Bedside autonomic risk stratification after myocardial infarction by means of short-term deceleration capacity of heart rate.

Aims: Twenty-four-hour deceleration capacity (DC24h) of heart rate is a strong predictor of mortality after myocardial infarction (MI). Assessment of DC from short-term recordings (DCst) would be of practical use in everyday clinical practice but its predictive value is unknown. Here, we test the usefulness of DCst for autonomic bedside risk stratification after MI. Methods and results: We included 908 patients after acute MI enrolled in Munich and 478 patients with acute (n = 232) and chronic MI (n = 246) enrolled in Tuebingen, both in Germany. We assessed DCst from high-resolution resting electrocardiogram (ECG) recordings (<30 min) performed under standardized conditions in supine position. In the Munich cohort, we also assessed DC24h from 24-h Holter recordings. Deceleration capacity was dichotomized at the established cut-off value of ≤ 2.5 ms. Primary endpoint was 3-year mortality. Secondary endpoint was 3-year cardiovascular mortality. In addition to DC, multivariable analyses included the Global Registry of Acute Coronary Events score >140 and left ventricular ejection fraction ≤ 35%. During follow-up, 48 (5.3%) and 48 (10.0%) patients died in the Munich and Tuebingen cohorts, respectively. On multivariable analyses, DCst ≤ 2.5 ms was the strongest predictor of mortality, yielding hazard ratios of 5.04 (2.68-9.49; P < 0.001) and 3.19 (1.70-6.02; P < 0.001) in the Munich and Tuebingen cohorts, respectively. Deceleration capacity assessed from short-term recordings ≤ 2.5 ms was also an independent predictor of cardiovascular mortality in both cohorts. Implementation of DCst ≤ 2.5 ms into the multivariable models led to a significant increase of C-statistics and integrated discrimination improvement score. Conclusion: Deceleration capacity assessed from short-term recordings is a strong and independent predictor of mortality and cardiovascular mortality after MI, which is complementary to existing risk stratification strategies.

Sex differences in outcomes of primary prevention implantable cardioverter-defibrillator therapy: combined registry data from eleven European countries.

Aims: Therapy with an implantable cardioverter defibrillator (ICD) is established for the prevention of sudden cardiac death (SCD) in high risk patients. We aimed to determine the effectiveness of primary prevention ICD therapy by analysing registry data from 14 centres in 11 European countries compiled between 2002 and 2014, with emphasis on outcomes in women who have been underrepresented in all trials. Methods and results: Retrospective data of 14 local registries of primary prevention ICD implantations between 2002 and 2014 were compiled in a central database. Predefined primary outcome measures were overall mortality and first appropriate and first inappropriate shocks. A multivariable model enforcing a common hazard ratio for sex category across the centres, but allowing for centre-specific baseline hazards and centre specific effects of other covariates, was adjusted for age, the presence of ischaemic cardiomyopathy or a CRT-D, and left ventricular ejection fraction ≤25%. Of the 5033 patients, 957 (19%) were women. During a median follow-up of 33 months (IQR 16-55 months) 129 women (13%) and 807 men (20%) died (HR 0.65; 95% CI: [0.53, 0.79], P-value < 0.0001). An appropriate ICD shock occurred in 66 women (8%) and 514 men (14%; HR 0.61; 95% CI: 0.47-0.79; P = 0.0002). Conclusion: Our retrospective analysis of 14 local registries in 11 European countries demonstrates that fewer women than men undergo ICD implantation for primary prevention. After multivariate adjustment, women have a significantly lower mortality and receive fewer appropriate ICD shocks.

