Non-invasive assessment of pulmonary vein isolation durability using late gadolinium enhancement magnetic resonance imaging.

AIMS: Electrical reconnection of pulmonary veins (PVs) is considered an important determinant of recurrent atrial fibrillation (AF) after pulmonary vein isolation (PVI). To date, AF recurrences almost automatically trigger invasive repeat procedures, required to assess PVI durability. With recent technical advances, it is becoming increasingly common to find all PVs isolated in those repeat procedures. Thus, as ablation of extra-PV targets has failed to show benefit in randomized trials, more and more often these highly invasive procedures are performed only to rule out PV reconnection. Here we aim to define the ability of late gadolinium enhancement (LGE)-magnetic resonance imaging (MRI) to rule out PV reconnection non-invasively. METHODS AND RESULTS: This study is based on a prospective registry in which all patients receive an LGE-MRI after AF ablation. Included were all patients that-after an initial PVI and post-ablation LGE-MRI-underwent an invasive repeat procedure, which served as a reference to determine the predictive value of non-invasive lesion assessment by LGE-MRI.: 152 patients and 304 PV pairs were analysed. LGE-MRI predicted electrical PV reconnection with high sensitivity (98.9%) but rather low specificity (55.6%). Of note, LGE lesions without discontinuation ruled out reconnection of the respective PV pair with a negative predictive value of 96.9%, and patients with complete LGE lesion sets encircling all PVs were highly unlikely to show any PV reconnection (negative predictive value: 94.4%). CONCLUSION: LGE-MRI has the potential to guide selection of appropriate candidates and planning of the ablation strategy for repeat procedures and may help to identify patients that will not benefit from a redo-procedure if no ablation of extra-PV targets is intended.

Progressive and Simultaneous Right and Left Atrial Remodeling Uncovered by a Comprehensive Magnetic Resonance Assessment in Atrial Fibrillation.

Background Left atrial structural remodeling contributes to the arrhythmogenic substrate of atrial fibrillation (AF), but the role of the right atrium (RA) remains unknown. Our aims were to comprehensively characterize right atrial structural remodeling in AF and identify right atrial parameters predicting recurrences after ablation. Methods and Results A 3.0 T late gadolinium enhanced-cardiac magnetic resonance was obtained in 109 individuals (9 healthy volunteers, 100 patients with AF undergoing ablation). Right and left atrial volume, surface, and sphericity were quantified. Right atrial global and regional fibrosis burden was assessed with validated thresholds. Patients with AF were systematically followed after ablation for recurrences. Progressive right atrial dilation and an increase in sphericity were observed from healthy volunteers to patients with paroxysmal and persistent AF; fibrosis was similar among the groups. The correlation between parameters recapitulating right atrial remodeling was mild. Subsequently, remodeling in both atria was compared. The RA was larger than the left atrium (LA) in all groups. Fibrosis burden was higher in the LA than in the RA of patients with AF, whereas sphericity was higher in the LA of patients with persistent AF only. Fibrosis, volume, and surface of the RA and LA, but not sphericity, were strongly correlated. Tricuspid regurgitation predicted right atrial volume and shape, whereas diabetes was associated with right atrial fibrosis burden; sex and persistent AF also predicted right atrial volume. Fibrosis in the RA was mostly located in the inferior vena cava-RA junction. Only right atrial sphericity is significantly associated with AF recurrences after ablation (hazard ratio, 1.12 [95% CI, 1.01-1.25]). Conclusions AF progression associates with right atrial remodeling in parallel with the LA. Right atrial sphericity yields prognostic significance after ablation.

Ablation Lesion Assessment with MRI.

