Niels Eske Bruun

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.

Cardiac imaging in infectious endocarditis

Infectious endocarditis remains both a diagnostic and a treatment challenge. A positive outcome depends on a rapid diagnosis, accurate risk stratification, and a thorough follow-up. Imaging plays a key role in each of these steps and echocardiography remains the cornerstone of the methods in use. The technique of both transthoracic echocardiography and transoesophageal echocardiography has been markedly improved across the last decades and most recently three-dimensional real-time echocardiography has been introduced in the management of endocarditis patients. Echocardiography depicts structural changes and abnormalities in the heart, but it does not uncover the underlying pathophysiological processes at the cellular or molecular level. This problem is addressed with introduction of new molecular imaging methods as (18)F-fluorodesoxyglucose ((18)F-FDG) PET-CT and single photon emission computed tomography fused with conventional CT (SPECT/CT). Of these methods, (18)F-FDG PET-CT carries the best promise for a future role in endocarditis. But there are distinct limitations with both SPECT/CT and (18)F-FDG PET-CT which should not be neglected. MRI and spiral CT are methods primarily used in the search for extra cardial infectious foci. A flowchart for the use of imaging in both left-sided and right-sided endocarditis is suggested.

Global Longitudinal Strain Is a Superior Predictor of All-Cause Mortality in Heart Failure With Reduced Ejection Fraction

OBJECTIVES The purpose of this study was to investigate the prognostic value of global longitudinal strain (GLS) in heart failure with reduced ejection fraction (HFrEF) patients in relation to all-cause mortality. BACKGROUND Measurement of myocardial deformation by 2-dimensional speckle tracking echocardiography, specifically GLS, may be superior to conventional echocardiographic parameters, including left ventricular ejection fraction, in predicting all-cause mortality in HFrEF patients. METHODS Transthoracic echocardiographic examinations were retrieved for 1,065 HFrEF patients admitted to a heart failure clinic. The echocardiographic images were analyzed, and conventional and novel echocardiographic parameters were obtained. RESULTS Many of the conventional echocardiographic parameters proved to be predictors of mortality. However, GLS remained an independent predictor of mortality in the multivariable model after adjusting for age, sex, body mass index, total cholesterol, mean arterial pressure, heart rate, ischemic cardiomyopathy, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery, noninsulin dependent diabetes mellitus, and conventional echocardiographic parameters (hazard ratio [HR]: 1.15; 95% confidence interval [CI]: 1.04 to 1.27; p = 0.008, per 1% decrease). No other echocardiographic parameter remained an independent predictor after adjusting for these variables. Furthermore, GLS had the highest C-statistics of all the echocardiographic parameters and added incremental prognostic value with a significant increase in the net reclassification improvement (p = 0.009). Atrial fibrillation (AF) modified the relationship between GLS and mortality (p value for interaction = 0.036); HR: 1.08 (95% CI: 0.97 to 1.19), p = 0.150 and HR: 1.22 (95% CI: 1.15 to 1.29), p < 0.001, per 1% decrease in GLS for patients with and without AF, respectively. Sex also modified the relationship between GLS and mortality (p value for interaction = 0.047); HR: 1.23 (95% CI: 1.16 to 1.30), p < 0.001 and HR: 1.09 (95% CI: 0.99 to 1.20), p = 0.083, per 1% decrease in GLS for men and women, respectively. CONCLUSIONS GLS is an independent predictor of all-cause mortality in HFrEF patients, especially in male patients without AF. Furthermore, GLS was a superior prognosticator compared with all other echocardiographic parameters.

Left bundle-branch block: the relationship between electrocardiogram electrical activation and echocardiography mechanical contraction

BACKGROUND The relationship between myocardial electrical activation by electrocardiogram (ECG) and mechanical contraction by echocardiography in left bundle-branch block (LBBB) has never been clearly demonstrated. New strict criteria for LBBB based on a fundamental understanding of physiology have recently been independently published for both ECG and echocardiography. The relationship between the 2 modalities and the relation to cardiac resynchronization therapy (CRT) response was investigated. METHODS Sixty-six patients with LBBB by conventional criteria had a standard 12-lead ECG and 2-dimensional strain echocardiography performed before CRT implantation. Criteria for LBBB by echocardiography included early termination of contraction in one wall and prestretch and late contraction in opposing wall(s). New strict criteria by ECG included QRS duration ≥140 ms (men) or 130 ms (women), QS or rS in leads V1 and V2, and mid-QRS notching or slurring in ≥2 of leads V1, V2, V5, V6, I, and aVL. Response was defined as >15% decrease in left ventricular end-systolic volume after 6 months. RESULTS In 64 of 66 patients, ECG analysis was possible. Echo and ECG readings for LBBB presence were concordant in 54 (84%) of 64. Thirty-seven (82%) of 45 patients with LBBB by strict ECG criteria responded to CRT, whereas only 4 (21%) of the 19 patients without LBBB responded (sensitivity 90% and specificity 65%). Thirty-six (95%) of 38 patients with concordance for the presence of LBBB responded to CRT. In patients with concordance for the absence of LBBB, 15 (94%) of 16 did not respond. CONCLUSION For the first time, a close relation has been demonstrated between electrical activation by ECG and mechanical contraction by echocardiography. These findings may help identify CRT candidates.

