Eva Korup

Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure

BACKGROUND The benefit of an implantable cardioverter-defibrillator (ICD) in patients with symptomatic systolic heart failure caused by coronary artery disease has been well documented. However, the evidence for a benefit of prophylactic ICDs in patients with systolic heart failure that is not due to coronary artery disease has been based primarily on subgroup analyses. The management of heart failure has improved since the landmark ICD trials, and many patients now receive cardiac resynchronization therapy (CRT). METHODS In a randomized, controlled trial, 556 patients with symptomatic systolic heart failure (left ventricular ejection fraction, ≤35%) not caused by coronary artery disease were assigned to receive an ICD, and 560 patients were assigned to receive usual clinical care (control group). In both groups, 58% of the patients received CRT. The primary outcome of the trial was death from any cause. The secondary outcomes were sudden cardiac death and cardiovascular death. RESULTS After a median follow-up period of 67.6 months, the primary outcome had occurred in 120 patients (21.6%) in the ICD group and in 131 patients (23.4%) in the control group (hazard ratio, 0.87; 95% confidence interval [CI], 0.68 to 1.12; P=0.28). Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31 to 0.82; P=0.005). Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group (P=0.29). CONCLUSIONS In this trial, prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary artery disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care. (Funded by Medtronic and others; DANISH ClinicalTrials.gov number, NCT00542945 .).

Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography

AIMS Staphylococcus aureus infective endocarditis (IE) is a critical medical condition associated with a high morbidity and mortality. In the present study, we prospectively evaluated the importance of screening with echocardiography in an unselected S. aureus bacteraemia (SAB) population. METHODS AND RESULTS From 1 January 2009 to 31 August 2010, a total of 244 patients with SAB at six Danish hospitals underwent screening echocardiography. The inclusion rate was 73% of all eligible patients (n= 336), and 53 of the 244 included patients (22%; 95% CI: 17-27%) were diagnosed with definite IE. In patients with native heart valves the prevalence was 19% (95% CI: 14-25%) compared with 38% (95% CI: 20-55%) in patients with prosthetic heart valves and/or cardiac rhythm management devices (P= 0.02). No difference was found between Main Regional Hospitals and Tertiary Cardiac Hospitals, 20 vs. 23%, respectively (NS). The prevalence of IE in high-risk patients with one or more predisposing condition or clinical evidence of IE were significantly higher compared with low-risk patients with no additional risk factors (38 vs. 5%; P < 0.001). IE was associated with a higher 6 months mortality, 14(26%) vs. 28(15%) in SAB patients without IE, respectively (P < 0.05). CONCLUSION SAB patients carry a high risk for development of IE, which is associated with a worse prognosis compared with uncomplicated SAB. The presenting symptoms and clinical findings associated with IE are often non-specific and echocardiography should always be considered as part of the initial evaluation of SAB patients.

Strain rate and tissue tracking imaging in quantitation of left ventricular systolic function in endurance and strength athletes

Aim: The aim of this study was to assess the impact of long‐term physical training on left ventricular longitudinal contraction by strain rate analysis and tissue tracking imaging.

Age and Outcomes of Primary Prevention Implantable Cardioverter-Defibrillators in Patients With Nonischemic Systolic Heart Failure