Autonomic Nervous System Activity for Risk Stratification of Emergency Patients With Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) causes appreciable morbidity and mortality in adults, especially in those ≥65 years of age. At hospital admission, an immediate and reliable risk assessment is necessary to detect patients with possible fatal outcome. OBJECTIVE: We aimed to evaluate markers of the autonomic nervous system based on an electrocardiogram to predict mortality in patients with CAP. METHODS: For this purpose, the deceleration capacity (DC) of heart rate was calculated in 253 patients who presented to the emergency department with CAP. The 30-day mortality rate was defined as the primary endpoint (PEP). The secondary endpoint was the total mortality within 180 days. RESULTS: PEP was reached in 33 patients (13%). The DC, measured in milliseconds, was significantly lower in patients who reached the PEP than in those who did not (2.3 ± 1.5 ms vs. 3.6 ± 2.3 ms, p = 0.004). The DC was also significantly lower in nonsurvivors than in survivors at the time of the secondary endpoint (2.3 ± 1.5 ms vs. 3.7 ± 2.4 ms, p < 0.001). Our results indicate that DC is an independent predictor of 30- and 180-day mortality. CONCLUSION: DC was independently associated with death from CAP in our study. As a practical consequence, DC could be useful in triage decisions. Patients with certain high risks could benefit from adjuvant treatment and special medical attention.

Autonomic nervous system activity as risk predictor in the medical emergency department: a prospective cohort study.

OBJECTIVES: To evaluate heart rate deceleration capacity, an electrocardiogram-based marker of autonomic nervous system activity, as risk predictor in a medical emergency department and to test its incremental predictive value to the modified early warning score. DESIGN: Prospective cohort study. SETTING: Medical emergency department of a large university hospital. PATIENTS: Five thousand seven hundred thirty consecutive patients of either sex in sinus rhythm, who were admitted to the medical emergency department of the University of Tübingen, Germany, between November 2010 and March 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Deceleration capacity of heart rate was calculated within the first minutes after emergency department admission. The modified early warning score was assessed from respiratory rate, heart rate, systolic blood pressure, body temperature, and level of consciousness as previously described. Primary endpoint was intrahospital mortality; secondary endpoints included transfer to the ICU as well as 30-day and 180-day mortality. One hundred forty-two patients (2.5%) reached the primary endpoint. Deceleration capacity was highly significantly lower in nonsurvivors than survivors (2.9 ± 2.1 ms vs 5.6 ± 2.9 ms; p < 0.001) and yielded an area under the receiver-operator characteristic curve of 0.780 (95% CI, 0.745-0.813). The modified early warning score model yielded an area under the receiver-operator characteristic curve of 0.706 (0.667-0.750). Implementing deceleration capacity into the modified early warning score model led to a highly significant increase of the area under the receiver-operator characteristic curve to 0.804 (0.770-0.835; p < 0.001 for difference). Deceleration capacity was also a highly significant predictor of 30-day and 180-day mortality as well as transfer to the ICU. CONCLUSIONS: Deceleration capacity is a strong and independent predictor of short-term mortality among patients admitted to a medical emergency department.

Autologous stem cell transplantation with thiotepa-based conditioning in patients with systemic sclerosis and cardiac manifestations.

OBJECTIVE: The aim of this study was to find a new and less cardiotoxic conditioning regimen for high-dose chemotherapy and autologous stem cell transplantation (aSCT) in patients with severe SSc and pre-existing cardiac involvement. METHODS: Six patients with cardiac involvement were treated for SSc with a conditioning regimen including reduced-dose CYC plus the non-cardiotoxic alkylant thiotepa. All patients received an implantable cardioverter defibrillator (ICD) before aSCT. The response at months 6 and 12 was measured according to reduction of the modified Rodnan skin score (mRSS). CT histography was used to monitor pulmonary manifestations, as were echocardiography, N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin for the cardiac involvement. Cardiac events were defined as death or hospitalisation due to heart failure or appropriate discharge of the ICD. RESULTS: Between December 2008 and May 2012, four male and two female patients with a median age of 41 years received aSCT. The median mRSS significantly decreased from 26.5 to 18 and 17.5 at month 6 and 12, respectively. The total lung volume also significantly improved. Within the median follow-up of 1.6 years (range 1-3.8) two patients experienced a relapse of SSc, which results in a progression-free survival rate of 66.6%. Three patients experienced ICD discharge. CONCLUSION: For patients with SSc and cardiac involvement, the use of thiotepa and reduced-dose CYC is feasible and effective. The rate of ICD discharge underlines the need for protection in these endangered patients. This preliminary experience allowed us to use this regimen for our currently recruiting prospective trial (NCT01895244).

