Mobile echodensities on intracardiac device leads: Is it always a cause for concern?

BACKGROUND: Patients with cardiac implantable electronic devices (CIEDs) frequently undergo transthoracic echocardiography (TTE). As a result, incidental mobile echodensities (MEDs) attached to device leads are commonly detected. The aim of this study was to estimate the incidence and clinical outcomes of incidental MEDs on CIED leads. METHODS: A retrospective analysis performed between 2011 and 2018 identified 3548 TTE studies performed on 1849 patients with CIEDs. RESULTS: MEDs were identified in 30 patients (1.6%) without clinical suspicion of infective endocarditis (IE). Patients with incidental MEDs were apyrexial, and those tested demonstrated low inflammatory markers and negative blood cultures (BC). In this group, the majority (83%) of MEDs were in the right atrium and no MEDs were detected near the tricuspid valve. Transesophageal echocardiography (TEE) did not influence clinical outcomes. No patient required long-term antibiotics or lead extraction and no IE-related deaths were identified from electronic health records during a mean follow-up period of 43 months (1-89). In contrast, nine patients with suspected IE were all pyrexial with elevated inflammatory markers, had positive BC, and had proven IE. In these cases, the majority of MEDs were at the device lead/tricuspid valve interface. MEDs close to the tricuspid valve were strongly associated with IE (P < .0001). CONCLUSIONS: The incidence of MEDs on CIED leads detected on routine TTE was 1.6%. Conservative management of asymptomatic patients with normal inflammatory markers and BC without TEE, antibiotics, or lead extraction did not reveal any signal for long-term adverse events within the limitations of the study.

The desire for physiological pacing: Are we there yet?

Pacing is a well established therapy for bradycardia support and certain types of heart failure. Despite technological advances the optimal pacing lead position remains controversial. Right ventricular pacing, particularly apical has been the site of choice but the induction of abnormal cardiac depolarization and the recognition of an increased risk of impairment of left ventricular systolic function, heart failure and mortality has driven a desire for a true physiological pacing system. A number of different lead positions have been determined and of these His bundle pacing appears to most closely mimic normal ventricular conduction. This article reviews the background to the development of physiological pacing, evaluates historical data for right ventricular pacing and the basis for change and new lead positions.

The quest for physiological pacing-Does one size fit all?

Pacing is an established and ubiquitous treatment of bradycardias and some types of heart failure. The optimal pacing lead position which maximizes cardiac function and minimizes deterioration of ventricular function remains controversial. The desire to achieve a physiological pacing system that mimics cardiac function has led to the investigation of several potential pacing sites. This editorial provides an overview of past and current pacing lead position and summaries the current and future direction of physiological pacing.

Search for the optimal right ventricular pacing site: design and implementation of three randomized multicenter clinical trials.

BACKGROUND: The optimal site to permanently pace the right ventricle (RV) has yet to be determined. To address this issue, three randomized prospective multicenter clinical trials are in progress comparing the long-term effects of RV apical versus septal pacing on left ventricular (LV) function. The three trials are Optimize RV Selective Site Pacing Clinical Trial (Optimize RV), Right Ventricular Apical and High Septal Pacing to Preserve Left Ventricular Function (Protect Pace), and Right Ventricular Apical versus Septal Pacing (RASP). METHODS: Patients that require frequent or continuous ventricular pacing are randomized to RV apical or septal pacing. Optimize RV excludes patients with LV ejection fraction <40% prior to implantation, whereas the other trials include patients regardless of baseline LV systolic function. The RV septal lead is positioned in the mid-septum in Optimize RV, the high septum in Protect Pace, and the mid-septal inflow tract in RASP. Lead position is confirmed by fluoroscopy in two planes and adjudicated by a blinded panel. The combined trials will follow approximately 800 patients for up to 3 years. RESULTS: The primary outcome in each trial is LV ejection fraction evaluated by radionuclide ventriculography or echocardiography. Secondary outcomes include echo-based measurements of ventricular/atrial remodeling, 6-minute hall walk distance, brain natriuretic peptide levels, and clinical events (atrial tachyarrhythmias, heart failure, stroke, or death). CONCLUSION: These selective site ventricular pacing trials should provide evidence of the importance of RV pacing site in the long-term preservation of LV function in patients that require ventricular pacing and help to clarify the optimal RV pacing site.

