Efficacy of Auricular Acupuncture and Lavender Oil Aromatherapy in Reducing Preinterventional Anxiety in Cardiovascular Patients: A Randomized Single-Blind Placebo-Controlled Trial.

Introduction: Auricular acupuncture at the "relaxation point" and lavender oil aromatherapy can reduce preoperative anxiety associated with increased mortality and morbidity. Data on the effect of combined auricular acupuncture and lavender oil aromatherapy in patients undergoing cardiovascular interventions with the use of local anesthesia or under conscious sedation are sparse. The authors sought to evaluate the efficacy of auricular acupuncture and lavender oil aromatherapy in reducing preinterventional anxiety in cardiovascular patients. Materials and Methods: Data of 80 consecutive patients undergoing diagnostic coronary angiography (n = 56) with or without percutaneous coronary intervention (n = 9) and right heart catheterization (n = 6), transcatheter aortic valve replacement (n = 17) and percutaneous mitral valve repair (MitraClip; n = 2) were analyzed. Patients were prospectively randomized to receive either preinterventional auricular acupuncture and lavender oil (Lavandula angustifolia) aromatherapy (verum group, n = 39) or combined sham auricular acupuncture and placebo oil aromatherapy (placebo group, n = 41). For the verum group bilateral auricular acupuncture was performed at the "relaxation point." State anxiety and blood pressure were assessed before and at 30 min after acupuncture and presternal oil application. State anxiety was defined as primary outcome measure and assessed using the Spielberger State Anxiety Inventory (STAI) for Adults form Y6. Intervention-specific anxiety was assessed by a 10-point numerical rating scale, and perceived treatment success by a single dichotomous question. Clinical blood pressure was further assessed. Results: After the intervention, the verum group had significantly decreased anxiety on the STAI compared with the placebo group (Δ = -4.18; 95% confidence interval = -8.31 to -0.05; p = 0.047). Significantly more patients reported subjective treatment success in the verum group (87.2%) than in the placebo group (65.9%, p = 0.035). No significant differences were observed regarding intervention-specific anxiety and blood pressure between the two groups. No serious adverse events occurred in any group. Conclusions: Combined auricular acupuncture and lavender oil aromatherapy can decrease preinterventional anxiety in cardiovascular patients and requires further investigation. German Clinical Trials Register (registration no. DRKS00023686).

Enhanced Cardiomyocyte Function in Hypertensive Rats With Diastolic Dysfunction and Human Heart Failure Patients After Acute Treatment With Soluble Guanylyl Cyclase (sGC) Activator.

AIMS: Our aim was to investigate the effect of nitric oxide (NO)-independent activation of soluble guanylyl cyclase (sGC) on cardiomyocyte function in a hypertensive animal model with diastolic dysfunction and in biopsies from human heart failure with preserved ejection fraction (HFpEF). METHODS: Dahl salt-sensitive (DSS) rats and control rats were fed a high-salt diet for 10 weeks and then acutely treated in vivo with the sGC activator BAY 58-2667 (cinaciguat) for 30 min. Single skinned cardiomyocyte passive stiffness (Fpassive) was determined in rats and human myocardium biopsies before and after acute treatment. Titin phosphorylation, activation of the NO/sGC/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) cascade, as well as hypertrophic pathways including NO/sGC/cGMP/PKG, PKA, calcium-calmodulin kinase II (CaMKII), extracellular signal-regulated kinase 2 (ERK2), and PKC were assessed. In addition, we explored the contribution of pro-inflammatory cytokines and oxidative stress levels to the modulation of cardiomyocyte function. Immunohistochemistry and electron microscopy were used to assess the translocation of sGC and connexin 43 proteins in the rat model before and after treatment. RESULTS: High cardiomyocyte Fpassive was found in rats and human myocardial biopsies compared to control groups, which was attributed to hypophosphorylation of total titin and to deranged site-specific phosphorylation of elastic titin regions. This was accompanied by lower levels of PKG and PKA activity, along with dysregulation of hypertrophic pathway markers such as CaMKII, PKC, and ERK2. Furthermore, DSS rats and human myocardium biopsies showed higher pro-inflammatory cytokines and oxidative stress compared to controls. DSS animals benefited from treatment with the sGC activator, as Fpassive, titin phosphorylation, PKG and the hypertrophic pathway kinases, pro-inflammatory cytokines, and oxidative stress markers all significantly improved to the level observed in controls. Immunohistochemistry and electron microscopy revealed a translocation of sGC protein toward the intercalated disc and t-tubuli following treatment in both control and DSS samples. This translocation was confirmed by staining for the gap junction protein connexin 43 at the intercalated disk. DSS rats showed a disrupted connexin 43 pattern, and sGC activator was able to partially reduce disruption and increase expression of connexin 43. In human HFpEF biopsies, the high Fpassive, reduced titin phosphorylation, dysregulation of the NO-sGC-cGMP-PKG pathway and PKA activity level, and activity of kinases involved in hypertrophic pathways CaMKII, PKC, and ERK2 were all significantly improved by sGC treatment and accompanied by a reduction in pro-inflammatory cytokines and oxidative stress markers. CONCLUSION: Our data show that sGC activator improves cardiomyocyte function, reduces inflammation and oxidative stress, improves sGC-PKG signaling, and normalizes hypertrophic kinases, indicating that it is a potential treatment option for HFpEF patients and perhaps also for cases with increased hypertrophic signaling.

