François Regoli

Characterization of Left Ventricular Activation in Patients With Heart Failure and Left Bundle-Branch Block

Background—Conventional activation mapping in the dilated human left ventricle (LV) with left bundle-branch block (LBBB) morphology is incomplete given the limited number of recording sites that may be collected in a reasonable time and given the lack of precision in marking specific anatomic locations. Methods and Results—We studied LV activation sequences in 24 patients with heart failure and LBBB QRS morphology with simultaneous application of 3D contact and noncontact mapping during intrinsic rhythm and asynchronous pacing. Approximately one third of the patients with typical LBBB QRS morphology had normal transseptal activation time and a slightly prolonged or near-normal LV endocardial activation time. A “U-shaped” activation wave front was present in 23 patients because of a line of block that was located anteriorly (n=12), laterally (n=8), and inferiorly (n=3). Patients with a lateral line of block had significantly shorter QRS (P <0.003) and transseptal durations (P <0.001) and a longer distance from the LV breakthrough site to line of block (P <0.03). Functional behavior of the line of block was demonstrated by a change in its location during asynchronous ventricular pacing at different sites and cycle lengths. Conclusions—A U-shaped conduction pattern is imposed on the LV activation sequence by a transmural functional line of block located between the LV septum and the lateral wall with a prolonged activation time. Assessment of functional block is facilitated by noncontact mapping, which may be useful for identifying and targeting specific locations that are optimal for successful cardiac resynchronization therapy.

A meta-analysis of remote monitoring of heart failure patients

OBJECTIVES The purpose of this study was to assess the effect of remote patient monitoring (RPM) on the outcome of chronic heart failure (HF) patients. BACKGROUND RPM via regularly scheduled structured telephone contact between patients and health care providers or electronic transfer of physiological data using remote access technology via remote external, wearable, or implantable electronic devices is a growing modality to manage patients with chronic HF. METHODS After a review of the literature published between January 2000 and October 2008 on a multidisciplinary heart failure approach by either usual care (in-person visit) or RPM, 96 full-text articles were retrieved: 20 articles reporting randomized controlled trials (RCTs) and 12 reporting cohort studies qualified for a meta-analysis. RESULTS Respectively, 6,258 patients and 2,354 patients were included in RCTs and cohort studies. Median follow-up duration was 6 months for RCTs and 12 months for cohort studies. Both RCTs and cohort studies showed that RPM was associated with a significantly lower number of deaths (RCTs: relative risk [RR]: 0.83, 95% confidence interval [CI]: 0.73 to 0.95, p = 0.006; cohort studies: RR: 0.53, 95% CI: 0.29 to 0.96, p < 0.001) and hospitalizations (RCTs: RR: 0.93, 95% CI: 0.87 to 0.99, p = 0.030; cohort studies: RR: 0.52, 95% CI: 0.28 to 0.96, p < 0.001). The decrease in events was greater in cohort studies than in RCTs. CONCLUSIONS RPM confers a significant protective clinical effect in patients with chronic HF compared with usual care.

Long-term survival in patients undergoing cardiac resynchronization therapy: the importance of performing atrio-ventricular junction ablation in patients with permanent atrial fibrillation

Aims To investigate the effects of cardiac resynchronization therapy (CRT) on survival in heart failure (HF) patients with permanent atrial fibrillation (AF) and the role of atrio-ventricular junction (AVJ) ablation in these patients. Methods and results Data from 1285 consecutive patients implanted with CRT devices are presented: 1042 patients were in sinus rhythm (SR) and 243 (19%) in AF. Rate control in AF was achieved by either ablating the AVJ in 118 patients (AVJ-abl) or prescribing negative chronotropic drugs (AF-Drugs). Compared with SR, patients with AF were significantly older, more likely to be non-ischaemic, with higher ejection fraction, shorter QRS duration, and less often received ICD back-up. During a median follow-up of 34 months, 170/1042 patients in SR and 39/243 in AF died (mortality: 8.4 and 8.9 per 100 person-year, respectively). Adjusted hazard ratios were similar for all-cause and cardiac mortality [0.9 (0.57–1.42), P = 0.64 and 1.00 (0.60–1.66) P = 0.99, respectively]. Among AF patients, only 11/118 AVJ-abl patients died vs. 28/125 AF-Drugs patients (mortality: 4.3 and 15.2 per 100 person-year, respectively, P < 0.001). Adjusted hazard ratios of AVJ-abl vs. AF-Drugs was 0.26 [95% confidence interval (CI) 0.09–0.73, P = 0.010] for all-cause mortality, 0.31 (95% CI 0.10–0.99, P = 0.048) for cardiac mortality, and 0.15 (95% CI 0.03–0.70, P = 0.016) for HF mortality. Conclusion Patients with HF and AF treated with CRT have similar mortality compared with patients in SR. In AF, AVJ ablation in addition to CRT significantly improves overall survival compared with CRT alone, primarily by reducing HF death.