Dyssynchrony, contraction efficiency and regional function with apical and non-apical RV pacing.

BACKGROUND: Recent work has shown no difference in change of LVEF between RV apical (RVA) pacing and non-RVA pacing in patients with normal LV function. We hypothesised that a more sensitive marker (global longitudinal strain, GLS) could identify a detrimental effect of RVA and that assessment of deformation could identify whether dyssynchrony, contraction inefficiency and regional LV impairment were responsible for functional changes. METHODS: In this substudy of Protect-PACE (The Protection of Left Ventricular Function During Right Ventricular Pacing. Does Right Ventricular High-septal Pacing Improve Outcome Compared With Right Ventricular Apical Pacing?), a randomised controlled trial of RVA and non-RVA pacing in pacemaker-dependent patients with preserved EF, 145 patients (76 with RVA) with echocardiograms of sufficient quality underwent measurement of LV longitudinal strain (GLS) from speckle tracking just after implantation and at 2 years. LV dyssynchrony, discoordination and regional apical longitudinal strain were also measured. RESULTS: Pacing was associated with reduced GLS after 2 years, although 2-year GLS was lower in RVA (-13.9 ± 4.1 vs -15.5 ± 4.6, p = 0.02). RVA was an independent correlate of ΔGLS, although there was a minor difference in ΔGLS between the RVA and non-RVA groups (-1.8 ± 3.6 vs -0.8 ± 3.4%, p= 0.07), reflecting impairment of GLS at baseline in RVA. Apical strain was significantly lower in RVA than those in non-RVA at baseline and 2 years (both p < 0.01). Dyssynchrony and discoordination parameters at 2 years also showed significant deterioration in RVA. Apical strain, dyssynchrony and discoordination parameters at 2 years were significantly associated with ΔGLS. CONCLUSIONS: Inefficient dyssynchronous contraction and the decrease in apical strain appear to be associated with global LV impairment in RVA. TRIAL REGISTRATION NUMBER: PROTECT-PACE ClinicalTrials.gov number NCT00461734.

Effect of Right Ventricular Pacing on Right Ventricular Mechanics and Tricuspid Regurgitation in Patients With High-Grade Atrioventricular Block and Sinus Rhythm (from the Protection of Left Ventricular Function During Right Ventricular Pacing Study).

Right ventricular (RV) pacing has been linked with lead-induced tricuspid regurgitation (TR), left ventricular (LV) dysfunction, and dyssynchrony, but the effect of pacing on RV function is unclear. We sought to investigate the effect of pacing on RV synchrony, RV function, and TR, and their association with LV function. In this substudy of the PROTECT-PACE (Protection of left ventricular function during right ventricular pacing) study of the effects of RV pacing in patients with preserved ejection fraction, 145 patients (76 RV apex and 69 non-RV apex pacing) had measurable RV parameters. We assessed tricuspid annular plane systolic excursion (TAPSE), time difference between peak TAPSE and peak mitral annular plane systolic excursion (TM-APSE-dif), global LV longitudinal strain, E/e', TR vena contracta, and TR peak gradient. Echocardiography was performed just after implantation and at 2 years. TR parameters significantly worsened after 2 years, but pacing site was not associated with changes in RV and TR parameters. No temporal change in TAPSE and TM-APSE-dif was observed overall, but worsening of TM-APSE-dif was associated with worsening TAPSE. Global longitudinal strain and E/e' both deteriorated over 2 years; these changes were significantly associated. In a multivariate regression, worsening global longitudinal strain and worsening TM-APSE-dif were significantly associated with deterioration of TAPSE. Furthermore, increased E/e' and its deterioration were associated with worsening TR vena contracta and TR peak gradient, respectively. Decreased TAPSE was also associated with deterioration of TR vena contracta. In conclusion, RV pacing appears to worsen TR, an effect which might be caused by elevated LV filling pressure due to LV dysfunction. In this study, RV pacing did not affect RV function during 2-year follow-up, but such an effect might occur if RV dyssynchrony or LV dysfunction occurred after pacing. The effect of RV pacing site on RV and TR mechanics was minor.

Incremental value of left atrial structural and functional characteristics for prediction of atrial fibrillation in patients receiving cardiac pacing.

