Statistical ranking of electromechanical dyssynchrony parameters for CRT.

Objective: Mechanical evaluation of dyssynchrony by echocardiography has not replaced ECG in routine cardiac resynchronisation therapy (CRT) evaluation because of its complexity and lack of reproducibility. The objective of this study was to evaluate the potential correlations between electromechanical parameters (atrioventricular, interventricular and intraventricular from the dyssynchrony model presented in 2000), their ability to describe dyssynchrony and their potential use in resynchrony. Methods: 455 sets of the 18 parameters of the model obtained in 91 patients submitted to various pacing configurations were evaluated two by two using a Pearson correlation test and then by groups according to their ability to describe dyssynchrony, using the Column selection method of machine learning. Results: The best parameter is duration of septal contraction, which alone describes 25% of dyssynchrony. The best groups of 3, 4 and ≥8 variables describe 59%, 73% and almost 100% of dyssynchrony, respectively. Left pre-ejection interval is highly and significantly correlated to a maximum of other variables, and its decrease is associated with the favourable evolution of all other correlated parameters. Increase in filling duration and decrease in duration of septum to lateral wall contraction difference are not associated with the favourable evolution of other parameters. Conclusions: No single electromechanical parameter alone can fully describe dyssynchrony. The 18-parameter model can be simplified, but still requires at least 4-8 parameters. Decrease in left pre-ejection interval favourably drives resynchrony in a maximum of other parameters. Increase in filling duration and decrease in septum-lateral wall difference do not appear to be good CRT targets.

Variability in obstructive sleep apnea: Analysis of pacemaker-detected respiratory disturbances.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with several cardiovascular conditions. Some pacemakers feature specific algorithms detecting respiratory cycles and deriving indices well correlated with the identification of polysomnography-confirmed severe OSA. OBJECTIVES: The purposes of this study were to analyze respiratory disturbances measured by a validated algorithm in clinical practice and to describe their variability over time and their association with atrial fibrillation. METHODS: Fifty-eight patients implanted with dual-chamber LivaNova REPLY 200 DR or KORA 100 DR pacemakers measuring a respiratory disturbance index (RDI) were included. An RDI >20 events per hour of sleep is well correlated with severe OSA as determined by polysomnography. Patients with >10% nights with invalid RDI measurements were excluded. RESULTS: The RDI could be measured during 98% of nights. During a mean follow-up of 187 ± 123 days, the individual mean RDI was 19.9 ± 12.7 and was superior to 20 in 24 patients (41%). An RDI >20 events/h in at least 1 night was observed in 52 patients (90%). The mean day-to-day RDI variability in individual patients was 19% ± 21%. Patients with the highest burden of severe OSA (as defined by ≥75% of nights with RDI >20 events/h) were older, had a higher prevalence of hypertension, and were more often implanted for atrioventricular block than patients with lower burden of severe OSA. No RDI burden or cutoff was a predictor of atrial fibrillation occurrence. CONCLUSION: OSA is frequent in patients with a pacemaker and is reliably detected by pacemakers. OSA is highly variable and could probably be best analyzed in terms of burden.

Causes-of-death analysis of patients with cardiac resynchronization therapy: an analysis of the CeRtiTuDe cohort study.

AIMS: The choice of resynchronization therapy between with (CRT-D) and without (CRT-P) a defibrillator remains a contentious issue. Cause-of-death analysis among CRT-P, compared with CRT-D, patients could help evaluate the extent to which CRT-P patients would have additionally benefited from a defibrillator in a daily clinical practice. METHODS AND RESULTS: A total of 1705 consecutive patients implanted with a CRT (CRT-P: 535 and CRT-D: 1170) between 2008 and 2010 were enrolled in CeRtiTuDe, a multicentric prospective follow-up cohort study, with specific adjudication for causes of death at 2 years. Patients with CRT-P compared with CRT-D were older (P < 0.0001), less often male (P < 0.0001), more symptomatic (P = 0.0005), with less coronary artery disease (P = 0.003), wider QRS (P = 0.002), more atrial fibrillation (P < 0.0001), and more co-morbidities (P = 0.04). At 2-year follow-up, the annual overall mortality rate was 83.80 [95% confidence interval (CI) 73.41-94.19] per 1000 person-years. The crude mortality rate among CRT-P patients was double compared with CRT-D (relative risk 2.01, 95% CI 1.56-2.58). In a Cox proportional hazards regression analysis, CRT-P remained associated with increased mortality (hazard ratio 1.54, 95% CI 1.07-2.21, P = 0.0209), although other potential confounders may persist. By cause-of-death analysis, 95% of the excess mortality among CRT-P subjects was related to an increase in non-sudden death. CONCLUSION: When compared with CRT-D patients, excess mortality in CRT-P recipients was mainly due to non-sudden death. Our findings suggest that CRT-P patients, as currently selected in routine clinical practice, would not potentially benefit with the addition of a defibrillator.