Timing and Magnitude of Regional Right Ventricular Function: A Speckle Tracking-Derived Strain Study of Normal Subjects and Patients with Right Ventricular Dysfunction

BACKGROUND The aim of this study was to evaluate the timing and magnitude of global and regional right ventricular (RV) function by means of speckle tracking-derived strain in normal subjects and patients with RV dysfunction. METHODS Peak longitudinal systolic strain (PLSS) and time to PLSS in 6 RV segments (the basal, mid, and apical segments of the RV free wall and septum) were obtained in 100 healthy volunteers and 76 patients with RV dysfunction by tracking speckles inside the myocardium using grayscale images. Global PLSS and time to PLSS were based on the average of the 6 regional values. RESULTS There was a significant and close correlation between RV contractility as measured by PLSS and tricuspid annular plane systolic excursion (r = -0.83, P < .001). In normal subjects, PLSS was significantly greater in the free wall than in the septum (-28.7 + or - 4.1% vs -19.8 + or - 3.4%, P < .001), whereas time to PLSS was similar in the different regions of the right ventricle. In patients with RV dysfunction, global and regional PLSS was significantly less than in normal subjects (-13.7 + or - 3.6% vs -24.2 + or - 2.9%, P < .001), and a global PLSS cutoff value of -19% was helpful in distinguishing the two groups. Furthermore, time to PLSS in all of the RV septal segments and dispersion in RV contraction timing were significantly longer. Global PLSS in the patients with RV dysfunction was also significantly less in the presence of moderate to severe pulmonary hypertension (-12.7 + or - 3.6% vs -14.4 + or - 3.4%, P = .038). CONCLUSIONS Speckle tracking not only makes it possible to quantify global RV function but also illustrates the physiology of RV contraction and the pattern of activation at regional level. Speckle tracking-derived strain could become an important new means of assessing and following up patients with impaired RV function and increased pulmonary pressure.

A simplified biventricular defibrillator with fixed long detection intervals reduces implantable cardioverter defibrillator (ICD) interventions and heart failure hospitalizations in patients with non-ischaemic cardiomyopathy implanted for primary prevention: the RELEVANT [Role of long dEtection window programming in patients with LEft VentriculAr dysfunction, Non-ischemic eTiology in primary prevention treated with a biventricular ICD] study

Aims To investigate the efficacy and safety of a cardiac resynchronization therapy with cardioverter–defibrillator (CRT-D) device with simplified ventricular tachycardia management in patients with non-ischaemic heart failure (HF) and primary prevention implantable cardioverter defibrillator (ICD) indication. Methods and results Prospective, controlled, parallel, multicentre, non-randomized study enrolling 324 primary prevention non-ischaemic HF patients implanted with CRT-D devices from 2004 to 2007: Protect group, 164 patients implanted with a Medtronic Insync III Protect device and Control group, 160 patients utilizing other Medtronic CRT-D devices. Efficacy was assessed by computing appropriate and inappropriate detections and therapies during follow-up; safety compared hospitalizations and syncopal events between groups. Ninety per cent of both ventricular and supraventricular tachyarrhythmias terminated within the 13–29 beat detection interval with the Protect algorithm. The Protect group showed a significantly better event-free survival to first delivered therapy for total (P = 0.0001), appropriately treated (P = 0.002), and inappropriately treated episodes (P = 0.017). The total number of delivered shocks was significantly lower in the Protect group (22 vs. 59, P < 0.0001). In the Protect group, a significantly reduced HF hospitalization (hazard ratio 0.38, 95% CI 0.15–0.98, P = 0.044) was observed without any increase of syncope or death. Conclusion A simplified CRT-D device with fixed long detection reduced overall ICD therapy burden and HF hospitalizations without entailing any additional adverse events in primary prevention non-ischaemic HF patients.

Evaluation of the left atrial appendage with real-time 3-dimensional transesophageal echocardiography: implications for catheter-based left atrial appendage closure.