BACKGROUND: Better prediction of cardiac pacing patients at risk of atrial fibrillation (AF) would enable more effective prophylaxis. We sought whether left atrial (LA) electromechanical conduction time (EMT) and myocardial mechanics were associated with incident AF in patients undergoing dual chamber pacemaker implantation, independent of left atrial volume (LAV). METHODS AND RESULTS: Clinical data were obtained prospectively in 146 enrollees (73±10 years) undergoing dual chamber pacemaker implantation in the Protect-Pace study. Echocardiograms and 2-dimensional strain analysis were obtained post implantation and at 2 years. Complete ascertainment of AF during follow-up was identified from interrogation of permanent pacemakers. Cox regression was used to identify correlates of AF. Incident AF (n=29, 20%) was associated with higher systolic blood pressure (P=0.01), lower left ventricular ejection fraction (P=0.03), lower LA strain at atrial contraction (LASac; P<0.001), higher LAV (P<0.003), and longer septal electromechanical conduction time (P<0.01). The associations of LAV and LASac with incident AF were independent of age, sex, systolic blood pressure, and left ventricular size and function. However, the combination of the 3 strongest predictors showed LASac (P=0.02) and systolic blood pressure (P=0.01) were independently associated with incident AF, but LAV was not (P=0.07). Using the optimal cut points from receiver operator characteristic curves (62 mL for LAV and 8.6% for LASac), we demonstrated that a significantly greater rate of AF was associated with both lower LASac at higher LAV and with lower LASac at lower LAV. CONCLUSIONS: The risk of AF in patients receiving dual chamber pacing is independently associated with LA size and function, not left ventricular structural and functional characteristics or right ventricular lead location. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00461734.

Clinical trials update from the American Heart Association meeting: Omega-3 fatty acids and arrhythmia risk in patients with an implantable defibrillator, ACTIV in CHF, VALIANT, the Hanover autologous bone marrow transplantation study, SPORTIF V, ORBIT and PAD and DEFINITE.

The American Heart Association meeting reported the results of several clinical trials of particular interest to those who care for patients with heart failure. Omega-3 fatty acids were associated with a trend to increased recurrence of ventricular arrhythmias but not mortality in patients with an implantable debrillator. The ACTIV in CHF study provides more evidence of a therapeutic role for arginine vasopressin antagonists in the treatment of heart failure. The VALIANT study provides further evidence to suggest that a combination of angiotensin receptor antagonist and ACE inhibitor does not reduce mortality but may reduce morbidity in post-MI patients with heart failure or major LV systolic dysfunction. A study of autologous bone marrow cell transplantation into myocardial scar give gave encouraging results. SPORTIF V showed ximelagation to be as effective as warfarin but with improved safety. ORBIT and PAD showed public access defibrillators saved lives but questioned their cost effectiveness. DEFINITE supported a role for ICDs in patients with non-ischemic cardiomyopathy, although cost-effectiveness remains in doubt.

Clinical trials update and cumulative meta-analyses from the American College of Cardiology: WATCH, SCD-HeFT, DINAMIT, CASINO, INSPIRE, STRATUS-US, RIO-Lipids and cardiac resynchronisation therapy in heart failure.

This article continues a series of reports on recent research developments in the field of heart failure. Key presentations made at the American College of Cardiology meeting, held in New Orleans, Louisiana, USA in March 2004 are reported. These new data have been added to existing data in cumulative meta-analyses. The WATCH study randomised 1587 patients with heart failure and left ventricular systolic dysfunction to warfarin, aspirin or clopidogrel. The study showed no difference between the effects of these agents on mortality or myocardial infarction, but hospitalisations for heart failure were higher on aspirin (22.2%) compared to warfarin (16.1%). The SCD-HeFT study showed that ICD therapy reduced all-cause mortality at 5 years by 23% in patients with predominantly NYHA class II heart failure and left ventricular systolic dysfunction, but amiodarone was ineffective. The DINAMIT study showed that ICD therapy was not beneficial in patients with left ventricular dysfunction after a recent MI, even in those with risk factors for arrhythmic death. In CASINO, levosimendan improved survival compared with dobutamine or placebo in patients with decompensated heart failure. INSPIRE showed that SPECT imaging can be used to assess risk early after acute MI safely and accurately. Rimonabant was shown to be safe and effective in treating the combined cardiovascular risk factors of smoking and obesity. An overview of new developments in cardiac resynchronisation therapy (CRT) in heart failure is also reported.