Phrenic nerve stimulation in cardiac resynchronization therapy.

In cardiac resynchronization therapy (CRT), the electrical impulse delivered by the left ventricular (LV) lead may incidentally cause phrenic nerve stimulation (PNS). The purpose of this state-of-the-art review is to describe the frequency, risk factors, and clinical consequences of PNS and to present the most recent options to successfully manage PNS. PNS occurs in 2 to 37% of implanted patients and is not always detected in the supine position during implantation. Lateral and posterior veins are at higher risk of PNS than anterior veins, and apical positions are at higher risk of PNS than basal positions. The management of PNS discovered during implantation may include mapping the course of the target vein in order to find a PNS-free site, targeting another vein if available, and pacing with alternative configurations before changing the lead location. Non-invasive options for management of post-operative PNS depend on the difference between PNS and LV stimulation thresholds and include reducing the LV pacing output, automatic determination of LV stimulation threshold and minimal output delivery by the device, increasing the pulse duration, and electronic repositioning. New quadripolar leads allow to pace from different cathodes, and the multiple pacing configurations available have proved superior to bipolar leads in mitigating PNS. This electronic repositioning addresses almost all of the clinically relevant PNS and should markedly reduce the need for invasive lead repositioning or CRT abandon, which is actually the last option for 2% of patients.

First experience of intraoperative echocardiography-guided optimization of cardiac resynchronization therapy delivery.

BACKGROUND: Insufficient correction of mechanical dyssynchrony is a cause of non-response to cardiac resynchronization therapy (CRT). AIMS: To determine if CRT delivery could be optimized during the implantation procedure by choosing the number and location of pacing sites using echocardiography guidance. METHODS: In patients with a QRS ≥ 150 ms or a QRS < 150 ms and criteria for mechanical dyssynchrony, the objective of the implantation procedure was to shorten the left pre-ejection interval (LPEI), measured online, by at least 10 ms compared with standard biventricular configuration, by moving the right ventricular (RV) lead at different locations and, if necessary, by adding a second RV lead. RESULTS: Ninety-one patients (70 men; mean age 73 ± 10 years; left ventricular [LV] ejection fraction 29 ± 10%) were included. The final pacing configuration was standard biventricular in 15 (17%) patients, optimized biventricular in 22 (24%) and triple-site ventricular in 54 (59%). LPEI was shortened by ≥ 10 ms compared with standard biventricular stimulation in 73 (80%) patients. Compared with standard biventricular pacing, the final optimized pacing configuration improved global intraventricular synchrony (decreasing LPEI from 158 ± 36 ms to 134 ± 29 ms; P<0.001), LV systolic efficiency (decreasing LPEI/LV ejection time from 0.58 ± 0.18 to 0.46 ± 0.13; P<0.001) and LV filling (increasing LV filling time/RR from 44 ± 8% to 47 ± 7%; P<0.001) and decreased mitral valve regurgitation. CONCLUSION: Intraoperative echocardiography-guided placement of RV lead(s) during CRT implantation is feasible and acutely improves LV synchrony compared with standard biventricular stimulation.

Detection of occult atrial fibrillation by pacemaker interrogation in cryptogenic stroke.