Incidence of asymptomatic oesophageal lesions after atrial fibrillation ablation using an oesophageal temperature probe with insulated thermocouples: a comparative controlled study.

AIMS: Oesophageal probes to monitor luminal oesophageal temperature (LET) during atrial fibrillation (AF) catheter ablation have been proposed, but their effects remain unclear. Aim of this study is to evaluate the effects of an oesophageal temperature probe with insulated thermocouples. METHODS AND RESULTS: Patients with symptomatic, drug-refractory paroxysmal or persistent AF who underwent left atrial radiofrequency (RF) catheter ablation were prospectively enrolled. Patients were ablated using a single-tip RF contact force ablation catheter. An intraluminal oesophageal temperature probe was used in Group 1. In Group 2, patients were ablated without LET monitoring. Assessment of asymptomatic endoscopically detected oesophageal lesions (EDEL) was performed by oesophagogastroduodenoscopy (EGD) in all patients. Eighty patients (mean age 63.7 ± 10.7 years; men 56%) with symptomatic, drug-refractory paroxysmal (n = 28; 35%) or persistent AF were included. Group 1 and Group 2 patients (n = 40 in each group) were comparable in regard to baseline characteristics, but RF duration on the posterior wall was significantly shorter in Group 1 patients. Overall, seven patients (8.8%) developed EDEL (four ulcerations, three erythema). The incidence of EDEL in Group 1 and Group 2 patients was comparable (7.5 vs. 10%, P = 1.0). No major adverse events were reported in both groups. CONCLUSION: According to these preliminary results, the use of oesophageal temperature probes with insulated thermocouples seems to be feasible in patients undergoing AF RF catheter ablation. The incidence of post-procedural EDEL when using a cut-off of 39°C is comparable to the incidence of EDEL without using a temperature probe.

A randomized comparison of 5 versus 12 hours per day of cardiac contractility modulation treatment for heart failure patients: A preliminary report.

