Trine K. Lauridsen

Identification of Typical Left Bundle Branch Block Contraction by Strain Echocardiography Is Additive to Electrocardiography in Prediction of Long-Term Outcome After Cardiac Resynchronization Therapy

BACKGROUND Current guidelines suggest that patients with left bundle branch block (LBBB) be treated with cardiac resynchronization therapy (CRT); however, one-third do not have a significant activation delay, which can result in nonresponse. By identifying characteristic opposing wall contraction, 2-dimensional strain echocardiography (2DSE) may detect true LBBB activation. OBJECTIVES This study sought to investigate whether the absence of a typical LBBB mechanical activation pattern by 2DSE was associated with unfavorable long-term outcome and if this is additive to electrocardiographic (ECG) morphology and duration. METHODS From 2 centers, 208 CRT candidates (New York Heart Association classes II to IV, ejection fraction ≤35%, QRS duration ≥120 ms) with LBBB by ECG were prospectively included. Before CRT implantation, longitudinal strain in the apical 4-chamber view determined whether typical LBBB contraction was present. The pre-defined outcome was freedom from death, left ventricular assist device, or heart transplantation over 4 years. RESULTS Two-thirds of patients (63%) had a typical LBBB contraction pattern. During 4 years, 48 patients (23%) reached the primary endpoint. Absence of a typical LBBB contraction was independently associated with increased risk of adverse outcome after adjustment for ischemic heart disease and QRS width (hazard ratio [HR]: 3.1; 95% CI: 1.64 to 5.88; p < 0.005). Adding pattern assessment to a risk prediction model including QRS duration and ischemic heart disease significantly improved the net reclassification index to 0.14 (p = 0.04) and improved the C-statistics (0.63 [95% CI: 0.54 to 0.72] vs. 0.71 [95% CI: 0.63 to 0.80]; p = 0.02). Use of strict LBBB ECG criteria was not independently associated with outcome in the multivariate model (HR: 1.72; 95% CI: 0.89 to 3.33; p = 0.11. Assessment of LBBB contraction pattern was superior to time-to-peak indexes of dyssynchrony (p < 0.01 for all). CONCLUSIONS Contraction pattern assessment to identify true LBBB activation provided important prognostic information in CRT candidates.

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}

Echocardiographic Findings Predict In-Hospital and 1-Year Mortality in Left-Sided Native Valve Staphylococcus aureus Endocarditis Analysis From the International Collaboration on Endocarditis-Prospective Echo Cohort Study

Background— Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown. Methods and Results— Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus . Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non- S aureus IE; P <0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non- S aureus IE; P <0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52–5.40; P <0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35–6.04; P =0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21–3.68; P =0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26–3.78; P =0.004) were the only independent predictors of 1-year mortality. Conclusions— S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality.Background—Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown. Methods and Results—Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus. Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non-S aureus IE; P<0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non-S aureus IE; P<0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52–5.40; P<0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35–6.04; P=0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21–3.68; P=0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26–3.78; P=0.004) were the only independent predictors of 1-year mortality. Conclusions—S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality.

Echocardiographic Findings Predict In-Hospital and 1 Year Mortality in Left-Sided Native Valve Staphylococcus aureus Endocarditis

Background— Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown. Methods and Results— Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus . Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non- S aureus IE; P <0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non- S aureus IE; P <0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52–5.40; P <0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35–6.04; P =0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21–3.68; P =0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26–3.78; P =0.004) were the only independent predictors of 1-year mortality. Conclusions— S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality.Background—Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown. Methods and Results—Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus. Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non-S aureus IE; P<0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non-S aureus IE; P<0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52–5.40; P<0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35–6.04; P=0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21–3.68; P=0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26–3.78; P=0.004) were the only independent predictors of 1-year mortality. Conclusions—S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality.

Infectious endocarditis caused by Escherichia coli

Abstract Although Escherichia coli is among the most common causes of Gram-negative bacteraemia, infectious endocarditis (IE) due to this pathogen is rare. A 67-y-old male without a previous medical history presented with a new mitral regurgitation murmur and persisting E. coli bacteraemia in spite of broad-spectrum intravenous antibiotics. Transthoracic and transoesophageal echocardiography revealed a severe mitral endocarditis. E. coli DNA was identified from the mitral valve and the vegetation, and no other pathogen was found. The case was further complicated by spondylodiscitis and bilateral endophthalmitis. Extra-intestinal pathogenic E. coli (ExPEC) are able to colonize tissue outside the gastrointestinal tract and contain a variety of virulence factors that may enable the pathogens to invade and induce infections in the cardiac endothelia. In these cases echocardiography as the imaging technology is of paramount importance for the correct diagnosis and treatment.

