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Cardiogenic shock (CS) is a hemodynamically complex multisystem syndrome associated with persistently high morbidity and mortality. As CS is characterized by progressive failure to provide adequate systemic perfusion, supporting end-organ perfusion using mechanical circulatory support (MCS) seems intriguing. Since most patients with CS present in the catheterization laboratory, percutaneously implantable systems have the widest adoption in the field. We evaluated feasibility, outcomes, and complications after the introduction of a full-percutaneous program for both the Impella CP device and venoarterial extracorporeal membrane oxygenator (VA-ECMO).PREPARE CardShock (PRospective REgistry of PAtients in REfractory cardiogenic shock) is a prospective single-center registry, including 248 consecutive patients between May 2019 and April 2021, who underwent cardiac catheterization and displayed advanced cardiogenic shock. The median age was 70 (58-77) years and 28% were female. Sixty-five percent of the cases had cardiac arrest, of which 66% were out-of-hospital cardiac arrest. A local standard operating procedure (SOP) indicating indications as well as relative and absolute contraindications for different means of MCS (Impella CP or VA-ECMO) was used to guide MCS use. The primary endpoint was in-hospital death and secondary endpoints were spontaneous myocardial infarction and major bleedings during the hospital stay.Overall mortality was 50.4% with a median survival of 2 (0-6) days. Significant independent predictors of mortality were cardiac arrest during the index event (odds ratio [OR] with 95% confidence interval [CI]: 2.53 [1.43-4.51]; p = 0.001), age 65 years (OR: 2.05 [1.03-4.09]; p = 0.036]), pH 7.30 (OR: 2.69 [1.56-4.66]; p 0.001), and lactate levels 2 mmol/L (OR: 4.51 [2.37-8.65]; p 0.001).Conclusive SOPs assist target-orientated MCS use in CS. This study provides guidance on the implementation, validation, and modification of newly established MCS programs to aid centers that are establishing such programs.

Human parvovirus B19 (B19V) is the predominant cardiotropic virus associated with dilated inflammatory cardiomyopathy (DCMi). Transcriptionally active cardiotropic B19V infection is clinically relevant and triggers adverse long-term mortality. During the study, we evaluated whether antiviral treatment with the nucleoside analogue telbivudine (LTD) is effective in suppressing transcriptional active B19V in endomyocardial biopsies (EMBs) of B19V positive patients and improving clinical outcomes. Seventeen B19V-positive patients (13 male, mean age 45.7 ± 13.9 years, mean left ventricular ejection fraction (LVEF) 37.7 ± 13.5%) with positive B19V DNA and transcriptional activity (B19V mRNA) in EMBs were treated with 600 mg/d LTD over a period of six months. Patients underwent EMBs before and after termination of the LTD treatment. B19V RNA copy numbers remained unchanged in 3/17 patients (non-responder) and declined or disappeared completely in the remaining 14/17 patients (responder) (p ≤ 0.0001). Notably, LVEF improvement was more significant in patients who reduced or lost B19V RNA (responder, p = 0.02) in contrast to non-responders (p = 0.7). In parallel, responder patients displayed statistically significant improvement in quality of life (QoL) questionnaires (p = 0.03) and dyspnea on exertion (p = 0.0006), reflecting an improvement in New York Heart Association (NYHA) Classification (p = 0.001). Our findings demonstrated for the first time that suppression of B19V transcriptional activity by LTD treatment improved hemodynamic and clinical outcome significantly. Thus, the present study substantiates the clinical relevance of detecting B19V transcriptional activity of the myocardium.

The aim was to investigate the applicability of a clinical decision support system in a real-world inpatient setting for patients with type 2 diabetes on general hospital wards. A total of 150 patients with type 2 diabetes requiring subcutaneous insulin therapy were treated with basal-bolus insulin therapy guided by a decision support system (GlucoTab) providing automated workflow tasks and suggestions for insulin dosing to health care professionals. By using the system, a mean daily blood glucose (BG) of 159 ± 32 mg/dL was achieved. 68.8% of measurements were in the target range (70 to 93% and 91%, respectively). The decision support system facilitates safe and efficacious inpatient diabetes care by standardizing treatment workflow and providing decision support for basal-bolus insulin dosing.

Aims: The diagnostic approach to idiopathic giant-cell myocarditis (IGCM) is based on identifying various patterns of inflammatory cell infiltration and multinucleated giant cells (GCs) in histologic sections taken from endomyocardial biopsies (EMBs). The sampling error for detecting focally located GCs by histopathology is high, however. The aim of this study was to demonstrate the feasibility of gene profiling as a new diagnostic method in clinical practice, namely in a large cohort of patients suffering from acute cardiac decompensation. Methods and Results: In this retrospective multicenter study, EMBs taken from n = 427 patients with clinically acute cardiac decompensation and suspected acute myocarditis were screened (mean age: 47.03 &plusmn, 15.69 years). In each patient, the EMBs were analyzed on the basis of histology, immunohistology, molecular virology, and gene-expression profiling. Out of the total of n = 427 patient samples examined, GCs could be detected in 26 cases (6.1%) by histology. An established myocardial gene profile consisting of 27 genes was revealed, this was narrowed down to a specified profile of five genes (CPT1, CCL20, CCR5, CCR6, TLR8) which serve to identify histologically proven IGCM with high specificity in 25 of the 26 patients (96.2%). Once this newly established profiling approach was applied to the remaining patient samples, an additional n = 31 patients (7.3%) could be identified as having IGCM without any histologic proof of myocardial GCs. In a subgroup analysis, patients diagnosed with IGCM using this gene profiling respond in a similar fashion to immunosuppressive therapy as patients diagnosed with IGCM by conventional histology alone. Conclusions: Myocardial gene-expression profiling is a promising new method in clinical practice, one which can predict IGCM even in the absence of any direct histologic proof of GCs in EMB sections. Gene profiling is of great clinical relevance in terms of a) overcoming the sampling error associated with purely histologic examinations and b) monitoring the effectiveness of therapy.