Background: The DANISH study (Danish Study to Assess the Efficacy of ICDs [Implantable Cardioverter Defibrillators] in Patients With Non-Ischemic Systolic Heart Failure on Mortality) did not demonstrate an overall effect on all-cause mortality with ICD implantation. However, the prespecified subgroup analysis suggested a possible age-dependent association between ICD implantation and mortality with survival benefit seen only in the youngest patients. The nature of this relationship between age and outcome of a primary prevention ICD in patients with nonischemic systolic heart failure warrants further investigation. Methods: All 1116 patients from the DANISH study were included in this prespecified subgroup analysis. We assessed the relationship between ICD implantation and mortality by age, and an optimal age cutoff was estimated nonparametrically with selection impact curves. Modes of death were divided into sudden cardiac death and nonsudden death and compared between patients younger and older than this age cutoff with the use of &khgr;2 analysis. Results: Median age of the study population was 63 years (range, 21–84 years). There was a linearly decreasing relationship between ICD and mortality with age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.003–1.06; P=0.03). An optimal age cutoff for ICD implantation was present at ⩽70 years. There was an association between reduced all-cause mortality and ICD in patients ⩽70 years of age (HR, 0.70; 95% CI, 0.51–0.96; P=0.03) but not in patients >70 years of age (HR, 1.05; 95% CI, 0.68–1.62; P=0.84). For patients ⩽70 years old, the sudden cardiac death rate was 1.8 (95% CI, 1.3–2.5) and nonsudden death rate was 2.7 (95% CI, 2.1–3.5) events per 100 patient-years, whereas for patients >70 years old, the sudden cardiac death rate was 1.6 (95% CI, 0.8–3.2) and nonsudden death rate was 5.4 (95% CI, 3.7–7.8) events per 100 patient-years. This difference in modes of death between the 2 age groups was statistically significant (P=0.01). Conclusions: In patients with systolic heart failure not caused by ischemic heart disease, the association between the ICD and survival decreased linearly with increasing age. In this study population, an age cutoff for ICD implantation at ⩽70 years yielded the highest survival for the population as a whole. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00542945.

Infections associated with permanent pacemakers and implanted cardioverter-defibrillator devices. A 10-year regional study in Denmark.

Abstract Endocarditis and localized pocket infections are recognized as serious adverse events in patients with implanted cardiac impulse generators. We have undertaken a 10-y retrospective study in North Denmark Region (population 0.5 million) in order to elucidate the clinical spectrum, causative microorganisms, management and outcome. Infections associated with permanent pacemakers (PPM) and implanted cardioverter-defibrillator (ICD) devices were identified by searching hospital databases. Ninety-one incident cases were recorded in 1999 through 2008: 26 patients had endocarditis, 39 patients had a localized pocket infection, and 9 patients developed surgical sepsis with or without local signs immediately after implantation or reoperation; the device was the likely but unconfirmed focus of infection in 17 patients with bacteraemia. Staphylococcus aureus, coagulase-negative staphylococci and other Gram-positive bacteria were the predominant causative agents; only 6 cases were culture-negative. Management included device and lead extraction and individualized antibiotic therapy. The all-cause 30-day case-fatality was 11%. Only 3 recurrences were recorded during 2 y of follow-up. In conclusion, infections associated with permanent impulse generators have a broader clinical spectrum than often reported in the literature. Most cases are culture-positive with staphylococcal predominance. The short-term mortality is notably high, but the risk of recurrence is low.

Partial oral treatment of endocarditis.

BACKGROUND Guidelines for the treatment of left-sided infective endocarditis (IE) recommend 4 to 6 weeks of intravenous antibiotics. Conversion from intravenous to oral antibiotics in clinically stabilized patients could reduce the side effects associated with intravenous treatment and shorten the length of hospital stay. Evidence supporting partial oral therapy as an alternative to the routinely recommended continued parenteral therapy is scarce, although observational data suggest that this strategy may be safe and effective. STUDY DESIGN This is a noninferiority, multicenter, prospective, randomized, open-label study of partial oral treatment with antibiotics compared with full parenteral treatment in left-sided IE. Stable patients (n = 400) with streptococci, staphylococci, or enterococci infecting the mitral valve or the aortic valve will be included. After a minimum of 10 days of parenteral treatment, stable patients are randomized to oral therapy or unchanged parenteral therapy. Recommendations for oral treatment have been developed based on minimum inhibitory concentrations and pharmacokinetic calculations. Patients will be followed up for 6 months after completion of antibiotic therapy. The primary end point is a composition of all-cause mortality, unplanned cardiac surgery, embolic events, and relapse of positive blood cultures with the primary pathogen. CONCLUSION The Partial Oral Treatment of Endocarditis study tests the hypothesis that partial oral antibiotic treatment is as efficient and safe as parenteral therapy in left-sided IE. The trial is justified by a review of the literature, by pharmacokinetic calculations, and by our own experience.