PURPOSE: Atrial fibrillation (AF) is a major cause of ischemic strokes, and it is assumed that occult intermittent episodes of AF are responsible for some of the seemingly cryptogenic strokes. Cardiac pacemakers feature rhythm diagnostic capabilities and data storage. We investigated whether pacemaker memory interrogation led to identification of undetected AF episodes prior to cryptogenic strokes. METHODS: The study enrolled all patients admitted between June 2010 and July 2013 for an acute cryptogenic stroke and who were implanted with a permanent pacemaker. Patients with a history of AF and a history of stroke with an identifiable origin were excluded. Pacemaker memories were interrogated to determine the presence of AF prior to the stroke and its temporal relationship with the stroke. RESULTS: Fourteen patients (nine men and five women) with a median (interquartile range) age of 84.5 (82.25-87.5) years were included. Median CHADS2 and CHA2DS2-VASc scores were 2 (1-2.75) and 3.5 (3-4), respectively. Pacemaker memories were activated in 13 patients with atrial arrhythmia detection based on an atrial cutoff rate in 8 patients and on the detection of atrial rate acceleration in 5 patients. Electrograms were available for review in 10 patients. Unknown AF or atrial flutter was diagnosed previous to the stroke in six (43 %) patients. Four patients experienced more than one arrhythmia episode. The last episode occurred in the 48 h prior to stroke in three patients and in the previous 4 weeks in five patients. Anticoagulation was started after the stroke in all of these six patients. CONCLUSIONS: Pacemaker interrogation has a high diagnostic yield in seemingly cryptogenic stroke, with frequent detection of occult AF. The causal link between AF and stroke is convincingly reinforced by their close temporal proximity, and anticoagulation is warranted in this clinical situation.

Femoral vein thrombosis after right-sided electrophysiological procedures.

PURPOSE: Electrophysiological studies and radiofrequency catheter ablations require single or multiple sheath placements through femoral vein cannulation. The objective of this study was to determine the incidence, predictors, and outcomes of deep vein thrombosis (DVT) following such procedures. METHODS AND RESULTS: We prospectively enrolled 220 consecutive patients with a median age of 70 [60-79] years. The median duration of the procedures from insertion to removal of sheaths was 45 [30-75] min. At least two sheaths were inserted in 158 (72%) of the cases. Duplex ultrasonography evaluation of the lower leg veins was performed 6 h after the procedure and revealed common femoral vein thrombosis in 11 (5%) patients. All thrombi were partial and none was complete. Thrombi were mobile in four patients and extended to the external iliac vein in three patients. None of the patients presented with clinical signs of DVT or pulmonary embolism. Anticoagulation was prescribed for 2-4 weeks and a follow-up duplex ultrasonography obtained in the first seven patients revealed complete resolution of thrombi in all cases. On multivariate analysis, two predictors of thrombosis occurrence were identified: a greater sum of sheath diameters (odds ratio, 1.41 [95% confidence interval, 1.25-1.60] per 1-French increase; p < 0.001) and a longer procedural duration (odds ratio, 1.02 [95% confidence interval, 1.00-1.04] per 1-min increase; p = 0.04). CONCLUSIONS: Asymptomatic femoral DVT occur in 5% of electrophysiological studies and right-heart radiofrequency catheter ablations, particularly when large sheaths are inserted for a longer period. The role of anticoagulation in this clinical setting warrants further evaluation.

Impact of comorbidity on medication use in elderly patients with cardiovascular diseases: the OCTOCARDIO study.

BACKGROUND: Recommended medications are under-prescribed in elderly patients with atrial fibrillation (AF), coronary artery disease (CAD), and congestive heart failure (CHF). The relationship between under-prescribing and comorbidity is unclear. DESIGN: Single-day observational study. METHODS: Analysis of medications taken by patients aged 80 years or over at the time of their admission to cardiology units of 32 French hospitals. Comorbidity was measured using the Charlson comorbidity index (CCI). RESULTS: The study included 510 patients (57% men, mean age 85 years). History of AF, CHF, and CAD was present in 213 (42%), 199 (39%), and 187 (37%) patients, respectively. CCI was 0 in 110 (22%), 1-2 in 215 (42%), and ≥3 in 185 (36%) patients. Vitamin K antagonists (VKA) were prescribed to 105 (49%) and aspirin to 86 (40%) patients with AF. CCI did not influence VKA prescription but influenced aspirin use, with lower prescription rates in patients with CCI 1-2 than CCI 0 or CCI ≥3 (p = 0.02). In CHF, angiotensin-converting enzyme inhibitors (ACEI) and ß-blockers were prescribed to 80 (40%) and 96 (48%) patients, respectively. Rates of prescription of ACEI, ß-blockers, statins, and aspirin in patients with CAD were 43%, 56%, 56%, and 66%, respectively. CCI level did not influence any medication use in CHF and CAD. CONCLUSION: Even in the absence of comorbidity, elderly patients with major cardiovascular diseases are denied from indicated medical treatments probably because of their age alone. Implementing measures to enhance awareness of treatment benefits and promote appropriate prescribing is necessary.