The majority of resuscitated patients present with underlying cardiac disease, and out of these myocardial infarction is most common. Immediate interventional treatment is recommended and routinely requires dual antiplatelet therapy including aspirin and a P2Y12-inhibitor. Therapeutic hypothermia or target temperature management is also recommended in these patients. Cardiogenic shock as well as reduced body temperature impacts platelet reactivity and its medical inhibition. The study aims to quantify aspirin- and P2Y12-mediated platelet inhibition in patients presenting with myocardial infarction and cardiopulmonary resuscitation. Twenty-five resuscitated patients were enrolled in this prospective, observational, non-randomized single-centre study. These patients were compared to 77 matched controls from the ATLANTIS-ACS database of non-resuscitated patients with myocardial infarction. Platelet function testing was performed by light transmittance aggregometry. Aspirin reactivity was monitored by inducing platelet aggregation with collagen and arachidonic acid, respectively. P2Y12 inhibition was recorded by stimulation of platelet aggregation with adenosine diphosphate. To quantify the overall platelet response, thrombin receptor-activated peptide was used. Aspirin-mediated platelet reactivity decreased significantly in resuscitated patients during the first days and was significantly weaker on day 3 (collagen AUC 253.8 (122.7–352.2) vs. 109.0 (73.0–182.0); p = 0.022). P2Y12-mediated platelet inhibition was also impaired in resuscitated patients on day 3 (mean ADP AUC (IQR): CPR 172.1 (46.7−346.5) vs. control 43.9 (18.9–115.2); p

Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminalprohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.

Background In chronic heart failure (CHF) NT-proBNP and left ventricular ejection fraction (LVEF) by echocardiography are standard diagnostic as well as follow-up markers and are known to correlate with prognosis. Speckle-tracking echocardiography is a more recent technique to quantify myocardial deformation as a measurement of left ventricular function with potential benefits over LVEF. Purpose The purpose of this investigation was to analyse the cross-sectional relationship between 2D speckle tracking-derived global longitudinal strain (GLS) and NT-proBNP plasma levels in a prospective cohort of ischemic and non-ischemic CHF patients. Methods We enrolled 205 patients with chronic heart failure. Major inclusion criteria were age over 18 years, stable disease with absence of unplanned hospitalization or change in medication or device therapy in the previous month or major surgery in the previous 3 months. CHF treatment had to be according to the recommendations of the ESC CHF guidelines 2016 and LVEF had to be below 50%. Patient history, physical examination and an extensive echocardiography exam were performed. Lab results included NT-proBNP. Manual longitudinal strain was calculated using EchoPAC (General Electric Medical Systems, Horten, Norway) by a single and blinded examiner. LVEF was measured using Simpson's biplane method. Results 205 patients included in the study. The baseline characteristics included mean age 65.0 years and 75% male. Mean GLS was −9.6% (SD ±4.5%) and median NT-proBNP 1269.5 (IQR 379.5–2759.5) ng/ml. The CHF aetiology was 70.0% ischemic vs 30.0% non-ischemic. There was a significant negative correlation between GLS and NT-proBNP (Pearson r=0.239, p=0.029), this was not significant for LVEF and NT-proBNP (Pearson r=0.149, p=0.228).In a multivariate regression analysis adjusted for age, sex, NYHA classification and HF aetiology, GLS remained significantly correlated with NT-proBNP (adjusted beta-coefficient= 0.289, p=0.011). Furthermore, in contrast to LVEF, GLS showed a significant correlation to NT-proBNP in patients with ischemic (Pearson r=0.266, p=0.049) as well as non-ischemic aetiology of heart failure (Pearson r=0.434, p=0.034). Conclusion Global longitudinal strain, not LVEF, was significantly correlated with NT-proBNP in patients with CHF, independently of age, sex, symptoms or heart failure aetiology. This shows that speckle-tracking might be superior to LVEF for the assessment of left ventricular function in CHF.

