BackgroundGrowing evidence exists for soluble Angiotensin Converting Enzyme-2 (sACE2) as a biomarker in definitive heart failure (HF), but there is little information about changes in sACE2 activity in hypertension with imminent heart failure and in reverse remodeling.Methods, FindingsPatients with systolic HF (NYHAII-IV, enrolled for cardiac resynchronisation therapy, CRT, n = 100) were compared to hypertensive patients (n = 239) and to a healthy cohort (n = 45) with preserved ejection fraction (EF>50%) in a single center prospective clinical study. The status of the heart failure patients were checked before and after CRT. Biochemical (ACE and sACE2 activity, ACE concentration) and echocardiographic parameters (EF, left ventricular end-diastolic (EDD) and end-systolic diameter (ESD) and dP/dt) were measured.sACE2 activity negatively correlated with EF and positively with ESD and EDD in all patient's populations, while it was independent in the healthy cohort. sACE2 activity was already increased in the hypertensive group, where signs for imminent heart failure (slightly decreased EF and barely increased NT-proBNP levels) were detected. sACE2 activities further increased in patients with definitive heart failure (EF<50%), while sACE2 activities decreased with the improvement of the heart failure after CRT (reverse remodeling). Serum angiotensin converting enzyme (ACE) concentrations were lower in the diseased populations, but did not show a strong correlation with the echocardiographic parameters.ConclusionsSoluble ACE2 activity appears to be biomarker in heart failure, and in hypertension, where heart failure may be imminent. Our data suggest that sACE2 is involved in the pathomechanism of hypertension and HF.
Background-Pulmonary vein isolation has increasingly been used to cure atrial fibrillation, but concerns have recently been raised that subclinical brain damage may occur because of microembolization during these procedures. We compared the occurrence of bubble formation seen on intracardiac echocardiography and the microembolic signals (MESs) detected by transcranial Doppler on the use of different ablation techniques and anticoagulation strategies. Methods and Results-This prospective study included 35 procedures in 34 consecutive patients (age, 52; SD, 12.8 years;female:male 9:25). Pulmonary vein isolation was performed with a cryoballoon and the conventional anticoagulation protocol (activated clotting time >250 s) in 10 procedures (group 1), with a multipolar duty-cycled radiofrequency pulmonary group 2), and with regime a pulmonary vein ablation catheter with an aggressive anticoagulation (activated clotting time >320 s) in 13 procedures (group 3). The mean total numbers of MESs detected during the procedures were 833.7 (SD, 727.4) in group 1, 3142.6 (SD, 1736.4) in group 2, and 2204.6 (SD, 1078.1) in group 3 (P=0.0005). MESs were detected mostly during energy delivery in the pulmonary vein ablation catheter groups, whereas a relatively even distribution of emboli formation was seen during cryoballoon ablations. A significant correlation was found in all groups between the degree of bubble formation on intracardiac echocardiography and the number of MESs (P=0.0000). Conclusions-Duty-cycled radiofrequency ablation is associated with significantly more MESs, even when more aggressive anticoagulation is applied. With both techniques most of these microemboli are gaseous in nature.
AimsThere is lack of conclusive evidence from randomized clinical trials on the efficacy and safety of upgrade to cardiac resynchronization therapy (CRT) in patients with implanted pacemakers (PM) or defibrillators (ICD) with reduced left ventricular ejection fraction (LVEF) and chronic heart failure (HF). The BUDAPEST-CRT Upgrade Study was designed to compare the efficacy and safety of CRT upgrade from conventional PM or ICD therapy in patients with intermittent or permanent right ventricular (RV) septal/apical pacing, reduced LVEF, and symptomatic HF.Methods and resultsThe BUDAPEST-CRT study is a prospective, randomized, multicentre, investigator-sponsored clinical trial. A total of 360 subjects will be enrolled with LVEF ≤ 35%, NYHA functional classes II–IVa, paced QRS ≥ 150 ms, and a RV pacing ≥ 20%. Patients will be followed for 12 months. Randomization is performed in a 3:2 ratio (CRT-D vs. ICD). The primary composite endpoint is all-cause mortality, a first HF event, or less than 15% reduction in left ventricular (LV) end-systolic volume at 12 months. Secondary endpoints are all-cause mortality, all-cause mortality or HF event, and LV volume reduction at 12 months. Tertiary endpoints include changes in quality of life, NYHA functional class, 6 min walk test, natriuretic peptides, and safety outcomes.ConclusionThe results of our prospective, randomized, multicentre clinical trial will provide important information on the role of cardiac resynchronization therapy with defibrillator (CRT-D) upgrade in patients with symptomatic HF, reduced LVEF, and wide-paced QRS with intermittent or permanent RV pacing.Clinical trials.gov identifierNCT02270840.
Presence of either resting or exercise-induced LAH identified AF patients with a distinct clinical profile, extensive LA substrate, and different clinical response to catheter ablation. Stratification of AF patients based on the LA exercise hemodynamics could help in the future to tailor the ablation strategy.
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