Automated assessment of cardiac autonomic function by means of deceleration capacity from noisy, nonstationary ECG signals: validation study.

BACKGROUND: Assessment of heart rate variability by means of deceleration capacity (DC) provides a noninvasive probe of cardiac autonomic activity. However, clinical use of DC is limited by the need of manual review of the ECG signals to eliminate artifacts, noise, and nonstationarities. OBJECTIVE: To validate a novel approach to fully automatically assess DC from noisy, nonstationary signals METHODS: We analyzed 100 randomly selected ECG tracings recorded for 10 minutes by routine monitor devices (GE DASH 4000, sample size 100 Hz) in a medical emergency department. We used a novel automated R-peak detection algorithm, which is mainly based on a Shannon energy envelope estimator and a Hilbert transformation. We transformed the automatically generated RR interval time series by phase-rectified signal averaging (PRSA) to assess DC of heart rate (DCauto ). DCauto was compared to DCmanual , which was obtained from the same manually preprocessed ECG signals. RESULTS: DCauto and DCmanual showed good correlation and agreement, particularly if a low-pass filter was implemented into the PRSA algorithm. Correlation coefficient between DCauto and DCmanual was 0.983 (P < 0.0001). Average difference between DCauto and DCmanual was -0.23±0.49 ms with limits of agreement ranging from -1.19 to 0.73 ms. Significantly lower correlations were observed when a different R-peak detection algorithm or conventional heart rate variability (HRV) measures were tested. CONCLUSIONS: DC can be fully automatically assessed from noisy, nonstationary ECG signals.

Deceleration capacity of heart rate predicts 1-year mortality in patients undergoing transcatheter edge-to-edge mitral valve repair.

BACKGROUND: Risk stratification for transcatheter procedures in patients with severe mitral regurgitation is challenging. Deceleration capacity (DC) has already proven to be a reliable risk predictor in patients undergoing transcatheter aortic valve implantation. We hypothesized, that DC provides prognostic value in patients undergoing transcatheter edge-to-edge mitral valve repair (TEER). METHODS: We retrospectively analyzed electrocardiogram signals from 106 patients undergoing TEER at the University Hospital of Tübingen. All patients received continuous heart-rate monitoring to assess DC following the procedure. One-year all-cause mortality was defined as the primary end point. RESULTS: Sixteen patients (15.1%) died within 1 year. The DC in nonsurvivors was significantly reduced compared to survivors (5.1 ± 3.0 vs. 3.0 ± 1.6 ms, p = 0.002). A higher EuroSCORE II and impaired left ventricular function were furthermore associated with poor outcome. In Cox regression analyses, a DC < 4.5 ms was found a strong predictor of 1-year mortality (hazard ratio: 0.10, 95% confidence interval: 0.13-0.79, p = 0.029). Finally, a significant negative correlation was found between DC and residual mitral regurgitation after TEER (r = -0.41, p < 0.001). CONCLUSION: In patients with severe mitral regurgitation undergoing TEER, DC may serve as a new predictor of follow-up mortality.

Prevalence and predictors of severe autonomic failure in patients with insulin-dependent type 2 diabetes mellitus and coronary artery disease: pilot study.

BACKGROUND: Presence of severe autonomic failure (SAF), defined as coincidence of abnormal heart rate turbulence and abnormal deceleration capacity, identifies a group of patients with very poor prognosis among post-infarction patients with diabetes mellitus. However, factors contributing to development of SAF are entirely unknown. Here, we aimed to identify clinical, biochemical, and hemodynamic factors predicting SAF in a consecutive cohort of diabetic patients with coronary artery disease (CAD). METHODS: Between January 2010 and July 2011, we prospectively enrolled 97 patients with insulin-dependent type 2 diabetes mellitus and stable CAD in sinus rhythm. Heart rate turbulence (as marker of autonomic reflex activity) and deceleration capacity (as marker of autonomic tonic activity) were calculated from 24-hour Holter recordings. Uni- and multivariable logistic regression analysis included duration of diabetes mellitus, diabetic neuropathy, retinopathy, nephropathy, level of HbA(1c), left ventricular ejection fraction (LVEF), brain natriuretic peptide, presence of multivessel disease, and history of myocardial infarction. RESULTS: Ten (10.3%) of the 97 patients exhibited signs of SAF. Patients with SAF were characterized by longer duration of diabetes (25 years vs 15 years), higher prevalence of diabetic neuropathy (70% vs. 36%), retinopathy (80% vs 45%) and nephropathy (90% vs 55%), significantly higher levels of HbA(1c) (9.0% vs 7.4%; P = .002) and a lower LVEF (30% vs.55%; P = .001). On multivariable analysis, LVEF ≤ 35% and HbA(1c) >8% were the only factors which were independently associated with SAF (odds ratios of 23.1 [95% CI, 1.8-287.0]; P = .015 and 6.6 [1.1-40.1]; P = .043). DISCUSSION: In patients with insulin-dependent type 2 diabetes mellitus and CAD, presence of SAF correlates with both glycemic control and diabetic complications. Impaired LVEF and increased level of HbA(1c) were independently associated with SAF.