BACKGROUND: Cardiac contractility modulation (CCM) signals are non-excitatory electrical signals delivered during the absolute refractory period intended to improve contraction and cardiac function. Clinical trials have shown that CCM treatment significantly improves exercise tolerance and quality of life in symptomatic heart failure patients. Studies with CCM therapy typically include CCM delivery for 3, 5 or 7 h per day, although other configurations are also commonly used. Each has been associated with improved outcomes in heart failure, but it is not clear whether different application durations are associated with the various degrees of benefit. The purpose of the current pilot evaluation study was to evaluate the quality of life, exercise tolerance, and cardiac function, over a 6-month period when CCM was delivered for 5 h/day vs. 12 h/day. Increasing the daily CCM therapy duration is safe and as good as the standard CCM periods of application per day. METHODS: This single center pilot evaluation study involved 19 medically refractory symptomatic patients with heart failure and reduced left ventricular function who underwent implantation of an Optimizer™ system (Impulse Dynamics, Orangeburg, NY, USA). Patients were randomized into one of two treatment groups; 5 h/day CCM treatment or 12 h/day CCM treatment. Subjects and evaluating physicians were blinded to the study group. Subjects returned to the hospital after 12 and 24 weeks. Efficacy evaluations included changes from baseline to 24 weeks in Minnesota Living With Heart Failure Questionnaire score (MLWHFQ), maximal oxygen consumption in the cardio-pulmonary stress test (peak VO2), New York Heart Association classification (NYHA), 6-min walk distance (6MWD), and ejection fraction (EF). RESULTS: At the end of 24 weeks, clinical improvement was observed in the entire cohort in all efficacy measures (mean change from baseline of -17.1 in MLWHFQ, -0.86 in NYHA, and improvement trend of 1.48 mL O2/kg/min in peak VO2, 31.3 m in 6MWD, and 2.25% in EF). There were no significant differences, either clinically or statistically, between the groups receiving CCM for 5 h/day vs. 12 h/day. Three subjects were voluntarily withdrawn before completing the study. One subject died from pneumonia after 125 days, and 6 serious adverse events were reported, none of which was classified as related to either the device or the procedure. CONCLUSIONS: Together with previously reported experience with CCM, delivery of CCM therapy is equally safe and appears similarly effective over the range of shorter (5 h) to longer (12 h) daily periods of application. Given the small sample size, further studies are warranted.

Initial Experience With Novel Oral Anticoagulants During the First 45 Days After Left Atrial Appendage Closure With the Watchman Device.

BACKGROUND: The use of oral anticoagulation or dual antiplatelet therapy (DAPT) is recommended within the first 45 days after left atrial appendage (LAA) closure using the Watchman device because of incomplete device endothelialization. This study reports for the first time the feasibility of novel oral anticoagulants (NOAC) in these patients. HYPOTHESIS: NOAC therapy is safe and effective after LAA closure. METHODS: Interventional LAA closure was performed successfully in 45 patients. Of these, 18 patients received NOAC during the first 45 days after implantation and 27 patients received DAPT. Transesophageal echocardiography was conducted 45 days after implantation. The primary study endpoint was abnormal thrombus apposition 45 days after implantation. Secondary study endpoints were death from any cause, major adverse cardiac and cerebrovascular events (MACCE), and major bleedings. RESULTS: After 45 days, transesophageal echocardiography revealed no abnormal thrombus apposition. During a follow-up of 417 ± 323 days, 7 patients died. No stroke or transient ischemic attack occurred. Nonfatal myocardial infarction occurred in 1 patient. There was a nonsignificant trend for lower all-cause mortality (P = 0.159) and occurrence of MACCE (P = 0.096) in the NOAC group compared with the DAPT group. Overall, 6 patients suffered from a major bleeding (NOAC, n = 3; DAPT, n = 3). In NOAC group, major bleedings (at day 205, 688, and 736) occurred long after termination of NOAC therapy. There was no significant difference in the frequency of major bleedings in different groups. CONCLUSIONS: Our pilot study suggests that NOAC therapy within the first 45 days after interventional LAA closure is safe and effective.

Utility of esophageal temperature monitoring during pulmonary vein isolation for atrial fibrillation using duty-cycled phased radiofrequency ablation.

INTRODUCTION: A novel ablation system has been introduced for rapid treatment of atrial fibrillation (AF). This system delivers duty-cycled phased radiofrequency (RF) energy via an over-the-wire catheter (PVAC® , Medtronic) to achieve pulmonary vein (PV) isolation. Lower power and depth control suggests that collateral damage might be minimized. However, no studies have investigated the potential for thermal effect and damage to the esophagus. METHODS AND RESULTS: Ninety consecutive patients undergoing PV-isolation were evaluated. Group A (48 patients) had continuous luminal esophageal temperature (LET) monitoring using a temperature probe with 3 metal electrodes located in the vicinity of the targeted PV ostia. Ablation ceased when LET exceeded 40 °C. Only patients with LET ≥ 39 °C underwent endoscopic evaluation to assess esophageal damage. Group B (42 patients) excluded LET monitoring but all patients underwent endoscopy. In Group A, 27 (56%) patients showed LET ≥ 39 °C (mean LET 40.5 °C). Endoscopy revealed esophageal alterations in 5 (8%) (3 erythema and 2 intramural bleeding). One hundred eighty-nine out of 190 (99.5%) targeted PVs were successfully isolated, with 1 PV unsuccessful due to high LET. In Group B all 165 targeted PVs (100%) were successfully isolated. Endoscopy in Group 2 revealed no esophageal alterations. CONCLUSIONS: Using a duty-cycled, phased RF ablation system is safe and effective to isolate PVs. No Eso alteration was documented after ablation when LET was not monitored. This suggests that the LET probe may contribute to the thermal effect. Whether the documented increments in LET are due to direct tissue heating or possible interaction between the LET probe requires further investigation.