Severity of Gentamicin's Nephrotoxic Effect on Patients with Infective Endocarditis: A Prospective Observational Cohort Study of 373 Patients

BACKGROUND Gentamicin is often used to treat infective endocarditis (IE). Gentamicin is highly effective, but its applicability is reduced by its nephrotoxic effect. The aim of this study was to quantify the nephrotoxic effect of gentamicin and the association between the nephrotoxic effect and mortality in patients with IE. METHODS A prospective observational cohort study was performed at 2 tertiary university hospitals in Copenhagen from October 2002 through October 2007; 373 consecutive patients with IE were included. A total of 287 (77%) of the patients received gentamicin treatment (median duration, 14 days); dosage was adjusted according to daily serum creatinine and trough serum gentamicin levels. Kidney function was determined by estimated endogenous creatinine clearance (EECC). Statistical correlation between gentamicin and EECC change was analyzed, and the association between mortality and nephrotoxicity was investigated. RESULTS The primary bacteriological etiologies were as follows: Streptococcus species (37.1%), Staphylococcus aureus (18.2%), and Enterococcus species (16.1%). In the gentamicin group, the mean EECC change was an 8.6% decrease, but in the no-gentamicin group, the mean change was an increase of 2.3% (P = .05). The decrease in EECC was significantly correlated with the duration of gentamicin treatment: a 0.5% EECC decrease per day of gentamicin treatment (P = .002). The decrease in EECC during hospitalization was not related to postdischarge mortality. The mean duration of follow-up was 562 days. CONCLUSIONS The nephrotoxic effect of gentamicin is directly related to treatment duration, with a decrease in EECC of 0.5% per day of gentamicin treatment. In patients treated with gentamicin, the in-hospital decrease in EECC was not related to postdischarge mortality. Consequently, this study does not support abolishment of gentamicin in treatment of IE.

Future challenges and treatment of Staphylococcus aureus bacteremia with emphasis on MRSA

Staphylococcus aureus bacteremia (SAB) is an urgent medical problem due to its growing frequency and its poor associated outcome. As healthcare delivery increasingly involves invasive procedures and implantable devices, the number of patients at risk for SAB and its complications is likely to grow. Compounding this problem is the growing prevalence of methicillin-resistant S. aureus (MRSA) and the dwindling efficacy of vancomycin, long the treatment of choice for this pathogen. Despite the recent availability of several new antibiotics for S. aureus, new strategies for treatment and prevention are required for this serious, common cause of human infection.

Enterococcus faecalis Infective Endocarditis A Pilot Study of the Relationship Between Duration of Gentamicin Treatment and Outcome

Background— Because of the nephrotoxic effects of aminoglycosides, the Danish guidelines on infective endocarditis were changed in January 2007, reducing gentamicin treatment in enterococcal infective endocarditis from 4 to 6 weeks to only 2 weeks. In this pilot study, we compare outcomes in patients with Enterococcus faecalis infective endocarditis treated in the years before and after endorsement of these new recommendations. Methods and Results— A total of 84 consecutive patients admitted with definite left-sided E faecalis endocarditis in the period of 2002 to 2011 were enrolled. Forty-one patients were treated before and 43 patients were treated after January 1, 2007. There were no significant differences in baseline characteristics. At hospitalization, the 2 groups had similar estimated glomerular filtration rates of 66 and 75 mL/min (P=0.22). Patients treated before January 2007 received gentamicin for a significantly longer period (28 versus 14 days; P<0.001). The primary outcome, 1-year event-free survival, did not differ: 66% versus 69%, respectively (P=0.75). At discharge, the patients treated before 2007 had a lower estimated glomerular filtration rate (45 versus 66 mL/min; P=0.008) and a significantly greater decrease in estimated glomerular filtration rate (median, 11 versus 1 mL/min; P=0.009) compared with those treated after 2007. Conclusions— Our present pilot study suggests that the recommended 2-week treatment with gentamicin seems adequate and preferable in treating non–high-level aminoglycoside-resistant E faecalis infective endocarditis. The longer duration of gentamicin treatment is associated with worse renal function. Although the certainty of the clinical outcomes is limited by the sample size, outcomes appear to be no worse with the shorter treatment duration. Randomized, controlled studies are warranted to substantiate these results.Background— Because of the nephrotoxic effects of aminoglycosides, the Danish guidelines on infective endocarditis were changed in January 2007, reducing gentamicin treatment in enterococcal infective endocarditis from 4 to 6 weeks to only 2 weeks. In this pilot study, we compare outcomes in patients with Enterococcus faecalis infective endocarditis treated in the years before and after endorsement of these new recommendations. Methods and Results— A total of 84 consecutive patients admitted with definite left-sided E faecalis endocarditis in the period of 2002 to 2011 were enrolled. Forty-one patients were treated before and 43 patients were treated after January 1, 2007. There were no significant differences in baseline characteristics. At hospitalization, the 2 groups had similar estimated glomerular filtration rates of 66 and 75 mL/min ( P =0.22). Patients treated before January 2007 received gentamicin for a significantly longer period (28 versus 14 days; P <0.001). The primary outcome, 1-year event-free survival, did not differ: 66% versus 69%, respectively ( P =0.75). At discharge, the patients treated before 2007 had a lower estimated glomerular filtration rate (45 versus 66 mL/min; P =0.008) and a significantly greater decrease in estimated glomerular filtration rate (median, 11 versus 1 mL/min; P =0.009) compared with those treated after 2007. Conclusions— Our present pilot study suggests that the recommended 2-week treatment with gentamicin seems adequate and preferable in treating non–high-level aminoglycoside-resistant E faecalis infective endocarditis. The longer duration of gentamicin treatment is associated with worse renal function. Although the certainty of the clinical outcomes is limited by the sample size, outcomes appear to be no worse with the shorter treatment duration. Randomized, controlled studies are warranted to substantiate these results. # Clinical Perspective {#article-title-50}