Effects of dexamethasone and atorvastatin on atrial sodium current and its early tachycardia-induced electrical remodeling in rabbits.

PURPOSE: Atrial fibrillation (AF) results in tachycardia-induced ionic remodeling. Pharmacological prevention of tachycardia-induced ionic remodeling not only with "classical" antiarrhythmics but also with drugs which provide a basis for some of the pillars of the so-called "upstream" therapy of AF like corticosteroids or statins has been proposed as a therapeutic strategy. Amongst other ion currents, atrial sodium current I(Na) and its tachycardia-induced alterations play an important role in AF pathophysiology. Thus, effects of a dexamethasone (DT) and atorvastatin treatment (AT) on atrial sodium current I(Na) and its tachycardia-induced remodeling were studied in a rabbit model. METHODS: 9 groups with 4 animals were examined. Atrial pacemaker leads were implanted in all animals. No rapid atrial pacing (600/min) was performed in the control group but for 24 or 120 hours in the respective pacing groups. Instrumentation and pacing did not differ from the respective drug groups but an additional treatment with dexamethasone or atorvastatin (7 days) was performed. RESULTS: Rapid atrial pacing (RAP, 600/min) reduced I(Na) after 24 hours (≈ -50%) with no further reduction after 120 hours. DT reduced I(Na) (≈ -20%), current densities in consecutively tachypaced animals did not differ from those in untreated animals. AT reduced INa similar as RAP, subsequent RAP did not further diminish I(Na). CONCLUSIONS: Impact of corticosteroids and statins on INa and its tachycardia-induced alterations also contribute to the mode of action of these substances in upstream treatment of atrial fibrillation.

Deceleration capacity for rapid risk stratification in patients suffering from acute ischemic stroke: A prospective exploratory pilot study.

ABSTRACT: Deceleration capacitiy for rapid risk stratification in stroke patientsCerebral ischemia is a major cause of neurologic deficit and patients suffering from ischemic stroke bear a relevant risk of mortality. Identifying stroke patients at high mortality risk is of crucial clinical relevance. Deceleration capacity of heart rate (DC) as a parameter of cardiac autonomic function is an excellent predictor of mortality in myocardial infarction and heart failure patients.The aim of our study was to evaluate whether DC provides prognostic information regarding mortality risk in patients with acute ischemic stroke.From September 2015 to March 2018 we prospectively enrolled consecutive patients presenting at the Stroke Unit of our university hospital with acute ischemic stroke who were in sinus rhythm. In these patients 24 hours-Holter-ECG recordings and evaluation of National Institute of Health Stroke Scale (NIHSS) were performed. DC was calculated according to a previously published algorithm. Primary endpoint was intrahospital mortality.Eight hundred seventy eight stroke patients were included in the study. Intrahospital mortality was 2.8% (25 patients). Both DC and NIHSS were significantly different between non-survivors and survivors (Mean ±â€ŠSD: DC: 4.1 ±â€Š2.8 ms vs 6.3 ±â€Š3.3 ms, P < .001) (NIHSS: 7.6 ±â€Š7.1 vs 4.3 ±â€Š5.5, P = .02). DC achieved an area under the curve value (AUC) of 0.708 for predicting intrahospital mortality, while the AUC value of NIHSS was 0.641. In a binary logistic regression analysis, DC, NIHSS and age were independent predictors for intrahospital mortality (DC: HR CI 95%: 0.88 (0.79-0.97); P = .01; NIHSS: HR CI 95%: 1.08 (1.02-1.15); P = .01; Age: HR CI 95%: 1.07 (1.02-1.11); P = .004. The combination of NIHSS, age and DC in a prediction model led to a significant improvement of the AUC, which was 0.757 (P < .001, incremental development index [IDI] 95% CI: 0.037 (0.018-0.057)), compared to the individual risk parameters.Our study demonstrated that DC is suitable for both objective and independent risk stratification in patients suffering from ischemic stroke. The application of a prediction model combining NIHSS, age and DC is superior to the single markers in identifying patients at high mortality risk.