How to optimise clopidogrel therapy? Reducing the low-response incidence by aggregometry-guided therapy modification.

The inhibitory platelet effect of clopidogrel is insufficient in approximately 5 to 30% of patients. These low responders (LR) face a significantly higher risk of cardiovascular complications. The therapeutic management of LR is still undefined. In the present study, we evaluate a novel therapeutic algorithm to reduce the incidence of clopidogrel resistance. One hundred sixty-one patients on 100 mg of aspirin co-medication underwent elective coronary stenting and were given an initial dosage of 600 mg clopidogrel, followed by 75 mg clopidogrel daily. 48 h later, the platelet responsiveness was tested with ADP (5-20 microM) stimulation by impedance aggregometry (Chronolog 590). A significant rise in impedance (>5 Omega after 6 minutes, aggregation index >65%) was defined as LR. In this subgroup, platelets were stimulated with the selective P2Y(12)-ADP receptor antagonist 2-MeS-AMP. One hundred twenty-three patients were clopidogrel-responders (76.4%) and 38 patients were LR (23.6%). A defect of the ADP-receptor P2Y(12) was found in three out of 38 LR (7.9%). Inhibition of platelet aggregation indicating clopidogrel-responsiveness was achieved with either a clopidogrel high-dose regimen (22/38, 57.9%); a repeat loading dose, doubling the maintenance dose) or with an alternative therapy with ticlopidine (8/38 (21.1%); 250 mg twice daily). Thus the incidence of LR was reduced from 23.6% to 5.0%. Our aggregometer-guided therapeutic algorithm reduced the relative percentage of clopidogrel LR by 78.9%. This approach could prove to be helpful in achieving a further decrease in the incidence of clopidogrel resistance.

Human histopathology of electroanatomic mapping after cooled-tip radiofrequency ablation to treat ventricular tachycardia in remote myocardial infarction.

INTRODUCTION: Catheter ablation of ventricular tachycardia (VT) in remote myocardial infarction (MI) often requires excessive mapping procedures. Documentation of the electrical substrate via electrogram amplitude may help to identify regions of altered myocardium resembling exit areas of reentrant VTs. METHODS AND RESULTS: A patient with multiple symptomatic monomorphic VTs (biventricular ICD, remote MI) underwent electroanatomic substrate mapping (CARTOtrade mark) for VT ablation. Regions of scar (bipolar electrogram amplitudes or=1.5 mV), and "altered" myocardium (0.5-1.5 mV) were identified. Ablation was directed to regions with "altered" myocardium based on pace map correlation. After ablation the clinical VT did not reoccur. The patient died due to worsening of heart failure 7 days afterward. During postmortal evaluation specified sites of electroanatomic mapping were correlated to histopathological findings. Annotated scar areas were documented to consist of areas with massive fibrosis (>or=80% of mural composition). Ablations were found to span through regions with intermediate fibrosis (21-79%) mapped as "altered" myocardium. Ablation produced transmural coagulation necrosis of mesh-like fibrotic tissue with interspersed remnants of myocardial cells up to a maximum depth of 7.0 mm. Subendocardial intramural bleedings were universal findings 7 days after ablation. CONCLUSIONS: Electroanatomic substrate mapping for VT ablation sufficiently identified regions of scar and normal myocardium. Regions with bipolar electrogram amplitudes between 0.5 and 1.5 mV were found to correlate to areas of "intermediate" fibrosis (21-79%) with only remnant strands of myocardial cells and were identified as target region for ablation. Cooled-tip endocardial radiofrequency ablation lead to transmural coagulation necrosis up to a depth of 7.0 mm.