Pacing site in pacemaker dependency: is right ventricular septal lead position the answer?

The right ventricular apex has been the traditional site for lead placement in patients with atrioventricular block. Pacing at the right ventricular apex may have long-term deleterious effects on left ventricular (LV) function, promoting heart failure and increasing mortality. Pacing at the right ventricular septum has been proposed to minimize deterioration in LV function. Although experimental data suggest that septal pacing protects LV function, clinical studies have provided conflicting results. A recent large study in patients with heart block did not show a protective effect with septal pacing. Other pacing approaches are becoming increasingly relevant; however, prediction of what method should be employed in which patient is not currently possible. Other factors such as baseline LV function and associated co-morbidities impact LV function, irrespective of pacing site. Continued monitoring of cardiac function post-implant is therefore critical to ongoing care. An algorithm for managing patients with atrioventricular block is proposed.

Culture negative mitral valve endocarditis caused by Neisseria gonorrhoeae confirmed by 16S rDNA sequence analysis of resected valvular tissue.

Infective endocarditis is a dynamic disease with changing epidemiology and diagnostic strategies. Culture negative endocarditis poses a particular problem for clinicians regarding appropriate antimicrobial therapy and adequate duration of therapy. Utilization of nucleic acid amplification techniques and subsequent sequencing has provided clinicians an alternative to traditional phenotypic microbial identification which has been extremely useful in identification of fastidious organisms. We report a case of a young male with culture negative native mitral valve endocarditis and subsequent 16S rDNA sequencing of Neisseria gonorrhoeae from excised valvular tissue and embolic material. Identification of this organism with novel nucleic acid amplification and 16S rDNA sequence analysis techniques permitted targeted antibiotic therapy and successful treatment of this potentially fatal disease.

Can transventricular intracardiac impedance measurement discriminate haemodynamically unstable ventricular arrhythmias in human?

AIMS: To measure changes in transventricular impedance during arrhythmias. METHODS AND RESULTS: Patients were studied during electrophysiological studies. A quadrapolar catheter was positioned at the right ventricular apex (RVA) and a decapolar catheter within the coronary sinus (CS). Transventricular impedance was measured by injecting a subthreshold biphasic rectangular pulse of 600 micro A between poles 1 of the CS catheter and pole 1 of the RVA catheter and the voltage measured between CS pole 10 and RVA catheter pole 4. Stroke impedance (SZ), surface ECG, intracardiac electrogram (IEGM), and invasive femoral artery blood pressure (FAP) were recorded. Twenty-eight patients were analysed, 5 with inducible, haemodynamically unstable ventricular tachycardia (VT) (HUSVT), 5 with stable VT (HSVT). During HUSVT, the SZ value reduced to 22% (range 0.15-0.32 P < 0.001) in comparison with sinus rhythm. For HSVT, the SZ value reduced to 58% (range 0.33-0.88) P < 0.01, significantly different from HUSVT (P < 0.01). There was a good correlation between reduction of SZ and arterial pulse pressure (PP) during arrhythmias (r = 0.95). CONCLUSION: Changes in SZ strongly correlated with PP amplitude. Transventricular impedance fell significantly during unstable arrhythmias and may be useful as a sensor capable of haemodynamic discrimination.

The use of unipolar intracardiac impedance for discrimination of haemodynamically stable and unstable arrhythmias in man.

AIMS: To determine the feasibility of discriminating haemodynamically stable from unstable arrhythmias using right ventricular (RV) unipolar intracardiac impedance (Z). METHODS AND RESULTS: A quadrapolar temporary pacing electrode was positioned at the RV apex and unipolar impedance was measured between the tip electrode and a surface patch electrode. Changes in peak-to-peak Z amplitude were measured simultaneously with surface ECG and blood pressure during induced arrhythmias. Haemodynamic instability was defined as a systolic pressure of <90 mmHg. There were 25 episodes of ventricular fibrillation (VF) induced in 15 patients, 18 episodes of ventricular tachycardia in 16 patients, and 33 episodes of supraventricular tachycardia (SVT) in 16 patients. Compared with the baseline rhythm, mean Z amplitude reduced from 51.3+/-7.7 to 11.2+/-7.4 Ohm (P<0.001) during VF, from 52.2+/-6.3 to 21.7+/-10.1 Ohm (P<0.01) during haemodynamically unstable VT, from 55.0+/-6.9 to 39.9+/-11 Ohm (ns) during stable VT, and from 56.4+/-8.4 to 36.9+/-9.3 Ohm during SVT (P<0.001). CONCLUSION: Right ventricular unipolar impedance is an adequate sensor for determining mechanical ventricular contraction and acts as a surrogate marker for a fall in arterial blood pressure during VF. However, for ventricular and supraventricular tachycardias, variations between patients did not allow adequate discrimination between stable and unstable arrhythmias.