Late gadolinium enhancement (LGE) MRI is capable of detecting not only native cardiac fibrosis, but also ablation-induced scarring. Thus, it offers the unique opportunity to assess ablation lesions non-invasively. In the atrium, LGE-MRI has been shown to accurately detect and localise gaps in ablation lines. With a negative predictive value close to 100% it can reliably rule out pulmonary vein reconnection non-invasively and thus may avoid unnecessary invasive repeat procedures where a pulmonary vein isolation only approach is pursued. Even LGE-MRI-guided repeat pulmonary vein isolation has been demonstrated to be feasible as a standalone approach. LGE-MRI-based lesion assessment may also be of value to evaluate the efficacy of ventricular ablation. In this respect, the elimination of LGE-MRI-detected arrhythmogenic substrate may serve as a potential endpoint, but validation in clinical studies is lacking. Despite holding great promise, the widespread use of LGE-MRI is still limited by the absence of standardised protocols for image acquisition and post-processing. In particular, reproducibility across different centres is impeded by inconsistent thresholds and internal references to define fibrosis. Thus, uniform methodological and analytical standards are warranted to foster a broader implementation in clinical practice.

Personalized assessment of the cumulative complication risk of the atrial fibrillation ablation track: The AF-TRACK calculator.

Background: Atrial fibrillation (AF) ablation strategy is associated with a non-negligible risk of complications and often requires repeat procedures (AF ablation track), implying repetitive exposure to procedural risk. Objective: The purpose of this study was to develop and validate a model to estimate individualized cumulative risk of complications in patients undergoing the AF ablation track (Atrial Fibrillation TRAck Complication risK [AF-TRACK] calculator). Methods: The model was derived from a multicenter cohort including 3762 AF ablation procedures in 2943 patients. A first regression model was fitted to predict the propensity for repeat ablation. The AF-TRACK calculator computed the risk of AF ablation track complications, considering the propensity for repeat ablation. Internal (cross-validation) and external (independent cohort) validation were assessed for discrimination capacity (area under the curve [AUC]) and goodness of fit (Hosmer-Lemeshow [HL] test). Results: Complications (N = 111) occurred in 3.7% of patients (2.9% of procedures). Predictors included female sex, heart failure, sleep apnea syndrome, and repeat procedures. The model showed fair discrimination capacity to predict complications (AUC 0.61 [0.55-0.67]) and likelihood of repeat procedure (AUC 0.62 [0.60-0.64]), with good calibration (HL χ2 12.5; P = .13). The model maintained adequate discrimination capacity (AUC 0.67 [0.57-0.77]) and calibration (HL χ2 5.6; P = .23) in the external validation cohort. The validated model was used to create the Web-based AF-TRACK calculator. Conclusion: The proposed risk model provides individualized estimates of the cumulative risk of complications of undergoing the AF ablation track. The AF-TRACK calculator is a validated, easy-to-use, Web-based clinical tool to calibrate the risk-to-benefit ratio of this treatment strategy.

Assessment of primary prevention patients receiving an ICD - Systematic evaluation of ATP: APPRAISE ATP.

BACKGROUND: The value of antitachycardia pacing (ATP) in the overall cohort of primary prevention patients who receive implantable cardioverter-defibrillators (ICDs) remains uncertain. ATP success reported in prior trials potentially included a large number of patients receiving unnecessary ATP for arrhythmias that may have self-terminated owing to the prematurity of the intervention. Although some patients derive benefit from initial ATP in terminating rapid ventricular arrhythmias and thereby preventing shocks, there are limited data allowing us to identify those patients a priori. OBJECTIVE: The purpose of APPRAISE ATP is to understand the role of ATP in primary prevention patients currently indicated for ICD therapy in a large prospective randomized controlled trial with modern programming parameters. METHODS: The study is a global, prospective, randomized, multicenter clinical trial conducted at up to 150 sites globally, enrolling approximately 2600 subjects The primary endpoint of the trial is time to first all-cause shock in a 2-arm study with an equivalent study design in which the incidence of all-cause shocks will be compared between primary prevention subjects programmed with shocks only vs subjects programmed to standard therapy (ATP and shock). RESULTS: An Electrogram and Device Interrogation Core Laboratory will review interrogation data to determine primary endpoints that occur in APPRAISE ATP. Their decisions are based on independent physician review of the data from device interrogation. CONCLUSION: The ultimate purpose of the study is to aid clinicians in the selection of ICD technologies based on hard endpoint evidence across the spectrum of indications for primary prevention implantation.

