Implantable cardiac defibrillator infections: the emerging importance of Mycobacterium fortuitum.

Infection is a clinically relevant complication associated with intracardiac devices. Atypical mycobacteria, particularly Mycobacterium fortuitum, have been increasingly implicated in cardiovascular implantable electronic device (CIED) infections. We present a case of M. fortuitum CIED infection in a patient with ischaemic cardiomyopathy occurring approximately 3 weeks after insertion. The recognition and adequate treatment, including device removal, tissue sampling and the determination of antimicrobial sensitivities, are essential in the proper management of these patients.

Novel Therapeutic Strategies for Reducing Right Heart Failure Associated Mortality in Fibrotic Lung Diseases.

Fibrotic lung diseases carry a significant mortality burden worldwide. A large proportion of these deaths are due to right heart failure and pulmonary hypertension. Underlying contributory factors which appear to play a role in the mechanism of progression of right heart dysfunction include chronic hypoxia, defective calcium handling, hyperaldosteronism, pulmonary vascular alterations, cyclic strain of pressure and volume changes, elevation of circulating TGF-ß, and elevated systemic NO levels. Specific therapies targeting pulmonary hypertension include calcium channel blockers, endothelin (ET-1) receptor antagonists, prostacyclin analogs, phosphodiesterase type 5 (PDE5) inhibitors, and rho-kinase (ROCK) inhibitors. Newer antifibrotic and anti-inflammatory agents may exert beneficial effects on heart failure in idiopathic pulmonary fibrosis. Furthermore, right ventricle-targeted therapies, aimed at mitigating the effects of functional right ventricular failure, include ß-adrenoceptor (ß-AR) blockers, angiotensin-converting enzyme (ACE) inhibitors, antioxidants, modulators of metabolism, and 5-hydroxytryptamine-2B (5-HT2B) receptor antagonists. Newer nonpharmacologic modalities for right ventricular support are increasingly being implemented. Early, effective, and individualized therapy may prevent overt right heart failure in fibrotic lung disease leading to improved outcomes and quality of life.

Mechanistic features associated with improvement in mitral regurgitation after cardiac resynchronization therapy and their relation to long-term patient outcome.

BACKGROUND: Mechanisms of mitral regurgitation (MR) reduction with cardiac resynchronization therapy (CRT) are complex, and their association with long-term outcome is unclear. We sought to elucidate mechanistic features of reduction in MR with CRT, which impact long-term patient survival. METHODS AND RESULTS: A prospective longitudinal study of 277 patients with heart failure with QRS width ≥ 120 ms and ejection fraction ≤ 35% for CRT was performed. Quantitative echocardiography, including dyssynchrony analysis, was performed at baseline. MR was quantified by color Doppler before and 6 months after CRT. Predefined end points of death, transplant, or left ventricular assist device were tracked during 4 years. There were 114 (48%) patients with CRT with significant MR (≥ moderate) at baseline; of whom 48 (42%) patients had MR improvement, and 24 (19%) patients had MR worsening after CRT. The 66 events (47 deaths, 10 transplantations, and 9 left ventricular assist devices) were strongly associated with significant MR after CRT (hazard ratio, 3.58; 95% confidence interval, 2.18-5.87; P<0.0001). Three echocardiographic features were independently associated with amelioration of significant MR after CRT by multivariable analysis: anteroseptal to posterior wall radial strain dyssynchrony >200 ms, lack of severe left ventricular dilatation (end-systolic dimension index <29 mm/m(2)), and lack of echocardiographic scar at papillary muscle insertion sites (all P<0.05) and, when combined, were additively associated with long-term survival (P=0.0001). CONCLUSIONS: Significant MR after CRT was strongly associated with less favorable long-term survival. Echocardiographic mechanistic features were identified that were associated with improvement in MR after CRT and favorable long-term survival.

Echocardiography-guided left ventricular lead placement for cardiac resynchronization therapy: results of the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region trial.

