Partial oral treatment of endocarditis Iversen, Kasper, MD, DMSc; Høst, Nis, MD, PhD; Bruun, Niels Eske, MD, DMSc ...
The American heart journal,
02/2013, Letnik:
165, Številka:
2
Journal Article
Recenzirano
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.
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).
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.
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).
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 .).
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.
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.
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 χ
analysis.
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;
=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;
=0.03) but not in patients >70 years of age (HR, 1.05; 95% CI, 0.68-1.62;
=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 (
=0.01).
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.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT00542945.
Identification of patients with nonischemic cardiomyopathy who may benefit from prophylactic implantation of a cardioverter-defibrillator. We hypothesized that periodic repolarization dynamics (PRD), ...a marker of repolarization instability associated with sympathetic activity, could be used to identify patients who will benefit from prophylactic implantable cardioverter defibrillator (ICD) implantation.
We performed a post hoc analysis of DANISH (Danish ICD Study in Patients With Dilated Cardiomyopathy), in which patients with nonischemic cardiomyopathy, left ventricular ejection fraction (LVEF) ≤35%, and elevated NT-proBNP (N-terminal probrain natriuretic peptides) were randomized to ICD implantation or control group. Patients were included in the PRD substudy if they had a 24-hour Holter monitor recording at baseline with technically acceptable ECG signals during the night hours (00:00-06:00). PRD was assessed using wavelet analysis according to previously validated methods. The primary end point was all-cause mortality. Cox regression models were adjusted for age, sex, NT-proBNP, estimated glomerular filtration rate, LVEF, atrial fibrillation, ventricular pacing, diabetes, cardiac resynchronization therapy, and mean heart rate. We proposed PRD ≥10 deg
as an exploratory cut-off value for ICD implantation.
A total of 748 of the 1116 patients in DANISH qualified for the PRD substudy. During a mean follow-up period of 5.1±2.0 years, 82 of 385 patients died in the ICD group and 85 of 363 patients died in the control group (
=0.40). In Cox regression analysis, PRD was independently associated with mortality (hazard ratio HR, 1.28 95% CI, 1.09-1.50 per SD increase;
=0.003). PRD was significantly associated with mortality in the control group (HR, 1.51 95% CI, 1.25-1.81;
<0.001) but not in the ICD group (HR, 1.04 95% CI, 0.83-1.54;
=0.71). There was a significant interaction between PRD and the effect of ICD implantation on mortality (
=0.008), with patients with higher PRD having greater benefit in terms of mortality reduction. ICD implantation was associated with an absolute mortality reduction of 17.5% in the 280 patients with PRD ≥10 deg
(HR, 0.54 95% CI, 0.34-0.84;
=0.006; number needed to treat=6), but not in the 468 patients with PRD <10 deg
(HR, 1.17 95% CI, 0.77-1.78;
=0.46;
for interaction=0.01).
Increased PRD identified patients with nonischemic cardiomyopathy in whom prophylactic ICD implantation led to significant mortality reduction.
Atrial fibrillation (AF) in heart failure (HF) patients has been associated with a worse outcome. Similarly, excessive supraventricular ectopic activity (ESVEA) has been linked to development of AF, ...stroke, and death. This study aimed to investigate AF and ESVEA's association with outcomes and effect of prophylactic implantable cardioverter defibrillator (ICD) implantation in nonischemic HF patients.
A total of 850 patients with nonischemic HF, left ventricle ejection fraction ≤35%, and elevated N-terminal pro-brain natriuretic peptides underwent 24 hours Holter recording. The presence of AF (≥30 seconds) and ESVEA (≥30 supraventricular ectopic complexes (SVEC) per hour or run of SVEC ≥20 beats) were registered. Outcomes were all-cause mortality, cardiovascular death (CVD), and sudden cardiac death (SCD).
AF was identified in 188 patients (22%) and ESVEA in 84 patients (10%). After 4 years and 11 months of follow-up, a total of 193 patients (23%) had died. AF was associated with all-cause mortality (hazard ratio HR 1.44; confidence interval CI 1.04-1.99; P = .03) and CVD (HR 1.59; CI 1.07-2.36; P = .02). ESVEA was associated with all-cause mortality (HR 1.73; CI 1.16-2.57; P = .0073) and CVD (HR 1.76; CI 1.06-2.92; P = .03). Neither AF nor ESVEA was associated with SCD. ICD implantation was not associated with an improved prognosis for neither AF (P value for interaction = .17), nor ESVEA (P value for interaction = .68).
Both AF and ESVEA were associated with worsened prognosis in nonischemic HF. However, ICD implantation was not associated with an improved prognosis for either group.
Abstract
Aims
Improved risk stratification to identify non-ischaemic heart failure patients who will benefit from primary prophylactic implantable cardioverter-defibrillator (ICD) is needed. We ...examined the potential of ventricular arrhythmia to identify patients who could benefit from an ICD.