Deceleration capacity is associated with acute respiratory distress syndrome in COVID-19.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is considered the main cause of COVID-19 associated morbidity and mortality. Early and reliable risk stratification is of crucial clinical importance in order to identify persons at risk for developing a severe course of disease. Deceleration capacity (DC) of heart rate as a marker of cardiac autonomic function predicts outcome in persons with myocardial infarction and heart failure. We hypothesized that reduced modulation of heart rate may be helpful in identifying persons with COVID-19 at risk for developing ARDS. METHODS: We prospectively enrolled 60 consecutive COVID-19 positive persons presenting at the University Hospital of Tuebingen. Arterial blood gas analysis and 24 h-Holter ECG recordings were performed and analyzed at admission. The primary end point was defined as development of ARDS with regards to the Berlin classification. RESULTS: 61.7% (37 of 60 persons) developed an ARDS. In persons with ARDS DC was significantly reduced when compared to persons with milder course of infection (3.2 ms vs. 6.6 ms, p < 0.001). DC achieved a good discrimination performance (AUC = 0.76) for ARDS in COVID-19 persons. In a multivariate analysis, decreased DC was associated with the development of ARDS. CONCLUSION: Our data suggest a promising role of DC to risk stratification in COVID-19.

Association of Heart Rate Variability With Silent Brain Infarcts in Patients With Atrial Fibrillation.

Purpose: Silent brain infarcts (SBI) are frequently detected in patients with atrial fibrillation (AF), but it is unknown whether SBI are linked to autonomic dysfunction. We aimed to explore the association of autonomic dysfunction with SBI in AF patients. Methods: 1,358 AF patients without prior stroke or TIA underwent brain MRI and 5-min resting ECG. We divided our cohort into AF patients who presented in sinus rhythm (SR-group, n = 816) or AF (AF-group, n = 542). HRV triangular index (HRVI), standard deviation of normal-to-normal intervals, mean heart rate, root mean square root of successive differences of normal-to-normal intervals, 5-min total power and power in the low frequency, high frequency and very low frequency range were calculated. Primary outcome was presence of SBI in the SR group, defined as large non-cortical or cortical infarcts. Secondary outcomes were SBI volumes and topography. Results: Mean age was 72 ± 9 years, 27% were female. SBI were detected in 10.5% of the SR group and in 19.9% of the AF group (p < 0.001). HRVI <15 was the only HRV parameter associated with the presence of SBI after adjustment for clinical covariates in the SR group [odds ratio (OR) 1.67; 95% confidence interval (CI): 1.03-2.70; p = 0.037]. HRVI <15 was associated with larger brain infarct volumes [ß (95% CI) -0.47 (-0.84; -0.09), p = 0.016] in the SR group and was more frequently observed in patients with right- than left-hemispheric SBI (p = 0.017). Conclusion: Impaired HRVI is associated with SBI in AF patients. AF patients with autonomic dysfunction might undergo systematic brain MRI screening to initiate intensified medical treatment. Clinical Trials Gov Identifier: NCT02105844.

Influence of dexamethasone on atrial ion currents and their early ionic tachycardia-induced electrical remodeling in rabbits.