Normal renal tubular response to changes of sodium intake in hypertensive man.

In a comparative study the influence of changes in dietary sodium intake on blood pressure, renal function, extracellular fluid volume, the renin-angiotensin-aldosterone system and plasma concentrations of arginine vasopressin, atrial natriuretic factor and cyclic guanosine monophosphate (GMP) was investigated in 12 patients with essential hypertension and in 10 normotensive controls. The subjects were studied after 4 days on a low (50 mmol/day), medium (180 mmol/day) or high (380 mmol/day) sodium intake. Renal sodium handling was assessed by simultaneous measurements of 51Cr-ethylenediaminetetraacetic acid (EDTA), lithium and sodium clearances. Identical values for the extracellular fluid volume, glomerular filtration rate and proximal and distal tubular resorption rates of sodium and water were found in the hypertensive patients and the controls at all three levels of sodium intake. In both groups, raising the sodium intake from low to high significantly increased 51Cr-EDTA and lithium clearance (an indirect measure of end-proximal fluid delivery), with intermediate values for the medium-sodium diet. The estimated values of fractional proximal and distal sodium resorption decreased when sodium intake was raised; the absolute proximal sodium resorption rate did not change, whereas the absolute distal sodium resorption rate as well as the extracellular fluid volume and sodium clearance increased. Blood pressure and the heart rate were unaffected by sodium intake. In both hypertensives and controls, plasma concentrations of active renin, angiotensin II and aldosterone decreased with increasing sodium intake, arginine vasopressin did not change, and atrial natriuretic factor and cyclic GMP increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanical dyssynchrony evaluated by tissue Doppler cross-correlation analysis is associated with long-term survival in patients after cardiac resynchronization therapy

AIMS Pre-implant assessment of longitudinal mechanical dyssynchrony using cross-correlation analysis (XCA) was tested for association with long-term survival and compared with other tissue Doppler imaging (TDI)-derived indices. METHODS AND RESULTS In 131 patients referred for cardiac resynchronization therapy (CRT) from two international centres, mechanical dyssynchrony was assessed from TDI velocity curves using time-to-peak opposing wall delay (OWD) ≥80 ms, Yu index ≥32 ms, and the maximal activation delay (AD-max) >35 ms. AD-max was calculated by XCA of the TDI-derived myocardial acceleration curves. Outcome was a composite of all-cause mortality, cardiac transplantation, or implantation of a ventricular assist device (left ventricular assist device) and modelled using the Cox proportional hazards regression. Follow-up was truncated at 1460 days. Dyssynchrony by AD-max was independently associated with improved survival when adjusted for QRS > 150 ms and aetiology {hazard ratio (HR) 0.35 [95% confidence interval (CI) 0.16-0.77], P = 0.01}. Maximal activation delay performed significantly better than Yu index, OWD, and the presence of left bundle branch block (P < 0.05, all, for difference between parameters). In subgroup analysis, patients without dyssynchrony and QRS between 120 and 150 ms showed a particularly poor survival [HR 4.3 (95% CI 1.46-12.59), P < 0.01, compared with the group with dyssynchrony and QRS between 120 and 150 ms]. CONCLUSION Mechanical dyssynchrony assessed by AD-max was associated with long-term survival after CRT and was significantly better associated compared with other TDI-derived indices. Patients without dyssynchrony and QRS between 120 and 150 ms had a particularly poor prognosis. These results indicate a valuable role for XCA in selection of CRT candidates.