Rationale, design, and baseline characteristics of the DANish randomized, controlled, multicenter study to assess the efficacy of Implantable cardioverter defibrillators in patients with non-ischemic Systolic Heart failure on mortality (DANISH)

BACKGROUND The effect of an implantable cardioverter defibrillator (ICD) in patients with symptomatic systolic heart failure (HF) caused by coronary artery disease is well documented. However, the effect of primary prophylactic ICDs in patients with systolic HF not due to coronary artery disease is much weaker. In addition, HF management has improved, since the landmark ICD trials and a large proportion of patients now receive cardiac resynchronization therapy (CRT) where the effect of ICD treatment is unknown. METHODS In the DANISH study, 1,116 patients with symptomatic systolic HF not caused by coronary artery disease have been randomized to receive an ICD or not, in addition to contemporary standard therapy. The primary outcome of the trial is time to all-cause death. Follow-up will continue until June 2016 with a median follow-up period of 5 years. Baseline characteristics show that enrolled patients are treated according to current guidelines. At baseline, 97% of patients received an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 92% received a β-blocker, 58% a mineralocorticoid receptor antagonist, and 58% were scheduled to receive CRT. Median age was 63 years (range, 21-84 years) at baseline, and 28% were women. CONCLUSION DANISH will provide pertinent information about the effect on all-cause mortality of a primary prophylactic ICD in patients with symptomatic systolic HF not caused by coronary artery disease on contemporary standard therapy including CRT.

Recurrent prosthetic valve endocarditis caused by Aspergillus delacroxii (formerly Aspergillus nidulans var. echinulatus)

We report Aspergillus delacroxii (formerly Aspergillus nidulans var. echinulatus) causing recurrent prosthetic valve endocarditis. The fungus was the sole agent detected during replacement of a mechanical aortic valve conduit due to abscess formation. Despite extensive surgery and anti-fungal treatment, the patient had a cerebral hemorrhage 4 months post-surgery prompting a diagnosis of recurrent prosthetic valve endocarditis and fungemia.

Age and effect of implantable cardioverter-defibrillator (ICD) in patients with non-ischemic systolic heart failure