Glycemic goals of inpatients should consider the prevention of hypoglycemia and hyperglycemia. To achieve glycemic control in the hospital, guidelines recommend basal-bolus insulin therapy as the preferred method for treatment of persistent hyperglycemia and the use of clinical decision support systems. The aim of this study was to investigate the efficacy, safety and usability of the GlucoTab® decision support system in hospital routine care of non-critically ill patients with type 2 diabetes at 3 general wards of a university medical center. In total, 150 patients with type 2 diabetes requiring insulin therapy (56 female, age 68 ± 11 years, HbA1c 77 ± 24 mmol/mol, diabetes duration 15 ± 11 years, BMI 30 ± 6 kg/m2, length of hospital stay 9 ± 7 days) were treated with basal-bolus insulin therapy guided by GlucoTab®, a mobile decision support system providing automated workflow tasks and suggestions for insulin dosing to nurses and physicians. In total 4879 capillary blood glucose values (BG) were documented. By using the GlucoTab® system in routine care, a mean daily BG of 159 ± 32 mg/dl could be achieved. 68.8% of all BG measurements were in the acceptable range (70-93% and 91%, respectively). The study confirmed that the GlucoTab® system supports a safe, efficacious and user-friendly glycemic management of basal-bolus insulin therapy in hospital routine care. Further research will include decision support for alternative therapy types for patients with less stringent goals to prevent hypoglycemia in hospital routine care. Disclosure K.M. Lichtenegger: None. F. Aberer: None. A.C. Tuca: None. K. Donsa: Stock/Shareholder; Self; decide Clinical Software GmbH. B. Höll: Employee; Self; decide Clinical Software GmbH. L. Schaupp: None. J. Plank: None. P. Beck: Employee; Self; decide Clinical Software GmbH. Stock/Shareholder; Self; decide Clinical Software GmbH. F. Fruhwald: None. T.R. Pieber: Advisory Panel; Self; ADOCIA, Arecor Limited, AstraZeneca, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; Novo Nordisk A/S. J.K. Mader: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Prediktor Medical, Roche Diabetes Care, Sanofi. Speaker's Bureau; Self; Abbott, AstraZeneca, Dexcom, Inc., Novo Nordisk Inc. Stock/Shareholder; Self; decide Clinical Software GmbH. Funding Research Studio Austria "GlucoTab“ (844737)

Rationale: Remodeling and fibrosis of the right ventricle (RV) may cause RV dysfunction and poor survival in patients with pulmonary hypertension. Objectives: To investigate the consequences of RV fibrosis modulation and the accompanying cellular changes on RV function. Methods: Expression of fibrotic markers was assessed in the RV of patients with pulmonary hypertension, the murine pulmonary artery banding, and rat monocrotaline and Sugen5416/hypoxia models. Invasive hemodynamic and echocardiographic assessment was performed on galectin-3 knockout or inhibitor-treated mice. Measurements and Main Results: Established fibrosis was characterized by marked expression of galectin-3 and an enhanced number of proliferating RV fibroblasts. Galectin-3 genetic and pharmacologic inhibition or antifibrotic treatment with pirfenidone significantly diminished RV fibrosis progression in the pulmonary artery banding model, without improving RV functional parameters. RV fibrotic regions were populated with mesenchymal cells coexpressing vimentin and PDGFRα (platelet-derived growth factor receptor-α), but generally lacked αSMA (α-smooth muscle actin) positivity. Serum levels of galectin-3 were increased in patients with idiopathic pulmonary arterial hypertension but did not correlate with cardiac function. No changes of galectin-3 expression were observed in the lungs. Conclusions: We identified extrapulmonary galectin-3 as an important mediator that drives RV fibrosis in pulmonary hypertension through the expansion of PDGFRα/vimentin-expressing cardiac fibroblasts. However, interventions effectively targeting fibrosis lack significant beneficial effects on RV function.

The later stages of heart failure are characterized by a steady decline in quality of life. Clinical priorities should be to maintain functional capacity and quality of life. In the absence of sufficient organs for transplantation, options include left ventricular assist devices and inotropic support. Areas covered: We examined data published in the last two decades on the use of inotropes and inodilators in advanced heart failure. Expert commentary: In the literature, use of conventional inotropes, including adrenergic agonists and phosphodiesterase inhibitors, appears to be suboptimal for achieving the clinical priorities of late-stage heart failure. Evidence suggests instead that the calcium-sensitizing inodilator levosimendan, administered intermittently, delivers improvements in functional capacity and quality of life and does so with no adverse impact on life expectancy. At a terminal or near-terminal stage of heart failure, the therapeutic philosophy should shift towards meeting patients' existential priorities rather than traditional heart failure-centric targets.

Summary The wearable cardioverter defibrillator (WCD) is a temporary treatment option for patients with potentially reversible risk of sudden cardiac death. This case demonstrates a pitfall during WCD usage in a pacemaker-dependent patient as well as a possible solution allowing continuation of WCD therapy. Bipolar stimulation may lead to double counting of the WCD detection algorithm resulting in false alarm or inappropriate therapy.

A healthy woman with acute onset of pulmonary oedema and severely depressed left ventricular function underwent endomyocardial biopsy under the clinical suspicion of fulminant myocarditis. While awaiting the results of biopsy, the situation deteriorated to Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) and extracorporeal membrane oxygenation was implanted. Finally, immunohistochemistry in biopsy specimen corresponded to fulminant lymphocytic myocarditis, although active myocarditis was excluded. Furthermore, gene expression profiling identified giant cell myocarditis although multinuclear cells were absent. This prompted the start of immunosuppression with cortisone and cyclosporine. The patient fully recovered.