BACKGROUND: Certain evidence points to a role of inflammation in AF pathophysiology. Thus, antiinflammatory treatment of AF is discussed. Effects of a dexamethasone treatment (7 days) on atrial ion currents (I(Ca,L), I(to), I(sus)) and their tachycardia-induced remodeling were studied in a rabbit model. METHODS: 6 groups of 4 animals each were built. Rapid atrial pacing (600 min) was performed for 24 and 120 hours with/ without dexamethasone treatment. Ion currents were measured using whole cell patch clamp method. RESULTS: Rapid atrial pacing reduced (I(Ca,L), I(to) was decreased after 24 hours but almost returned to control values after 120 hours. When dexamethasone-treated animals also underwent atrial tachypacing, pacing-induced reduction of I(Ca,L) was still observed after 24 hours and was even augmented after 120 hours compared to untreated but tachypaced animals. I(to) was not influenced by dexamethasone alone. In dexamethasone-treated animals, reduction of I(to) was not observed after 24 hours but occurred after 120 hours of atrial tachypacing. I(sus) was neither influenced by rapid atrial pacing nor by dexamethasone. Biophysical properties of all currents were affected neither by rapid atrial pacing nor by dexamethasone. CONCLUSION: Dexamethasone influenced tachycardia-induced alterations of atrial I(to). Our experiments give evidence that - amongst other anti-inflammatory action - impact of dexamethasone on ion currents and their tachycardia-induced alterations might also play a role in treatment/prevention of AF with steroids.

Heart Rate Variability Triangular Index as a Predictor of Cardiovascular Mortality in Patients With Atrial Fibrillation.

Background Impaired heart rate variability (HRV) is associated with increased mortality in sinus rhythm. However, HRV has not been systematically assessed in patients with atrial fibrillation (AF). We hypothesized that parameters of HRV may be predictive of cardiovascular death in patients with AF. Methods and Results From the multicenter prospective Swiss-AF (Swiss Atrial Fibrillation) Cohort Study, we enrolled 1922 patients who were in sinus rhythm or AF. Resting ECG recordings of 5-minute duration were obtained at baseline. Standard parameters of HRV (HRV triangular index, SD of the normal-to-normal intervals, square root of the mean squared differences of successive normal-to-normal intervals and mean heart rate) were calculated. During follow-up, an end point committee adjudicated each cause of death. During a mean follow-up time of 2.6±1.0 years, 143 (7.4%) patients died; 92 deaths were attributable to cardiovascular reasons. In a Cox regression model including multiple covariates (age, sex, body mass index, smoking status, history of diabetes mellitus, history of hypertension, history of stroke/transient ischemic attack, history of myocardial infarction, antiarrhythmic drugs including ß blockers, oral anticoagulation), a decreased HRV index ≤ median (14.29), but not other HRV parameters, was associated with an increase in the risk of cardiovascular death (hazard ratio, 1.7; 95% CI, 1.1-2.6; P=0.01) and all-cause death (hazard ratio, 1.42; 95% CI, 1.02-1.98; P=0.04). Conclusions The HRV index measured in a single 5-minute ECG recording in a cohort of patients with AF is an independent predictor of cardiovascular mortality. HRV analysis in patients with AF might be a valuable tool for further risk stratification to guide patient management. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.

Alcohol-induced electrical remodeling: effects of sustained short-term ethanol infusion on ion currents in rabbit atrium.