Background— Precise knowledge of left atrial appendage (LAA) orifice size is crucial for correct sizing of LAA closure devices. The aim of the present study was to determine the performance of real-time 3D transesophageal echocardiography (RT3DTEE) for LAA orifice size assessment, compared with 2D transesophageal echocardiography (2DTEE), and to investigate the impact of atrial fibrillation (AF) on LAA orifice size. Methods and Results— One hundred thirty-seven patients (38 control subjects, 31 with paroxysmal AF, 38 with persistent AF and 30 with permanent AF) underwent 2DTEE and RT3DTEE. Both techniques were used to measure LAA orifice area. Clinically-indicated 64-slice computed tomography (CT) was used as reference technique in 46 patients. Two-dimensional TEE underestimated LAA orifice area, compared with RT3DTEE (1.99±0.94 cm2 versus 3.05±1.27 cm2; P <0.001). RT3DTEE showed higher correlation with CT for the assessment of LAA orifice area, compared with 2DTEE ( r =0.92; 95% confidence interval, 0.85 to 0.95, versus r =0.72; 95% confidence interval, 0.54 to 0.83, respectively). At Bland–Altman analysis, RT3DTEE and 2DTEE underestimated LAA orifice area, compared with CT. However, RT3DTEE showed smaller bias (0.07 cm2 versus 0.72 cm2) and narrower limits of agreement (−0.71 to 0.85 cm2 versus −0.58 to 2.02 cm2) with CT, compared with 2DTEE. Among AF patients, a progressive increase in RT3DTEE-derived LAA orifice area was observed with increasing frequency of AF ( P <0.001). At multivariate analysis, AF and left atrial volume index ( P <0.001 for both) were independently associated with RT3DTEE-derived LAA orifice area. Conclusions— RT3DTEE is more accurate than 2DTEE for the assessment of LAA orifice size. A progressive increase in LAA orifice area is observed with increasing frequency of AF.Background— Precise knowledge of left atrial appendage (LAA) orifice size is crucial for correct sizing of LAA closure devices. The aim of the present study was to determine the performance of real-time 3D transesophageal echocardiography (RT3DTEE) for LAA orifice size assessment, compared with 2D transesophageal echocardiography (2DTEE), and to investigate the impact of atrial fibrillation (AF) on LAA orifice size. Methods and Results— One hundred thirty-seven patients (38 control subjects, 31 with paroxysmal AF, 38 with persistent AF and 30 with permanent AF) underwent 2DTEE and RT3DTEE. Both techniques were used to measure LAA orifice area. Clinically-indicated 64-slice computed tomography (CT) was used as reference technique in 46 patients. Two-dimensional TEE underestimated LAA orifice area, compared with RT3DTEE (1.99±0.94 cm2 versus 3.05±1.27 cm2; P<0.001). RT3DTEE showed higher correlation with CT for the assessment of LAA orifice area, compared with 2DTEE (r=0.92; 95% confidence interval, 0.85 to 0.95, versus r=0.72; 95% confidence interval, 0.54 to 0.83, respectively). At Bland–Altman analysis, RT3DTEE and 2DTEE underestimated LAA orifice area, compared with CT. However, RT3DTEE showed smaller bias (0.07 cm2 versus 0.72 cm2) and narrower limits of agreement (−0.71 to 0.85 cm2 versus −0.58 to 2.02 cm2) with CT, compared with 2DTEE. Among AF patients, a progressive increase in RT3DTEE-derived LAA orifice area was observed with increasing frequency of AF (P<0.001). At multivariate analysis, AF and left atrial volume index (P<0.001 for both) were independently associated with RT3DTEE-derived LAA orifice area. Conclusions— RT3DTEE is more accurate than 2DTEE for the assessment of LAA orifice size. A progressive increase in LAA orifice area is observed with increasing frequency of AF.

Economic impact of remote patient monitoring: an integrated economic model derived from a meta-analysis of randomized controlled trials in heart failure.

To assess the cost‐effectiveness and the cost utility of remote patient monitoring (RPM) when compared with the usual care approach based upon differences in the number of hospitalizations, estimated from a meta‐analysis of randomized clinical trials (RCTs).

Feasibility, safety, and short-term outcome of leadless ultrasound-based endocardial left ventricular resynchronization in heart failure patients: results of the wireless stimulation endocardially for CRT (WiSE-CRT) study.