Dual antiplatelet therapy is the standard of care for patients with myocardial infarction (MI), who have been resuscitated and treated with therapeutic hypothermia (TH). We compare the antiplatelet effect and bleeding risk of intravenous cangrelor to oral P2Y12-inhibitors in patients with MI receiving TH in a prospective comparison of two matched patient cohorts. Twenty-five patients within the CANGRELOR cohort were compared to 17 patients receiving oral P2Y12-inhibitors. CANGRELOR group (NCT03445546) and the ORAL P2Y12 Group (NCT02914795) were registered at clinicaltrials.gov. Platelet function testing was performed using light-transmittance aggregometry and monitored for 4 days. P2Y12-inhibition was stronger in CANGRELOR compared to ORAL P2Y12 (adenosine diphosphate (ADP) (area under the curve (AUC)) 26.0 (5.9&ndash, 71.6) vs. 160.9 (47.1&ndash, 193.7)) at day 1. This difference decreased over the following days as more patients were switched from CANGRELOR to oral P2Y12-inhibitor treatment. There was no difference in the effect of aspirin between the two groups. We did not observe significant differences with respect to thrombolysis in myocardial infarction (TIMI) or Bleeding Academic Research Consortium (BARC) classified bleedings, number of blood transfusions or drop in haemoglobin B (Hb) or hematocrit (Hct) over time. Cangrelor treatment is not only feasible and effective in resuscitated patients, but also inhibited platelet function more effectively than orally administered P2Y12-inhibitors without an increased event rate for bleeding.

Background: This study investigated the efficacy, safety, and usability of standardized glycemic management by a computerized decision support system for non-critically ill hospitalized patients with type 2 diabetes on four different wards. Materials and Methods: In this open, noncontrolled intervention study, glycemic management of 99 patients with type 2 diabetes (62% acute admissions; 41 females; age, 67±11 years; hemoglobin A1c, 65±21 mmol/mol; body mass index, 30.4±6.5 kg/m2) on clinical wards (Cardiology, Endocrinology, Nephrology, Plastic Surgery) of a tertiary-care hospital was guided by GlucoTab® (Joanneum Research GmbH [Graz, Austria] and Medical University of Graz [Graz, Austria]), a mobile decision support system providing automated workflow support and suggestions for insulin dosing to nurses and physicians. Results: Adherence to insulin dosing suggestions was high (96.5% bolus, 96.7% basal). The primary outcome measure, percentage of blood glucose (BG) measurements in the range of 70–140 mg/dL, occurred in 50.2±22.2% of all measurements. The overall mean BG level was 154±35 mg/dL. BG measurements in the ranges of 60–70 mg/dL, 40–60 mg/dL, and

Aims To evaluate the influence of endomyocardial biopsy (EMB)-proven intramyocardial inflammation on mortality in patients with cardiac transthyretin amyloid (ATTR) or amyloid light-chain (AL) amyloidosis. Methods and results We included 54 consecutive patients (mean age 68.83 ± 9.59 years; 45 men) with EMB-proven cardiac amyloidosis. We followed up patients from first diagnostic biopsy to as long as 36 months (mean 11.5 ± 12 months) and compared their outcome with information on all-cause mortality with or without proof of inflammation on EMB. Intramyocardial inflammation was assessed by quantitative immunohistology. Patients suffering from amyloidosis revealed a significant poor prognosis with proof of intramyocardial inflammation in contrast to those without inflammation (log-rank P = 0.019). Re-grouping of patients indicated AL amyloidosis to have a significant impact on all-cause mortality (log-rank P = 0.012). The detailed subgroup analysis showed that patients suffering from AL amyloidosis with intramyocardial inflammation have a significantly worse prognosis compared with AL amyloidosis without inflammation and ATTR with or without inflammation, respectively (log-rank P = 0.014, contingency Fisher's exact test, P = 0.008). Conclusion Our study reports for the first time a high incidence (48.1%) of intramyocardial inflammation in a series of patients with EMB-proven cardiac amyloidosis and could show that in patients with AL amyloidosis, intramyocardial inflammation correlated significantly with increased mortality. Our data have a direct clinical impact because one can hypothesize that additional immunomodulating/anti-inflammatory treatment regimens in patients with biopsy-proven inflammation of heart muscle tissue could be beneficial for patients suffering from cardiac AL amyloidosis.

Heart failure is a common cardiac disease in elderly patients. After discharge, approximately 50% of all patients are readmitted to a hospital within six months. Recent studies show that home monitoring of heart failure patients can reduce the number of readmissions. Still, a large number of false positive alarms as well as underdiagnoses in other cases require more accurate alarm generation algorithms. New low-cost sensors for leg edema detection could be the missing link to help home monitoring to its breakthrough. We evaluated a 3D camera-based measurement setup in order to geometrically detect and quantify leg edemas. 3D images of legs were taken and geometric parameters were extracted semi-automatically from the images. Intra-subject variability for five healthy subjects was evaluated. Thereafter, correlation of 3D parameters with body weight and leg circumference was assessed during a clinical study at the Medical University of Graz. Strong correlation was found in between both reference values and instep height, while correlation in between curvature of the lower leg and references was very low. We conclude that 3D imaging might be a useful and cost-effective extension of home monitoring for heart failure patients, though further (prospective) studies are needed.