Past, present and future of cardiac resynchronization.

The growing interest in dyssynchrony and cardiac resynchronization therapy has opened the field of cardiac stimulation to new haemodynamic indications. French investigators have played a key role in the formulation of new concepts, all arising from clinical observations, and the development (in collaboration with industry) and clinical evaluation of resynchronization devices. This review summarizes recent knowledge and perspectives pertaining to atrial, atrioventricular and ventricular dyssynchrony and resynchronization. Some of these concepts have been validated by robust clinical evidence, on the basis of which scientific recommendations have been formulated. Other concepts have been less successful but probably merit further attention.

Endocardial acceleration (sonR) vs. ultrasound-derived time intervals in recipients of cardiac resynchronization therapy systems.

AIMS: Optimization of cardiac resynchronization therapy (CRT) requires the gathering of cardiac functional information. An accurate timing of the phases of the cardiac cycle is key in the optimization process. METHODS AND RESULTS: We compared Doppler echocardiography to an automated system, based on the recording of sonR (formerly endocardial acceleration), in the detection of mitral and aortic valves closures and measurements of the duration of systole and diastole. We prospectively studied, under various conditions of cardiac stimulation, 75 recipients of CRT systems (69% men), whose mean age was 72 ± 9.2 years, left ventricular ejection fraction 35 ± 11%, baseline QRS duration 154 ± 29 ms, and New York Heart Association functional class 3.0 ± 0.7. We simultaneously recorded (i) sonR, detected by a non-invasive piezoelectric micro-accelerometer sensor clipped onto an electrode located in the parasternal region, (b) electrocardiogram, and (c) Doppler audio signals, using a multichannel data acquisition and analysis system. The correlation between timing of mitral and aortic valve closure by sonR vs. Doppler signals was examined by linear regression analysis. Correlation coefficients and the average absolute error were calculated. A concordance in the timing of the mitral (r = 0.86, error = 9.7 ms) and aortic (r = 0.93, error = 9.7 ms) valves closure was observed between the two methods in 94% of patients. Similarly, sonR and the Doppler-derived measurements of systolic (r = 0.85, error = 13.4 ms) and diastolic (r = 0.99, error = 12 ms) interval durations were concordant in 80% of patients. CONCLUSION: A high concordance was found between sonR and the cardiac ultrasound in the timings of aortic and mitral valve closures and in the estimation of systolic and diastolic intervals durations. These observations suggest that sonR could be used to monitor cardiac function and adaptively optimize CRT systems.

Mathematical modeling of electrocardiograms: a numerical study.

This paper deals with the numerical simulation of electrocardiograms (ECG). Our aim is to devise a mathematical model, based on partial differential equations, which is able to provide realistic 12-lead ECGs. The main ingredients of this model are classical: the bidomain equations coupled to a phenomenological ionic model in the heart, and a generalized Laplace equation in the torso. The obtention of realistic ECGs relies on other important features--including heart-torso transmission conditions, anisotropy, cell heterogeneity and His bundle modeling--that are discussed in detail. The numerical implementation is based on state-of-the-art numerical methods: domain decomposition techniques and second order semi-implicit time marching schemes, offering a good compromise between accuracy, stability and efficiency. The numerical ECGs obtained with this approach show correct amplitudes, shapes and polarities, in all the 12 standard leads. The relevance of every modeling choice is carefully discussed and the numerical ECG sensitivity to the model parameters investigated.