Methods and results
A total of 850 non-ischaemic systolic heart failure patients with left ventricle ≤35% and elevated N-terminal pro-brain natriuretic peptides had a 24-h Holter monitor recording performed. We examined present non-sustained ventricular tachycardia (NSVT), defined as ≥3 consecutive premature ventricular contractions (PVCs) with a rate of ≥100/min, and number of PVCs per hour stratified into low (<30) and high burden (≥30) groups. Outcome measures were overall mortality, sudden cardiac death (SCD), and cardiovascular death (CVD). In total, 193 patients died, 49 from SCD and 125 from CVD. Non-sustained ventricular tachycardia (365 patients) was significantly associated with increased all-cause mortality hazard ratio (HR) 1.47; 95% confidence interval (CI) 1.07–2.03; P = 0.02 and to CVD (HR 1.89; CI 1.25–2.87; P = 0.003). High burden PVC (352 patients) was associated with increased all-cause mortality (HR1.38; CI 1.00–1.90; P = 0.046) and with CVD (HR 1.78; CI 1.19–2.66; P = 0.005). There was no statistically significant association with SCD for neither NSVT nor PVC. In interaction analyses, neither NSVT (P = 0.56) nor high burden of PVC (P = 0.97) was associated with survival benefit from ICD implantation.
Conclusion
Ventricular arrhythmia in non-ischaemic heart failure patients was associated with a worse prognosis but could not be used to stratify patients to ICD implantation.
Background The effect of an implantable cardioverter defibrillator (ICD) in patients with symptomatic systolic heart failure caused by coronary artery disease is well documented. However, the effect ...of primary prophylactic ICDs in patients with systolic heart failure not due to coronary artery disease is much weaker. In addition, heart failure 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 randomized, controlled, multicenter study to assess the efficacy of Implantable cardioverter defibrillator in patients with non-ischemic Systolic Heart failure on mortality (DANISH) , 1116 patients with symptomatic systolic heart failure 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 five years. Baseline characteristics show that enrolled patients are treated according to current guidelines. At baseline 97% of patients received an ACE-inhibitor or angiotensin receptor blocker, 92% received a beta 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 heart failure not caused by coronary artery disease on contemporary standard therapy including CRT.
Implantable cardioverter-defibrillator (ICD) implantation reduce the risk of sudden cardiac death, but not all-cause death in patients with non-ischaemic systolic heart failure (HF). Whether ...co-existence of diabetes affects ICD treatment effects is unclear.
We examined the effect of ICD implantation on risk of all-cause death, cardiovascular death, and sudden cardiac death (SCD) according to diabetes status at baseline in the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischaemic Systolic Heart Failure on Mortality (DANISH) trial. Outcomes were analysed by use of cumulative incidence curves and Cox regressions models. Of the 1116 patients enrolled, 211 (19%) had diabetes at baseline. Patients with diabetes were more obese, had worse kidney function and more were in New York Heart Association Class III/IV. The risk of device infections and other complications in the ICD group was similar among patients with and without diabetes (6.1% vs. 4.6% P = 0.54). Irrespective of treatment group, diabetes was associated with higher risk of all-cause death, cardiovascular death, and SCD. The treatment effect of ICD in patients with diabetes vs. patients without diabetes was hazard ratio (HR) = 0.92 (0.57-1.50) vs. HR = 0.85 (0.63-1.13); Pinteraction = 0.60 for all-cause mortality, HR = 0.99 (0.58-1.70) vs. HR = 0.70 (0.48-1.01); Pinteraction = 0.25 for cardiovascular death, and HR = 0.81 (0.35-1.88) vs. HR = 0.40 (0.22-0.76); Pinteraction = 0.16 for sudden cardiac death.
Among patients with non-ischaemic systolic HF, diabetes was associated with higher incidence of all-cause mortality, primarily driven by cardiovascular mortality including SCD. Treatment effect of ICD therapy was not significantly modified by diabetes which might be due to lack of power.
Abstract
Aim
The Danish Study to Assess the Efficacy of Implantable Cardioverter-Defibrillators (ICD) in Patients with Non-ischaemic Systolic Heart Failure (HF) on Mortality (DANISH) found no overall ...effect on all-cause mortality. The effect of ICD implantation on health-related quality of life (HRQoL) remains to be established as previous trials have demonstrated conflicting results. We investigated the impact of ICD implantation on HRQoL in patients with non-ischaemic systolic HF, a prespecified secondary endpoint in DANISH.
Methods and results
In DANISH, a total of 1116 patients with non-ischaemic systolic HF were randomly assigned (1:1) to ICD implantation or usual clinical care (control). Patients completed disease-specific HRQoL as assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ; 0–105, high indicating worse). Changes in HRQoL 8 months after randomization were assessed with a mixed-effects model. At randomization, MLHFQ was completed by 935 (84%) patients (n = 472 in the ICD group and n = 463 in the control group) and was reassessed in 274 (58%) and 292 (63%) patients, respectively after 8 months for the primary analysis. Patients in the ICD group vs. the control group had similar improvements in MLHFQ after 8 months least square mean −7.0 vs. −4.2 (P = 0.13). A clinically relevant improvement (decrease ≥5) in the MLHFQ overall score at 8 months was observed in 151 patients in the ICD group and 148 patients in the control group 55% vs. 51%, respectively (P = 0.25).
Conclusion
Implantable cardioverter-defibrillator implantation in patients with non-ischaemic systolic HF did not significantly alter HRQoL compared with patients randomized to usual clinical care.
PDF