[Abstract] AIMS: The European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT-R) was set up with the aim of describing the clinical epidemiology and the 1-year outcomes of patients with heart failure (HF) with the added intention of comparing differences between participating countries. METHODS AND RESULTS: The ESC-HF-LT-R is a prospective, observational registry contributed to by 211 cardiology centres in 21 European and/or Mediterranean countries, all being member countries of the ESC. Between May 2011 and April 2013 it collected data on 12 440 patients, 40.5% of them hospitalized with acute HF (AHF) and 59.5% outpatients with chronic HF (CHF). The all-cause 1-year mortality rate was 23.6% for AHF and 6.4% for CHF. The combined endpoint of mortality or HF hospitalization within 1 year had a rate of 36% for AHF and 14.5% for CHF. All-cause mortality rates in the different regions ranged from 21.6% to 36.5% in patients with AHF, and from 6.9% to 15.6% in those with CHF. These differences in mortality between regions are thought reflect differences in the characteristics and/or management of these patients. CONCLUSION: The ESC-HF-LT-R shows that 1-year all-cause mortality of patients with AHF is still high while the mortality of CHF is lower. This registry provides the opportunity to evaluate the management and outcomes of patients with HF and identify areas for improvement.

SummaryObjective: Telemonitoring of vital signs is an established option in treatment of patients with chronic heart failure (CHF). In order to allow for early detection of atrial fibrillation (AF) which is highly prevalent in the CHF population telemonitoring programs should include electrocardiogram (ECG) signals. It was therefore the aim to extend our current home monitoring system based on mobile phones and Near Field Communication technology (NFC) to enable patients acquiring their ECG signals autonomously in an easy-to-use way.Methods: We prototypically developed a sensing device for the concurrent acquisition of blood pressure and ECG signals. The design of the device equipped with NFC technology and Bluetooth allowed for intuitive interaction with a mobile phone based patient terminal. This ECG monitoring system was evaluated in the course of a clinical pilot trial to assess the system’s technical feasibility, usability and patient’s adherence to twice daily usage.Results: 21 patients (4f, 54 ± 14 years) suffering from CHF were included in the study and were asked to transmit two ECG recordings per day via the telemonitoring system autonomously over a monitoring period of seven days. One patient dropped out from the study. 211 data sets were transmitted over a cumulative monitoring period of 140 days (overall adherence rate 82.2%). 55% and 8% of the transmitted ECG signals were sufficient for ventricular and atrial rhythm assessment, respectively.Conclusion: Although ECG signal quality has to be improved for better AF detection the developed communication design of joining Bluetooth and NFC technology in our telemonitoring system allows for ambulatory ECG acquisition with high adherence rates and system usability in heart failure patients.

Objectives This study was designed to investigate whether selected baseline variables and early response markers predict the effects of cardiac resynchronization therapy (CRT) on long-term mortality. Background Cardiac resynchronization therapy reduces long-term morbidity and mortality in patients with moderate or severe heart failure and markers of cardiac dyssynchrony, but not all patients respond to a similar extent. Methods In the CARE-HF (Cardiac Resynchronization in Heart Failure) study, 813 patients with heart failure and markers of cardiac dyssynchrony were randomly assigned to receive or not receive CRT in addition to pharmacological treatment and were followed for a median of 37.6 months. A model including assigned treatment, 15 pre-specified baseline variables, and 8 markers of response at 3 months was constructed to predict all-cause mortality. Results On multivariable analysis, plasma concentration of amino terminal pro–brain natriuretic peptide (univariate and multivariable model chi-square test: 105.0 and 48.4; both p Conclusions Patients who have more severe mitral regurgitation or persistently elevated amino terminal pro–brain natriuretic peptide despite treatment for heart failure, including CRT, have a higher mortality. However, patients assigned to CRT had a lower mortality even after adjusting for variables measured before and 3 months after intervention. The effect of CRT on mortality cannot be usefully predicted using such information. (CARE-HF CArdiac Resynchronization in Heart Failure; NCT00170300 )

Aims The Cardiac Resynchronization-Heart Failure (CARE-HF) study demonstrated that cardiac resynchronization therapy (CRT) could reduce morbidity and mortality and improve cardiac function in patients with moderate or severe heart failure secondary to left ventricular systolic dysfunction and markers of cardiac dyssynchrony. The purpose of this analysis was to investigate the effect of CRT on plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-pro-BNP), a powerful marker of cardiac dysfunction and prognosis. Methods and results Blood samples were collected routinely at baseline and 3 and 18 months. Plasma was separated by cool centrifugation and stored at −70°C until transported to a central laboratory for analysis of NT-pro-BNP using a standard commercial assay. Cardiac function was assessed echocardiographically. At baseline, median plasma concentration of NT-pro-BNP was similar in patients assigned to CRT or medical therapy [1920 pg/mL (inter-quartile range (IQR) 744–4288) and 1809 pg/mL (IQR 719–3949), respectively]. The differences in medians between the CRT and medical therapy groups were highly significant at both 3 months (537 pg/mL; P < 0.0001) and 18 months of follow-up (567 pg/mL; P < 0.0001). These differences could not be accounted for by changes in pharmacological therapy or renal function but were associated with improvement in ventricular volumes and function. Conclusion CRT exerts an early and sustained reduction in NT-pro-BNP. This appears to reflect improvements in ventricular function. NT-pro-BNP may be a simple method for monitoring the effects of CRT.