BACKGROUND: Cardiac resynchronization therapy improves mortality and morbidity in patients with heart failure (HF) with wide QRS complex and diminished left ventricular (LV) function, but response is variable. METHODS AND RESULTS: The Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) was a prospective, double-blind, randomized controlled trial testing the hypothesis that an incremental benefit to cardiac resynchronization therapy would be gained by echo-guided (EG) transvenous LV lead placement versus a routine fluoroscopic approach. EG LV lead placement was attempted at the site of latest time to peak radial strain by speckle tracking echocardiography. The prespecified primary end point was first HF hospitalization or death. Of 187 New York Heart Association class II to IV patients with HF (62% ischemic; ejection fraction 26±6%; QRS 159±27 ms), 110 were randomized to EG and 77 to routine strategies. Primary events included 30 deaths and 37 HF hospitalizations over 1.8 years. Using intention-to-treat, patients randomized to an EG strategy had a significantly more favorable event-free survival (hazard ratio, 0.48; 95% confidence interval, 0.28-0.82; P=0.006). Exact or adjacent concordance of LV lead with latest site could be achieved in 85% of the EG group and occurred fortuitously in 66% of controls (P=0.010) and was associated with an improvement in event-free survival (hazard ratio, 0.40; 95% confidence interval, 0.22-0.71; P=0.002). CONCLUSIONS: A strategy of EG LV lead placement for cardiac resynchronization therapy improved patient outcomes by reducing the combined risk of death or HF hospitalizations and has implications for delivery of cardiac resynchronization therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00156390.

The relationship of QRS morphology and mechanical dyssynchrony to long-term outcome following cardiac resynchronization therapy.

AIMS: Because benefits of cardiac resynchronization therapy (CRT) appear to be less favourable in non-left bundle branch block (LBBB) patients, this prospective longitudinal study tested the hypothesis that QRS morphology and echocardiographic mechanical dyssynchrony were associated with long-term outcome after CRT. METHODS AND RESULTS: Two-hundred and seventy-eight consecutive New York Heart Association class III and IV CRT patients with QRS ≥120 ms and ejection fraction ≤35% were studied. The pre-specified primary endpoint was death, heart transplant, or left ventricular assist device over 4 years. Dyssynchrony assessed before CRT included interventricular mechanical delay (IVMD) and speckle-tracking radial strain using pre-specified cut-offs for each. Of 254 with baseline quantitative echocardiographic data available, 128 had LBBB, 81 had intraventricular conduction delay (IVCD), and 45 had right bundle branch block (RBBB). Radial dyssynchrony was observed in 85% of the patients with LBBB, 59% with IVCD*, and 40% with RBBB* (*P < 0.01 vs. LBBB). Of 248 (98%) with follow-up, LBBB patients had a significantly more favourable long-term survival than non-LBBB patients. However, non-LBBB patients with dyssynchrony had a more favourable event-free survival than those without dyssynchrony: radial dyssynchrony hazard ratio 2.6, 95% confidence interval (CI) 1.47-4.53 (P = 0.0008) and IVMD hazard ratio 4.9, 95% CI 2.60-9.16 (P = 0.0007). Right bundle branch block patients who lacked dyssynchrony had the least favourable outcome. CONCLUSION: Non-LBBB patients with dyssynchrony had a more favourable long-term survival than non-LBBB patients who lacked dyssynchrony. Mechanical dyssynchrony and QRS morphology are associated with outcome following CRT.

A practical approach to imaging dyssynchrony for cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is believed to benefit patients by primarily correcting heterogeneity in regional ventricular mechanical contraction, known as dyssynchrony. Although many symptomatic heart failure patients with depressed left ventricular ejection fraction and widened electrocardiographic QRS complexes have clinical improvement from CRT, a significant subset of approximately one-third do not seem to respond. Because the degree of mechanical dyssynchrony may be widely variable, interest has remained high to attempt to improve patient selection for CRT using cardiac imaging as a means to quantify dyssynchrony. This article will review the principal echocardiographic methods of dyssynchrony analysis by tissue Doppler imaging, (opposing wall delay, 12-site standard deviation or Yu index, and longitudinal strain), routine pulsed-Doppler (interventricular mechanical delay, pre-ejection delay and filling time ratio), and speckle tracking (including radial, circumferential, and longitudinal strain). In addition, dyssynchrony analysis by cardiac magnetic resonance imaging is introduced as a potential alternative technique. The technical features, strengths and limitations, and clinical evidence for these methods are discussed, including a practical clinical approach.

Relationship of echocardiographic dyssynchrony to long-term survival after cardiac resynchronization therapy.