AIMS Left ventricular (LV) endocardial pacing may address the limitations in the selection of an LV pacing site and provide improvements in cardiac resynchronization therapy (CRT) effectiveness. We report on the feasibility, the safety, and the short-term outcome of a leadless ultrasound-based technology for LV endocardial resynchronization in heart failure (HF) patients enroled into the Wireless Stimulation Endocardially for CRT (WiSE-CRT) study. METHODS AND RESULTS Seventeen HF patients were enroled and categorized as: (i) patients in whom attempted coronary sinus lead implantation for CRT had failed (n = 7); (ii) patients with a previously implanted CRT device, not responding to CRT (n = 2); and (iii) patients with previously implanted pacemakers or implantable cardioverter-defibrillator and meeting the standard indications for CRT (n = 8). System implantation was achieved in 13 patients (76.5%); mean R-wave amplitude was 5.6 ± 3.2 mV and the mean pacing threshold was 1.6 ± 1.0 V, respectively. In one patient, no sufficient pacing thresholds were found; in three patients pericardial effusion occurred. Biventricular pacing was recorded in 83% and 92% of the patients at 1 month and 6 months, respectively. QRS duration was shorter during biventricular pacing compared with right ventricular pacing at 1 month (-41 ms; P = 0.0002) and 6 months (-42 ms; P = 0.0011), respectively. At the 6-month follow-up, two-thirds of the patients had at least one functional class change. Left ventricular ejection fraction significantly increased (P < 0.01) by 6 points at the 6-month follow-up. CONCLUSION The feasibility of providing an endocardial stimulation for CRT with a leadless technology was successfully demonstrated. Despite the promising results for a novel technology, further study is required to definitively conclude the safety and the performance of the system. CLINICAL TRIAL REGISTRATION INFORMATION NCT01294527.

Resumption of sinus rhythm in patients with heart failure and permanent atrial fibrillation undergoing cardiac resynchronization therapy: a longitudinal observational study

AIMS To investigate the temporal patterns, predictors, and prognostic impact of spontaneous sinus rhythm resumption (SRR) of heart failure (HF) patients with permanent atrial fibrillation (AF) treated with cardiac resynchronization therapy (CRT). METHODS AND RESULTS This multicentre, retrospective, longitudinal study analysed 330 consecutive HF patients with permanent AF treated with a CRT device (mean age 70 +/- 9 years, male 83%, ischaemic aetiology 44%, NYHA class III-IV 93%, mean QRS duration 167 +/- 40 ms, and mean ejection fraction 26 +/- 7%). Clinical, echocardiographic, and outcome data were collected during follow-up. Thirty-four patients experienced SRR after CRT (10.3%) at a median 4-month follow-up. The strongest independent predictors were end-diastolic diameter (EDD) [hazard ratios (HR) 4.03, 95% confidence intervals (95% CI) 1.43-11.36, P = 0.008], post-CRT QRS <or=150 ms (HR 2.63, 95% CI 1.02-6.67, P = 0.05), left atrium (LA) diameter <or=50 mm (HR 4.76, 95% CI 1.72-11.82, P = 0.002), and atrioventricular junction (AVJ) ablation (HR 4.27, 95% CI 1.54-11.84, P = 0.02). The coexistence of three predictors vs. zero to two predictors increased by 3.5-fold the likelihood of SRR; while the presence of all four factors improves the probability by a factor of 5.7-fold. Sinus rhythm resumption was associated with a significantly better long-term survival (log rank P = 0.03). CONCLUSION One in every 10 HF patients with permanent AF may experience SRR after CRT. Baseline EDD <or=65 mm, CRT-paced QRS <or=150 ms, LA <or=50 mm, and AVJ ablation appear to be predictive of this phenomenon.

Impact of cardiac resynchronization therapy on the severity of mitral regurgitation

AIMS Functional mitral regurgitation (MR) could be managed by both cardiac resynchronization therapy (CRT) and mitral-valve surgery. Clinical decision making regarding the appropriateness of mitral-valve surgery vs. CRT is a challenging task. This study assessed the prevalence and prognosis of various degrees of functional MR in CRT candidates. Additionally, we sought to identify functional MR patients who either can be adequately managed by CRT only or will need surgery. METHODS AND RESULTS Cardiac resynchronization therapy recipients (n= 794) were followed-up for 26 ± 18 months. Mitral regurgitation severity was quantified on scale 0-4. Cardiac resynchronization therapy responders were identified based on improvement in the New York Heart Association class and left-ventricular ejection fraction. Severity of MR and LV reverse remodelling were assessed at 3 and 12 months. Predictors of long-term MR change and CRT response were explored with multivariable models. Mitral regurgitation was present in 86%, with 35% prevalence of advanced MR (grade 3-4). Improvement of MR ≥ 1° after 12 months occurred in 46% of patients. It was relatively more frequent in patients with advanced MR at baseline (63%, P< 0.01). Baseline MR severity and change in MR at 3-month follow-up predicted response to CRT. Patients with ≥ 1° MR improvement at 12 months had more reverse remodelling compared with those with no change or worsening of MR. CONCLUSIONS Mitral regurgitation improvement at 3 months predicts CRT response and MR improvement at 12-month follow-up. This finding could have implications for subsequent MR surgical therapies.