Background: Metoprolol is a beta1-selective beta-adrenergic antagonist while carvedilol is a non-selective beta-blocker with additional blockades of alpha1-adrenoceptors. Administration of metoprolol has been shown to cause up-regulation of beta-adrenoceptor density and to decrease nocturnal melatonin release, whereas carvedilol lacks these typical effects of beta-blocking drugs. Aims: To compare beta-blocking effects of metoprolol and carvedilol when applied orally in healthy subjects. Methods: We investigated the effects of single oral doses of clinically recommended amounts of metoprolol (50, 100 and 200 mg) and carvedilol (25, 50 and 100 mg) to those of a placebo in a randomised, double-blind, cross-over study in 12 healthy male volunteers. Two hours after oral administration of the drugs heart rate and blood pressure were measured at rest, after 10 min of exercise, and after 15 min of recovery. Results: Metoprolol tended to decrease heart rate during exercise (−21%, −25% and −24%) to a greater extent than carvedilol (−16%, −16% and −18%). At rest, increasing doses of metoprolol caused decreasing heart rates (62, 60 and 58 beats/min) whereas increasing doses of carvedilol caused increasing heart rates (62, 66 and 69 beats/min), 50 and 100 mg carvedilol failed to differ significantly from the placebo (71 beats/min). Conclusions: We conclude that clinically recommended doses of carvedilol cause a clinically relevant beta-blockade in humans predominantly during exercise where it appears to be slightly (although not significantly) less effective than metoprolol. On the other hand, the effects of carvedilol on heart rate at rest appear rather weak, particularly in subjects with a low sympathetic tone. This might be caused by a reflex increase on sympathetic drive secondary to peripheral vasodilation resulting from the alpha-blocking effects of the drug. These results might be helpful in explaining why carvedilol, in contrast to metoprolol, may fail to cause up-regulation of beta-adrenoceptor density and does not decrease nocturnal melatonin release. This, in turn, may be a reason for the weak side-effects of carvedilol resulting from the beta-blockade. In addition, our data might be of interest in the interpretation of the forthcoming results of the COMET trial, although it has to be emphasised that they were derived from healthy subjects and, therefore, cannot be directly extrapolated to patients with heart failure.

Purpose The aim of this study was to evaluate differences in the left atrial (LAD), total ventricular end-diastolic (TEDD), end-systolic diameters (TESD), and left ventricular shortening fraction (SF) compared with heart rate (HR) and systolic blood pressure (SBP) during exercise and recovery. Methods Healthy young male (N = 15) and female (N = 16) subjects performed an incremental cycle ergometer test in upright position, and three phases of energy supply were defined by means of blood lactate concentration (LA) and respiratory gas exchange variables (I: aerobic; II: aerobic-anaerobic transition; III: anaerobic). Subjects were required to rest their arms on a steering bar and to lean their upper body forward; two dimensional (2-D) echocardiograms were obtained over the left parasternal area at rest (R), at the end of each phase, immediately within 15 s post, and 6 min after exercise (6 min). By using VINGMED’s “Anatomical M-Mode,” it was possible to extract M-Mode Sweeps from stored 2-D-Loops and perform the M-Mode measurement. Results In contrast to the significant decrease in TEDD and TESD from III to 15 s up to resting values and the significant increase in SF from III to 15s, the moderate decrease in HR immediately post exercise (15 s) was not significant. The SBP showed a significantly decrease from III to 15s; in contrast to TEDD, TESD, and SF, the values at 15 s were comparable with the values at II. For LAD, significant increase during exercise and a decrease during recovery were observed. Sex-specific differences of changes in measured variables could not be found. Conclusion We concluded that post exercise measurement of left ventricular and atrial dimensions or SF were not valid to describe heart function at maximal exercise although immediately post exercise HR was near maximal level.