BACKGROUND: In some patients, above-average alcohol consumption before occurrence of atrial fibrillation (AF) in terms of a "holiday heart syndrome" (HHS) can be determined. There is evidence that long before development of apparent alcohol-induced cardiomyopathy, above-average alcohol consumption generates an arrhythmogenic substrate which abets the onset of AF. Changes of atrial current densities in terms of an electrical remodeling after sustained short-term ethanol infusion in rabbits as a potential part of HHS pathophysiology were examined in this study. METHODS: Rabbits of the ethanol group (EG) received sustained short-term intravenous alcohol infusion for 120 hours (during infusion period, blood alcohol level did not fall below 158 mg/dl), whereas NaCl 0.9% was infused in the placebo group (PG). Using patch clamp technique in whole-cell mode, atrial current densities were measured and compared between both groups. RESULTS: Ethanol infusion did not alter current densities of I(to) [58.7 +/- 5.0 pA/pF (PG, n = 20 cells) vs. 53.9 +/- 5.0 pA/pF (EG, n = 24)], I(sus) [11.3 +/- 1.4 pA/pF (PG, n = 20) vs. 10.2 +/- 1.0 pA/pF (EG, n = 24)], and I(K1) [-1.6 +/- 0.3 pA/pF (PG, n = 17) vs. -2.0 +/- 0.3 pA/pF (EG, n = 22)]. However, alcohol infusion resulted in a remarkable reduction of I(Ca,L) current densities [-28.4 +/- 1.8 pA/pF (PG, n = 20) vs. -15.2 +/- 1.4 pA/pF (EG, n = 22)] and I(Na) [-75.4 +/- 3.6 pA/pF (PG, n = 17) vs. -35.4 +/- 4.4 pA/pF (EG, n = 21)], respectively. CONCLUSION: Sustained short-term ethanol infusion in rabbits alters atrial current densities. HHS might be favored by alcohol-induced atrial electrical remodeling.

Mitral Valve Endocarditis due to Lactobacillus.

Lactobacillus species are Gram-positive, facultative anaerobic, rod-shaped bacteria. They belong to the lactic acid bacteria group and are also known as a usual part of the normal flora of the gastrointestinal tract as well as of the urinary and genital tracts. They are an infrequent human pathogen but can induce several infections such as bacteremia and infectious endocarditis. We report the case of an 81-year-old woman with Lactobacillus bacteremia and mitral valve endocarditis as well as splenic abscesses.

Nocturnal respiratory rate as a predictor of mortality in patients with acute coronary syndrome.

Background: Patients with acute coronary syndrome (ACS) are at risk especially in the period shortly after the event. Alterations in respiratory control have been associated with adverse prognosis. The aim of our study was to assess if the nocturnal respiratory rate (NRR) is a predictor of mortality in patients with ACS presenting in the emergency department. Methods: Clinically stable consecutive patients with ACS aged ≥ 18 years were prospectively enrolled. The Global Registry of Acute Coronary Events (GRACE) score and left ventricular ejection fraction (LVEF) were assessed for all patients. The average NRR over a period of 6 hours was determined by the records of the surveillance monitors in the first night after admission. Primary and secondary endpoints were intrahospital and 2 years all-cause mortality, respectively. Results: Of the 860 patients with ACS, 21 (2.4%) died within the intrahospital phase and 108 patients (12.6%) died within the subsequent 2 years. The NRR was a significant predictor of both endpoints and was independent from the GRACE score and LVEF. Implementing the NRR into the GRACE risk model leads to a significant increase of the C-statistics especially for prediction of intrahospital mortality. Conclusion: The NRR is an independent predictor of mortality in patients with ACS.

Peri-interventional combined anticoagulation and antithrombotic therapy in atrial fibrillation ablation: A retrospective safety analysis.

BACKGROUND: Catheter ablation (CA) of atrial fibrillation (AF) requires an intensified peri-inter-ventional anticoagulation scheme to avoid thromboembolic complications. In patients with cardiac or extracardiac artery disease, an additional antiplatelet treatment (AAT) is at least temporally necessary especially after a percutaneous intervention with stent implantation. This raises the question whether these patients have a higher peri-interventional bleeding risk during CA of AF. METHODS: The data of 1235 patients with CA of AF were retrospectively analyzed in terms of bleeding events, ablation type, antithrombotic medication and comorbidities such as coronary artery disease and components of the HAS- BLED score. Peri-interventional bleeding events were classified in accordance with the BARC classification. Differentiations were made between slight femoral bleeding (based on type 1), severe femoral bleeding and pericardial effusion without pericardiocentesis (based on type 2) with the need of further hospitalization, the need of transfusion (based on type 3a) and pericardial tamponades requiring pericardiocentesis (based on type 3b). RESULTS: 1131/1235 (91.6%) patients were exclusively under anticoagulation and 187 (15.3%) patients were also on AAT. There were no statistically significant differences in type 1 and 3b bleeding complica-tions or the occurrence of femoral pseudoaneurysms between both groups. However, type 2/3a bleeding complications, mostly femoral bleedings, were significantly more frequent in the patient group with AAT (3.2% vs. 7.5%, p = 0.006). CONCLUSIONS: An additional antiplatelet therapy increases the risk of severe femoral bleeding events during CA of AF. It appears reasonable to perform the elective procedure of AF ablation after the dis-continuation of AAT.