Gain in real-world cardiac resynchronization therapy efficacy with SyncAV dynamic optimization: Heart failure hospitalizations and costs.

BACKGROUND: SyncAV, a device-based cardiac resynchronization therapy (CRT) algorithm, promotes electrical optimization by dynamically adjusting atrioventricular intervals. OBJECTIVE: The purpose of this study was to evaluate the impact of SyncAV on heart failure hospitalizations (HFHs) and related costs in a real-world CRT cohort. METHODS: Patients with SyncAV-capable CRT devices followed by remote monitoring and enrolled in Medicare fee-for-service for at least 1 year preimplant and up to 2 years postimplant were studied. Patients with SyncAV OFF were 4:1 matched to those with SyncAV ON on preimplant HFH rate, demographics, comorbidities, disease etiology, and left bundle branch block. HFHs were determined from the primary diagnosis of inpatient hospitalizations, and the cost for each event was the sum of Medicare, supplemental insurance, and patient payment. RESULTS: After 4:1 propensity score matching, 3630 patients were studied (mean age 75 ± 8 years; 1386 [38%] female), including 726 (25%) patients with SyncAV ON. The pre-CRT HFH rate was 0.338 HFH events per patient-year. Overall, CRT diminished the HFH rate to 0.204 events per patient-year (P < .001). SyncAV elicited a larger reduction in HFH rate (SyncAV ON: hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.41-0.66; P < .001 and SyncAV OFF: HR 0.68; 95% CI 0.59-0.77; P < .001). After 2 years, the HFH rate was lower in the SyncAV ON group than in the SyncAV OFF group (0.143 HFHs per patient-year vs 0.193 HFHs per patient-year; HR 0.70; 95% CI 0.55-0.89; P = .003) and fewer HFHs were followed by 30-day HFH readmissions (4.41% vs 7.68%; P = .003) and 30-day all-cause hospital readmissions (7.04% vs 10.01%; P = .010). The total 2-year HFH-associated costs per patient were lower with SyncAV ON (difference $1135; 90% CI $93-$2109; P = .038). CONCLUSION: This large, real-world, propensity score-matched study demonstrates that SyncAV CRT is associated with significantly reduced HFHs and associated costs, incremental to standard CRT.

Dynamic risk assessment to improve quality of care in patients with atrial fibrillation: the 7th AFNET/EHRA Consensus Conference.

AIMS: The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes. METHODS AND RESULTS: This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence. CONCLUSION: The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.

The role of clinical assessment and electrophysiology study in Brugada syndrome patients with syncope.

BACKGROUND: Cardiogenic syncope in Brugada syndrome (BrS) increases the risk of major events. Nevertheless, clinical differentiation between cardiogenic and vasovagal syncope can be challenging. We characterized the long-term incidence of major events in a large cohort of BrS patients who presented with syncope. METHODS: From a total of 474 patients, syncope was the initial manifestation in 135 (28.5%) individuals (43.9 ±â€¯13.9 years, 71.1% male). The syncope was classified prospectively as cardiogenic, vasovagal, or undefined if unclear characteristics were present. Clinical, electrocardiographic, genetic, and electrophysiologic features were analyzed. Cardiogenic syncope, sustained ventricular arrhythmias, and sudden death were considered major events in follow-up. RESULTS: In 66 patients (48.9%), the syncope was cardiogenic; in 51 (37.8%), vasovagal and in 18 (13.3%); undefined. The electrophysiology study (EPS) inducibility was more frequent in patients with cardiogenic syncope and absent in all patients with undefined syncope (28 [53.8%] vs 5 [12.2%] vs 0 [0%]; P < .01). During follow-up (7.7 ±â€¯5.6 years), only patients with cardiogenic syncope presented major events (16 [11.9%]). Among patients with inducible EPS, 7 (21.2%) presented major events (P = .04). The negative predictive value of the EPS for major events was 92.4%. The incidence rate of major events was 2.6% person-year. Parameters associated with major events included cardiogenic syncope (hazard ratio [HR] 6.3; 95% CI 1.1-10.4; P = .05), spontaneous type 1 electrocardiogram (HR 3.7; 95% CI 1.3-10.5; P = .01), and inducible EPS (HR 2.8; 95% CI 1.1-8.8; P = .05). CONCLUSIONS: An accurate syncope classification is crucial in BrS patients for risk stratification. In patients with syncope of unclear characteristics, the EPS may be helpful to prevent unnecessary implantable cardioverter defibrillators.