Clinical utility of 18 F-FDG positron emission tomography/computed tomography scan vs. 99m Tc-HMPAO white blood cell single-photon emission computed tomography in extra-cardiac work-up of infective endocarditis

The extra-cardiac work-up in infective endocarditis (IE) comprises a search for primary and secondary infective foci. Whether 18FDG-PET/CT or WBC-SPECT/CT is superior in detection of clinically relevant extra-cardiac manifestations in IE is unexplored. The objectives of this study were to identify the numbers of positive findings detected by each imaging modality, to evaluate the clinical relevance of these findings and to define the reproducibility for extra-cardiac foci in patients with definite IE. Each modality was evaluated for numbers and location of positive extra-cardiac foci in patients with definite IE. A team of 2 × 2 cardiologists evaluated each finding to determine clinical relevance. Clinical utility was determined by 4 criteria converted into an ordinal scale. Using the manifestation with highest clinical utility rating in each patient, the clinical impact of the two imaging modalities was expressed in a clinical utility score. To evaluate reproducibility for each modality, an imaging core laboratory reviewed all findings. In 55 IE patients, 91 pathological foci were found by FDG-PET/CT and 37 foci were identified by WBC-SPECT/CT (p < 0.001). The clinical utility of FDG-PET/CT was significantly higher than that of WBC-SPECT/CT when comparing clinical utility score (2.06 vs. 1.17; p = 0.01). In assessment of extra-cardiac diagnostics in IE, inter-observer reproducibility was substantial for WBC-SPECT/CT (k 0.69, 95% CI 0.49–0.89) and substantial to excellent for FDG-PET/CT (k 0.79, 95% CI 0.61–0.98). FDG-PET/CT has a significantly higher clinical utility score than WBC SPECT/CT and is potentially superior to WBC-SPECT/CT in detection of extra-cardiac pathology in patients with IE.

Risk Factors of Endocarditis in Patients With Enterococcus faecalis Bacteremia: External Validation of the NOVA Score

BACKGROUND The NOVA score is a recently developed diagnostic tool used to identify patients with increased risk of infective endocarditis (IE) among patients with Enterococcus faecalis bacteremia. We aimed to validate the NOVA score and to identify risk factors for IE. METHODS From 1 January 2010 to 31 December 2013, we included 647 consecutive patients with E. faecalis bacteremia. The NOVA score was used in a slightly adapted form; 2/2 positive blood cultures resulted in 5 points, unknown origin of infection in 4 points, prior valve disease in 2 points, and heart murmur in 1 point. RESULTS IE was diagnosed in 78 patients (12%). Monomicrobial E. faecalis bacteremia (hazard ratio [HR], 3.60; 95% confidence interval [CI], 1.6-8.0), prosthetic heart valve (HR, 6.2; 95% CI, 3.8-10.1), male sex (HR, 2.0; 95% CI, 1.1-3.8), and community acquisition (HR, 1.8; 95% CI, 1.1-2.9) were independently associated with IE. The adapted NOVA score was applied in the 240 patients examined by echocardiography. A low score (<4) was found in 40 patients (17%), implying a low likelihood of IE. Of the 78 patients with IE, 76 had a high score (≥4), resulting in a sensitivity of 97%, specificity of 23%, a negative predictive value of 95%, and a positive predictive value of 38%. CONCLUSIONS Monomicrobial E. faecalis bacteremia, community acquisition, prosthetic heart valve, and male sex are associated with increased risk of IE. In our retrospective cohort, the adapted NOVA score performed well, suggesting that it could be useful in guiding clinical decisions.