Responders to cardiac resynchronization therapy with narrow or intermediate QRS complexes identified by simple echocardiographic indices of dyssynchrony: the DESIRE study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is recommended for patients with NYHA class III-IV refractory heart failure (HF), ejection fraction <35% and a QRS >120 ms. We attempted to identify responders to CRT from echocardiographic (echo) indices of mechanical dyssynchrony in patients with QRS<150 ms. METHODS AND RESULTS: The study enrolled 51 men and 9 women (mean age: 64.5 years) in NYHA class III (n=54) or IV (n=6) presenting with a mean ejection fraction: 25.7%, LV end-diastolic diameter: 69.1 mm, and QRS=121+/-19 ms. All patients were implanted with a CRT system and followed for 1 year. Implantation was preceded and followed by clinical, functional and Doppler (D)-echo evaluation. The primary combined endpoint included 1) death from any cause, 2) HF-related hospitalisations, and 3) NYHA class at 6 months. Before implant, 27 patients had > or =1 echo criterion of mechanical dyssynchrony (DES+ group) and 33 had no evidence of dyssynchrony (DES- group). At 12 months, 8 patients (4 per group) had died, 7 from HF. As regards the primary endpoint at 6 months, 33 patients (55%) had improved, 10 (16%) were unchanged, and 17 (29%) had deteriorated. Clinical improvement was observed in 19 of 27 DES+ (70%), versus 14 of 33 DES- (42%) patients (P<0.04). Baseline QRS duration did not predict response to CRT. CONCLUSIONS: In this population of HF patients with QRS<150 ms, the presence of mechanical dyssynchrony at baseline D-echo examination, but not the QRS width, predicted 6-month clinical response to CRT.

Physiological approach to monitor patients in congestive heart failure: application of a new implantable device-based system to monitor daily life activity and ventilation.

AIMS: We examine an expert system designed to permanently monitor patients with congestive heart failure (CHF) using data of a dual-sensor pacemaker and to allow warning of significant changes in physiological indices. METHODS AND RESULTS: This study included 67 implanted patients divided into two groups: a control group without history of CHF (n = 19) who had received DDDR pacemakers (DDD group) and a test group (n = 48) who had received cardiac resynchronization therapy systems (CRT group) for severe CHF (NYHA III or IV, LVEF <40%). The embedded monitoring system measures minute ventilation (MV) and activity (ACT) at rest and at exercise. All devices collect data, and all adverse medical events were recorded. Data are stored daily for up to 3 months. The mean ACT was similar for both groups. Mean rest and exercise MV were significantly higher in CRT group. On 195 periods of 1-month follow-up in the CRT group, 31 events were suspected, 22 were true positive, 9 were false-positive, and 3 clinical adverse events were not predicted (sensitivity: 88%, specificity: 94.7%, positive predictive value: 71%, negative predictive value: 98.2%) CONCLUSION: A new diagnostic expert system that holds promise for the long-term ambulatory monitoring of CHF was developed.

Upgrading from single chamber right ventricular to biventricular pacing in permanently paced patients with worsening heart failure: The RD-CHF Study.

BACKGROUND: Biventricular (BiV) stimulation lowers morbidity and mortality in patients with drug-refractory congestive heart failure (CHF), depressed left ventricular (LV) function, and ventricular dyssynchrony in absence of indication for permanent cardiac pacing. This pilot, single-blind, randomized, cross-over study examined the safety and efficacy of upgrading conventional pacing systems to BiV stimulation in patients with advanced CHF. METHODS: We included 56 patients in New York Heart Association (NYHA) functional classes III or IV despite optimal drug treatment and ventricular dyssynchrony (interventriclar delay > 40 ms or LV preejection delay > 140 ms) in need of pacemaker replacement. We compared the patients' functional status, arrhythmias, and standard echocardiographic measurements during 3 months of conventional, single right ventricular (RV) versus 3 months of BiV stimulation. RESULTS: There were 44 patients in the cross-over phase. QRS duration was shortened by 23% and LV preejection delay by 16% with BiV stimulation. NYHA functional class, 6-minute hall walk and quality of life score were significantly improved with BiV stimulation compared with single RV pacing by 18%, 29%, and 19%, respectively. No significant difference was observed in the ventricular arrhythmia burden or LV reverse remodeling between the 2 periods. CONCLUSIONS: This pilot study showed that upgrading from RV pacing to BiV pacing significantly improves symptoms and exercise tolerance in chronically paced patients with advanced CHF and mechanical dyssynchrony.

Left bundle branch block as a risk factor for progression to heart failure.

The prevalence of conduction disturbances, particularly left bundle branch block (LBBB), is strongly correlated with age and with the presence of cardiovascular disease. LBBB has been reported to affect approximately 25% of the heart failure (HF) population and it is likely that the deleterious role of such conduction disorders in the progression to HF has been underestimated. The purpose of this article is to review the data from the literature indicating that LBBB may have a causative role, mediated through the resulting intra-ventricular asynchrony, in the deterioration of cardiac function and the development of cardiac remodelling and HF. It also aims to address the potential for future clinical therapies for this conduction disorder.