Atrial high-rate episodes: prevalence, stroke risk, implications for management, and clinical gaps in evidence.

Self-terminating atrial arrhythmias are commonly detected on continuous rhythm monitoring, e.g. by pacemakers or defibrillators. It is unclear whether the presence of these arrhythmias has therapeutic consequences. We sought to summarize evidence on the prevalence of atrial high-rate episodes (AHREs) and their impact on risk of stroke. We performed a comprehensive, tabulated review of published literature on the prevalence of AHRE. In patients with AHRE, but without atrial fibrillation (AF), we reviewed the stroke risk and the potential risk/benefit of oral anticoagulation. Atrial high-rate episodes are found in 10-30% of AF-free patients. Presence of AHRE slightly increases stroke risk (0.8% to 1%/year) compared with patients without AHRE. Atrial high-rate episode of longer duration (e.g. those >24 h) could be associated with a higher stroke risk. Oral anticoagulation has the potential to reduce stroke risk in patients with AHRE but is associated with a rate of major bleeding of 2%/year. Oral anticoagulation is not effective in patients with heart failure or survivors of a stroke without AF. It remains unclear whether anticoagulation is effective and safe in patients with AHRE. Atrial high-rate episodes are common and confer a slight increase in stroke risk. There is true equipoise on the best way to reduce stroke risk in patients with AHRE. Two ongoing trials (NOAH-AFNET 6 and ARTESiA) will provide much-needed information on the effectiveness and safety of oral anticoagulation using non-vitamin K antagonist oral anticoagulants in patients with AHRE.

Management of anticoagulation in patients undergoing leadless pacemaker implantation.

BACKGROUND: The Micra transcatheter pacing system (Micra TPS) is often implanted in patients with atrial fibrillation and thus with increased thromboembolic risk. It is unknown whether the use of anticoagulants, associated with the use of a large venous introducer, implies an increased risk of bleeding in this group of patients. OBJECTIVE: The purpose of this study was to assess the incidence of bleeding and thromboembolic complications after Micra TPS implantation with and without therapeutic anticoagulation. METHODS: This single-center observational study included 107 consecutive patients receiving the Micra TPS from 2014 to 2018. At procedure completion, a figure-of-eight suture was placed at the femoral puncture site after sheath withdrawal and was maintained for 24 hours. In patients receiving enoxaparin or new oral anticoagulants, treatment was discontinued 12 or 24 hours before the procedure, respectively, and was reinitiated 4-6 hours postprocedure. In those receiving vitamin K antagonists (VKAs), dosing was not discontinued and the procedure was performed if the international normalized ratio was less than 3. RESULTS: Sixty-four patients (60%) did not receive anticoagulants. Of the 43 (40%) who did, 29 (67%) received VKAs, 8 (19%) received new oral anticoagulants, and 6 (14%) received enoxaparin. Two patients presented hemorrhagic or thromboembolic complications during short-term follow-up: 1 woman receiving VKAs presented hemorrhagic pericardial effusion without tamponade and 1 woman not receiving anticoagulants presented thrombosis of the ipsilateral saphenous vein. CONCLUSION: Bleeding and thromboembolic complications after receiving Micra TPSs are infrequent. The use of anticoagulant therapy, regardless of the type, does not increase the complications associated with the procedure.

Rationale and design of AXAFA-AFNET 5: an investigator-initiated, randomized, open, blinded outcome assessment, multi-centre trial to comparing continuous apixaban to vitamin K antagonists in patients undergoing atrial fibrillation catheter ablation.