Doxorubicin induced cardiotoxicity is a well-recognized complication of chemotherapy, and its prevention remains an important challenge in cancer survivorship. An angiogenic hormone prokineticin via its receptor PKR1 promotes angiogenesis, differentiation of cardiac stem cells, and survival of the cardiomyocytes. PKR1 has been recently shown to protect heart against myocardial infarction in mice model. Thus, we hypothesized that PKR1 agonist can be a promising target to prevent doxorubicin-mediated cardiotoxicity. Methods and Results: In vitro, we showed that IS20 attenuates apoptosis induced by DOX treatment in H9c2 cardiomyocytes and human epicardial derived progenitor cells. However, IS20 does not interfere DOX-mediated cytotoxicity in cancer cell line. In vivo, IS20 administration in juvenile mice model promotes survival, proliferation and differentiation of WT1+EPDCs into vasculogenic cells. Similarly, IS20 on chronic mice model preserves vascular structure, reduces apoptosis and inflammation. IS20 also improves systolic and diastolic parameters that impaired by DOX. Conclusions: Multi effects of IS20 on the activation of cardiac progenitor cells, cardiac cells survival, vascular stability and cardiac parameters show a strong cardioprotective potential of PKR1 agonist that can be used in cancer patients during anthracyclines chemotherapy. P2008 Growth differentiation factor 15 as a predictor of acute kidney injury formation IR Vishnevskaya1; HF Barahmeh2 1Government institution “L.T. Malaya Therapy National institute of the National academy of medical sci”, Kharkiv, Ukraine; 2V.N. Karazin Kharkiv National University, Kharkiv, Ukraine The development of acute kidney injury (AKI) in patient with acute coronary syndrome (ACS), especially in those who underwent angiography, is an actual problem, because it worsens the prognosis. In order to diagnose this condition in time the search for biomarkers is going. Stress-induced marker growth differentiation factor 15 (GDF 15), a member of the transforming growth factor-β cytokine superfamily is being actively studied. Purpose: to determine the prognostic significance of GDF 15 and other markers in development of AKI in patients with ACS. Methods: 73 patients were enrolled with different forms of ACS (55 male and 18 female), mean age was 61, 8± 1, 3 years. All patients underwent a baseline investigation which includes: standard electrocardiography, echocardiography, angiography and determination of marker of myocardial necrosis – cardiac troponin T. Based on the results of the examination glomerular filtration rate (GFR) was calculated by Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI). A group of patients has been selected (n=54), their creatinine level was determined during the first 24 hours and after 48 hours. All patients were divided into two groups according to acute kidney injury network classification (AKIN): 21 patient in the first group with negative dynamic (1st stage AKIN and higher), 33 patient in the second group without creatinine dynamic. In addition, the level of GDF 15 was determined during the first day of hospitalization (normal range of GDF 15< 1200 pg / ml). Results: By comparing selected groups significant difference was found in creatinine level and GFR in both groups (p< 0.001; p< 0.01, respectively). The effects of various variables were assessed on formation of AKI in patients with different level of GFR. To identify the main risk factors for AKI, we have used logistic regression (LR): ejection fraction of left ventricle (area under curve (AUC) 0.7; p< 0.01; 95% confidence interval (CI): 0.560 – 0,842), GDF 15 (AUC 0.77; p< 0.03; 95% CI: 0.53 – 0.92) and age (AUC 0.77; p< 0.01) were main risk factors for predicting development of AKI. During the statistical analysis the predictive value for estimated parameters was calculated: GDF 15 > 2200 pg/ml (specificity (Spe) 87%, sensitivity (Se) 65%), ejection fraction of left ventricle >46% (Spe 80 %, Se 71 %), age >55 year (Spe 39 %, Se 96 %) We have developed a prognostic model to predict reduced kidney function formation (AUC 0.8; p < 0.001). This model with 96% of Se and 68% of Spe can predict development of AKI in patients with different levels of GFR after ACS. Conclusion: the prognostic multifactor model can be used in clinical practice to improve risk stratification in patients with ACS to prevent formation of AKI. P2009 Neladenoson, a partial adenosine A1-receptor agonist, improves mitochondrial function in skeletal muscle of dogs with chronic heart failure HN Hani Sabbah1; RC Gupta1; V Singh-Gupta1; K Zhang1; J Xu1; B Albrecht-Kuepper2 1Henry Ford Hospital, Detroit, United States of America; 2Bayer AG, Wuppertal, Germany Funding Acknowledgements: Bayer AG Background: Exercise intolerance (Ex-Int) is a feature of chronic heart failure (HF) and in particular, HF with preserved ejection fraction (HFpEF) and attributable, in part, to skeletal muscle (SM) abnormalities of fiber type composition and mitochondrial (MITO) dysfunction. In patients and dogs with HF, SM aerobic, MITO-dependent, type-I fibers decrease in number while anaerobic type-II fibers increase; a maladaptation that contributes to Ex-Int. We previously showed that chronic therapy with capadenoson, a partial adenosine A1-receptor agonist (pA1RA), improves LV function in HF dogs and therapy with neladenoson (NELA), a novel pA1RA, normalizes MITO function in failing cardiomyocytes. This study examined the effects of NELA on MITO function in SM biopsies from normal (NL) dogs and dogs with microembolization-induced HF. Methods: Fresh SM open biopsies ( ̃6 grams) were obtained from the hind leg Vastus Lateralis muscle of 6 NL and 6 HF anesthetized dogs. Samples were cut into thin sections, divided into 4 equal portions, and one portion each incubated in 0 (vehicle), 3, 10, and 30 nM concentration of NELA respectively for one hour at 37∘C. At end of incubation, MITO were isolated from SM and their function assessed. MITO ADP-stimulated state-3 respiration (ADPresp) was measured using a Strathklein respirometer, MITO complex-IV (COX-IV) activity was measured polarographically and MITO maximum rate of ATP synthesis (ATPsyn) was measured using the bioluminescent ApoSENSOR assay kit. Results: Increasing concentration of NELA had no effect on measures of MITO function in SM from NL dogs (Table). In SM from HF dogs, depressed levels of MITO ADPresp, ATPsyn, and COX-IV activity increased significantly in a dose-dependent manner after exposure to NELA (Table). Conclusions: The results indicate that NELA improves MITO function of SM of dogs with HF. These improvements can potentially reduce/reverse Ex-Int in HF. MITO Function Measures Vehicle 3 nM NELA 10 nM NELA 30 nM NELABackground and purpose: To estimate healthcare resource utilization among patients with heart failure (HF) with preserved (HFpEF) versus reduced (HFrEF) ejection fraction using population data from ...