The aim of our study was to determine neopterin levels in patients with chronic and acute coronary syndromes.In chronic and acute coronary syndromes the release of different cytokines activates cellular defense. Infiltration of neutrophils and monocytes/macrophages is detected in the vessel wall as well as in the myocardium. Neopterin, which is a by-product of the guanosine triphosphate-biopterin pathway, is a marker for those activated macrophages.We studied 123 subjects: 1) 21 consecutive patients (17 men, 4 women; mean age +/- SD 66 +/- 15 years, range 31 to 87) with acute myocardial infarction (AMI); 2) 62 consecutive patients (50 men, 12 women; mean age 61 +/- 8 years, range 43 to 81) with signs and symptoms of clinically stable coronary artery disease (CAD); and 3) 40 healthy blood donors (28 men, 12 women; mean age 35 +/- 13 years). Neopterin levels were determined with a commercially available enzyme-linked immunosorbent assay method.In patients with AMI before thrombolytic therapy, neopterin levels were significantly higher than levels in patients with CAD and control subjects (13.7 vs. 8.6 and vs. 6.8 nmol/liter, p0.0001). Values also differed significantly between patients with CAD and control subjects (p0.0001). Neopterin levels in patients with AMI were measured seven times during a 72-h period. Within-group comparison showed significant differences over this period (p0.00001). The lowest value (11.4 nmol/liter) was observed after 4 h and differed significantly from the initial value and values after 24 and 72 h (p0.05). After 72 h, neopterin increased to 14.9 nmol/liter, a value significantly different from all values other than the initial one. There was no correlation between neopterin and creatine kinase (CK); CK, MB isoenzyme; or lactate dehydrogenase as markers for the extent of the myocardial infarction during the observation period.Our data support the hypothesis of an activation of monocytes and macrophages in patients with an acute or chronic coronary syndrome. Neopterin as a marker for macrophage activation is significantly increased in patients with chronic CAD and more pronounced in patients with AMI shortly after the onset of symptoms.

BackgroundTelemonitoring of patients with chronic heart failure (CHF) is an emerging concept to detect early warning signs of impending acute decompensation in order to prevent hospitalization. ObjectiveThe goal of the MOBIle TELemonitoring in Heart Failure Patients Study (MOBITEL) was to evaluate the impact of home-based telemonitoring using Internet and mobile phone technology on the outcome of heart failure patients after an episode of acute decompensation. MethodsPatients were randomly allocated to pharmacological treatment (control group) or to pharmacological treatment with telemedical surveillance for 6 months (tele group). Patients randomized into the tele group were equipped with mobile phone–based patient terminals for data acquisition and data transmission to the monitoring center. Study physicians had continuous access to the data via a secure Web portal. If transmitted values went outside individually adjustable borders, study physicians were sent an email alert. Primary endpoint was hospitalization for worsening CHF or death from cardiovascular cause. ResultsThe study was stopped after randomization of 120 patients (85 male, 35 female); median age was 66 years (IQR 62-72). The control group comprised 54 patients (39 male, 15 female) with a median age of 67 years (IQR 61-72), and the tele group included 54 patients (40 male, 14 female) with a median age of 65 years (IQR 62-72). There was no significant difference between groups with regard to baseline characteristics. Twelve tele group patients were unable to begin data transmission due to the inability of these patients to properly operate the mobile phone (“never beginners”). Four patients did not finish the study due to personal reasons. Intention-to-treat analysis at study end indicated that 18 control group patients (33%) reached the primary endpoint (1 death, 17 hospitalizations), compared with 11 tele group patients (17%, 0 deaths, 11 hospitalizations; relative risk reduction 50%, 95% CI 3-74%, P = .06). Per-protocol analysis revealed that 15% of tele group patients (0 deaths, 8 hospitalizations) reached the primary endpoint (relative risk reduction 54%, 95% CI 7-79%, P= .04). NYHA class improved by one class in tele group patients only (P< .001). Tele group patients who were hospitalized for worsening heart failure during the study had a significantly shorter length of stay (median 6.5 days, IQR 5.5-8.3) compared with control group patients (median 10.0 days, IQR 7.0-13.0; P= .04). The event rate of never beginners was not higher than the event rate of control group patients. ConclusionsTelemonitoring using mobile phones as patient terminals has the potential to reduce frequency and duration of heart failure hospitalizations. Providing elderly patients with an adequate user interface for daily data acquisition remains a challenging component of such a concept.

Aims The Cardiac Resynchronization in Heart Failure (CARE-HF) study showed that cardiac resynchronization therapy (CRT) reduces mortality in HF patients with markers of dyssynchrony. Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) might predict which patients benefit most from CRT. We evaluated whether the prognostic value of NT-proBNP was influenced by CRT and the effects of CRT stratified according to NT-proBNP. Methods and results A total of 813 patients were enrolled in CARE-HF. Baseline log-transformed NT-proBNP independently predicted all-cause mortality, sudden death, and death from pump failure. In a multivariable model including log-transformed NT-proBNP, assignment to CRT remained independently associated with better prognosis without evidence of interaction. Stratifying patients according to the median NT-proBNP and to CRT treatment allocation, all-cause mortality was 12% if