AIMS: Catheter ablation is the most efficacious rhythm control therapy in atrial fibrillation (AF) patients. There is growing evidence that catheter ablation procedures are best performed during continuous oral anticoagulation, but outcomes are variable depending on the anticoagulation strategy or agent chosen. Specifically, there is a need to evaluate the peri-procedural use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients undergoing catheter ablation of AF. The AXAFA-AFNET 5 trial will test whether peri-procedural anticoagulation therapy using apixaban is a safe alternative to vitamin K antagonist (VKA) therapy for patients undergoing catheter ablation of AF. METHODS AND RESULTS: AXAFA-AFNET 5 is a randomized, prospective multi-centre study conducted in Europe and the USA. A total of 650 patients scheduled for AF ablation will be randomized 1:1 to undergo AF ablation on continuous treatment with the NOAC apixaban or with a VKA. Patients can undergo AF ablation after at least 30 days of continuous effective anticoagulation or after exclusion of atrial thrombi by transoesophageal echocardiogram. The trial includes a post-ablation magnetic resonance imaging substudy that will quantify silent brain lesions that can occur in neurologically asymptomatic patients after AF ablation. Patients will be followed on continuous anticoagulation for 3 months after the ablation. The primary outcome parameter of AXAFA-AFNET 5 is a composite of all-cause death, stroke, and major bleeding events. CONCLUSION: The results of AXAFA-AFNET 5 will provide evidence informing about the safety of apixaban in ablation patients and on its efficacy including effects on silent brain lesions. AXAFA - AFNET 5 is an investigator-initiated trial sponsored by AFNET. The trial is supported by the DZHK (German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research) and by Bristol-Myers Squibb/Pfizer Alliance.

MRI Assessment of Ablation-Induced Scarring in Atrial Fibrillation: Analysis from the DECAAF Study.

BACKGROUND: There is limited knowledge on the extent and location of scarring that results from catheter ablation and its role in suppressing atrial fibrillation (AF). We examined the effect of atrial fibrosis and ablation-induced scarring on catheter ablation outcomes in AF. METHODS: We conducted a prospective multicenter study that enrolled 329 AF patients presenting for catheter ablation. Delayed enhancement magnetic resonance imaging (DE-MRI) of the left atrium was obtained preablation. Scarring was evaluated in 177 patients with a DE-MRI scan obtained 90 days postablation. We evaluated residual fibrosis, defined as preablation atrial fibrosis not covered by ablation scar. The primary outcome was freedom from recurrent atrial arrhythmia. RESULTS: In the analysis cohort of 177 patients, preablation fibrosis was 18.7 ± 8.7% of the atrial wall. Ablation aimed at pulmonary vein (PV) isolation was performed in 163 patients (92.1%). Ablation-induced scar averaged 10.6 ± 4.4% of the atrial wall. Scarring completely encircled all 4 PVs only in 12 patients (7.3%). Residual fibrosis was calculated at 15.8 ± 8.0%. At 325 days follow-up, 35% of patients experienced recurrent arrhythmia. Multivariable Cox proportional hazards models demonstrated that baseline atrial fibrosis (HR and 95% CIs) (1.09 [1.06-1.12], P < 0.001) and residual fibrosis (1.09 [1.05-1.13], P < 0.001) were associated with atrial arrhythmia recurrence, while PV encirclement and overall scar were not. CONCLUSIONS: Catheter ablation of AF targeting PVs rarely achieves permanent encircling scar in the intended areas. Overall atrial fibrosis present at baseline and residual fibrosis uncovered by ablation scar are associated with recurrent arrhythmia.

Effects of enhanced pacing modalities on health care resource utilization and costs in bradycardia patients: An analysis of the randomized MINERVA trial.