Cardiac resynchronization therapy: redefining the role of device therapy in heart failure.

That cardiac dyssynchrony can contribute to a decline in cardiac efficiency has been recognized in one form or another for at least 50 years. Although revascularization and beta-blockers can improve cardiac synchrony, there was little interest in or awareness of this clinical entity until the advent of specific, highly effective therapy using atriobiventricular pacing, often described as cardiac resynchronization therapy. Over the last few years, significant advances in cardiac resynchronization therapy technology and the publication of large-scale clinical trials using cardiac resynchronization therapy devices in patients with heart failure have led to the widespread use of these devices. This review will briefly describe the complex nature of cardiac dyssynchrony, what is known about its epidemiology, the effects of cardiac resynchronization therapy, appropriate patient selection, practical aspects, such as implantation and monitoring, and some still unanswered questions.

Cardiac resynchronization therapy with or without an implantable defibrillator: only indicated when everything else has failed?

Cardiac resynchronization therapy (CRT) is potentially an important new treatment for patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony. There is growing evidence that CRT can improve symptoms although it is possible that similar benefits could be obtained by skillful manipulation of pharmacological therapy. There is also preliminary but inconclusive evidence to suggest that CRT alone or in synergy with an implantable cardiac defibrillator (ICD) may reduce morbidity and mortality. However, fashion is in danger of overtaking facts and it is important to ensure that benefits are not only statistically proven but clinically meaningful and cost-effective. Optimal timing of intervention and patient selection will be essential to ensure that treatment is deployed efficiently. If CRT with or without ICD becomes part of mainstream therapy for heart failure this will have far-reaching consequences for heart failure management. Implantation is a skilled and often time-consuming procedure. Long-term management of both CRT and ICD is likely to provide challenges in terms of lead technology, pacing thresholds and device management. Heart failure physicians will have to learn new skills and collaborate more closely with electrophysiologists. Such developments, in addition to the need for complex pharmacological interventions will accelerate the move away from general practice and towards specialist care for this most common of malignant diseases. If CRT does reduce mortality, it will graduate from an adjunctive therapy which could be used to an essential one that should be used as part of routine therapy for appropriate patients. Currently, CRT is a symptomatic therapy for patients with severe heart failure resistant to intensive pharmacological therapy delivered by a heart failure specialist.

Outcome studies with device therapy in patients with heart failure.

Heart failure is a common debilitating condition for which pharmacologic therapy thus far has provided only partial relief. Despite, and sometimes because of, medical therapy, the overall prognosis remains poor, with high rates of sudden death and death from progressive heart failure. Device-based therapies offer considerable promise for relief of symptoms and for improving prognosis. It is clear that implantable defibrillators should be considered for patients with heart failure who have been resuscitated from ventricular fibrillation or sustained ventricular tachycardia. Several large studies currently are investigating the effects of implantable defibrillators on total mortality in patients with major left ventricular systolic dysfunction but without other risk factors for sudden death. Cardiac resynchronization is a promising new therapy that may relieve the symptoms of heart failure in appropriately selected patients resistant to optimal pharmacologic therapy. Two large trials (CARE-HF and COMPANION) currently are investigating the effects of cardiac resynchronization therapy (CRT) on morbidity and mortality. It is important that those involved in these trials enroll patients quickly and minimize device implantation into patients who have not been assigned this therapy (cross-overs). Overenthusiasm for the benefits that doctors believe devices might bring could destroy the future basis for our clinical practice, denying future generations of patients and the doctors themselves access to what they believe to be effective treatments.