This study was designed to investigate whether selected baseline variables and early response markers predict the effects of cardiac resynchronization therapy (CRT) on long-term mortality.Cardiac resynchronization therapy reduces long-term morbidity and mortality in patients with moderate or severe heart failure and markers of cardiac dyssynchrony, but not all patients respond to a similar extent.In the CARE-HF (Cardiac Resynchronization in Heart Failure) study, 813 patients with heart failure and markers of cardiac dyssynchrony were randomly assigned to receive or not receive CRT in addition to pharmacological treatment and were followed for a median of 37.6 months. A model including assigned treatment, 15 pre-specified baseline variables, and 8 markers of response at 3 months was constructed to predict all-cause mortality.On multivariable analysis, plasma concentration of amino terminal pro-brain natriuretic peptide (univariate and multivariable model chi-square test: 105.0 and 48.4; both p0.0001) and severity of mitral regurgitation (chi-square test: 44.0 and 17.9; both p0.0001) at 3 months, regardless of assigned treatment, were the strongest predictors of mortality. Ischemic heart disease as the cause of ventricular dysfunction (chi-square test: 34.9 and 7.4; p0.0001 and p = 0.0066), being in New York Heart Association functional class IV (chi-square test: 18.8 and 9.6; p0.0001 and p = 0.0020), or having less interventricular mechanical delay (chi-square test: 29.8 and 8.8; p0.0001 and p = 0.0029) at baseline all predicted a worse outcome. However, the reduction in mortality in patients assigned to CRT was similar before (hazard ratio: 0.602; 95% confidence interval: 0.468 to 0.774) and after (hazard ratio: 0.679; 95% confidence interval: 0.494 to 0.914) adjustment for variables measured at baseline and at 3 months.Patients who have more severe mitral regurgitation or persistently elevated amino terminal pro-brain natriuretic peptide despite treatment for heart failure, including CRT, have a higher mortality. However, patients assigned to CRT had a lower mortality even after adjusting for variables measured before and 3 months after intervention. The effect of CRT on mortality cannot be usefully predicted using such information. (CARE-HF CArdiac Resynchronization in Heart Failure; NCT00170300).

Background: Treatment of chronic heart failure is based on the results of large clinical trials, which form the basis of treatment guidelines, such as those from the European Society of Cardiology (ESC). The aim of this study was to record treatment-modalities and the implementation of guidelines of chronic heart failure in clinical practice in Austria. Methods: Overall 96 general physicians, specialists for internal medicine in private practice or in hospital outpatient departments participated in the survey. Physicians were asked to prospectively document 30 consecutive patients with chronic heart failure. Results: 1880 patients were documented. The majority of patients were treated by general physicians (57%). Coronary artery disease was the most frequent aetiology for heart failure (47%). The most frequently used drugs were blockers of the renin–angiotensin-system (RAS-blocker including ACE-inhibitors and angiotensin-receptor-blockers, 78%), diuretics (76%) and beta-blockers (49%). Other drugs like digitalis and spironolactone were used infrequently. Average doses of ACE-inhibitors were approximately 90% of those recommended by the ESC, average doses of beta-blockers were approximately 50% of those recommended. Treatment among the three classes of physicians differed with respect to RAS-blockers and beta-blockers, which were used infrequently by general practitioners. Both groups of drugs were given more frequently to younger patients (

This editorial refers to ‘Effects of selective heart rate reduction with ivabradine on left ventricular remodelling and function: results from the SHIFT echocardiographic substudy’ by J.C. Tardif et al. , doi:10.1093/eurheartj/ehr311 Tardif and co-workers have published the echocardiographic substudy of the SHIFT trial.1 This pre-defined substudy included 611 out of 6505 patients from SHIFT, or, in other words, 9.3% of the entire cohort studied in SHIFT.2 The authors report that of these 611 patients, 96 ivabradine- and 104 placebo-treated patients had to be excluded, mainly due to incomplete or unreadable echo recordings, which left 208 patients in the ivabradine group and 203 in the placebo group for analysis. The echoes were analysed centrally and the investigations were done at baseline and after 8 months, with the primary endpoint of change of left ventricular systolic volume index (LVESVI) at 8 months. This well-treated population [92% were on beta-blockers, with 56% taking 50% of the recommended dose, and 94% were treated with a renin–angiotensin system (RAS) antagonist] was not different from the entire SHIFT cohort, except for a lower rate of hypertension and a …

OBJECTIVE—To investigate the diastolic Doppler filling pattern in patients with idiopathic dilated cardiomyopathy and its relation to N-terminal pro-atrial natriuretic peptide (NT-pro-ANP). METHODS—32 patients (26 male, six female) with idiopathic dilated cardiomyopathy were investigated. All were in sinus rhythm. Conventional M mode echocardiography and Doppler echocardiography was done in each patient. Pulsed wave Doppler inflow signals were obtained and the following variables were measured: maximum E wave, maximum A wave, E/A ratio, E wave deceleration time, A wave deceleration time. NT-pro-ANP was measured using radioimmunoassay. RESULTS—Mean (SD) left ventricular ejection fraction was 34 (7)% and mean left ventricular end diastolic diameter on M mode echocardiography was 69 (7) mm. Left ventricular filling indices were as follows: maximum E wave velocity, 0.86 (0.22) m/s; maximum A wave velocity, 0.71 (0.24) m/s; E/A ratio, 1.41 (0.65). Mean E wave deceleration time was 140 (50) ms; mean A wave deceleration time was 100 (20) ms. In a stepwise forward regression model, NT-pro-ANP correlated significantly with left atrial diameter (r = 0.603; p

This Figure⇓ shows a case of a rare syndrome, Loffler’s endocarditis, in vivo by echocardiography in an apical four-chamber view with biventricular apical thrombi. The patient, a 50-year-old white man, revealed …