BACKGROUND: The ability of echocardiographic dyssynchrony to predict response to cardiac resynchronization therapy (CRT) has been unclear. METHODS AND RESULTS: A prospective, longitudinal study was designed with predefined dyssynchrony indexes and outcome variables to test the hypothesis that baseline dyssynchrony is associated with long-term survival after CRT. We studied 229 consecutive class III to IV heart failure patients with ejection fraction ≤35 and QRS duration ≥120 milliseconds for CRT. Dyssynchrony before CRT was defined as tissue Doppler velocity opposing-wall delay ≥65 milliseconds, 12-site SD (Yu Index) ≥32 milliseconds, speckle tracking radial strain anteroseptal-to-posterior wall delay ≥130 milliseconds, or pulsed Doppler interventricular mechanical delay ≥40 milliseconds. Outcome was defined as freedom from death, heart transplantation, or left ventricular assist device implantation. Of 210 patients (89) with dyssynchrony data available, there were 62 events: 47 deaths, 9 transplantations, and 6 left ventricular assist device implantations over 4 years. Event-free survival was associated with Yu Index (P=0.003), speckle tracking radial strain (P=0.003), and interventricular mechanical delay (P=0.019). When adjusted for confounding baseline variables of ischemic origin and QRS duration, Yu Index and radial strain dyssynchrony remained independently associated with outcome (P<0.05). Lack of radial dyssynchrony was particularly associated with unfavorable outcome in those with QRS duration of 120 to 150 milliseconds (P=0.002). CONCLUSIONS: The absence of echocardiographic dyssynchrony was associated with significantly less favorable event-free survival after CRT. Patients with narrower QRS duration who lacked dyssynchrony had the least favorable long-term outcome. These observations support the relationship of dyssynchrony and CRT response.

Dyssynchrony by speckle-tracking echocardiography and response to cardiac resynchronization therapy: results of the Speckle Tracking and Resynchronization (STAR) study.

AIMS: The Speckle Tracking and Resynchronization (STAR) study used a prospective multi-centre design to test the hypothesis that speckle-tracking echocardiography can predict response to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: We studied 132 consecutive CRT patients with class III and IV heart failure, ejection fraction (EF) < or =35%, and QRS > or =120 ms from three international centres. Baseline dyssynchrony was evaluated by four speckle tracking strain methods; radial, circumferential, transverse, and longitudinal (> or =130 ms opposing wall delay for each). Pre-specified outcome variables were EF response and three serious long-term events: death, transplant, or left ventricular assist device. Of 120 patients (91%) with baseline dyssynchrony data, both short-axis radial strain and transverse strain from apical views were associated with favourable EF response 7 +/- 4 months and long-term outcome over 3.5 years (P < 0.01). Radial strain had the highest sensitivity at 86% for predicting EF response with a specificity of 67%. Serious long-term unfavourable events occurred in 20 patients after CRT, and happened three times more frequently in those who lacked baseline radial or transverse dyssynchrony than in patients with dyssynchrony (P < 0.01). Patients who lacked both radial and transverse dyssynchrony had unfavourable clinical events occur in 53%, in contrast to events occurring in 12% if baseline dyssynchrony was present (P < 0.01). Circumferential and longitudinal strains predicted response when dyssynchrony was detected, but failed to identify dyssynchrony in one-third of patients who responded to CRT. CONCLUSION: Dyssynchrony by speckle-tracking echocardiography using radial and transverse strains is associated with EF response and long-term outcome following CRT.

Usefulness of echocardiographic dyssynchrony in patients with borderline QRS duration to assist with selection for cardiac resynchronization therapy.

OBJECTIVES: To test the hypothesis that echocardiographic dyssynchrony may assist in the selection of patients with borderline QRS duration for cardiac resynchronization therapy (CRT). BACKGROUND: Although echocardiographic dyssynchrony is currently not recommended to select patients with QRS duration widening for CRT, its utility in patients with borderline QRS widening is unclear. METHODS: Of 221 consecutive heart failure patients with an ejection fraction (EF) < or =35% referred for CRT, 86 had a borderline QRS duration of 100 to 130 ms (115 +/- 8 ms) and 135 patients had wide QRS >130 ms (168 +/- 26 ms). Dyssynchrony was assessed using interventricular mechanical delay, tissue Doppler imaging longitudinal velocity opposing wall delay, and speckle tracking radial strain for septal to posterior wall delay. Response to CRT was defined as > or =15% increase in EF, and reverse remodeling as > or =10% decrease in end-systolic volume. RESULTS: There were 201 patients with baseline quantitative echocardiographic data available, and 187 with follow-up data available 8 +/- 5 months after CRT. A smaller proportion of borderline QRS duration patients (53%) were EF responders compared with 75% with widened QRS (p < 0.05). Interventricular mechanical delay > or =40 ms and opposing wall delay > or =65 ms were predictive of EF response in the wide QRS duration group, but not the borderline QRS duration group. Speckle tracking radial dyssynchrony > or =130 ms, however, was predictive of EF response in both wide QRS interval patients (88% sensitivity, 74% specificity) and borderline QRS interval patients (79% sensitivity, 82% specificity) and associated reverse remodeling with reduction in end-systolic volume (p < 0.0005). CONCLUSIONS: Radial dyssynchrony by speckle tracking strain was associated with EF and reverse remodeling response to CRT in patients with borderline QRS duration and has the potential to assist with patient selection.