaging techniques.

Primary cardiac sarcomas are rare. A 63-year-old woman presented with progressive symptoms of fatigue, palpitations, and dyspnea. Transthoracic echocardiography detected a mass in the left atrium, fixed and probably attached to the interatrial septum suggestive of myxoma. Transesophageal echocardiography confirmed the existence of a large lobulated mass in the left atrium measuring 45 mm × 25 mm in diameter. Subsequent cardiac magnetic resonance imaging showed a mass of heterogeneous appearance, with broad base of implantation on the posterior wall of the left atrium. The extension study with multidetector computed tomography showed superficial infiltration of the atrial wall, without involvement of the mitral valve or pulmonary veins and no extension to other extracardiac structures. The patient underwent surgery resecting a bilobed mass, smooth and yellowish, strongly attached to the posterior wall of left atrium. The pathologic study was consistent with the diagnosis of myxofibrosarcoma. .

Percutaneous balloon pericardiotomy as the initial and definitive treatment for malignant pericardial effusion.

INTRODUCTION AND OBJECTIVES: Malignant pericardial effusion has a high recurrence rate after pericardiocentesis. We sought to confirm the efficacy of percutaneous balloon pericardiotomy as the initial treatment of choice for these effusions. METHODS: Retrospective analysis of the clinical, echocardiographic, and follow-up characteristics of a consecutive series of percutaneous balloon pericardiotomies carried out in a single center in patients with advanced cancer. RESULTS: Seventeen percutaneous balloon pericardiotomies were performed in 16 patients with a mean age of 66.2 (15.2) years. Fourteen patients had pathologically confirmed metastatic neoplastic disease, 3 had previously required pericardiocentesis, and in the remaining patients percutaneous balloon pericardiotomy was the first treatment for the effusion. All patients had a severe circumferential effusion, and most presented evidence of hemodynamic compromise on echocardiography. In all cases, the procedure was successful, there were no acute complications, and it was well tolerated at the first attempt. There were no infectious complications during follow-up (median, 44 [interquartile range, 36-225] days). One patient developed a large pleural effusion that did not require treatment. Three patients needed a new pericardial procedure: 2 had elective pericardial window surgeries and 1 had a second percutaneous balloon pericardiotomy. CONCLUSIONS: Percutaneous balloon pericardiotomy is a simple, safe technique that can be effective in the prevention of recurrence in many patients with severe malignant pericardial effusion. The characteristics of this procedure make it particularly useful in this group of patients to avoid more aggressive, poorly tolerated approaches.

Incidence and predictors of sudden cardiac arrest in adults with congenital heart defects repaired before adult life.

Many adult survivors of repaired congenital heart disease (CHD) are at premature risk of death. Sudden cardiac arrest (SCA) is 1 of the leading causes of death but little is known about determinants for SCA in adults with repaired lesions. We sought to determine incidence and risk factors for SCA in a study population of 936 adults with previously repaired CHD who had completed follow-up at a single tertiary center during a mean period of 9 ± 7 years. Mean age at first examination in our institution was 21 ± 7 years. Diagnostic categories included tetralogy of Fallot (216), coarctation of the aorta (157), transposition complexes (99), single ventricle (55), and other CHD (409). During a total follow-up of 8,387 person-years, 22 patients (2.6 per 1,000 person-years) presented with SCA. Incidence of SCA varied widely between specific lesions; the highest incidence was observed in transposition complexes (10 per 1,000 person-years). Independent predictors of SCA were retrospectively identified using multivariate Cox proportional hazard modeling. Age at initial examination and severely impaired subaortic ventricular systolic function were independent risk factors for SCA (severe subaortic ventricular systolic dysfunction, adjusted hazard ratio 29, 95% confidence interval 11 to 72, p <0.001). SCA occurred in 23% of patients with severe subaortic ventricular systolic dysfunction versus 0.7% of patients with nonsevere decreased subaortic ventricular function (p <0.001). In conclusion, severe subaortic ventricular systolic dysfunction is a dominant multivariate predictor of SCA in an unselected population of adult survivors after surgery for CHD. Our data support the consideration of primary prevention strategies in these patients.