Galectin-3 is associated with left ventricular reverse remodeling and outcome after percutaneous mitral valve repair.

BACKGROUND: Plasma Galectin-3 is a marker of myocardial inflammation and fibrosis, was associated with left ventricular (LV) reverse remodeling after conventional surgical mitral valve repair (MVR) and predicted clinical events in patients undergoing transcatheter aortic valve replacement (TAVR). We aimed to evaluate the association between pre-interventional Galectin-3 levels and (1) reverse LV remodeling and (2) major adverse cardiovascular events (MACE) in patients undergoing percutaneous MVR. METHODS: Forty-four consecutive patients (median age 79 years, LV ejection fraction 39.5 ±â€¯11.4%, 91% in NYHA functional class ≥III) with symptomatic moderate to severe mitral regurgitation undergoing percutaneous MVR were prospectively included. Plasma Galectin-3 levels were measured before the procedure. Echocardiographic and clinical assessment was performed at baseline and after 3 months. LV reverse remodeling was prospectively defined as a ≥10% increase in global longitudinal strain. MACE included death, myocardial infarction, heart failure related rehospitalization and stroke and was assessed after a mean follow-up time of 2 years. RESULTS: 72.7% of the patients showed LV reverse remodeling. Pre-interventional Galectin-3 < 10 ng/ml was an independent predictor of LV reverse remodeling (OR 10.3, 95% CI 1.2-83.9, p = 0.036). 25 patients (56.8%) experienced a MACE. Patients with Galectin-3 levels ≥ 10 ng/ml had significantly more MACE than patients with Galectin-3 levels < 10 ng/ml (100% vs. 45.5%, p = 0.003). Diabetes independently predicted MACE (HR 3.1, 95% CI 1.0-9.4, p = 0.049); Galectin-3 ≥ 10 ng/ml was of borderline significance (HR 2.2, 95% CI 0.9-5.4, p = 0.088). CONCLUSIONS: Pre-interventional plasma Galectin-3 levels are associated with LV reverse remodeling and with clinical outcome after percutaneous MVR.

Influence of verapamil on tachycardia-induced alterations of PP1 and PP2A in rabbit atrium.

BACKGROUND: Long-term atrial fibrillation changes in many regulatory and structural processes may result in stabilization of the arrhythmia. There is evidence that decreased amplitude of L-type Ca(2+) current - probably a key mechanism of atrial remodelling -resulting from changes in expression of regulatory proteins is at least jointly responsible. OBJECTIVES: To assess the expressions of protein phosphatases PP1 and PP2A, as well as the effect of verapamil pretreatment (VPT), in the early phases of atrial fibrillation in a rabbit model. METHODS: FOUR GROUPS, EACH CONSISTING OF SIX ANIMALS, WERE STUDIED: 'not paced, no drug' group; 'paced, no drug' group (rapid atrial pacing [RAP] 600 beats/min for 24 h); 'not paced, verapamil' (NPV) group (duration of VPT was seven days, verapamil 7.5 mg/kg was administered every 12 h); and 'paced, verapamil' (PV) group (pacemaker stimulation after VPT). Protein expression was evaluated by Western blot analysis. RESULTS: RAP resulted in an augmented (32%) PP1 expression (not paced, no drug group versus paced, no drug group). The increase in PP1 expression was prevented with VPT (NPV group versus PV group). Expression of PP2A was not influenced by RAP. However, VPT led to an increase of PP2A expression (16%) after RAP (NPV group versus PV group). CONCLUSIONS: Fortified expression of protein phosphatases might be - besides transcriptional downregulation of channel subunits - another important cause of reduced L-type Ca(2+) current after RAP. Blocking L-type Ca(2+) channels with verapamil to prevent tachycardia-induced changes of PP1 expression might be expedient.