Antiarrhythmic medication is superior to catheter ablation in suppressing supraventricular ectopic complexes in patients with atrial fibrillation

BACKGROUND Supraventricular ectopic complexes (SVEC) originating in the pulmonary veins are known triggers of atrial fibrillation (AF) which led to the development of pulmonary vein isolation for AF. However, the long-term prevalence of SVEC after catheter ablation (CA) as compared to antiarrhythmic medication (AAD) is unknown. Our aims were to compare the prevalence of SVEC after AAD and CA and to estimate the association between baseline SVEC burden and AF burden during 24months of follow-up. METHODS Patients with paroxysmal AF (N=260) enrolled in the MANTRA PAF trial were treated with AAD (N=132) or CA (N=128). At baseline and 3, 6, 12, 18 and 24months follow-up patients underwent 7-day Holter monitoring to assess SVEC and AF burden. We compared SVEC burden between treatments with Wilcoxon sum rank test. RESULTS Patients treated with AAD had significantly lower daily SVEC burden during follow-up as compared to CA (AAD: 19 [6-58] versus CA: 39 [14-125], p=0.003). SVEC burden increased post-procedurally followed by a decrease after CA whereas after AAD SVEC burden decreased and stabilized after 3months of follow-up. Patients with low SVEC burden had low AF burden after both treatments albeit this was more pronounced after CA at 24months of follow-up. CONCLUSION AAD was superior to CA in suppressing SVEC burden after treatment of paroxysmal AF. After CA SVEC burden increased immediately post-procedural followed by a decrease whereas after AAD an early decrease was observed. Lower SVEC burden was highly associated with lower AF burden during follow-up especially after CA.

The impact of supraventricular ectopic complexes in different age groups and risk of recurrent atrial fibrillation after antiarrhythmic medication or catheter ablation

INTRODUCTION Supraventricular ectopic complexes (SVEC) are known risk factors of recurrent atrial fibrillation (AF). However, the impact of SVEC in different age groups is unknown. We aimed to investigate the risk of AF recurrence with higher SVEC burden in patients ±57years, respectively, after treatment with antiarrhythmic medication (AAD) or catheter ablation (CA). METHODS In total, 260 patients with LVEF >40% and age ≤70 years were randomized to AAD (N=132) or CA (N=128) as first-line treatment for paroxysmal AF. All patients underwent 7-day Holter monitoring at baseline, and after 3, 6, 12, 18 and 24months and were categorized according to median age ±57years. We used multivariate Cox regression analyses and we defined high SVEC burden at 3months of follow-up as the upper 75th percentile >195SVEC/day. AF recurrence was defined as AF ≥1min, AF-related cardioversion or hospitalization. RESULTS Age >57years were significantly associated with higher AF recurrence rate after CA (58% vs 36%, p=0.02). After CA, we observed a higher SVEC burden during follow-up in patients >57years which was not observed in the younger age group treated with CA (p=0.006). High SVEC burden at 3months after CA was associated with AF recurrence in older patients but not in younger patients (>57years: HR 3.4 [1.4-7.9], p=0.005). We did not find any age-related differences after AAD. CONCLUSION We found that younger and older patients respond differently to CA and that SVEC burden was only associated with AF recurrence in older patients.

Long-term causes of death in patients with infective endocarditis who undergo medical therapy only or surgical treatment: a nationwide population-based study

OBJECTIVES It is known that patients surviving infective endocarditis have a poor long-term prognosis; however, few studies have addressed the long-term causes of death in patients surviving the initial hospitalization. METHODS Using Danish administrative registries, we identified patients admitted to a hospital with 1st time infective endocarditis in the period from January 1996 to December 2014, who were alive at the time of discharge. The study population was categorized into (i) patients undergoing medical therapy only and (ii) patients undergoing surgical and medical treatment. We examined the cardiovascular and non-cardiovascular causes of death. Using the Cox analysis, we investigated the associated risk of dying from a specific prespecified cause of death (heart failure, infective endocarditis and stroke) within the surgery group when compared with the medically treated group. RESULTS We identified 5576 patients: 4220 patients belonged to the medically treated group and 1356 patients to the surgery group. At the 10-year follow-up, the mortality rate was 63.1% and 41.6% in the medically treated group and the surgery group, respectively. Cardiovascular disease was the most frequent cause of death in both groups accounting for 52.5% in the medically treated group and 55.2% in the surgery group. Patients undergoing surgery were associated with a lower risk of dying from heart failure and stroke when compared with medically treated patients [hazard ratio = 0.66 (95% confidence interval: 0.46-0.94) and hazard ratio = 0.59 (95% confidence interval: 0.37-0.96), respectively]. CONCLUSIONS No major differences were found in the main causes of death between groups. Patients in the surgical group were associated with a lower risk of dying from heart failure and stroke when compared with medically treated patients.