BACKGROUND: Many patients who suffer from bradycardia and need cardiac pacing also have atrial fibrillation (AF). New pacemaker algorithms, such as atrial preventive pacing and atrial antitachycardia pacing (DDDRP) and managed ventricular pacing (MVP), have been specifically designed to reduce AF occurrence and duration and to minimize the detrimental effects of right ventricular pacing. The randomized MINimizE Right Ventricular pacing to prevent Atrial fibrillation and heart failure trial established that DDDRP + MVP pacing modality reduced permanent AF in bradycardia patients as compared with standard dual-chamber pacing (DDDR). OBJECTIVE: The aim of this study was to estimate the cost savings due to lower AF-related health care utilization events based on health care costs from the United States and the European Union. METHODS: Dual-chamber pacemaker patients with a history of paroxysmal or persistent AF were randomly assigned to receive DDDR (n = 385) or the advanced features (DDDRP + MVP; n = 383). We used published health care costs from the United States and the European Union (Italy, Spain, and the United Kingdom) to estimate the costs associated with AF-related hospitalizations and emergency visits. RESULTS: The rate of AF-related hospitalizations was significantly lower in the DDDRP + MVP group than in the conventional pacemaker group (DDDR group; 42% reduction; incidence rate ratio 0.58). Similarly, a significant reduction of 68% was observed for AF-related emergency department visits (incidence rate ratio 0.32; P < .001). As a consequence, DDDRP + MVP could potentially reduce health care costs by 40%-44%. Over a ten-year period, the cost savings per 100 patients ranged from $35,702 in the United Kingdom to $121,831 in the United States. CONCLUSION: New pacing algorithms such as DDDRP + MVP used in the MINimizE Right Ventricular pacing to prevent Atrial fibrillation and heart failure trial successfully reduced AF-related health care utilization, resulting in significant cost savings to payers.

Atrial antitachycardia pacing and managed ventricular pacing in bradycardia patients with paroxysmal or persistent atrial tachyarrhythmias: the MINERVA randomized multicentre international trial.

AIMS: Atrial fibrillation (AF) is a common comorbidity in bradycardia patients. Advanced pacemakers feature atrial preventive pacing and atrial antitachycardia pacing (DDDRP) and managed ventricular pacing (MVP), which minimizes unnecessary right ventricular pacing. We evaluated whether DDDRP and MVP might reduce mortality, morbidity, or progression to permanent AF when compared with standard dual-chamber pacing (Control DDDR). METHODS AND RESULTS: In a randomized, parallel, single-blind, multi-centre trial we enrolled 1300 patients with bradycardia and previous atrial tachyarrhythmias, in whom a DDDRP pacemaker had recently been implanted. History of permanent AF and third-degree atrioventricular block were exclusion criteria. After a 1-month run-in period, 1166 eligible patients, aged 74 ± 9 years, 50% females, were randomized to Control DDDR, DDDRP + MVP, or MVP. Analysis was intention-to-treat. The primary outcome, i.e. the 2-year incidence of a combined endpoint composed of death, cardiovascular hospitalizations, or permanent AF, occurred in 102/385 (26.5%) Control DDDR patients, in 76/383 (19.8%) DDDRP + MVP patients [hazard ratio (HR) = 0.74, 95% confidence interval 0.55-0.99, P = 0.04 vs. Control DDDR] and in 85/398 (21.4%) MVP patients (HR = 0.89, 95% confidence interval 0.77-1.03, P = 0.125 vs. Control DDDR). When compared with Control DDDR, DDDRP + MVP reduced the risk for AF longer than 1 day (HR = 0.66, 95% CI 0.52-0.85, P < 0.001), AF longer than 7 days (HR = 0.52, 95% CI 0.36-0.73, P < 0.001), and permanent AF (HR = 0.39, 95% CI 0.21-0.75, P = 0.004). CONCLUSION: In patients with bradycardia and atrial tachyarrhythmias, DDDRP + MVP is superior to standard dual-chamber pacing. The primary endpoint was significantly lowered through the reduction of the progression of atrial tachyarrhythmias to permanent AF. CLINICALTRIALSGOV IDENTIFIER: NCT00262119.

Comparison of hemodynamic versus dyssynchrony assessment for interventricular delay optimization with echocardiography in cardiac resynchronization therapy.

BACKGROUND: Best practice for cardiac resynchronization therapy (CRT) device optimization is not established. This study compared Tissue Doppler Imaging (TDI) to study left ventricular (LV) synchrony and left ventricular outflow tract velocity-time integral (LVOT VTI) to assess hemodynamic performance. METHODS: LVOT VTI and LV synchrony were tested in 50 patients at three interventricular (VV) delays (LV preactivation at -30 ms, simultaneous biventricular pacing, and right ventricular preactivation at +30 ms), selecting the highest VTI and the greatest degree of superposition of the displacement curves, respectively, as the optimum VV delay. RESULTS: In 39 patients (81%), both techniques agreed (Kappa = 0.65, p < 0.0001) on the optimum VV delay. LV preactivation (VV - 30) was the interval most frequently chosen. CONCLUSIONS: Both TDI and LVOT VTI are useful CRT programming methods for VV optimization. The best hemodynamic response correlates with the best synchrony. In most patients, the optimum VV interval is LV preactivation.

Plasma tissue inhibitor of matrix metalloproteinase-1 (TIMP-1): an independent predictor of poor response to cardiac resynchronization therapy.

AIMS: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in left ventricular structural remodelling. The aim of our study was to analyse MMP-2 and TIMP-1 levels as predictors of poor response to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: A cohort of 42 CRT patients from our centre was prospectively evaluated at baseline and after 12-month follow-up. MMP-2 and TIMP-1 assays were performed prior to CRT implant. Cardiac resynchronization therapy responders were defined as patients who survived, were not transplanted, and increased their basal 6 min walking distance test (6MWDT) by >or=10% or improved their NYHA functional class. Overall, 25 patients (60%) were classed as responders. At 12-month follow-up, six patients (14.2%) had died and one (2.4%) patient had been transplanted. Compared with responders, non-responders had higher levels of TIMP-1 (277 +/- 59 vs. 216 +/- 46 ng/mL, P = 0.001), MMP-2 (325 +/- 115 vs. 258 +/- 56 ng/mL, P = 0.02), and creatinine (1.76 +/- 0.8 vs. 1.25 +/- 0.3 mg/dL, P = 0.01). In a multivariate analysis, TIMP-1 was the only independent predictor of non-response to CRT [OR 0.97, 95% (CI 0.96-0.99) P = 0.005]. TIMP-1>or=248 ng/mL predicted non-response with 71% sensitivity and 72% specificity. CONCLUSION: TIMP-1 is an independent predictor of non-response in patients treated with CRT.

Assessment of left ventricular dyssynchrony by real-time three-dimensional echocardiography.

INTRODUCTION AND OBJECTIVES: A number of different imaging methods have been proposed as possible tools for assessing left ventricular (LV) mechanical dyssynchrony. The aim of this study was to evaluate the usefulness of real-time three-dimensional echocardiography (RT3DE) for studying LV mechanical dyssynchrony. METHODS: In total, 60 individuals underwent RT3DE, including 10 healthy volunteers, 23 patients with acute ST-segment elevation myocardial infarction and 27 patients with dilated cardiomyopathy. The LV volume was recorded throughout the full cardiac cycle using RT3DE, after which LV mechanical dyssynchrony was determined. The extent of LV mechanical dyssynchrony was characterized using the systolic dyssynchrony index (SDI), which was calculated from the variation in the time required to reach the minimum regional systolic volume in the 16 LV segments analyzed. RESULTS: The SDI was significantly higher in patients with dilated cardiomyopathy, at 14.3%+/-7.5% compared with 1.5%+/-0.7% in healthy volunteers and 8.1%+/-7.1% in acute myocardial infarction patients (ANOVA, P< .001). Basal and mid ventricular segments showed the greatest delays. All patients with dilated cardiomyopathy received cardiac resynchronization therapy. In this patient subgroup, the SDI exhibited an immediate significant decrease (to 9.7%+/-6.8%; P< .05) and a progressive decrease during 6 months of follow-up (to 4.9%+/-3.1%; P< .05). CONCLUSIONS: The new imaging technique of RT3DE can be used to assess LV mechanical dyssynchrony and is able to identify the LV segments with the greatest time delays.